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--- Do with heme ---

Type II Hypersensitivity Disorders - Cytotoxic:

Transfusion Reaction
- Antibody against ABO blood glycoproteins
- IgM isohemagglutinins formed naturally in response to
bacterial flora cause opsonization and complement
activation
- Leads to hemolysis

**Hemolytic Disease of the Newborn (Erythroblastosis


fetalis)

Antibody = Anti-RhD+ IgG


- Formed in Rh- mother carrying Rh+ child
- First pregnancy sensitizes (doesn't have to be viable
pregnancy)
- Antibody crosses placenta and injures subsequent fetuses
- Prevent with RhoGAM (anti-Rh, binds fetal red cells and
prevents mothers immune system from reacting)

Opsoclonus-Myoclonus Ataxia Syndrome is Opsoclonus-Myoclonus Ataxia Syndrome is


a paraneoplastic syndrome associated with a paraneoplastic syndrome associated with Small Cell Lung
Neuroblastoma in children Cancer in adults

- Opsoclonus = rapid, unpredictable, involuntary - Opsoclonus = rapid, unpredictable, involuntary


multivectorial conjugate fast eye movements; these do multivectorial conjugate fast eye movements; these do NOT
NOT have intersaccadic eye intervals have intersaccadic eye intervals ABO blood typing and screening for other preformed Abs;
always done in case of transplants.

Universal donor: type O

Universal recipient: type AB

(Ex) Type A can donate to type A and type AB. Type A can
receive donations from type A and type O.
- Anti-B antibodies prevent donation from type B and type
AB.

HLA Typing - Microcytotoxicity test

Tests for MHC class I (HLA-A, HLA-B)

Test hundreds of different haplotypes to find a potential


match.

Cells recognized by antibody will be attacked by


complement and thus become leaky and take up dye.

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HLA Typing - Mixed lymphocyte reaction

Tests for MHC class II (HLA-DR)

Take donor cells and irradiate them (prevent proliferation).


Irradiated cells are mixed with donor cells to see if
proliferation occurs.

Higher radioactivity (thymidine) signifies lower


compatibility.

--- Skipped for now --- :)

Lymphoid Cell Function

B & T cells

- Found in bloodstream, lymph nodes, spleen,


submucosa, and epithelia

B cells: contain markers CD19, CD20, CD21


- Mature into plasma cells
- Function is to produce antibodies 2-Napthylamine is a carcinogenic aromatic amine found in 2-Napthylamine is a carcinogenic aromatic amine found in
cigarette smoke associated with Transitional Cell Carcinoma cigarette smoke associated with Transitional Cell Carcinoma
TH cells: contain markers CD3 and CD4 of the Bladder of the Bladder
- Function is to regulate immune responses
Cigarette smoke carcinogens get concentrated in the urine, Cigarette smoke carcinogens get concentrated in the urine,
Cytotoxic T cells: contain markers CD3 and CD8 and then hangout in the bladder and then hangout in the bladder
- Function is to kill infected cells

NK cells
- Contain markers CD16 and CD56
- Function is to kill tumor/virus cell targets or
antibody-coated target cells

- T cells can only bind peptides that have been


processed and presented by major histocompatibility
complexes (MHCs)

A characteristic of the transformation from normal cells


to dysplastic cells is that there is a loss of tissue orientation

A Choristoma is normal tissue in a foreign location A Hamartoma is a disorganized overgrowth of tissues in a


native location
ex. Gastric tissue located in distal ileum in Meckel
Diverticulum Ex. Peutz-Jeghers polyps

Here you can see how the cervical epithelial cells lose

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orientation as they become more dysplastic:

A characteristic of the transformation from normal


A characteristic of the transformation from normal cells
cells to dysplastic cells is that there is is an increased
to dysplastic cells is that they become pleomorphic
nuclear to cytoplasmic ratio
there is a loss of uniformity of cell size and shape
Additionally, nuclei display clumped chromatin

A germline P53 mutation predisposes you to what tumor


syndrome?

Li-Fraumeni (SBLA) Syndrome

Here you can see how the cervical epithelial cells


Here you can see how the cervical epithelial cells become When patients develop a somatic hit of the normal P53, the
change in their nuclear to cytoplasmic ratio as they
more pleomorphic as they become more dysplastic: absence of both alleles of this tumor suppressor results in
become more dysplastic:
pathology

A hapten is a small antigen that may conjugate with larger


proteins to elicit an immune response A loss of function mutation to a tumor suppressor gene
A gain of function mutation converts a proto-oncogene
increases the risk of cancer
to an oncogene
e.g. penicillin may act as a hapten and bind to RBCs,
causing immune hemolytic anemia - with Tumor Suppressor genes, you need loss of function
this increases the risk of cancer
mutations in BOTH alleles
Rx// example of type II hypersensitivity

Acanthosis Nigricans can present as a paraneoplastic Activated regulatory T Activated regulatory T


syndrome associated with gastric cancer and other cells produce IL-10 and TGF-β (anti-inflammatory cells produce IL-10 and TGF-β (anti-inflammatory
visceral malignancies cytokines) cytokines)

Activation of the inflammasome leads to increased


production of IL-1B and IL-18

the inflammasome cleaves pro-IL-1B/18 to their active


forms

Acute inflammation typically results in resolution and Acute inflammation typically results in resolution and
healing, which is mediated by IL-10 and TGF-B healing, which is mediated by IL-10 and TGF-B

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Administration of toxoid is an example of active


Administration of antitoxin or monoclonal Administration of vaccines is an example of active
immunization
antibody is an example of passive immunization immunization
e.g. tetanus, diphtheria

An example of when the tumor staging factor of tumor size /


invasiveness is the most important is in Melanoma (Breslow
Thickness)

After the regional lymph nodes, what are the two most
common sites of metastasis?
Anti-NMDA receptor encephalitis can present as
a paraneoplastic syndrome associated with Ovarian
Liver and Lung
Teratoma

Both HIGHLY vascularized areas

Antigen loading onto MHC I occurs in the RER after Antigen loading onto MHC II occurs following release of Antigen loading onto MHC II occurs following release of
delivery of endogenous antigen via TAP (transporter the invariant chain in an acidified endosome the invariant chain in an acidified endosome
associated with antigen processing)

Antigen-independent antibody diversity in heavy chains is Antigen-independent antibody diversity in light chains is
Antigen-independent antibody
generated by V(D)J gene recombination generated by VJ gene recombination
diversity in heavy chains is generated by V(D)J gene
recombination

Antigen-independent antibody Antigen-independent antibody diversity is generated Antigen-independent antibody diversity is generated via
diversity in light chains is generated by VJ gene via insertion of random nucleotides during V(D)J random combination of heavy and light chains
recombination recombination by the enzyme terminal
deoxyribonucleotidyl transferase (Tdt)

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Antigens are brought into a lymph


node via afferent lymphatics

lymph nodes have many afferents and one or more


efferent

Are acute phase reactants produced by liver in acute or


Antigens that lack a peptide component are
chronic inflammatory states?
not recognizable by T cells and thus stimulate B
cells directly
Both :)
thymus-independent antigens; T cell receptors
can only bind peptides presented by MHC
notably induced by IL-6

B-cell activation begins with presentation of foreign


antigen on MHC II, which is recognized by a T-cell
receptor
Asbestos acts as a carcinogen by physically destroying
Arthus reaction leads to immune complex
cellular chromosomes
formation in the skin; characterized
by edema, necrosis, and activation of complement
the very slim fibers of asbestos tangle destructively with
chromosomes

BRCA1 and BRCA2 are tumor suppresors that are involved


in mediating the Homologous Recombination pathway of
DNA repair

- This is a form of double stranded break repair that


requires a template strand (thus must occur after S phase)

B-cell activation requires a costimulatory signal from - dsDNA breaks can be detected by ATM and the FA Core
binding between the CD40 receptor (B cell) Complex, acting as a nidus to recruit BRCA enzymes, which
and CD40 ligand (Th2 cell) then recruit RAD51 and others to fix the break

the Th2 cell then secretes cytokines to induce Ig class


switching; CD40 ligand is also known as CD154 B-cells with self-reactivity in the bone marrow are destroyed
by clonal deletion

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Before a tumor can be classified as benign or malignant


Because PSA can be also elevated in BPH and Because PSA can be also elevated in BPH and prostatitis with certainty, biopsy or excision must be performed
prostatitis besides Prostate Cancer, there is a questional besides Prostate Cancer, there is a questional risk/benefit for
risk/benefit for screening screening This is because some benign tumors can grow in a
malignant-like fashion, some malignant tumors can grow in
a benign-like fashion

Blastic bone metastases present with high alkaline


Benzidine is a carcinogenic aromatic amine found Benzidine is a carcinogenic aromatic amine found in textile
phosphatase levels
in textile dyes associated with Transitional Cell dyes associated with Transitional Cell Carcinoma of the
Carcinoma of the Bladder Bladder Thus prostate mets to the pelvis will present with high
alkaline phosphatase levels

Both G6PD and the Androgen Receptor are located on


which chromosome?

X Chromosome By age 1, the total IgA level is approximately 20%


By age 1, the total antibody level is approximately 60%
of adult levels
of adult levels
- HOWEVER one chromosome of the two is hence why breastfeeding is very important
randomly inactivated by Lyonization in each cell,
which eventually leads to cells in a sample of tissue
having an average expression of 1:1 isoform A:isoform
B

Cachexia is a syndrome of weight loss, muscle atrophy, and


fatigue that occurs in chronic diseases
CEA is elevated in gastrointestinal diseases (ex. Crohns,
CD14 is a marker of the monocyte-macrophage cell patients will have temporal wasting, clavicles become
Pancreatitis)
lineage apparent, interosseous wasting loss of fat in the triceps area
Also elevated in hypothyroidism, liver disease (liver and orbital areas
CD14 acts as a coreceptor for TLR4 binding of LPS
metabolizes CEA), and COPD
Ex. cancer, AIDS, HF, COPD; all of these have chronic
inflammation

Carcinogens are agents that damage cellular DNA of stem


Cancers that are detected late by screening tend to have a
Cachexia is mediated by what four cellular factors? cells
poor prognosis
TNF, IFN-y, IL-1, IL-6 - important carcinogens include chemicals, oncogenic
- this is because they will have had the time to accumulate
viruses, radiation
tons of divisions and mutations
Thus chronic disease and chronic inflammation are - damage is mediated via a variety of mechanisms;
- ex. Ovarian / Pancreatic / Lung carcinoma (lots of room to
intrinsically linked; these are also responsible for including adduct formation (ex alkylating agent
grow so unless they produce bioactive substances, will often
constitutional symptoms (ex. IL-6 in Cardiac Myxoma) chemotherapy), mutation of DNA (ex EBV incorporating
be asymptomatic)
into host DNA), or physical damage (ex asbetos fibers)

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Carcinogens are agents that damage cellular DNA of


stem cells

- important carcinogens include chemicals, oncogenic Carcinomas can also directly seed peritoneal structures
viruses, radiation Carcinoma implies epithelial origin, whereas Sarcoma
denotes mesenchymal origin - malignancies can penetrate into a natural "open field"
- damage is mediated via a variety of mechanisms; lacking physical barriers, such as the pleural cavity,
both terms generally imply malignancy
including adduct formation (ex alkylating agent pericardial space, subarachnoid space
chemotherapy), mutation of DNA (ex EBV
incorporating into host DNA), or physical damage (ex
asbetos fibers)

Cardiovascular manifestations of lupus include Cardiovascular manifestations of lupus include accelerated


accelerated atherosclerosis, small-vessel necrotizing atherosclerosis, small-vessel necrotizing vasculitis,
Cell-mediated immunity is used to defend against intra-
vasculitis, pericarditis, and libman-sacks endocarditis pericarditis, and libman-sacks endocarditis
cellular agents
These patients have a cutaneous vasculitis (palpable These patients have a cutaneous vasculitis (palpable
purpura, urticaria, pustules, subcu nodules, livedo purpura, urticaria, pustules, subcu nodules, livedo
reticularis) and is the most common cause of vasculitis reticularis) and is the most common cause of vasculitis in
in patients with SLE patients with SLE

Chronic exposure to Aflatoxins may cause cancer by


Chronic exposure to Aflatoxins may cause cancer by Chronic exposure to Aflatoxins may cause cancer by
causing a G:C --> T:A transversion in codon 249 of
causing a G:C --> T:A transversion in codon 249 of the causing a G:C --> T:A transversion in codon 249 of the
the TP53 gene
TP53 gene TP53 gene
- Aflatoxin levels can be detected in humans by
- Aflatoxin levels can be detected in humans by measuring - Aflatoxin levels can be detected in humans by measuring
measuring the levels of the AFB1-Guanine adduct in a
the levels of the AFB1-Guanine adduct in a patients urine the levels of the AFB1-Guanine adduct in a patients urine
patients urine

Chronic exposure to Beryllium can occur with patients


Chronic exposure to Arsenic may cause cancer by
who work in the aerospace industry, in electronics Chronic exposure to Chromium can occur with patients who
metabolites (ex. Dimethyl-Arsenic) inhibiting zinc
manufacturing, or with nuclear reactors work with metallurgy, dye and pigment manufacturing,
finger motifs in Base-Excision Repair and Nucleotide-
wood preservatives
Excision Repair enzymes - Beryllium is used to make semiconductors and missile fuel,
thus is an integral part of a wide array of fields

Chronic exposure to Nickel can occur with patients Chronic heart transplant rejection typically presents as Chronic kidney transplant rejection typically presents as
who work with stainless-steel arc welding, or in the accelerated atherosclerosis chronic graft nephropathy
production of batteries or ceramics

- Also seen in people who do any kind of nickel plating

Chronic mucocutaneous candidiasis can result from


congenital genetic defects in IL-17 or its receptor

thus these mutations cause TH17 dysfunction


Chronic liver transplant rejection typically presents Chronic lung transplant rejection typically presents as
as vanishing bile duct syndrome bronchiolitis obliterans IL-17 is secreted by TH17 and is a proinflammatory
cytokine that is involved in
affects small airways; presents with lymphocytic - production of neutrophil chemokines (recruits neutrophils
inflammation, fibrosis, and destruction of bronchioles to a site of inflammation)
- production of proinflammatory cytokines (IL-6, IL-1B,
TNFa)
- production of PGE2
- production of antimicrobial peptides by keratinocytes

Class switching to IgA is promoted by IL-5 and TGF-β

Cigarette Smoke contains a wide variety of


Class switching of IgM is mediated
carcinogenic compounds, with the most carcinogenic
by CD40L and cytokines from Th2 cells
being Polycyclic Aromatic Hydrocarbons

Class switching to IgA is promoted by IL-5 and Class switching to IgE is promoted by IL-4 and IL-13 Class switching to IgE is promoted by IL-4 and IL-13
TGF-β

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class switching to IgG is also promoted by IL-4 class switching to IgG is also promoted by IL-4

Colon metastases have a high predilection for the liver due


to its venous drainage into the portal vein

Consumption of IgA in breast milk is an example


Clonality of T lymphocytes can be determined by of passive immunization
looking for T-Cell Receptor rearrangement

If a single allele for the V region of the TCR


predominates in a lymphocytic population, monoclonal
proliferation is suspected

Cytotoxic T cells may induce apoptosis of target cells


via binding of Fas ligand to Fas, which causes release
of TNF

Cushing Syndrome and SIADH can present Cytotoxic (CD8+) T-cells kill virus infected, neoplastic, and
as paraneoplastic syndromes associated with Small donor graft cells by inducing apoptosis
Cell Lung Cancer

- SCLC can produce ADH and ACTH

Cytotoxic T cells may induce apoptosis of target cells


via release of perforins and granzymes, which leads
to activation of caspases

perforins create pores in the membrane of the cell,


granzymes activate caspases Death from Hereditary Angioedema is usually due to Deficiency of autoimmune regulator (AIRE) protein
Airway Swelling causes autoimmune polyendocrine syndrome-1

- patients must be sedated and intubated ASAP characterized by a range of autoimmune diseases, most
commonly hypoparathyroidism, Addison disease, and
- patients are worst at 24 hours, and this resolves by 48-72 candidiasis
hours (APECED)

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Differentiation of helper T
cells to Th17 is induced by IL-6 and TGF-β

Deficiency of autoimmune regulator (AIRE) protein


causes autoimmune polyendocrine syndrome-1
Dermatomyositis can present as a paraneoplastic syndrome
associated with adenocarcinomas
characterized by a range of autoimmune diseases,
most commonly hypoparathyroidism, Addison disease,
Especially Ovarian adenocarcinoma
and candidiasis
(APECED)

Differentiation of helper T
cells to Th17 is induced by IL-6 and TGF-β

Differentiation of helper T Differentiation of helper T


cells to Th17 is inhibited by IFN-y and IL-4 (from Th1 and cells to Th17 is inhibited by IFN-y and IL-4 (from Th1 and
Th2 cells) Th2 cells)

Differentiation of helper T Differentiation of helper T cells to Th1 is inhibited by IL-4


Differentiation of helper T
cells to Th1 is induced by IFN-γ and IL-12 and IL-10 (from Th2 cells)
cells to Th1 is induced by IFN-γ and IL-12

Differentiation of helper T Differentiation of helper T Differentiation of helper T


cells to Th1 is inhibited by IL-4 and IL-10 (from Th2 cells to Th2 is induced by IL-2 and IL-4 cells to Th2 is induced by IL-2 and IL-4
cells)

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Differentiation of helper T Differentiation of helper T


Differentiation of helper T cells to Treg is induced by TGF-β
cells to Th2 is inhibited by IFN-γ (from Th1 cells)
cells to Th2 is inhibited by IFN-γ (from Th1 cells)

Differentiation of helper T
cells to Treg is induced by TGF-β

Do both alleles of a tumor suppressor gene need to be


Do both alleles of a protooncogene need to be mutated in
mutated in order for expression of disease?
order for expression of disease?
Yes
No

As opposed to protooncogenes, where only one needs to be


Only need to damage one allele of a proto-oncogene
mutated

Do killed/inactivated Do live attenuated


vaccines induce cellular or humoral responses? vaccines induce cellular or humoral responses?

Humoral Both cellular and humoral :)


Do malignant tumors have metastatic potential?

yes

This is the hallmark of malignancy

Do severely dysplastic / carcinoma in situ cells


penetrate the intact basement membrane?

No
Do thymus-dependent antigens result in immunologic
Do thymus-independent antigens result in immunologic
memory?
memory?
Yes
No
class switching and immunologic memory occur as a result
weakly immunogenic; vaccines often require boosters and
of direct contact between B cells and Th cells (e.g.
adjuvants (e.g. pneumococcal polysaccharide vaccine)
diphtheria vaccine)

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This can be observed with this slice of cervical


epithelium, where dysplastic change is seen over the
entire thickness, but NOT penetrating the basement
membrane

Does Acanthosis Nigricans typically present as a


Do women's cells undergoing Neoplasia maintain a paraneoplastic syndrome?
1:1 ratio of G6PD isoforms? Do women's cells undergoing hyperplasia maintain a 1:1
ratio of G6PD isoforms? No
No
Yes
More commonly associated with Obesity and Insulin
These only have ONE isoform (as they are resistance
MONOclonal) - in insulin resistance, abundance of insulin leads to
activation of IGF1-receptors on keratinocytes

Does IgG cross the placenta?


Does IgA fix complement?
Does IgA cross the placenta?
Yes
No
No
provides infants with passive immunity

Does IgM cross the placenta? Does IgM fix complement?


Does IgG fix complement?
No Yes
Yes

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Does innate immunity have a memory response?


Does adaptive immunity have a memory response?
No
Yes
Does administration of the Toxoid vaccine itself have any
potential for causing disease?

No

Stimulates the immune system to make antibodies against


the toxin itself (which will only be found exogenously)

Does the medial track of the superficial lymphatic system of


Does the lateral track of the superficial lymphatic
the lower extremity bypass the popliteal nodes?
system of the lower extremity bypass the popliteal
nodes?
Yes
No
Thus lesions on the medial foot cause inguinal
lymphadenopathy only
thus lesions on the lateral foot are more likely to cause
lymphadenopathy in the popliteal and inguinal areas

Elevated hCG can be a paraneoplastic syndrome, such as in


pinealomas or large cell carcinoma

patients can present with galactorrhea, gynecomastia, or


precocious puberty due to hCG's shared alpha subunit with
FSH / LH

Elevated hCG can be a paraneoplastic syndrome, such Elevated β-hCG is seen in pregnancy, especially when there
as in pinealomas or large cell carcinoma are multiple gestations
Elevated α-fetoprotein (AFP) can be associated with
patients can present with galactorrhea, gynecomastia, abdominal wall defects (ex. Omphalocele) Therefore, in a pregnant female with higher than
or precocious puberty due to hCG's shared alpha expected β-hCG keep this on your differential as an easy
subunit with FSH / LH thing to rule out

Ethanol has many methods of carcinogenic activity Excluding skin cancer, which of the listed three
including: Ethanol has many methods of carcinogenic activity demographics count the incidence of the following cancers
(1) - metabolites forming DNA adducts including: as their top 3 most common in the United States?
(2) - depletion of S-adenosylmethionine (SAM) (1) - metabolites forming DNA adducts
(3) - stimulating the Epithelial-Mesenchymal (2) - depletion of S-adenosylmethionine (SAM) Children
Transition (3) - stimulating the Epithelial-Mesenchymal Transition

(1) - DNA adducts impair DNA repair processes from (1) - DNA adducts impair DNA repair processes from
working correctly working correctly
(2) - depletion of SAM leads to global DNA (2) - depletion of SAM leads to global DNA hypomethylation
hypomethylation (3) - stimulation of the EMT makes ordinary cancer cells
(3) - stimulation of the EMT makes ordinary cancer able to become metastatic
cells able to become metastatic

Excluding skin cancer, which of the listed three Excluding skin cancer, which of the listed three Exposure to carcinogenic Asbestos is most commonly seen
demographics count the incidence of the following demographics count the incidence of the following cancers in:
cancers as their top 3 most common in the United as their top 3 most common? - construction workers
States? - shipyard workers
Men - plumbers
Women

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- Asbestos was once hailed a miracle material as it was an


extremely good insulator; thus was infused into cement,
woven into mats / fabrics, or used as insulation for house
building

In contrast, #1 in women is Breast


In contrast, for men #1 is prostate

Exposure to carcinogenic Asbestos is most commonly Exposure to carcinogenic Asbestos is most commonly seen GVHD of the liver presents with similar histologic findings
seen in: in: to what immune disorder?
- construction workers - construction workers
- shipyard workers - shipyard workers Primary biliary cholangitis
- plumbers - plumbers

Another cause of Vanishing Bile Duct Syndrome; both


- Asbestos was once hailed a miracle material as it - Asbestos was once hailed a miracle material as it was an show lymphocytic inflammation with destruction of the
was an extremely good insulator; thus was infused into extremely good insulator; thus was infused into cement, small intrahepatic bile ducts; granulomas and bile staining
cement, woven into mats / fabrics, or used as woven into mats / fabrics, or used as insulation for house of hepatocytes are common findings; both have rise in ALP
insulation for house building building

Generation of antibody specificity occurs Generation of antibody specificity occurs


via somatic hypermutation with affinity maturation via somatic hypermutation with affinity maturation
Good Syndrome refers to the presence of
random point mutations in the Fab region are selected random point mutations in the Fab region are selected for
hypogammaglobulinemia that appears near simultaneously
for by clonal selection by clonal selection
as a thymoma

thus these patients present in adulthood with an anterior


mediastinal mass and recurrent sinopulmonary infections

Hereditary Angioedema presents in childhood with


recurrent episodes of swelling without urticaria

- patients develop swelling of skin (swollen extremities), GI


tract (severe abdominal pain), upper airway (dysphagia)
Hematopoetic Stem Cells, as well as Interstitial Cells of
Cajal, Mast Cells, and Melanocytes all express the c-Kit - often proceded by a prodrome of fatigue and flu-like
receptor symptoms
Graft-versus-host disease is potentially beneficial in
bone marrow transplants for patients with leukemia
- c-kit binds Stem Cell Factor, and thus plays a role in
graft-versus tumor effect hematopoesis

- activating mutations in c-kit can thus lead to GIST,


systemic mastocytosis, and melanoma

Histologically, the nuclei of benign tumors are uniform,


whereas the nuclei of malignant tumors are pleomorphic
and hyperchromatic

- hyperchromasia means the nucleus is very active and cell


is rapidly making protein

- Compare and contrast follicular adenoma of


thyroid (benign) and anaplastic carcinoma of the
High levels of α-fetoprotein (AFP) are seen in
thyroid (malignant)
Trisomy 13 (Patau) Histologically, in benign tumors there is absence of invasion
of basement membrane / local tissue, whereas in malignant
tumors there is presence of invasion

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How many classes of MHC I are expressed on a single cell?


How do lymphocyte levels change post-splenectomy? How do platelet levels change post-splenectomy?
Six
Increased (lymphocytosis) Increased (thrombocytosis)
three from each parent (codominant expression); the same
due to loss of sequestration due to loss of sequestration and removal
is true for MHC II

How much of the epithelium do cells that are severely


dysplastic or have become carcinoma in situ involve?

Entire thickness*

How many identical antigens can a single IgM


molecule bind?

10
* pathoma distinguishes epithelial involvement severe
pentamer with two antigen binding sites per Fab dysplasia from carcinoma in situ as slightly less than the
How specific is the serum tumor marker CEA?
region whole thickness vs the whole thickness
very nonspecific
- This can be observed with the following slice of cervical
epithelium, where dysplastic change is seen over the entire
thickness This is normally produced by GI tissue during fetal
development, production stops before birth and should be
present at very low levels in blood of healthy adults

Hypertrophic Osteoarthropathy can present as


Humoral immunity is used to defend against extra- Hypertrophic Osteoarthropathy is caused by abnormal
a paraneoplastic syndrome associated with Adenocarcinoma
cellular agents proliferation of skin and bone at distal extremities
of the Lung

IPEX syndrome is associated with a variety of IPEX syndrome is associated with a variety of
dermatological findings, but in particular patients dermatological findings, but in particular patients present
present with dermatitis, nail dystrophy, and other with dermatitis, nail dystrophy, and other autoimmune
autoimmune dermatologic conditions (especially dermatologic conditions (especially autoimmune alopecia)
autoimmune alopecia)
- Bullous Pemphigoid is also commonly seen
- Bullous Pemphigoid is also commonly seen
If a patient has moderately elevated serum Alkaline
phosphatase levels, you should determine if hepatobiliary
or bony origin by checking GGT levels

GGT = γ-glutamyl transpeptidase, increased in various liver


and biliary disease but NOT in bone disease

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IgA is transported through the mucosa via binding between


the J chain of IgA and the poly Ig receptor on epithelial
cells

IgA crosses epithelial cells by transcytosis IgA exists as a monomer in circulation

IgA is transported through the mucosa


via binding between the J chain of IgA and the poly Ig
receptor on epithelial cells

IgE cross-links when exposed to allergen, mediating type I


IgM exists as a monomer on the surface of B cells
hypersensitivity reactions

IgM exists as a pentamer held by a J chain when secreted

IgA exists as a dimer held by a J chain when secreted IgA exists as a dimer held by a J chain when secreted

In between the red and white pulp of the spleen is the In coagulative necrosis, there is increased cytoplasmic
marginal zone, which binding of eosin stain
IgM exists as a pentamer held by a J contains macrophages and specialized B cells
chain when secreted Results in the eosinophilic (red/pink) color of coagulative
necrosis

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In invasive carcinoma, cell-cell contacts are lost by


inactivation of E-cadherin

- Normally, this is how epithelial cells maintain


attachment (and prevent cellular overgrowth)

- once cells detach via cadherin connections, cells will


continue to grow outwards and over each other (aided
by the resultant inactivation of the Merlin tumor
suppressor protein)

In lymph nodes, secondary follicles have pale, central


In lymph nodes, primary follicles are dense and dormant
germinal centers and are active

In regards to cervical epithelium, if the tissue sample on the In regards to cervical epithelium, if the tissue sample on the
left is normal, is the tissue sample on the right: mildly left is normal, is the tissue sample on the right: mildly
dysplastic, moderately dysplastic, or severely dysplastic / dysplastic, moderately dysplastic, or severely dysplastic /
carcinoma in situ? carcinoma in situ?

Mildly Dysplastic Moderately Dysplastic

In lymph nodes, secondary follicles have pale, central


germinal centers and are active

VS VS

- mildly increased nuclear to cytoplasmic ratio of cells - moderately increased nuclear to cytoplasmic ratio of cells
- mild loss of tissue orientation - moderate loss of tissue orientation
- mildly pleomorphic cells - modeteraly pleomorphic cells

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In regards to cervical epithelium, if the tissue sample


on the left is normal, is the tissue sample on the
right: mildly dysplastic, moderately dysplastic,
or severely dysplastic / carcinoma in situ?

Severely Dysplastic / Carcinoma in Situ

In the "seed and soil" theory of metastasis: the "soil" (target


organ) is often the first encountered capillary bed

In terms of bone tumors, are bone metastases or 1* bone Ex. Liver, Lungs, Bone, Brain
tumors more common?

Metastases, significantly

VS

- Involves the entire thickness of the epithelium but


does NOT penetrate the intact basement membrane

In the "seed and soil" theory of metastasis: the seed is


the tumor embolus
In the United States, cancer is the second leading cause of
death in which of the following age groups? In the setting of chronic inflammation, macrophages can
be activated to M1 macrophages by stimulation from Th1
cells, resulting in a proinflammatory phenotype

This is the classical activation pathway, and is mediated by


IFN-y

In the setting of chronic inflammation, macrophages can In the setting of chronic inflammation, macrophages can
In the setting of chronic inflammation, macrophages
be activated to M2 macrophages by stimulation from Th2 be activated to M2 macrophages by stimulation from Th2
can be activated to M1 macrophages by stimulation
cells, resulting in a antiinflammatory phenotype cells, resulting in a antiinflammatory phenotype
from Th1 cells, resulting in
a proinflammatory phenotype This is the alternative activation pathway, and is mediated This is the alternative activation pathway, and is mediated
by IL-4/IL-13 by IL-4/IL-13
This is the classical activation pathway, and is
mediated by IFN-y
These macrophages are also involved in repair processes These macrophages are also involved in repair processes

In the thymic medulla, the T cell differentiates into a In type III HSRs, antigen-antibody In type III HSRs, antigen-antibody
CD4+ or CD8+ T cell complexes activate complement, which complexes activate complement, which
attracts neutrophils attracts neutrophils

neutrophils then release lysosomal enzymes neutrophils then release lysosomal enzymes

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In what sole population is the Adenovirus vaccine


indicated? In which type of immunity (innate or adaptive)
In which type of immunity (innate or adaptive) is microbial
does microbial resistance persist through generations?
resistance not heritable?
Military recruits
Innate immunity
Adaptive immunity
Used to prevent ARDS; not given to children due to
worry over lack of attenuation and oncogenic potential This does NOT change within a organism's lifetime
of these vaccines

Incidence of lung cancer in the United States has


decreased in men, but has only since the 2000's started
to decrease in women
Invasive carcinoma cells first bind to basement membrane
- According to the ACS Cancer Statistics report in via laminin Invasive carcinoma invades through the basement
2016, it has begun to decrease in women membrane using matrix metalloproteinases to access the
(corresponding to decline in tobacco use) They then release collagenase to cleave up the basement extracellular matrix
membrane to mediate invasion into extracellular matrix
- According to that same statistics report, the Ex. collagenases and hydrolases; basement membrane is
differences between incidence in men vs women has to normally, laminin in basement membranes may pose a made of type IV collagen
do with historical patterns in tobacco use (women physical barrier to the sprouting of new blood vessels
began smoking in large numbers many years later than
men)

Invasive carcinomas become metastatic when they


invade the lymphatics or blood

Hematogenous metastasis is MUCH less common


Is a Choristoma neoplastic? Is a Hamartoma neoplastic?

No No

Is adaptive immunity specific or nonspecific?

Highly specific
Is carcinoma in situ reversible? Is cell-mediated immunity primarily mediated
by B-cells or T-cells?
No
T-cells

However, there is a slight chance that severe dysplasia may


become reversible (ex. CIN III)

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Is innate immunity specific or nonspecific?

Non-specific

Is humoral immunity primarily mediated


by B-cells or T-cells? Is mild/moderate dysplasia reversible?

B-cells Potentially

however, B cells require Th2 cells for an effective


May regress with alleviation of inciting cause
response

Is this histology of this Cervical Epithelium normal, mildly


dysplastic, moderately dysplastic, or severe dysplasia /
carcinoma in situ?

Normal
Is the T-cell antigen receptor mobile or rigid?

Rigid (no hinge region)

Is the conjugate vaccine or the polysaccharide vaccine the


only meningococcal vaccine indicated for people older
than 55?

Polysaccharide

Normal cells with basal to apical polarity

Ischemia can occur due to hypoperfusion (ex. shock)

This impairs tissue oxygenation, decreasing oxidative


phosphorylation, leading to build up of NADH and shunting
Ischemia can occur due to decreased arterial perfusion Ischemia can occur due to decreased venous drainage of pyruvate to lactic acid; thus patients with septic shock
may develop increased AG metabolic acidosis
ex. atherosclerosis ex testicular torsion, budd-chiari syndrome
additionally, in septic shock hepatic hypoperfusion
contributes to build up of lactic acid as liver is the primary
site of lactate clearance

LDH can be used as an indicator of tumor burden Lambert Eaton Myasthenic Syndrome is a paraneoplastic
LPS, bacterial flagellin, and viral nucleic acids are detected
syndrome associated with Small Cell Lung Cancer
Tumor Burden refers to the number of cancer cells, the by the innate immune system via Pattern-Recognition
size of a tumor, or the amount of cancer in the body Receptors proximal muscle weakness + ocular / bulbar symptoms
(Also called tumor load) syndrome that gets better throughout the day

Li-Fraumeni Syndrome is also known as "SBLA"


Li-Fraumeni Syndrome is also known as "SBLA" Li-Fraumeni Syndrome is also known as "SBLA"
Syndrome, which stands for:
Syndrome, which stands for: Syndrome, which stands for:
S - Sarcoma
S - Sarcoma S - Sarcoma
B - Breast Cancer
B - Breast Cancer B - Breast Cancer
L - Leukemia
L - Leukemia L - Leukemia
A - Adrenal Gland tumor
A - Adrenal Gland tumor A - Adrenal Gland tumor

Loss of the P53 tumor suppressor results in a


Loss of the P53 tumor suppressor results in a constellation Loss of the P53 tumor suppressor results in a constellation
constellation of tumors due to absence of G1-S
of tumors due to absence of G1-S checkpoint regulation of tumors due to absence of G1-S checkpoint regulation
checkpoint regulation

Li-Fraumeni Syndrome is also known as "SBLA"


Syndrome, which stands for:
Live attenuated vaccines are Live attenuated vaccines are
often contraindicated in pregnancy and immunodeficiency often contraindicated in pregnancy and immunodeficiency
S - Sarcoma
B - Breast Cancer
due to potential to cause significant disease due to potential to cause significant disease
L - Leukemia
A - Adrenal Gland tumor

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Loss of the P53 tumor suppressor results in a


constellation of tumors due to absence of G1-S
checkpoint regulation

Low levels of α-fetoprotein (AFP) are seen in Low levels of α-fetoprotein (AFP) are seen in Trisomy 21
Trisomy 21 (Down's) and decreased levels are seen in (Down's) and decreased levels are seen in Turner Lung metastases have a high predilection for the brain due
Turner Syndrome Syndrome to the proximity of the cerebral vasculature

The lungs drain into azygos / hemiazygos circulations which


routes to the heart; immediately leaving the heart, the aortic
arch gives off the carotids and the subclavians, both of
which supply the cerebral vasculature (directly or
indirectly)

MHC II binds to the T-cell receptor (TCR) and CD-4 MHC II binds to the T-cell receptor (TCR) and CD-4

rule of 8: MHC II * CD4 = 8; MHC I * CD8 = 8 rule of 8: MHC II * CD4 = 8; MHC I * CD8 = 8
Lytic bone metastases present with hypercalcemia

Thus lung mets to the bone will present with


hypercalcemia (be wary if the patient has squamous
cell carcinoma of the lung, as that can also produce
PTHrP)

MHC I binds to the T-cell receptor (TCR) and CD-8

rule of 8: MHC II * CD4 = 8; MHC I * CD8 = 8

MHC II presents exogenously synthesized antigens MHC II presents exogenously synthesized antigens
to CD4+ helper T cells to CD4+ helper T cells

MHC I presents endogenously synthesized antigens MHC I presents endogenously synthesized antigens
to CD8+ cytotoxic T cells to CD8+ cytotoxic T cells

MHC I binds to the T-cell receptor (TCR) and CD-8

rule of 8: MHC II * CD4 = 8; MHC I * CD8 = 8

Manifestations of acute kidney transplant rejection include


increased creatinine, hypertension, and reduced urine output

can be antibody mediated or cell mediated is associated


with a lymphocytic infiltrate Marantic Endocarditis and Trousseau Syndrome can
present as paraneoplastic syndromes associated with
usually seen within the first 6 months after renal transplant, visceral Aaenocarcinomas
with most episodes occuring in the early postoperative
Major histocompatibility complexes (MHCs) are
period - Particularly with Pancreatic, colon, lung cancers, also
encoded by HLA genes
seen with Gliomas

- Marantic endocarditis is also known as Nonbacterial


thrombotic endocarditis (endocarditis that can affect both
sides of the valve)

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Metastases to the bone have a predilection for the axial


skeleton
Medullary sinuses within lymph nodes communicate with
the efferent lymphatics

Maternal IgG crossing the placenta is an example


of passive immunization

Metastasis to bone may be bone forming (blastic), Metastasis to bone may be bone forming (blastic), bone
bone destructive (lytic), or mixed destructive (lytic), or mixed Most cases of serum sickness are now caused
by drugs acting as haptens
The only blastic of note are prostate mets, and the only The only blastic of note are prostate mets, and the only
mixed of note are breast mets mixed of note are breast mets

Most notably, the serum tumor marker β-hCG is elevated


in with patients with Gestational Trophoblastic Disease
(GTD), Testicular Cancer (non-seminomatous), and Mixed
Most notably, the serum tumor marker CA 15-3 / CA
Germ Cell tumors
27-29 are seen elevated in Breast Cancer
Most cases of serum sickness are now caused - the hCG hormone is composed of two subunits, alpha and
- elevated levels of CA 15-3 / CA 27-29 with
by drugs acting as haptens beta; the alpha subunit is shared by other hormones so it is
ALP are associated with an increased chance of early
not utilized as a serum tumor marker
recurrence in breast cancer
- GTD includes hydatidiform moles, choriocarcinomas;
- Also seen in sarcoidosis, lupus, and cirrhosis
because levels of hCG can reach extremely high levels,
patients can rarely present with hyperthyroidism (due to
TSH sharing alpha-subunit)

Most notably, the serum tumor marker CA-125 is seen


elevated in Ovarian Adenocarcinoma
Most notably, the serum tumor marker CA 19-9 is seen
elevated in Pancreatic Adenocarcinoma mucin that advances tumorigenesis and proliferation by
several mechanisms:
- This is the Sialyl-LewisA antigen and like Sialyl- Most notably, the serum tumor marker Calcitonin is seen
elevated in Medullary Thyroid Carcinoma
Lewisx is involved in cell to cell recognition processes - suppresses natural killer response
Alone and in MEN2A / 2B
- also elevated in esophageal, HCC, and advanced - binds to mesothelin glycoprotein which is expressed
colorectal cancer; thus used more to distinguish mesothelial cells of the peritoneum (thus aiding in omental
between cancer and other diseases of the pancreas caking)

- facilitates invasion by downregulating E-cadherin

Most notably, the serum tumor marker Alkaline Most notably, the serum tumor marker Chromogranin is Most notably, the serum tumor marker LDH is elevated in
Phosphatase (ALP) is elevated in patients with elevated in with patients with neuroendocrine tumors testicular germ tumors and ovarian dysgerminoma
metastases to bone or liver, Paget Disease of Bone, or

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chromogranin is a prohormone that is present in the


Seminoma secretory granules of a wide variety of endocrine cells, act LDH is lactate dehydrogenase, highly found in cells that
as negative feedback for neuroendocrine function of utlilize lots of glycolysis
releasing cells / nearby cells

Mutations in CCND1 can cause Mantle Cell Lymphoma via


a t(11;14) translocation to the Ig Heavy Chain locus

- the Ig Heavy Chain locus is constitutively expressed, thus Mutations in CDK4 can cause Melanoma due to a resultant
Cyclin-D1 becomes constitutively expressed when amplification of the proteins activity
translocated; thus in lymph nodes, the region next to the
follicle (the mantle) expands

- note: this is NOT producing a fusion protein like with the


Philadelphia chromosome, instead just swapping positions

Most notably, the serum tumor marker PSA is elevated


in Prostate Cancer

PSA is Kallikrein 3, an enzyme produced by the


prostate that liquefies semen

Mutations in PTEN lead to overactivity of mTOR proto-


oncogene

- PTEN is tumor suppressor that works by


dephosphorylating PIP3 to PIP2 (PIP3 normally leads to
activation of mTOR)

Mutations in MYCN can cause Neuroblastoma due to a


Mutations in MYCL1 can cause Small Cell Lung
resultant amplification of the transcription factors activity
Carcinoma due to a resultant amplification of the
transcription factors activity - activating mutations are associcated with neuroblastoma,
and are associated with poor prognosis

Mutations in c-Myc can cause Burkitt Lymphoma via a Mutations in which proto-oncogene can lead to Chronic Mutations in which proto-oncogene can lead to Colon
t(8;14) translocation to the Ig Heavy Chain locus Myeloproliferative Disorders? Cancer, Non-Small Cell Lung Adenocarcinoma, and
Pancreatic Cancer?
- the Ig Heavy Chain locus is constitutively expressed, JAK2
thus c-Myc becomes constitutively expressed when KRAS
translocated
- JAK2 is a non-receptor tyrosine kinase that when mutated
- note: this is NOT producing a fusion protein like with at the 617 position to Phenylalanine becomes exquisitely KRAS is a member of the RAS family, and when GTP bound
the Philadelphia chromosome translocation, instead sensitive to growth factors like EPO / TPO this protein allosterically activates RAF kinase, activating
just swapping positions the MAPK pathway
- JAK/STAT pathway is involved with lots of cytokines (ex.
IL-2, IFN, G-CSF) and anterior pituitary hormones (ex.
Prolactin, GH)

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Mutations in which tumor suppressor gene can lead


to FAP associated Colorectal Cancer?

Mutations in which proto-oncogene can lead to Non- Mutations in which tumor suppressor gene can lead to APC
Small Cell Lung Adenocarcinoma and Anaplastic Breast, Prostate, Endometrial Cancer, and Cowden
Large-cell Lymphoma? Syndrome?
- Endogenously involved in regulation of the B-catenin/WNT
ALK PTEN Pathway

- Mutations in this begin the "Chromosomal Instability"


ALK is an RTK that is involved in development of the - Cowden Syndrome is a AD inherited disorder pathway of colorectal cancer; "You need A PC to FAP"
brain; gets its name from "Anaplastic Lymphoma (macrocephaly, intestinal hamartomatous polyps, benign
Kinase" skin tumors, and cerebellar tumor)

Mutations in which tumor suppressor gene can lead


to Juvenile Polyposis Syndrome, Colon
Adenocarcinoma, and Pancreatic Cancer?
Mutations in which tumor suppressor gene can lead
Mutations in which tumor suppressor gene can lead to Melanoma, Pancreatic Cancer, and Dysplastic Nevus
SMAD4
to MEN I? Syndrome?

- This is also known as DPC4; involved in TGF-B Menin CDKN2A


signalling pathway; in colon cancer, LOH 18q21
results in loss of SMAD 2 / SMAD 4
Menin is a tumor suppressor of unknown mechanism Encodes two different tumor suppresor genes that enforce
the G1-->S restriction point
– JPS is characterized by hamartomatous polyps in GI
tract; usually benign but there is a greater risk of
developing colon cancer

Mutations in which tumor suppressor gene can lead Mutations in which tumor suppressor gene can lead to von
to Neurofibromatosis II? Hippel-Lindau disease?

Merlin (Schwannomin) VHL


Mutations in which tumor suppressor gene can lead
to Neurofibromatosis I?
- Merlin is involved in contact inhibition; a behavior - pVHL is a E3 ubiquitination ligase that regulates HIF1a
Neurofibromin expressed by fibroblast like cells when they adhere to each under conditions of normoxia, marking for degradation by
other or come into contact proteasome

- this is a Ras GAP protein - If the cells adhere to each other, this signals each cell to - In hypoxia, HIF1a can dimerize with HIF1b to activate
stop growing outwards; when cadherins link this leads to transcription of VEGF, PDGF, EPO (resulting in formation
dephosphorylation of Merlin which causes cell cycle of new vasculature and RBCs)
arrest and tumor suppression (for as long as the cells are in
contact - linked by cadherins)

- if mutated, fibroblast like cells divide and grow over each


other in an uncontrolled manner (important in cancer
invasion / metastasis)

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Mutations in which tumor suppressor genes can lead


to Tuberous Sclerosis?

TSC1 & TSC2

- TSC1 and TSC2 form a complex that is a GAP (GTPase


activating protein) for Rheb; When Rheb is GTP bound it
activates mTORC1, stimulation of the GTPase activity
means Rheb turns off more quickly Mutations in which tumor suppressor genes can lead to
Mutations in which tumor suppressor genes can lead to
Wilms Tumors?
Breast, Ovarian, and Pancreatic cancers? - mTORC1 is involved in cell growth and cell size, thus
mutations in TSC complex lead to more mTORC1 activity WT1 and CDKN1C (WT2)
BRCA1/BRCA2 (observed in the hamartomas of Tuberous Sclerosis)

- WT1 is a protein expressed by the metanephric


- These are involved in mediating dsDNA repair
mesenchyme that helps initiate reciprocal-inductive
development of the kidney; involved in WAGR Complex and
- patients can have inherited Autosomal Dominant
Denys-Drash
germline mutations in these genes; these display
incomplete penetrance and are more common among
- CDK1NC (WT2) is a paternally imprinted inhibitor of the
ashkenazi jews
IGF2 gene; involved in Beckwith-Wiedemann Syndrome

Mutations that cause overexpression of the Mutations that cause overexpression of the
HER2 receptor can precipitate development of HER2 receptor can precipitate development of Breast* and Mutations that cause overexpression of the PDGFB proto-
Breast* and Gastric* Cancers by amplifying the signal Gastric* Cancers by amplifying the signal transduction oncogene can precipitate development of an Astrocytoma by
transduction creating an autocrine loop
- *a subset of breast and gastric cancers that are HER2+;
- *a subset of breast and gastric cancers that are this is overexpressed in 20-30% of breast cancers and is - Because Astrocytes have a PDGF receptor, and also when
HER2+; this is overexpressed in 20-30% of breast associated with poorly differentiated, rapidly growing stimulated produce PDGF, overexpression mutations can
cancers and is associated with poorly differentiated, tumors cause a positive feedback loop of Astrocyte growth
rapidly growing tumors
- these can then be treated by HER2 blocking agents, like
- these can then be treated by HER2 blocking agents, Trastuzumab
like Trastuzumab

Mutations that cause overexpression of


the PDGFB proto-oncogene can precipitate Natural infection is an example of active immunization
Myasthenia Gravis is a paraneoplastic
development of an Astrocytoma by creating an
syndrome associated with Thymoma
autocrine loop
proximal muscle weakness + ocular / bulbar symptoms
- Because Astrocytes have a PDGF receptor, and also
syndrome that gets worse throughout the day
when stimulated produce PDGF, overexpression
mutations can cause a positive feedback loop of

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Astrocyte growth

Natural killer cells may kill cells via binding Natural killer cells may kill cells via binding
between CD16 (NK cells) and the Fc region of Ig-bound between CD16 (NK cells) and the Fc region of Ig-bound
antigen antigen

antibody-dependent cellular cytotoxicity antibody-dependent cellular cytotoxicity


(ADCC); neutrophils, macrophages, and eosinophils may (ADCC); neutrophils, macrophages, and eosinophils may
kill cells via similar mechanisms kill cells via similar mechanisms

Natural killer cells may induce apoptosis of virally


infected cells and tumors cells via release
of perforins and granzymes

Once past the basement membrane, Invasive


Nowadays, patients typically can get chronically carcinomas are able to spread locally via attachment to
Nowadays, patients typically can get chronically exposed fibronectin
exposed to Arsenic in a couple of different situations,
to Arsenic in a couple of different situations, including:
including:
(1) - cigarette smoke Fibronectin allows traversal of the extracellular matrix by
(1) - cigarette smoke
(2) - Herbicides used in vineyards the carcinoma so they can enter the lymphatic or blood
(2) - Herbicides used in vineyards
(3) - metal smelting supply
(3) - metal smelting

(2) - also used as a pesticide in Asia


(2) - also used as a pesticide in Asia
(3) - specifically, melting of zinc or copper ores
(3) - specifically, melting of zinc or copper ores
you can test for arsenic poisoning in patients by testing
you can test for arsenic poisoning in patients by testing
fingernails / hair
fingernails / hair
acute exposures are insecticides / contaminated water
acute exposures are insecticides / contaminated water

One hallmark of cancer is the Warburg effect, in which


cancer cells shift glucose metabolism from mitochondria
toward glycolysis

One cardinal sign of inflammation is Functio laesa, or One example of a thymus-independent


loss of function antigen is lipopolysaccharides (LPS) from gram negative
bacteria
occurs when rubor, calor, tumor, dolor impair function
of affected tissue (ex patients hand has cellulitis and
patient cannot make fist) Recognized by TLR-4

One hallmark of cancer is the ability to be insensitive One risk of passive immunotherapy is IgE One use of Mammography as a screening tool is to detect
to anti-growth signals, such as TGF-Beta production and anaphylaxis, especially in patients invasive carcinoma before it becomes clinically palpable

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with selective IgA deficiency - average size of the tumor is 2 cm before it becomes
clinically palpable
TGF-Beta prevents phosphorylation of Rb protein
these patients must be given IgA-depleted globulins
- mammography can catch the tumor at 1 cm

P-glycoprotein is encoded for by the MDR1 gene

- This is an efflux pump normally used by gut and kidney to


One use of the Hemoccult test and Colonoscopy as P-glycoprotein is classically seen in adrenocortical pump out toxins, tumors can use these to pump out
screening tools is to detect colonic carcinoma before it carcinoma but is also expressed in various other cancers chemotherapeutics
spreads
- particularly, colon and liver cancer - In contrast, the MDR2 gene encodes for another efflux
pump that the liver uses to excrete conjugated bilirubin /
kidney uses to excrete toxins (defective in Dubin-Johnson
syndrome)

P-glycoprotein is normally found in the intestinal and renal P-glycoprotein is normally found in the intestinal and renal
tubular epithelial cells to eliminate foreign compounds from tubular epithelial cells to eliminate foreign compounds from
P-glycoprotein is found in the capillary endothelium
the body the body
of the blood brain barrier
Efflux pump for toxins, but also can pump out Efflux pump for toxins, but also can pump out
chemotherapeutics chemotherapeutics

Paraneoplastic Cerebellar Degeneration is a Paraneoplastic Encephalomyelitis is a paraneoplastic


paraneoplastic syndrome associated with antibodies against syndrome associated with antibodies against antigens in
PSA can be used as a surveillance marker for recurrent antigens in purkinje cells Neurons
disease after prostatectomy
- Because this affects all portions of the cerebellum, patients - this is a patchy multifocal inflammatory disorder that
present with truncal ataxia, scanning dysarthria, limb affects the brain, brainstem, cerebellum, DRG, and spine;
ataxia, and nystagmus resulting in dysfunction of all of these areas

Patients get exposed to Aflatoxins produced by Aspergillus Patients get exposed to Aflatoxins produced by Aspergillus
Patients get chronically exposed to Vinyl Chloride if
by way of eating improperly stored grains and nuts by way of eating improperly stored grains and nuts
they manufacture PVC
- improper storage can be due to prolonged exposure to - improper storage can be due to prolonged exposure to
- Vinyl Chloride is used to make PVC (polyvinyl
high humidity environment or stressful conditions like high humidity environment or stressful conditions like
chloride); working with PVC pipes is fine, it is the
drought (thus in some countries in Africa, HCC is the most drought (thus in some countries in Africa, HCC is the most
people who make the PVC pipes who are at risk
common cancer) common cancer)
- this is sometimes also used as a refrigerant, and
- regularly found in improperly stored staple commodities; - regularly found in improperly stored staple commodities;
historically was used as an inert aerosol propellant in
rice, cassava, chili peppers, corn, grains, peanuts, sesame rice, cassava, chili peppers, corn, grains, peanuts, sesame
pressurized containers
seeds seeds

Patients typically get exposed to Ionizing radiation via Patients typically get exposed to Non-Ionizing radiation via
nuclear reactor accidents or radiotherapy exposure to the sunlight
Patients undergoing splenectomy should
- Ex people who were affected by the fallout of the - This is primarily due to UV-B radiation be vaccinated against encapsulated organisms
Chernobyl accident in Russia
- Sunblock will help prevent melanoma and squamous cell e.g. pneumococcal, Hib, and meningococcal vaccines
- Ex Patients who are undergoing radiation therapy for carcinoma, however it will NOT help prevent basal cell
cancer carcinoma

Patients with Good Syndrome have deficient levels of what


Patients who are smokers have higher levels of what Patients who get chronically exposed to Nickle, Chromium,
types of lymphocytes?
serum tumor marker? Beryllium, or Silica are at risk for what cancer?
B & T lymphocytes
CEA Lung Cancer

These patients also have an inverted CD4/CD8+ ratio

Patients with systemic mastocytosis are prone to


Patients with ataxia-telangiectasia have vitiligo,
developing gastric ulcers
granulomas, and a high recurrence of sinopulmonary
Patients with systemic mastocytosis can present with
infections
syncope, flushing, hypotension, pruritis, and urticaria due to
This is due to excessive gastric acid secretion; excess massive histamine release
recurrent sinopulmonary infections can lead to
gastric acid also leads to diarrhea due to inactivation of
bronchiectasis; due to being IgA, IgG, and IgE
pancreatic / intestinal enzymes; patients also present with
deficient
nausea, vomiting, and abdominal cramps

Patients with systemic mastocytosis have clonal mast Pattern-Recognition Receptors recognize PAMPs which Polycyclic Aromatic Hydrocarbons (PAH) cause
cell proliferation in the bone marrow, skin, and other leads to activation of NF-kB carcinogenesis through their metabolites forming DNA
organs adducts
PAMPs = pathogen-associated molecular patterns (ex LPS
Thus can present with symptoms due to invasion - ex. being recognized by TLR4) Additionally, they can bind to the Aryl Hydrocarbon

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arthralgias, bone pain / sclerotic bone lesions; as well


Receptor, which upregulates P450 enzymes involved in
as symptoms due to mast cell degranulation - ex.
making PAH metabolites
episodic blisters, flushing, peptic ulcers

Prostate metastases have a high predilection for the


spine due to the prostates venous plexus connection to
Batson's venous plexus

- this is a network of veins with no valves that connect


the deep pelvic veins that drain the bladder, prostate,
and rectum to the internal vertebral venous plexus;
this
Proto-oncogenes are essential for cell growth and
- the vertebral venous plexus also connects to many differentiation
other venous supplis from organs in the pelvis as well
as connecting to the venous supply of the brain via a - Mutations of proto-oncogenes form oncogenes that lead to
valveless system, allowing for bidirectional flow and unregulated cellular growth
regulation of intracranial pressure
- categories of proto-oncogenes include: growth factors,
growth factor receptors, signal transducers, and cell cycle
regulators

Pure Red Cell Aplasia and Good Syndrome can present


as paraneoplastic syndromes associated with Thymoma

Thus a patient can have decreased RBCs and WBCs

Rupture of the thoracic duct can cause chylothorax

Rupture is due to trauma; usually surgical in nature,


particularly in patients who have open heart surgery (ex for
CABG)

Serum sickness presents


Regarding the incidence of the three main types of skin
with fever, urticaria, arthralgia, proteinuria,
cancer in the United States, Basal > Squamous >>
and lymphadenopathy 5 - 10 days after antigen exposure
Melanoma

Some killed vaccines are conjugated to a protein to elicit


a stronger immune response (e.g. immunologic memory)

Serum tumor markers should only be used for: Serum tumor markers should only be used for: typically a polysaccharide vaccine attached to a protein
- monitoring tumor recurrence - monitoring tumor recurrence antigen (e.g. Hib, meningococcal, pneumococcal vaccines)
- monitoring response to therapy - monitoring response to therapy

These should not be used as a primary tool for cancer These should not be used as a primary tool for cancer
diagnosis or screening as some can be associated with diagnosis or screening as some can be associated with non-
non-neoplastic conditions neoplastic conditions

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Systemic amyloidosis can have hematologic


Splenic sinusoids are long, vascular channels manifestations, including splenomegaly and periorbital
with fenestrated basement membranes that constitute purpura
the red pulp
"Raccoon Eyes" depicted (periorbital purpura):

Systemic amyloidosis can have gastrointestinal


manifestations, including hepatomegaly, malabsorption
and macroglossia

Systemic mastocytosis can be characterized by prominent


Systemic amyloidosis can result in a peripheral Systemic amyloidosis can result in a peripheral neuropathy
expression of mast cell tryptase
neuropathy and carpal tunnel syndrome and carpal tunnel syndrome
These cells are CD117 (c-kit) positive

TNF-α is a cytokine released from macrophages that


T-cells and B-cells become anergic when exposed to
T-cells that are self-reactive in the periphery are inactivated mediates cachexia and shock
their antigen without a costimulatory signal
by clonal anergy
activates endothelium and causes WBC
mechanism of self-tolerance
recruitment/vascular leak

Th1 cells secrete IFN-γ and IL-2 Th1 cells secrete IFN-γ and IL-2
Talcosis is a disease that causes granulomas of the lung

Often seen in heroin users where the heroin has been


cut with talc OR injection of drugs intended for oral
administration (ex benzos), regardless of route
(inhalation or injection) talc causes pulmonary effects

The APC tumor suppresor regulates the Wnt


signalling pathway by destroying B-catenin in the
The Bcl-2 proto-oncogene becomes constitutively activated
absence of a Wnt receptor-ligand interaction
in Follicular Lymphoma and diffuse Large B cell
Lymphoma
- However, in the presence of Wnt-receptor/ligand
- Translocation of Bcl-2 to the Ig Heavy Chain (14;18) locus
interaction, B-catenin is not destroyed and is free to
results in the protein becoming constitutively active
upregulate proteins involved in cell growth and cell
(resulting in defective B cells being able to proliferate) The Carcinoembryonic antigen (CEA) is a serum tumor
cycle progression
marker that has major associations with colorectal and
pancreatic cancers
- the Wnt signaling pathway is an important
embryological pathway involved in body axis
used to monitor treatment, recurrences after resection
patterning and cell fate specification, and also plays
(failure to normalize elevated levels after surgery suggests
an important role in adult tissue regeneration
this), staging, and localize cancer spread through
measurement of biological fluids

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The DCC tumor suppressor gene is involved in apoptotic


regulation of the GI tract epithelium

- In GI tract, epithelial cells proliferate at the base of the


villi and are rapidly pushed upwards by subsequent
divisions to the tip; as the cells get closer to the tip there is a
decreased concentration of nectrin so there are more
apoptotic signals, resulting in cells sloughing off into the
lumen

- when mutated, the DCC has no survival or apoptotic


signaling, thus cells can proliferate unchecked (and cancer
can precipitate)

The DCC gene is a tumor suppresor that is frequently


mutated in advanced colorectal cancer
The Carcinoembryonic antigen (CEA) is a serum
tumor marker that has minor associations with gastric, - This gene is a Dependence Receptor, meaning it has two
breast, and medullary thyroid carcinomas functions when it is bound and when it is not bound (as
opposed to a classical receptor which is "on-off")
Furthermore, it is also elevated in IBD, Pancreatitis,
Cirrhosis, Hypothyroidism - when DCC is bound by nectrin-1, this induces a survival
signal; when DCC is not bound by nectrin-1, this induces an
apoptotic signal

The PALS and lymphoid follicles of the spleen constitute


the white pulp

The P-glycoprotein is an ATP-dependent efflux pump


that tumors can produce to generate chemotherapeutic The P-glycoprotein is an ATP-dependent efflux pump that
resistance tumors can produce to generate chemotherapeutic resistance

This actively removes chemotherapeutic agents This actively removes chemotherapeutic agents (particularly
(particularly hydrophobic agents like the hydrophobic agents like the anthracyclines)
anthracyclines)

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The RET proto-oncogene is expressed by cells of neural


The RET proto-oncogene is expressed by cells of crest lineage, and activating mutations are seen in MEN II
neural crest lineage, and activating mutations are seen syndromes
in MEN II syndromes
- Particularly implicated in development of the Kidneys and
- Particularly implicated in development of the Enteric Nervous System
Kidneys and Enteric Nervous System
- MENII syndromes involve tumors of the Adrenal Medulla,
- MENII syndromes involve tumors of the Adrenal The Sign of Leser-Trélat can present as a paraneoplastic
Parathyroid, Parafollicular Cells, etc; also associated with
Medulla, Parathyroid, Parafollicular Cells, etc; also syndrome associated with gastrointestinal adenocarcinoma
sporadic thyroid medullary carcinoma
associated with sporadic thyroid medullary carcinoma and other visceral malignancies (ex. Lymphoid
malignancies)

The Sign of Leser-Trélat can present as


a paraneoplastic syndrome associated with The antigen receptors of B
gastrointestinal adenocarcinoma and other visceral lymphocytes have two heavy and light chains (bivalent)
malignancies (ex. Lymphoid malignancies)
The amino acid asparagine is essential for rapidly dividing
tumor cells

Thus certain chemotherapeutic regimens will include


asparaginase

The antigen receptors of B lymphocytes have a hinge The antigen receptors of B lymphocytes have a hinge
region, which allows for flexibility region, which allows for flexibility
The antigen receptors of T
lymphocytes have one α and β chain (monovalent)

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The first signal for T-cell activation is binding between


the TCR and MHC/peptide complex

e.g. antigen is presented on MHC II and recognized by TCR


The delayed response of mast on CD4+ T cell
cell and basophil activation is production The enzymes responsible for gene
of arachidonic acid metabolites, recombination in heavy and light chains are encoded by the
particularly leukotrienes genes RAG1 and RAG2

allows for maintenance of the acute inflammatory defect in these genes results in Omenn syndrome
response

The hypercalcemia seen in patients with Humoral


Hypercalcemia of Malignancy is mediated by PTHrP

- PTHrP can act on the PTH receptor, resulting in


hypercalcemia

- endogenously, PTHrP has other functions in the body


including regulation of the endochondral growth plate
and formation of the mammary glands

The hypercalcemia seen in patients with Lymphoma is


The immediate response of mast
mediated by Calcitriol
cell and basophil activation is release
of preformed histamine granules
Lymphomas do NOT secrete PTHrP, instead they generate
Calcitriol
causes vasodilation of arterioles and increased vascular
permeability; other preformed granules
include heparin and eosinophil chemotactic factor

The inner layer of lymph nodes is the medulla, which


consists of medullary cords and sinuses

The incidence of pancreatic cancer in women has


slowly increased over the last century

This is now the fourth most common cause of cancer


mortality in women

The initial lymphatic spread of a carcinoma is to regional


draining lymph nodes

Ex breast cancer: into lymphatics --> axillary lymph nodes

The intermediate filament Cytokeratin is found in The intermediate filament Desmin is found in muscle cells The intermediate filament Glial Fibrillary Acidic Protein
Epithelial cells (GFAP) is found in neuroglial cells (ex. astrocytes,
- Thus IHC stains can be developed for tumors of muscle Schwann cells, oligodendrocytes)
- Thus IHC stains can be developed for tumors of cells
epithelial cells - Thus IHC stains can be developed for tumors of neuroglial
- endogenously, Desmins role is to maintain cell structure in cells; do not rely on this for schwannoma as it also has

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S-100
- endogenously, Cytokeratins role is to maintain cell muscle cells (Smooth, cardiac, skeletal)
- endogenously, GFAPs role is to maintain cell structure in
structure in epithelial cells
Neuroglia

The lymph node paracortex contains high endothelial


venules (HEV), through which T and B cells enter from
the blood

The intermediate filament Vimentin is found in homing receptors on lymphocytes, such as L selectins, bind
mesenchymal tissue (ex fibroblasts, endothelial cells,
to addressins present on HEVs
macrophages)

- Thus IHC stains can be developed for tumors of


mesenchymal origin
The intermediate filament Neurofilament is found in
neurons - endogenously, Vimentin's role is to maintain cell structure
in mesenchymal cells
- Thus IHC stains can be developed for tumors of
neurons (ex. Neuroblastoma)

- endogenously, Neurofilaments role is to maintain cell


structure in neurons

The lymph node paracortex contains high endothelial


venules (HEV), through which T and B cells enter
from the blood

homing receptors on lymphocytes, such as L selectins, The mature, naive T cell expresses a single T-cell
bind to addressins present on HEVs receptor on its surface

The macrophage-lymphocyte interaction is also enhanced


by interaction of T cell CD40L with CD40 on macrophages

The medullary cords within lymph nodes contain The medullary sinuses within lymph The most common body cavity seeded by a tumor is the
closely-packed lymphocytes and plasma cells nodes contain reticular cells and macrophages peritoneal cavity

- Ovarian adenocarcinomas or appendiceal carcinomas can


spread to peritoneal surfaces in the peritoneal cavity (ex.
omental caking)

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The most common type of metastases to the bone from The most common type of metastases to the bone from
The most common type of metastases to
Non-Small Cell Lung Cancer are lytic the breast are mixed
the bone from Small Cell Lung Cancer are blastic
Thyroid and Kidney are all lytic This is the only mixed met of note

The most common type of metastases to the bone from The most common type of metastases to the bone from the The most common type of metastases to the bone from the
the kidney are lytic prostate are blastic thyroid are lytic

Thyroid, and Kidney are all lytic This is the only blastic met of note Thyroid, and Kidney are all lytic

The outer cortex of a lymph node contains aggregates of


cells called follicles

The normal neonatal thymus appears "sail-shaped" on a


Chest X-Ray

This will then involute with age


The nephrotoxicity caused by calcineurin
inhibitors can result in histologic findings that include
early arteriolar hyalinization and tubular vacuolization

these agents reduce renal blood flow and cause direct


damage to renal endothelial and tubular cells

The primary tumors for Bone metastases can be ranked and The primary tumors for Bone metastases can be ranked and
remembered by the following mnemonic: (Pb (lead) remembered by the following mnemonic: (Pb (lead)
KeTlLe) KeTlLe)

Prostate > Breast > Kidney, Thyroid, Lung Prostate > Breast > Kidney, Thyroid, Lung

Ex of bone mets to the femoral head on CT and biopsy Ex of bone mets to the femoral head on CT and biopsy
The oxidative burst also leads to an influx of K+,
which releases lysosomal enzymes

The primary tumors for Bone metastases can be The primary tumors for Bone metastases can be ranked and The primary tumors for Bone metastases can be ranked and
ranked and remembered by the following mnemonic: remembered by the following mnemonic: (Pb (lead) remembered by the following mnemonic: (Pb (lead)
(Pb (lead) KeTlLe) KeTlLe) KeTlLe)

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Prostate > Breast > Kidney, Thyroid, Lung Prostate > Breast > Kidney, Thyroid, Lung
Prostate > Breast > Kidney, Thyroid, Lung

Ex of bone mets to the femoral head on CT and biopsy Ex of bone mets to the femoral head on CT and biopsy
Ex of bone mets to the femoral head on CT and biopsy

The primary tumors for brain metastases can be ranked The primary tumors for brain metastases can be ranked in The primary tumors for brain metastases can be ranked in
in the following order: the following order: the following order:

Lung > Breast > Melanoma, Colon, Kidney Lung > Breast > Melanoma, Colon, Kidney Lung > Breast > Melanoma, Colon, Kidney

("Lead Bullets Meckel" - LB MeCKel) ("Lead Bullets Meckel" - LB MeCKel) ("Lead Bullets Meckel" - LB MeCKel)

The primary tumors for liver metastases can be The primary tumors for liver metastases can be ranked in The primary tumors for liver metastases can be ranked in
ranked in the following order (patients with liver mets the following order (patients with liver mets Cant Get the following order (patients with liver mets Cant Get
Cant Get Pints): Pints): Pints):

Colon >> Gastric > Pancreas Colon >> Gastric > Pancreas Colon >> Gastric > Pancreas

Liver mets as seen on CT and on biopsy: Liver mets as seen on CT and on biopsy: Liver mets as seen on CT and on biopsy:

The protein S-100 is found in cells of neural crest The second signal for T-cell activation is The signal transduction region of B lymphocytes includes
lineage (ex. schwann cells, melanocytes, langerhans a costimulatory signal via interaction between B7 (APC) a heterodimer of Ig-α and Ig-β
cells) and CD28 (T cell)
also has CD19, CD21, and CD81, which form a "co-
note: B7 is also known as CD80/86 receptor" that helps with signal transduction
- Thus IHC stains can be developed for
tumors/proliferations of cells with neural crest lineage

- endogenously, S-100 protein is involved in various

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intracellular homeostatic processes

The spleen is located in the LUQ of the abdomen, behind


The source of alkaline phosphatase can be determined by an the 9th - 11th ribs
ALP isozyme test, which works by gel electrophoresis
The signal transduction
region of T lymphocytes consists of a multi-chain - Different isozymes of ALP are created by different sources
structure known as CD3 in the body, and each isozyme has a different net charge
(allowing you to seperate different isozymes on
electrophoresis)

The tumor suppressors encoded by the CDKN2A gene The tumor suppressors encoded by the CDKN2A gene
enforce the G1-->S restriction point by: enforce the G1-->S restriction point by:

(1) - inhibiting CDK4/6 (1) - inhibiting CDK4/6


The tissue-restricted self-antigens expressed in
the thymus for negative selection are due to the action (2) - relieving inhibition of P53 (2) - relieving inhibition of P53
of autoimmune regulator (AIRE)

(1) this is done via the P16 protein encoded by CDKN2A (1) this is done via the P16 protein encoded by CDKN2A

(2) CDK2NA also encodes P14arf, which inhibits MDM2 (2) CDK2NA also encodes P14arf, which inhibits MDM2
(the regulator of P53) (the regulator of P53)

The two goals of cancer screening are to catch:


The two goals of cancer screening are to catch:
(1) to catch dysplasia before it becomes carcinoma
(1) to catch dysplasia before it becomes carcinoma
(2) detect carcinoma before clinical symptoms arise
(2) detect carcinoma before clinical symptoms arise
The affinity of an antibody refers to the binding
strength for an epitope
- this is a form of Secondary disease prevention
- this is a form of Secondary disease prevention
- one of the reasons why lung cancer is #2 in incidence
- one of the reasons why lung cancer is #2 in incidence but
but #1 in mortality is that there is no good screening
#1 in mortality is that there is no good screening method
method

The cortex of the thymus is dense and comprised The cortex of the thymus is dense and comprised
of immature T cells of immature T cells

The avidity of an antibody refers to the number of


sites available to bind epitopes

The heavy chain contributes to The immature B cell is characterized by surface IgM, The inflammasome is a cytoplasmic protein complex that
the Fab and Fc region of an antibody but no surface IgD recognizes products of dead cells, microbial products, and
crystals

- inflammasome leads to increased IL-1B / IL-18 production


which leads to inflammatory response (neutrophilic

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recruitment and invasion)

The light chain only contributes to the Fab region of


an antibody
The medulla of the thymus is pale and comprised The medulla of the thymus is pale and comprised
of mature T cells and Hassall corpuscles of mature T cells and Hassall corpuscles

The paracortex is the region of a lymph The progenitor B cell lacks cytoplasmic μ and surface
node between follicles and medulla The precursor B cell is characterized by cytoplasmic μ
IgM/IgD

The right lymphatic duct drains lymph from the right


side of the body above the diaphragm
The thymus is an encapsulated lymphoid organ located in
the anterosuperior mediastinum

The secondary lymphoid organs allow immune cells to


react with antigen

e.g. spleen, lymph nodes, tonsils, Peyer patches

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The idio-type of an antibody is determined by the Fab The iso-type of an antibody is determined by the Fc
The idio-type of an antibody is determined by the Fab
region (Fc or Fab) region (Fc or Fab)
region (Fc or Fab)
fragment, antigen binding; determines what antigen can be Constant region, Carboxy terminal; determines class (e.g.
fragment, antigen binding; determines what antigen
bound IgG, IgM, etc.)
can be bound

The thoracic duct drains most lymph into the junction of The thoracic duct drains most lymph into the junction of
the left subclavian and internal jugular veins the left subclavian and internal jugular veins
The iso-type of an antibody is determined by the Fc
region (Fc or Fab)

Constant region, Carboxy terminal; determines class


(e.g. IgG, IgM, etc.)

The thoracic duct drains most lymph into


the junction of the left subclavian and internal
jugular veins

Thymoma is a benign neoplasm of thymus associated Thymoma is a benign neoplasm of thymus associated
with myasthenia gravis, SVC syndrome, and Good with myasthenia gravis, SVC syndrome, and Good
syndrome syndrome

also may be seen with pure red cell aplasia also may be seen with pure red cell aplasia

To remember the most common neoplasias that spread To remember the most common neoplasias that spread To remember the most common neoplasias that spread
hematogenously (Every Hematogenous Spreading hematogenously (Every Hematogenous Spreading hematogenously (Every Hematogenous Spreading
Cancer Reigns Foolishly) Cancer Reigns Foolishly) Cancer Reigns Foolishly)

Embryonal carcinoma Embryonal carcinoma Embryonal carcinoma


Hepatocellular carcinoma Hepatocellular carcinoma Hepatocellular carcinoma
Sarcoma Sarcoma Sarcoma
Choriocarcinoma Choriocarcinoma Choriocarcinoma
Renal cell carcinoma Renal cell carcinoma Renal cell carcinoma
Follicular carcinoma of the thyroid Follicular carcinoma of the thyroid Follicular carcinoma of the thyroid

To remember the most common neoplasias that spread To remember the most common neoplasias that spread To remember the most common neoplasias that spread
hematogenously (Every Hematogenous Spreading hematogenously (Every Hematogenous Spreading hematogenously (Every Hematogenous Spreading

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Cancer Reigns Foolishly) Cancer Reigns Foolishly) Cancer Reigns Foolishly)

Embryonal carcinoma Embryonal carcinoma Embryonal carcinoma


Hepatocellular carcinoma Hepatocellular carcinoma Hepatocellular carcinoma
Sarcoma Sarcoma Sarcoma
Choriocarcinoma Choriocarcinoma Choriocarcinoma
Renal cell carcinoma Renal cell carcinoma Renal cell carcinoma
Follicular carcinoma of the thyroid Follicular carcinoma of the thyroid Follicular carcinoma of the thyroid

Toxins that require passive immunity in Toxins that require passive immunity in Toxins that require passive immunity in
exposed, unvaccinated patients may be remembered exposed, unvaccinated patients may be remembered with exposed, unvaccinated patients may be remembered with
with the mnemonic "To Be Healed Very Rapidly": the mnemonic "To Be Healed Very Rapidly": the mnemonic "To Be Healed Very Rapidly":

T: Tetanus toxin T: Tetanus toxin T: Tetanus toxin


B: Botulinum toxin B: Botulinum toxin B: Botulinum toxin
H: HBV H: HBV H: HBV
V: Varicella V: Varicella V: Varicella
R: Rabies virus R: Rabies virus R: Rabies virus

also diphtheria antitoxin; combined active and passive also diphtheria antitoxin; combined active and passive also diphtheria antitoxin; combined active and passive
immunizations can be given for hepatitis B and rabies immunizations can be given for hepatitis B and rabies immunizations can be given for hepatitis B and rabies
exposure exposure exposure

Rx// compared this to IgG being delivered Rx// compared this to IgG being delivered transplacentally Rx// compared this to IgG being delivered transplacentally
transplacentally (passive immunity) (passive immunity) (passive immunity)

Toxins that require passive immunity in Toxins that require passive immunity in
exposed, unvaccinated patients may be remembered exposed, unvaccinated patients may be remembered with
with the mnemonic "To Be Healed Very Rapidly": the mnemonic "To Be Healed Very Rapidly":

T: Tetanus toxin T: Tetanus toxin


B: Botulinum toxin B: Botulinum toxin
H: HBV H: HBV
Toxoid vaccines are composed of a denatured bacterial
V: Varicella V: Varicella
toxin with an intact receptor binding site
R: Rabies virus R: Rabies virus

also diphtheria antitoxin; combined active and passive also diphtheria antitoxin; combined active and passive
immunizations can be given for hepatitis B and rabies immunizations can be given for hepatitis B and rabies
exposure exposure

Rx// compared this to IgG being delivered Rx// compared this to IgG being delivered transplacentally
transplacentally (passive immunity) (passive immunity)

Translocations of the Abl proto-oncogene with the


Translocations of the Abl proto-oncogene with the Breakpoint Cluster Region (BCR) on chromosome 22 are
Breakpoint Cluster Region (BCR) on chromosome associated with:
22 are associated with:
- Chronic Myelogenous Leukemia
- Chronic Myelogenous Leukemia - adult Acute Lymphoblastic Leukemia
- adult Acute Lymphoblastic Leukemia

- when seen in adult ALL, this is associated with POOR


- when seen in adult ALL, this is associated with prognosis
POOR prognosis
- the resultant fusion protein (Bcr-Abl) can be treated with
- the resultant fusion protein (Bcr-Abl) can be treated Imatinib / Dasatinib (specifically designed to inhibit this
with Imatinib / Dasatinib (specifically designed to fusion protein)
inhibit this fusion protein) Trousseau Syndrome is a migratory superficial
thrombophlebitis

- In this syndrome, procoagulant factors (ex. mucin)


secreted by the tumors (ex. pancreatic adenocarcinoma)
cause clotting in the superficial veins

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Tumor cells that downregulate MHC class I can be detected


and destroyed by Natural Killer cells

- normally, NK cells seperately bind an activating ligand as


well as MHC I resulting in NK inactivation; However if
Tumor cells can evade apoptosis / immune surveillance by MHC I is downregulated, NK cells only receive activating
downregulating expression of MHC class I or alternative signals and release cytotoxic mediators to kill tumor cells
splicing of the Fas receptor
Trousseau Syndrome is a migratory superficial
thrombophlebitis - Thus Immunodeficiency (both primary and secondary)
increases risk for cancer; alternative splicing of the Fas
- In this syndrome, procoagulant factors (ex. mucin)
receptor splices out transmembrane domain converting it to
secreted by the tumors (ex. pancreatic
a soluble form not expressed on cell surface
adenocarcinoma) cause clotting in the superficial veins
- this is an example of the cancer hallmark: evasion of
apoptosis

Tumor stage is classified by the TNM Staging System,


which represents:
- Tumor size / invasiveness
- Node involvement
Tumor staging is based on clinical (c) or pathological (p)
- Metastases
findings

- clinical vs pathological can change the criteria for staging


T involves:
(ex. Breast tumor pN1 = 1-3 axillary lymph nodes have
- TX (main tumor can't be measured)
cancer vs cN1 = axillary lymph nodes have cancer but can
- T0 (main tumor can't be found)
be moved around) Tumor grade is the degree of cellular differentiation and
- T1-4 (refers to size / extent of tumor, can be
subdivided into a or b) mitotic activity on histology
example:breast cancer with cT3N1M0 means:
grading a cancer involves a microscopic assesment of
N involves:
- based on clinical findings differentiation that takes into account architectural and
- NX (cancer in nearby lymph nodes can't be
nuclear features
measured)
- tumor is larger than 5 cm (T1 is 2 cm or smaller)
- N0 (no cancer in nearby lymph nodes)
- N1-4 (refers to # and location of lymph nodes that
- axillary lymph nodes have cancer, but can be moved
contain cancer)
around (vs pN1 = 1-3 axillary lymph nodes have cancer)
M involves:
- no metastasis
- MX (metastasis can't be measured)
- M0 (cancer has not spread to other parts of body)
- M1 (cancer Has spread to other parts of the body)

Tumor stage is the degree of localization / spread


based on site and size of 1* lesion, spread to regional Tumors are classified as either benign or malignant Tumors of Bone are known as Osteomas when benign and
lymph nodes, and presence of metastases Osteosarcomas when malignant
Malignant = Cancer
Staging is often more important than grading

Tumors of Bone are known as Osteomas Tumors of Connective Tissue are known as Fibromas Tumors of Connective Tissue are known as Fibromas
when benign and Osteosarcomas when malignant when benign and Fibrosarcomas when malignant when benign and Fibrosarcomas when malignant

Tumors of Melanocytes are known as a Nevus (Mole) Tumors of Melanocytes are known as a Nevus (Mole) Tumors of Smooth Muscle are known as Leiomyomas
when benign and a Melanoma when malignant when benign and a Melanoma when malignant when benign and Leiomyosarcomas when malignant

Tumors of Smooth Muscle are known as Leiomyomas Tumors of Striated Muscle are known as Rhabdomyoma Tumors of Striated Muscle are known as Rhabdomyoma
when benign and Leiomyosarcomas when malignant when benign and Rhabdomyosarcoma when malignant when benign and Rhabdomyosarcoma when malignant

Tumors that are high grade are poorly differentiated, Tumors that are low grade are well differentiated Tumors that cause a paraneoplastic polycythemia can be
undifferentiated, or anaplastic remembered with the mnemonic: Paraneoplastic rise
- Thus they resemble parent tissue and have better to high hematocrit levels
- thus they do not resemble parent tissue and prognosis than poorly differentiated tumors
have worse prognosis than well differentiated tumors
- Thus a follicular adenoma of thyroid [L image] (well Pheochromocytoma
- Thus a anaplastic carcinoma of the thyroid [R image] differentiated) has a better outcome than a anaplastic Renal cell carcinoma
(no differentiation) has a worse outcome than a carcinoma of the thyroid [R image] (no differentiation) Hepatocellular Carcinoma
follicular adenoma of thyroid [L image] (well Hemangioblastoma
differentiated) Leiomyoma

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normal thyroid follicle depicted below: normal thyroid follicle depicted below: - These tumors secrete EPO, resulting in an inappropriate
absolute polycythemia

Tumors that cause a paraneoplastic polycythemia can Tumors that cause a paraneoplastic polycythemia can be Tumors that cause a paraneoplastic polycythemia can be
be remembered with the mnemonic: Paraneoplastic remembered with the mnemonic: Paraneoplastic rise remembered with the mnemonic: Paraneoplastic rise
rise to high hematocrit levels to high hematocrit levels to high hematocrit levels

Pheochromocytoma Pheochromocytoma Pheochromocytoma


Renal cell carcinoma Renal cell carcinoma Renal cell carcinoma
Hepatocellular Carcinoma Hepatocellular Carcinoma Hepatocellular Carcinoma
Hemangioblastoma Hemangioblastoma Hemangioblastoma
Leiomyoma Leiomyoma Leiomyoma

- These tumors secrete EPO, resulting in - These tumors secrete EPO, resulting in an inappropriate - These tumors secrete EPO, resulting in an inappropriate
an inappropriate absolute polycythemia absolute polycythemia absolute polycythemia

Tumors that present with PSaMMoma bodies are: Tumors that present with PSaMMoma bodies are:

Papillary carcinoma of thyroid Papillary carcinoma of thyroid


Serous papillary cystadenocarcinoma of ovary Serous papillary cystadenocarcinoma of ovary
Meningioma Meningioma
Malignant Mesothelioma Malignant Mesothelioma
Tumors that cause a paraneoplastic polycythemia can
be remembered with the mnemonic: Paraneoplastic
rise to high hematocrit levels These are Laminated, concentric spherules with dystrophic These are Laminated, concentric spherules with dystrophic
calcifcation calcifcation

Pheochromocytoma
Renal cell carcinoma
Hepatocellular Carcinoma
Hemangioblastoma
Leiomyoma

- These tumors secrete EPO, resulting in


an inappropriate absolute polycythemia

Tumors that present with PSaMMoma bodies are: Tumors that present with PSaMMoma bodies are: Type I HSR occurs due to cross-
linking of IgE on presensitized mast cells and basophils by
Papillary carcinoma of thyroid Papillary carcinoma of thyroid antigen
Serous papillary cystadenocarcinoma of ovary Serous papillary cystadenocarcinoma of ovary
Meningioma Meningioma
Malignant Mesothelioma Malignant Mesothelioma

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These are Laminated, concentric spherules with dystrophic


These are Laminated, concentric spherules with calcifcation
dystrophic calcifcation

Type I Interferons downregulate protein synthesis to resist Type I Interferons increase cell surface expression of MHC
potential viral replication proteins to facilitate recognition of infected cells

Type I HSR occurs due to cross-


linking of IgE on presensitized mast
cells and basophils by antigen

Type IV HSRs may occur via delayed-type Type IV HSRs may occur via direct cell cytotoxicity, which V(D)J recombination in heavy chains begins with
hypersensitivity, which involves CD4+ T-cells involves CD8+ T cells D-J joining, followed by V-D/J joining

sensitized helper T cells encounter antigen and release


cytokines

V(D)J recombination in heavy chains begins with What HLA subtype is associated with Goodpasture What HLA subtype is associated with Rheumatoid
D-J joining, followed by V-D/J joining syndrome? arthritis?

DR2 DR4

there are 4 walls in a "rheum" (room)

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What HLA subtype is associated with hay fever? What HLA subtype is associated with hemochromatosis? What HLA subtype is associated with multiple sclerosis?

DR2 A3 DR2

What HLA subtype is associated with seronegative


What HLA subtype is associated with pernicious arthropathies?
What HLA subtypes are associated with Addison disease?
anemia?
B27
B8, DR3, and DR4
DR5
e.g. Psoriatic arthritis, Ankylosing spondylitis, IBD-
associated arthritis, and Reactive arthritis (PAIR)

What HLA subtypes are associated with Addison What HLA subtypes are associated with Addison disease? What HLA subtypes are associated with Graves disease?
disease?
B8, DR3, and DR4 B8 and DR3
B8, DR3, and DR4

What HLA subtypes are associated with Graves What HLA subtypes are associated with Hashimoto What HLA subtypes are associated with SLE?
disease? thyroiditis?
DR2 and DR3
B8 and DR3 DR3 and DR5
"2-3, S-L-E"

What HLA subtypes are associated with celiac What HLA subtypes are associated with type I diabetes
What RBC abnormalities (2) are seen on blood smear post-
disease? mellitus?
splenectomy?
DQ2 and DQ8 DR3 and DR4
Howell-Jolly bodies and target cells
Rx// whites with T1D, 95% have DR-3, DR-4 or both

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What acute phase reactant is downregulated during What acute phase reactant is downregulated during
What acute phase reactant can be measured clinically
inflammation by being internalized into macrophages to inflammation to conserve amino acids for positive
as a nonspecific sign of ongoing inflammation?
sequester iron? reactants?
C-reactive protein
Transferrin Albumin

What acute phase reactant is upregulated during


inflammation that correlates with ESR
What acute phase reactant is upregulated during What acute phase reactant is upregulated during
Fibrinogen inflammation to bind and sequester iron to inhibit microbial inflammation to opsonize targets, fixing complement and
iron scavenging? facilitate phagocytosis?

Products of inflammation (eg, fibrinogen) coat RBCs Ferritin C-reactive protein


and cause aggregation; the denser RBC aggregates
fall at a faster rate within a pipette tube

ESR is often co-tested with CRP levels

What acute phase reactant is upregulated during


inflammation to prevent iron release from
macrophages and enterocytes?

Hepcidin What are anatomical locations that receive blood supply


from the most distal branches of 2 arteries with limited
collateral vascularity known as?
This protein binds and inhibits the Ferroportin
channel through which macrophages / enterocytes
What acute phase reactant is upregulated during Watershed areas (border zones)
release iron to be bound by transferrin for transport
through the blood stream inflammation to promote endothelial repair?

Fibrinogen These are very vulnerable to ischemia from hypoperfusion;


This protein is involved in negative feedback in normal examples include:
iron homeostasis; in hemochromatosis the negative
feedback loop is disrupted due to inhibition of the HFE
protein --> iron is free to leave through ferroportin

What country consumes a large amount of smoked meats in


their diet, resulting high rates of intestinal gastric cancer?

Japan

What class of acute phase reactant that


One of the staple Japanese food preparation devices is the
when upregulated during chronic inflammation can lead to
"Donabe", a smoker pot which helps contribute to the mass
amyloidosis?
consumption of smoked meats
serum amyloid A proteins
What branchial pouch develops into the thymus?

Third branchial pouch (ventral wing)


These proteins have a wide variety of roles:
- transport cholesterol to liver for bile (bile has
antimicrobial membrane disruption properties)
- recruitment of immune cells to inflammatory sites
- induction of enzymes that degrade extracellular matrix
(allowing inflammatory cells to migrate more rapidly)

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What is the first type of immunoglobulin produced in


a neonate?

IgM

What is an advantage of inactivated What is the embryonic origin of lymphocytes in


vaccines compared to live attenuated? the thymus?

Inactivated vaccines are safer Mesenchymal origin

What is the most abundant immunoglobulin


isotype in serum?

IgG

What is the most common cancer overall in the United


What is the least abundant immunoglobulin
States?
isotype in serum?
Skin cancer
IgE

What is the only useful immunoglobulin for


What is the most effective preventitive intervention in diagnosing neonatal infections?
almost all patients in reducing mortality risk?
IgM
Smoking cessation
cannot use IgG because maternal IgG persists for up to one
What is the only immunoglobulin that can be secreted in year
response to thymus-independent antigens?

IgM

class switching cannot occur without the help of Th cells

What part of an antigen should be preserved to elicit an


What percent of brain tumors are from metastases?
immune response when given as an inactivated/killed
What non-nucleated cell expresses MHC class I? vaccine?
50%
Platelets Epitope
commonly seen as multiple well-circumscribed tumors at
i.e. the precise region on the immunogen that interacts with
gray / white matter junction
the antibody

What protein is associated with MHC I? What test is used to diagnose type II hypersensitivity
What protein is associated with MHC II? reactions?
β2-microglobulin
Invariant chain Coombs test

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What tests are used to diagnose type I hypersensivity


What type of graft is from a non-identical individual of the
reactions? What type of graft is from a different species?
same species?
Skin tests or blood tests (ELISA) for allergen-specific Xenograft
Allograft
IgE

What type of hypersensitivity is acute hemolytic


transfusion reaction?

Type II HSR

What type of graft is from an identical twin or clone? What type of graft is from self?

Syngeneic graft (isograft) Autograft

What type of hypersensitivity is febrile nonhemolytic


What type of hypersensitivity is allergic transfusion
transfusion reaction?
reaction?
Type II HSR
Type I HSR

What type of hypersensitivity reaction is Goodpasture


syndrome?

Type II HSR (cytotoxic)

What type of hypersensitivity reaction is Graves What type of hypersensitivity reaction is Myasthenia
What type of hypersensitivity reaction is Pernicious
disease? gravis?
anemia?
Type II HSR (non-cytotoxic) Type II HSR (non-cytotoxic)
Type IV HSR

What type of hypersensitivity reaction is contact What type of hypersensitivity reaction is graft-versus-host-
What type of hypersensitivity reaction is autoimmune dermatitis (e.g. poison ivy, nickel allergy)? disease?
hemolytic anemia?
Type IV HSR (delayed-type hypersensitivity) Type IV HSR (delayed-type hypersensitivity)
Type II HSR (cytotoxic)

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What type of hypersensitivity


What type of hypersensitivity reaction is hemolytic reaction is hyperacute transplant rejection? What type of hypersensitivity reaction is immune
disease of the newborn? thrombocytopenic purpura?
Type II HSR (cytotoxic)
Type II HSR (cytotoxic) Type II HSR (cytotoxic)

What type of hypersensitivity reaction is patch test?

Type IV HSR (delayed-type hypersensitivity)

What type of hypersensitivity reaction is polyarteritis What type of hypersensitivity reaction is poststreptococcal
nodosa? glomerulonephritis (PSGN)?

Type III Type III

What type of hypersensitivity reaction is the Candida


What type of hypersensitivity reaction is rheumatic
What type of hypersensitivity reaction is serum sickness? extract test?
fever?
Type III HSR Type IV HSR (CD4 Mediated)
Type II HSR (cytotoxic)

Used to determine T-cell immune function (ex. in patients


with chronic mucocutaneous candidiasis)

What type of hypersensitivity reaction is tuberculin What type of hypersensitivity reaction is type I diabetes
What type of hypersensivitity reaction is the Arthus
skin test (PPD)? mellitus?
reaction?
Type IV HSR (delayed-type cytotoxicity) Type IV HSR (direct cell cytotoxicity)
Type III HSR

caused by antigen-antibody complexes

What type of vaccine is the BCG vaccine?


What type of vaccine are the Meningococcal
What type of vaccine is the Adenovirus vaccine?
vaccines? Live attenuated
Live non-attenuated
Subunit

Non-attenuated live Adenovirus types 4, 7 and sometimes 21


There are two conjugate vaccines (MCV-4) and one
are packaged into enteric capsules so they bypass
polysaccharide vaccine (MPSV-4); quadrivalent
respiratory epithelium and only replicate once they reach
meningococcal vaccines contain polysaccharides from
intestine --> asymptomatic infection of intestine
major serotypes (A, C, Y, and W) of n meningitidis

What type of vaccine is the Diphtheriae vaccine? What type of vaccine is the HPV vaccine?
What type of vaccine is the HBV vaccine?
Toxoid Subunit
Subunit

Both the DT and Td; stimulates Utilizes antigens from HPV types 6,11,16, and 18; contain
Utilizes the HBsAg antigen
circulating IgG against the exotoxin B subunit inactive L1 proteins (ex. Gardasil)

What type of vaccine is the MMR vaccine?

What type of vaccine is the Hib vaccine? Live attenuated What type of vaccine is the Pneumococcal vaccine?

Subunit measles, mumps, rubella Subunit

This is a conjugate vaccine that takes a capsular Two types of pneumoccocal vaccines - conjugate (much
antigen (PRP) and conjugates it to carrier protein more effective, memory, but small range of serotypes
(inactivated tetanospasmin, mutant diptheria protein, covered) and polysaccharide (wider range of serotypes
or meningococcal group B OMP) targeted, much less effective)

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What type of vaccine is the acellular pertussis (aP) What type of vaccine is the hepatitis A vaccine?
vaccine?
Inactivated/killed
Subunit
What type of vaccine is the Tetanus vaccine?

Toxoid advantage of using acellular vaccine over the whole vaccine


is that acellular has fewer side effects

can contain pertussis toxin, filamentous hemagglutinin,


pertactin (OMP that promotes adhesion to tracheal
epithelial cells), and fimbriae

What type of vaccine is the injected influenza What type of vaccine is the intranasal influenza vaccine? What type of vaccine is the rabies vaccine?
vaccine?
Live attenuated Inactivated/killed
Inactivated/killed

What type of vaccine is the rotavirus vaccine? What type of vaccine is the varicella vaccine? What type of vaccine is the yellow fever vaccine?

Live attenuated Live attenuated Live attenuated

When IgA is released into the mucosa, the poly Ig


receptor becomes the secretory component,
which protects IgA from luminal proteases

When examining a tumor, differentiation refers to the


degree to which a tumor resembles its tissue of origin
When a patient is pregnant, low levels of β-hCG should be - A well differentiated tumor resembles its tissue of origin,
concerning for failing or ectopic pregnancies but a poorly differentiated one does not

- the more poorly differentiated a tumor is, the worse


outcomes the tumor has

Where does negative selection of T cells occur?

Thymic medulla

When performing Immunohistochemistry; TRAP can


Where does class switching of IgM take place?
be used to identify Hairy Cell Leukemia
Germinal centers of lymph nodes
-Aka Tartrate-Resistant Acid Phosphatase; however,
TRAP stain has largely been replaced by Flow
mediated by CD40L and cytokines from Th2 cells
Cytometry for this condition

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Where in the lymph Where in


node do B-cells localize and proliferate? the lymph node do T-cells localize and proliferate?

Follicles (outer cortex) Paracortex


Where does positive selection of T cells occur?

Thymic cortex

Where in the spleen do APCs capture blood-borne


Where in the spleen are T-cells found?
Where in the spleen are B-cells found? antigens for recognition by lymphocytes?
Periarterial lymphatic sheath (white pulp)
Follicles (white pulp) Marginal zone

Which CD marker(s) (CD4, CD8) does the T-cell express in


Which CD marker(s) (CD4, CD8) does Which CD markers (CD4, CD8) does
the thymic medulla?
the T-cell express in the thymic cortex? the T-cell precursor express in the bone marrow?
Either CD4 or CD8
Double Positive (Both CD4 and CD8) None :)
also expresses the T-cell receptor (TCR) and CD3
also expresses the T-cell receptor (TCR) and CD3

Which MHC class has a larger peptide binding Which MHC class has a smaller peptide binding groove (8 Which MHC class is associated with the gene products
groove (13 - 17 AA)? - 10 AA)? of HLA-A, HLA-B, and HLA-C?

MHC II MHC I MHC I

"MHC 1 loci have 1 letter"

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Which MHC class is associated with the gene products Which MHC class is expressed on all nucleated Which MHC class is expressed on antigen presenting cells
of HLA-DP, HLA-DQ, and HLA-DR? cells and platelets? (APCs), only?

MHC II MHC I MHC II

"MHC 2 loci have 2 letters" not expressed on RBCs e.g. B cells, macrophages, dendritic cells

Which MHC class is formed by 1 long chain and 1 Which MHC class is formed by 2 equal length chains? Which blood transfusion reaction can be caused
short chain? by cytokines which are created and accumulate during
MHC II the storage of blood products
MHC I
Febrile nonhemolytic transfusion reaction

Which blood transfusion reaction is caused by


cytokines that are created by WBCs and accumulate during
the storage of blood products against donor HLA
antigens/WBCs?
Which blood transfusion reaction is caused by donor anti-
Which blood transfusion reaction is a reaction Febrile nonhemolytic transfusion reaction leukocyte antibodies against recipient neutrophils
against plasma proteins in transfused blood? and pulmonary endothelial cells?

Allergic/anaphylactic reaction Transfusion-related acute lung injury (TRALI)


- IL-1 is particularly responsible for this

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Which blood transfusion reaction is caused by


host antibodies against donor ABO blood groups or
foreign antigen on donor RBCs?

Acute hemolytic transfusion reaction


Which blood transfusion reaction is caused by Which blood transfusion reaction presents
host antibodies against donor HLA antigens/WBCs? with fever, headaches, chills, and flushing?
Rx// (type B recipient receives kidney from type A
donor) The recipient would possess anti-type A
Febrile nonhemolytic transfusion reaction Febrile nonhemolytic transfusion reaction
antibodies, which react to the A antigen present not
only on RBCs but on most other cell types.
Hyperacute rejection occurs almost immediately, as
the antidonor antibodies bind directly to vascular
endothelial cells, initiating complement and clotting
cascades and resulting in hemorrhage and necrosis of
the transplanted kidney

Which blood transfusion reaction presents


with fever, hypotension, hemoglobinuria*,
Which blood transfusion reaction presents with respiratory Which blood transfusion reaction presents with urticaria,
and jaundice?
distress and noncardiogenic pulmonary edema? pruritus, hypotension, and shock?
Acute hemolytic transfusion reaction
Transfusion-related acute lung injury (TRALI) Allergic/anaphylactic reaction
*hemoglobinuria is a helpful clue that you're dealing
with an acute hemolytic transfusion rather than an
allergic reaction

Which class of helper T cell activates


macrophages and cytotoxic T cells?

Which cellular adaptation is usually preceded by Th1


Which class of helper T cell are believed to play a role
persistent metaplasia or pathologic hyperplasia? in tissue damage associated with autoimmune disease?
macrophages secrete IL-12 causing differentiation to
Dysplasia Th1; Th1 cells then secrete IFN-γ to stimulate macrophages Th17 cells

Which class of helper T cell promotes cell-mediated


immunity?

Th1
Which class of helper T cell promotes IgE production by
Which class of helper T cell helps maintain specific B cells?
immune tolerance by suppressing CD4 and CD8
T-cell effector functions? Th2

Regulatory T (TReg) cells

helps prevent autoimmunity and T cell overactivity

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Which class of helper T cell promotes humoral


immunity?

Th2
Which class of helper T cell recruits eosinophils for
parasite defense?
Which class of helper T cell promotes immunity against
extracellular microbes
Th2
Th17

this is through the induction of neutrophillic inflammation

Which class of helper T cell secretes IL-17, -21, and -22?

Which class of helper T cell secretes IFN-γ and IL-2? Th17

Th1 Which class of helper T cell secretes IL-4, -5, -6, -10,
IL-17 stimulates cells to produce neutrophil chemokines and -13?
(results in neutrophil recruitment)
Th2
IL-21 promotes more TH17 differentiation, enhances
cytotoxicity of CTL / NK / NKT cells

IL-22 upregulates innate inflammatory responses (ex.


defensins)

Which class of helper T cell secretes TGF-B, IL-10,


and IL-35?
Which class of helper T cell when deficient results in Which class of helper T cell when deficient results in
Regulatory T cell
Hyper-IgE syndrome? mendelian susceptibility to mycobacterial disease?

Th17 Th1
TGF-B has numerous effects; anti-inflammatory
overall
IL-10 inhibits Th1 cells
IL-35 induces proliferation of Tregs, reduces activity of
Th17

Which cytokine is primarily responsible for stimulating


Which cytokine increases MHC expression and Which cytokine is responsible for maintaining
macrophages?
antigen presentation on all cells? granulomas in TB infection?
IFN-γ
IFN-γ TNF-α (from macrophages)
also inhibits differentiation into Th2 cells

Which immune cell has the cell surface


Which immune cell has the cell surface protein CCR5?
protein B7 (CD80/86)?
Macrophages (early HIV infection) & CTLs
APCs (B cells, macrophages, dendritic cells)

Which has more prognostic value, tumor stage or


grade?

Tumor Stage

ex a high stage yet low grade tumor is usally worse


than a low-stage yet high grade tumor

Which immune cell has the cell surface protein CD19, Which immune cell has the cell surface protein CD28? Which immune cell has the cell surface protein CD34?
CD20, and CD21?
T cells Hematopoietic stem cells

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B cells

Which immune cell has the cell surface Which immune cell has the cell surface protein CD40L? Which immune cell has the cell surface protein CD56?
protein CD4 and CD25?
Helper T cells NK cells
Regulatory T cells

Which immune cell has the cell surface


protein CXCR4 (CXRCR4)?

T cells (late HIV infection)

Which immune cell is a lymphocyte member of the innate


Which immune cell(s) secretes IFN-γ?
immune system?
NK cells and Th1 cells
Natural killer (NK) cells

Which immune cell(s) secretes IL-12? Which immune cell(s) secretes IL-1? Which immune cell(s) secretes IL-2?

Macrophages Macrophages T cells (both Th1 and Th2)

Which immune cell(s) secretes IL-3? Which immune cell(s) secretes IL-4? Which immune cell(s) secretes IL-5?

T cells (both Th1 and Th2) Th2 cells Th2 cells

Which immune cell(s) secretes IL-6? Which immune cell(s) secretes IL-8? Which immunodeficiency is associated with an infiltrative
lymphohistiocytosis?
Macrophages Macrophages

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Chediak-Higashi

This is an "accelerated phase" that some patients with


chediak-higashi can experience; this is a fulminant
multiorgan infiltration by lymphoid cells, results in bone
marrow failure / hepatosplenomegaly

Which immunoglobulin binds directly to mast Which immunoglobulin contributes to immunity to


Which immunoglobulin has the highest affinity?
cells and basophils? worms by activating eosinophils?
IgG
IgE IgE

Which immunoglobulin is decreased with splenic


dysfunction?
Which immunoglobulin is produced first in response to an
Which immunoglobulin has the highest avidity?
IgM infection?
IgM
thus decreased complement activation and C3b IgM
opsonization (increases susceptibility to encapsulated
organisms); the spleen contains roughly half of the total
immunoglobulin-producing B lymphocytes in the body

Which immunoglobulin is produced in the GI


Which immunoglobulin is released into breast Which immunoglobulin is released into secretions (tears,
tract and protects against gut infections?
milk (colostrum)? saliva, mucus)?
IgA
IgA IgA
e.g. Giardia

Which immunoglobulin is the main antibody produced


Which immunoglobulin is the main antibody produced
during the secondary response to antigen?
during the primary response to antigen?
IgG
IgM

Which immunoglobulin is the most produced antibody


overall?

IgA

however, has lower serum concentration than IgG

Which immunoglobulin isotypes are expressed by Which immunoglobulin opsonizes bacteria?


mature, naive B-cells?
IgG
IgM and IgD
also neutralizes bacterial toxins and viruses
Which immunoglobulin isotypes can exist as a monomer?

All Ig types

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Which immunoglobulin(s) can be secreted by plasma


cells?

IgA, IgG, or IgE (one type per plasma cell)

Which immunoglobulin typically mediates antibody-


dependent cellular cytotoxicity (ADCC)? Which immunoglobulin(s) cross the placenta?

IgG IgG

IgE can mediate ADCC when the target is a parasitic provides infants with passive immunity
worm

Which interferons enhance activity of natural killer cells?


Which immunoglobulins mediate type II hypersensivitity
Which immunoglobulin(s) fix complement?
reactions?
Interferon-α and Interferon-β
IgM and IgG
IgM and IgG

Which interleukin is primarily responsible for acute-phase


reactant production?

IL-6
Which interleukin is a major chemotactic for Which interleukin is primarily responsible for attenuating
neutrophils? the inflammatory response?

IL-8 IL-10

Which interleukin is primarily responsible


for fever and acute inflammation?

IL-1 Which interleukin is primarily responsible for stimulating Which interleukin is primarily responsible for stimulating
IgA production? IgE production?
Rx// Streptococcus pyogenes causes increased
production of interleukin-1 (IL-1) in macrophages. IL-5 IL-4
IL-1 is an endogenous pyrogen and acts on the
anterior hypothalamus to increase production of
prostaglandins, which increase the hypothalamic set-
point temperature. These mechanisms include
shivering and vasoconstriction of blood vessels in the
skin. Fever can also be caused by release of IL-6 and
TNF-α,both of which are endogenous pyrogens.

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Which interleukin is primarily responsible for Which interleukin is primarily responsible for stimulating
stimulating T cells and NK cells? growth and differentiation of bone marrow?

IL-2 IL-3 (similar to GM-CSF)


Which interleukin is responsible for activating NK
cells and inducing differentiation of T cells into Th1 cells?

IL-12

Which lymph node cluster drains the bladder?

Internal iliac

Which interleukins enhance activity of natural killer Which is more common, serum sickness or arthus
cells? reaction?

IL-2 and IL-12 Serum sickness

Which lymph node cluster drains the colon from splenic Which lymph node cluster drains the colon up to the
Which lymph node cluster drains the cervix? flexure to upper rectum? splenic flexure?

Internal iliac Inferior mesenteric Superior mesenteric

Which lymph node cluster drains the dorsolateral Which lymph node cluster drains the head and neck? Which lymph node cluster drains the jejunum and ileum?
foot?
Cervical Superior mesenteric
Popliteal

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Which lymph node cluster drains the lower duodenum? Which lymph node cluster drains the lungs?
Which lymph node cluster drains the kidney?
Superior mesenteric Hilar
Para-aortic

Which lymph node cluster drains the prostate? Which lymph node cluster drains the scrotum and vulva?
Which lymph node cluster drains the posterior calf?
Internal iliac Superficial inguinal
Popliteal

Which lymph node cluster drains the skin below the Which lymph node cluster drains
Which lymph node cluster drains the skin above the
umbilicus? the stomach, spleen, liver, and pancreas?
umbilicus?
Superficial inguinal Celiac
Axillary

Which lymph node cluster drains Which lymph node cluster drains Which lymph node cluster drains the upper duodenum?
the testes and ovaries? the trachea and esophagus?
Celiac
Para-aortic Mediastinal

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Which lymph node cluster drains the upper Which lymph node cluster drains the uterus?
limb and breast?
Para-aortic
Axillary Which of the following types of tumors tends to be rapid
growing, poorly circumscribed, infiltrative, and fixed to
surrounding tissues and local structures?

Malignant

- rapid as in grown within a year or within a couple months


- poorly circumscribed in that its hard to distinguish borders

Which of the listed three demographics count


Which of the following types of tumors tends to be Which of the listed three demographics count the mortality of the following cancers as their top 3 most
slow growing, well circumscribed, distinct, and the mortality of the following cancers as their top 3 most fatal in the United States?
mobile? fatal in the United States?
Men
Benign Children (age 0-14)

- well circumscribed means that it is clearly distinct


and seperate from the adjacent tissue in which it is
growing

- mobile means that you can move it around on a Unlike men and women, no change from incidence to For both men and women, lung cancer is 2nd most common
physical exam (not invading) mortality in children but most deadly overall (no adequate screening technique
for lung cancer)

Which of the listed three demographics count


the mortality of the following cancers as their top
3 most fatal in the United States?

Women Which oncogenic microbe is associated with the following


Which oncogenic microbe is associated with the following
cancers?:
cancers?:
H Pylori
Clonorchis Sinesis
Gastric Adenocarcinoma
Cholangiocarcinoma
MALT Lymphoma

For both men and women, lung cancer is 2nd most


common but most deadly overall (no adequate
screening technique for lung cancer)

Which paraneoplastic syndrome presents with a sudden


Which paraneoplastic syndrome is associated with onset of multiple seborrheic keratoses?
Which oncogenic microbe is associated with the
Squamous Cell Carcinomas of Lung, Head, and Neck; along
following cancers?: Sign of Leser-Trélat
with Renal, Bladder, Breast, and Ovarian Carcinoma?
Schistosoma Haematobium
Humoral Hypercalcemia of Malignancy
Squamous Cell Carcinoma of the Bladder
Hypercalcemia due to ectopic production of the PTHrP
hormone

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Which paraneoplastic syndrome presents with digital


clubbing, arthralgias, joint effusions, and periostosis of
tubular bones?

Hypertrophic Osteoarthropathy

Marked periostitis with cortical and periosteal


thickening can be seen in the following image: Which paraneoplastic syndrome presents with progressive
Which paraneoplastic syndrome presents with proximal muscle weakness, papules on the knuckles, and a
hyperpigmented velvety plaques in the arm-pit and neck? rash around the eyes?

Acanthosis Nigricans Dermatomyositis

Which polio vaccine is a live attenuated vaccine? Which polio vaccine is an inactivated/killed vaccine?
Which paraneoplastic syndrome presents with
psychiatric disturbances, memory deficits, seizures, Sabin Salk
dyskinesias, autonomic instability, and language
dysfunction?

Anti-NMDA Receptor Encephalitis

antibodies against the NR1 subunit of the NMDA


receptor

Which primary lymphoid organ is the site for immune Which primary lymphoid organ is the site of B-cell Which primary lymphoid organ is the site of T-cell
cell production? maturation? differentiation and maturation?

Bone marrow Bone marrow Thymus

Which region of the lymph node enlarges during Which transplants (2) are associated with graft-versus-host
Which region of the lymph node is not well
an extreme cellular immune reponse (e.g. viral disease?
developed in DiGeorge syndrome?
infection)?
bone marrow and liver
Paracortex
Paracortex
rich in lymphocytes

Which type of antibody digestion results in 1 bivalent Which type of antibody digestion results in 2 monovalent
Fab region and 1 Fc region? Fab regions and 1 Fc region?
Which type of hypersensitivity mediates anaphylaxis (e.g.
Pepsin cleavage Papain cleavage
food, drug, or bee sting allergies)?
can still agglutinate particulate antigen due to cannot agglutinate antigen due to lack of bivalence
Type I
bivalence of Fab region

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Which type of hypersensitivity reaction is characterized


Which type of hypersensitivity reaction is T-cell mediated?
Which type of hypersensitivity mediates atopic by circulating immune complexes?
reactions (e.g. asthma, allergic rhinitis)?
Type IV
Type III HSR
Type I
commonly associated with vasculitis and systemic
manifestations

Which type of hypersensitivity reaction is mediated by


cross-linking IgE on presensitized mast
cells and basophils?

Type I HSR

Which type of immunity (humoral or cell-mediated)


Which type of hypersensitivity reaction is mediated by responds to antigens with activated cytotoxic T-cells?
binding of antibodies to cell-surface antigens?
Cell-mediated immunity
Type II HSR

Which type of immunity (innate or adaptive) develops over Which type of immunity (innate or adaptive)
long periods? has extensive diversity?

Adaptive immunity Adaptive immunity

Which type of immunity (humoral or cell-mediated)


responds to antigens with antibodies from plasma
cells?

Humoral immunity

Which type of immunity (innate or adaptive) includes NK


cells? Which type of immunity (innate or adaptive) includes T
Which type of immunity (innate or adaptive)
cells and B cells?
has limited diversity?
Innate immunity
Adaptive immunity
Innate immunity
even though NK cells are derived from lymphoid precursors,
they are still considered part of innate immunity

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Which type of immunity (innate or adaptive) Which type of immunity (innate or adaptive) Which type of immunity (innate or adaptive)
includes chemical barriers, such includes circulating antibodies? includes complement?
as lysozyme and defensins?
Adaptive immunity Innate immunity
Innate immunity

Which type of immunity (innate or adaptive)


Which type of immunity (innate or adaptive)
Which type of immunity (innate or adaptive) includes physical barriers, such as skin and mucous
includes neutrophils and dendritic cells?
includes macrophages and monocytes? membranes?
Innate immunity
Innate immunity Innate immunity

Which type of immunity (innate or adaptive) Which type of immunity (innate or adaptive) occurs
includes physiologic barriers, such rapidly, over minutes to hours?
as temperature and pH?
Innate immunity
Innate immunity
Which type of immunity (innate or adaptive) utilizes
C-Reactive Protein and Complement?

Innate immunity

Which type of immunization has a long-lasting Which type of immunization has a short span of duration?
Which type of immunization has a rapid onset?
protection (memory)?
Passive immunization
Passive immunization
Active immunization
antibody half-life ~ 3 weeks

Which type of immunization is acquired by exposure to Which type of immunization is acquired


Which type of immunization has a slow onset? foreign antigens? by receiving preformed antibodies?

Active immunization Active immunization Passive immunization

Which type of selection allows survival of T cells Which type of selection causes apoptosis of T cells Which type of transplant rejection is due to pre-
expressing TCRs capable of binding self-MHC on expressing TCRs with high affinity for self antigens on existing recipient antibodies to donor antigen?
cortical epithelial cells? cortical epithelial cells?
Hyperacute

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Negative selection
"antibody-mediated hypersensitivity" (type II); antibodies
Positive selection
subsequently result in complement activation
these antigens are tissue-restricted self-antigens

Which type of transplant rejection occurs within months to Which type of transplant rejection occurs within weeks to
Which type of transplant rejection occurs within years? months?
minutes?
Chronic Acute
Hyperacute

Which type of transplant rejection presents Which type of transplant rejection presents with vascular
with maculopapular rash, jaundice, diarrhea, smooth muscle proliferation, parenchymal atrophy,
and hepatosplenomegaly? and interstitial fibrosis?

Graft-versus-host-disease (GVHD) Chronic

Which type of transplant rejection presents


as grafted immunocompetent T cells proliferating
and rejecting host cells with "foreign" proteins?

Graft-versus-host-disease (GVHD)

results in severe organ dysfunction; type IV HSR

Which type of transplant rejection presents


with vasculitis of graft vessels with dense interstitial
lymphocytic infiltrate?

Acute Which type of vaccine has the lowest chance of adverse


reactions?
Which type of transplant rejection presents
Subunit
with widespread thrombosis of graft vessels, causing
ischemia/necrosis?
Think of the lowest chance of molecular mimicry and
Hyperacute
antigenicity; subunits are typically capsular antigens
(polysaccharides) vs toxoids (which are typically proteins),
often seen while operating; graft must be removed
thus while both should not be found in the normal body,
subunit will typically have a less chance of causing an
adverse reaciton

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Which type of vaccine includes only the antigens which Which type of vaccine induces a relatively weak immune
Which type of vaccine has the potential to revert to a
best stimulate the immune system? response?
virulent form?
Subunit Inactivated/killed vaccines
Live, attenuated vaccines
booster shots are usually required

Which type of vaccine induces a strong, often lifelong


immunity? Which type of vaccine is a pathogen that has
been inactivated by heat or chemicals?
Live, attenuated vaccines
Inactivated/killed vaccine
Which type of vaccine is typically the most expensive?
comprised of live organisms which lose pathogenicity
but can still replicate in the host
Subunit

Which type(s) of hypersensitivity reactions are antibody-


mediated?

I, II, and III

Which type of vaccine may require a booster?


Which type of vaccine protects against bacterial toxins?
Toxoid
Toxoid

This is because antitoxin levels decrease with time

Within the spleen, central


arterioles are surrounded by periarterial lymphatic
sheaths (PALS)

Which types of vaccines usually requires booster


shots?
While carcinomas typically spread lymphatically, sarcomas
Killed/inactivated vaccine spread hematogenously

As opposed to a toxoid which MAY require a booster

p53 restricts the cell cycle to G1 by engendering the


inhibition of CDK4, maintaining the
hypophosphorylated state of Rb
Acute phase reactants are liver produced factors whose Acute phase reactants are liver produced factors whose
However when stimulated, CDK4 binds Cyclin D1 to serum concentrations change significantly in response to serum concentrations change significantly in response to
initiate the hyperphosphorylation of Rb inflammation inflammation

This is a systemic manifestation of inflammation This is a systemic manifestation of inflammation

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Anaplasia is the complete lack of differentiation of


cells in a malignant neoplasm

- Compare and contrast follicular adenoma of


thyroid [L image] (well differentiated) and anaplastic
carcinoma of the thyroid [R image] (no
differentiation) to the normal thyroid follicle [bottom
image]

Arthus reaction is a local subacute antibody-mediated


Anergy refers to a state in which an immune cell cannot
HSR to antigen in intradermal injection
become activated by exposure to its antigen
occurs in pre-sensitized individuals (has circulating IgG)

Cytotoxic type II
HSRs cause inflammation and/or cellular destruction of
tissue

e.g. Goodpasture syndrome, rheumatic fever


Chronic transplant rejection is dominated Chronic transplant rejection is dominated
by arteriosclerosis by arteriosclerosis

Hassall's corpuscles are eosinophilic areas in Interferon-α and -β are glycoproteins synthesized by virus-
the thymus composed of epithelial reticular cells infected cells that act locally on uninfected cells, "priming"
them for viral defense
help local cells by degrading viral nucleic acid and protein
Ischemia occurs when there is inadequate blood supply to
meet demand

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Memory B cells are mature, differentiated B


cells characterized by surface IgG, IgA, or IgE

Non-cytotoxic type II
HSRs cause abnormal blockade or activation of
downstream cellular processes

e.g. Graves disease, myasthenia gravis


Major histocompatibility complexes (MHCs) present
antigen fragments to T cells and bind T-cell receptors
(TCRs)

Plasma cells are mature, differentiated B


cells characterized by cytoplasmic Ig

Poorly differentiated tumors are often more aggressive, Serum sickness is an immune complex disease in
whereas well differentiated tumors are often less aggresive which antibodies to foreign serum proteins are produced

- thus better outcomes in well differentiated vs poorly immune complexes form and are deposited in membranes,
differentiated where they fix complement (leads to tissue damage)

Superantigens are antigens that cross- Superantigens are antigens that cross- Superantigens can activate any CD4+ T-cell, resulting
link the β region of T-cell receptors to MHC link the β region of T-cell receptors to MHC in massive release of cytokines
II on APCs outside the normal peptide-binding groove II on APCs outside the normal peptide-binding groove

results in loss of specificity with overactivation of results in loss of specificity with overactivation of T-cells (up
T-cells (up to 20%) to 20%)

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Well differentiated tumors closely resemble their tissue


Acute transplant rejection can be prevented/reversed with Acute transplant rejection can be prevented/reversed with
of origin, whereas poorly differentiated tumors look
immunosuppressants immunosuppressants
almost nothing like tissue of origin
however, it is still possible for acute transplant rejection to however, it is still possible for acute transplant rejection to
Well differentiated tumors have better outcomes than
occur occur
more poorly differentiated tumors

Gynecological and Breast cancers can produce anti-Yo Gynecological and Breast cancers can produce anti-Yo
Hodgkin Lymphoma can produce anti-Tr antibodies which
antibodies which can cause Paraneoplastic antibodies which can cause Paraneoplastic Cerebellar
can cause Paraneoplastic Cerebellar Degeneration
Cerebellar Degeneration Degeneration
The Tr antigen is a receptor expressed by Purkinje cells
The Yo antigens are found in the Purkinje Cells The Yo antigens are found in the Purkinje Cells

Hodgkin Lymphoma can produce anti-Tr antibodies


which can cause Paraneoplastic Cerebellar MMR and varicella are live vaccines that can be given MMR and varicella are live vaccines that can be given
Degeneration
to HIV patients with CD4 counts > 200/mm3 to HIV patients with CD4 counts > 200/mm3
The Tr antigen is a receptor expressed by Purkinje
cells

Natural killer cells are induced to kill cells that have Natural killer cells are induced to kill cells that have
an absence of MHC I on their cell surface an absence of MHC I on their cell surface

or when exposed to a non-specific activation signal on or when exposed to a non-specific activation signal on
target cells target cells

MMR and varicella are live vaccines that can be given


to HIV patients with CD4 counts > 200/mm3

Reversible cellular injury is characterized Reversible cellular injury is characterized ultrastructurally


ultrastructurally with clumping of nuclear chromatin with clumping of nuclear chromatin

Small Cell Lung Cancer can produce anti-Hu antibodies


which can cause both Paraneoplastic Cerebellar
Degeneration and Paraneoplastic Encephalomyelitis

Hu antigens are found in both neurons and purkinje cells

Small Cell Lung Cancer can produce anti-Hu Regulatory T cells are identified by expression of CD3, Regulatory T cells are identified by expression of CD3,

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antibodies which can cause both Paraneoplastic


Cerebellar Degeneration and Paraneoplastic
Encephalomyelitis CD4, CD25, and FOXP3 CD4, CD25, and FOXP3

Hu antigens are found in both neurons and purkinje


cells

α-fetoprotein (AFP) is a serum tumor marker elevated in


(mnemonic: HE-MAN is the alpha male)

α-fetoprotein (AFP) is a protein that is normally made by - Hepatocellular carcinoma


the fetus - Endodermal sinus (yolk sac) tumor
- Mixed germ cell tumor
Regulatory T cells are identified by expression of
- believed to be a "fetal albumin"; binds copper, nickel, fatty - Ataxia-telangiectasia
CD3, CD4, CD25, and FOXP3
acids, and bilirubin - Neural tube defects

- this is the major plasma protein produced by the yolk sac


and fetal liver during fetal development
- One exception to the neural tube defects is spina bifida
occulta; confirm NTD with measurement of fetal AChE
levels

α-fetoprotein (AFP) is a serum tumor marker elevated α-fetoprotein (AFP) is a serum tumor marker elevated in α-fetoprotein (AFP) is a serum tumor marker elevated in
in (mnemonic: HE-MAN is the alpha male) (mnemonic: HE-MAN is the alpha male) (mnemonic: HE-MAN is the alpha male)

- Hepatocellular carcinoma - Hepatocellular carcinoma - Hepatocellular carcinoma


- Endodermal sinus (yolk sac) tumor - Endodermal sinus (yolk sac) tumor - Endodermal sinus (yolk sac) tumor
- Mixed germ cell tumor - Mixed germ cell tumor - Mixed germ cell tumor
- Ataxia-telangiectasia - Ataxia-telangiectasia - Ataxia-telangiectasia
- Neural tube defects - Neural tube defects - Neural tube defects

- One exception to the neural tube defects is spina - One exception to the neural tube defects is spina bifida - One exception to the neural tube defects is spina bifida
bifida occulta; confirm NTD with measurement of fetal occulta; confirm NTD with measurement of fetal AChE occulta; confirm NTD with measurement of fetal AChE
AChE levels levels levels

α-fetoprotein (AFP) is a serum tumor marker elevated


in (mnemonic: HE-MAN is the alpha male)

- Hepatocellular carcinoma
- Endodermal sinus (yolk sac) tumor
- Mixed germ cell tumor α-fetoprotein (AFP) is transiently elevated in pregnancy
- Ataxia-telangiectasia
- Neural tube defects - major plasma protein produced by yolk sac and liver
during fetal development

- One exception to the neural tube defects is spina


bifida occulta; confirm NTD with measurement of fetal
AChE levels

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