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Immunology Usmle Hsu Notes PDF
Immunology Usmle Hsu Notes PDF
Lymph node:
Cortex Outer most layer
Consist of:
-follicles
-subcapsular macrophages
dendritic cells
(in cortex) -site of b cell localization + prolif
Germinal Follicle -size increase in viral infection (reactive lymphadenopathy)
-shrink when healthy or no use (e.g bruton agamaglobenimia)
subtype:
Hsu notes usmle immunology
primary or secondary
-primary: dense, dormant
-secondary: pale, active (contain oporlif b cell and follicular dendritic cell)
clinical: agammaglobenima: germinal center and primary lymphoid follicles do nto form due to absence
of b cell
Paracortex -house t cell
-coontain high endothelial venules through which T and B cell enter from blood
-note
clinical:
rd th
-not well developed in Di George (3 and 4 pharyngeal pouch fail to develop and dont have T cell**)
-enlarge in cellular immune response (E.g viral infection)
Medulla Consist of: cords + sinuses
Cords:
Hsu notes usmle immunology
-consist of lymphocyte (e.g hisocyte) + plasma cells
Sinsues: -> communicate with -> efferent lymphatics
-contain reticular cells + macrophages
Note:
Histiocytosis X
-prolif of medullary sinuses
SCID
-low B and T cell
-see just medullary sinus(as prolif histiocyte but nothing other cells)
SPLEEN:
Located in LUQ of abdomen, anto to l eft kidney, 9-11 ribs
White pulp
-artieroles
-deliver of rbc
resident macrophage
-ingest dying rbc and encap bacteria
sinusoids with fenestrated basememt membrane to
-allow for red rbc exist
innate immunity vs adaptive immunity
Innate immunity Adaptive immunity
Component -neutrophil, macrophage, monocyte, dendritic cell, NK cell, T cell, B cell, circulating antibody
complement (soluble proteins e.g)
-others: physical barriers,
Mechanism Germline encoded Variation through V(D)J recombinaing
during lympho cyte production
Resistance Persist through generation Not heritable
Response to Non specific Specific
pathogens Occur rapidly (min to hrs) Refined ver time
Non memory response Develop over long periods,
memory response fast, robus t
Physical barriers Epithelial tight junction, mucus
Secreted protein Lysozyme, complement, CRP, defensins Immunoglobins
Pattern recognition Toll like receptor (TLR): -> recognizes pathogen associated Memory cells -> activate -> B and T ells ->
molecular patterns (PAMPS) strong quicker immune response
-> trigger acute inflammatory response*
e.g LipoPolySaccharides (gram neg nbact), lipoteichoic acid in gram
positive bacteria, flagellin (bacteria), nucleic acid ds rna (viruses)
(PAMP NOT PRESNT on mamilian cell == innate immunity does not
damage the host)
MHC histocompatibility complex
Hsu notes usmle immunology
Notes uworld:
HLA region of Chromosome 6.The human leukocyte antigen system (HLA) is the name of the major histocompatibility
complex (MHC) in humans. The super locus contains a large number of genes related to immune system function in humans.
This group of genes reside on chromosome 6, and encode cell-surface antigen-presenting proteins and many other genes.
The HLA genes are the human versions of the MHC genes that are found in most vertebrates (and thus are the most
studied of the MHC genes). The proteins encoded by certain genes are also known as antigens, as a result of their historic
discovery as factors in organ transplantations. The major HLA antigens are essential elements for immune function. Different
classes have different functions:
HLA antigens corresponding to MHC class I (A, B & C) present peptides from inside the cell (including viral peptides if present).
These peptides are produced from digested proteins that are broken down in the proteasomes. The peptides are generally small
polymers, about 9 amino acids in length. Foreign antigens attract killer T-cells (also called CD8 positive- or cytotoxic T-cells) that
destroy cells.
HLA antigens corresponding to MHC class II (DP,DM, DOA,DOB,DQ, & DR) present antigens from outside of the cell to T-
lymphocytes. These particular antigens stimulate T-helper cells to multiply, and these T-helper cells then stimulate antibody-
producing B-cells to produce Antibodies to that specific antigen. Self-antigens are suppressed by suppressor T-cells.
General notes:
-ALSO refer to as section of the genome wich codes for HLA proteins***
-surface antigen presenting protein
-protein can either process some foreign antigen and present outside OR present self made molecule and present outside
-both have anchorage in lipid membrane (but MHC2 has 2 anchorage) (MHC1 has 1 anchorage)
-both have peptide binding site
-
-recognize only specific foreign particles
-found on eukaryote cell
-all nucleated cell has MHC1 but vary between person and cells
-MHC2 only found in antigen presenting cels (in immune systes like macrophage, dendritic cell, b cell)**
-(antigen presenting cell function: engulf pathogen by phagocytosis and turn it into fragments called antigen then load them on receptor MHC1
and MHC2 to all immune cells)
-(function of MHC1: to designate one cell to be sick and to be killed)
MHC1:
-virus -> chewed up by proteasome -> form antigen peptide -> brought into RER via TAP1 -> loaded onto MHC1 -> MHC1 then fuse with cell
membrane -> brought onto outside surface
MHC2:
If detect bacteria -> then fuse into cell into endosome -> break down -> fragments fuse with MHC2 molecule and CLIP released from MHC2 ->
load onto MHC -< go onto outsie cell surface
how to prepare MHC structure (present load etc):
-all in RER
-in cytosol have proteasome (break down protein in to small fragemtns)
-when there is an engulfment o fsmall pathogen -> endocytosis -> now inside cytosl -> fuse with lysosome -> fragements in cytosol -> further
broken down by proteasome into very tiny fragments -> go into RER (between RER membrane and cytsol via transporters)-> loaded ONTO
MHC***
MHC2
-inside RER, have MHC complexes ready (e.g in MHC2, alpha and beta chain prepared and there is a protein that blocks binding region normally;
and when fragments taken into RER then blocking protein released (but still has CLIP present on attachement binding site)-> CLIP released and
antigen replaces it -> NOW MHC2 loaded with antigen is now fused with cell membrane thus cell has MHC2 with antigen on SURFACE OF CELL
MHC 1 MHC2
Loci (ususally 3 genes: code for HLA-A, HLA-B, HLA-C HLA-DP, HLA-DQ, HLA-DR
on arm of
chromosome 6)
binding TCR, CD8 TCR, CD4
-CD8: cytotoxic t cell (fct: kill the target cell***) -CD4: T helper cells (fct: active other t cell, active B cell,
proliferate macrophage or other APC)
structure 1 long chain, 1 short chain 2 equal length
expression All nucleated cell, APC, platelet, not on RBC APC: macrophage, dendritic cell, B cell
Hsu notes usmle immunology
fct Present by ALL NUCLEATED CELL an endogenously Apresent endogenously synthesized antigen (e.g bacterial
synthesized antigens (e.g viral or cytosolic proteins) -> protein) to CD4 T helper cell
to CD8+ cytotoxic t cell
Antigen Antigen peptides -> delivery via TAP (Transporter Antigen loaded following release of invariant chain in an
loading associated with antigen processing)-> loaded onto acidified endosome
MHC 1 in RER
Hsu notes usmle immunology
Structure 2 chains: polymorphic alpha chain (1+2+3) + partial Polymorphic Alpha chain (1+2) + Beta chain
beta 2 microglobulin (2)
Note: Viral vaccine DO NOT ACTIVATE CD8 t cell
cytotic tx cell DUE TO virus NOT REPLIACTE
within cell thus viral antigen not presented
with class 1 MHC
HLA
Human leukocyte antigens (HLA) are encoded by HLA genes on MHC regions of the genome which is located on the short arm of chr
6
HLA are alloantigen (i.e. they differ among members of the same sepcicies)
3 of these genes (HLA-A, HlA-B, HLA-c) code for the class 1 MHC proteins
HLA DP, DQ DR code cfor class 2
Each person has 2 haplotypes (2 sets of these genes) (one on paternal and t he other on maternal chr 6)
These genes are diverse (polymorphic = many alleles of the class 1 and 2 genes)(e.g 47 different HLAA genes)
But any individual inherits only a single allele at each locus from each parents thus can make no more than 2 class 1 and 2 proteins
at each gene locus
Expression is codominait: proteins encoded by both paternal and ma ternal genes are produced
Codominant means that each indivudal inherit a complete set or haplotype from each parent THUS 2 genetically unrelated indivudal
will have distinctive differences in the antigens expressed n their cells
(note there is a class 3 which is a third gene loci: encodes 2 ctyokines (TNF, llymphotoxins) and 2 compmenet (c2 and c4)) (but does
nto encode MHC)
HLA subtype associated with diseases:
A3 Hemochromatosis A3 freaking 3
Hsu notes usmle immunology
B8 Addison disease, myasthenia gravis, graves disease
B27 Psoriatic arthritis, ank spon, IBD associated arthritis, reactive arthritis PAIR
(acute jection in kindey; diffuse cellular infiltrate)
- chronic rejection:
- after graft survive an acute allograft
- occur months to years after negraftment
- t cell mediated
chronic rejection
is a major cause of morbidity and mortality and occurs in almost half of all patients within 5 yearss of transplantation.
these patients commonly present with dyspnea and a dry cough.spirometry shows an airflow limitation with a drop in
both the forced expiratry volume in 1 seconds (FEV1)and the FEV1 to forces vital capacity (FVC) ratio.
chronic rejection affects the small bronchioli producing the obstructive lung disease knowns as bronchiolitis
obliterans.
initially histopathilogy shows lymphocytic inflammation and destruciton of the epithelium of the small
airways.subsequently fibrinopurulent exudate and granulation tissue are found in the lumen of the bronchioli. which
ultimtely results in fibrosis, scarring and the progressive obliteration of small airways.
origin of cells:
notes:
in general,
(1) start with pluripotent stem cells in bone marrow
(2) divie into common lymphoid stem cell or myeloid stem cell
(3) common lymphoid stem cell -> T progenitor or B progenitor
(4) myeloid stem cell -> Granulocyte progenitor, eosinophil progenitor, basophil progenitor, megakaryocyte, erythroid progenitor
different cells:
Leukocyte : Granulocyte (nuetohil, eosinophil, basophil, mast NLMEB
cell), mononuclear (monocyte, lymphocyte) From highest count to lowest
Neutrophil, lymphocyte, monocyte, eosinophil, basophl
Hsu notes usmle immunology
Neutrophil acute infl response cell
increase in bacterial infection
phagocytic, relase degrading enzymes enzymes
multilobed nucleus
specific granules contain: LAP (leukocyte alkaline
phosphatase), collagenase, lysozyme, lactoferin
lysosomes contain proteinase, acid phosphatase,
myeloperoxidase, beta glucorinadase
structure:
cd 14
cytoplasmic grnaules that stain a pale pink (neutral) colour with
blod stain such as wright stain (in contrast to eosinophisl and
basophils)(whose granule stain red and blue respectivitely)
NOTE: DO NOT display class 2 mhc on surface THUS DO NOT
present antigen to helper t cell
clinical:
hypersegmented neutrophil (> 6 lobes) seen in vit b12/folat def
increase band cells (immature neturophils) = increase myeloid
prolif (bact infection or cml)
important neutrophil chemotactic agents (c5a, IL8, LTB4,
kallikrein, platelet activating factor)
Monocyte Fct: diff into macrophage in tissue
Structure:
Large, kidney shaped nucleus, frosted glass cytoplasm, found
in blood
Macrophage Fct:
phagocyte bacteria ,cellular debris, senescent rbc
-macrophage ingest bacteria etc
-macrophage have surface Fc receptors -> interact with -> fc
portion of IgG thus enhance uptake of opsonized organisms
-also have receptor for c3b (opsonin)
Granuloma formation
(lipid A from bacterial LPS bind CD14 on macrophage to initiate
septic shock)
antigen presentation
-foreing material ingest -> froegin antigen present on cell
surface with class 2 mhc with TCR of cd4
cytokine production
-e.g IL1 nad TNF
-iL1 is fever
structure:
CD 14
agranlocyte with a ruffled cytoplasmic membrane and cytoplasmic
vacuoles and e sicules
Note
Diff from circulating blood moocyte
Activated by gamma IFN
Can function as apc via mhc 2
Hsu notes usmle immunology
Macrophage activation:
(1) macrophage activiated initially by substances e.g
LPS (bacterial lipopolysaccharide, endotoxin) OR
bacterial peptidoglycan OR by bacterial DNA
(bacterial dna is unmethylated, human dna is
methylated)
these -> interact with-> TOLL LIKE RECEPTORS on
macrophage
(2) macrophage ecna also be activated by gamma
IFN by helper t cell (Gamma IFN increase syntehssi of
class 2 MHC -> enhance antigen presentation thus
increase microbial acivity of macropahges)
Fct:
Eosinophils: Defend against helminthic infection (major basic protein)
Highly phagocytic for antigen antibody complexes
Produce histaminase, major basic protein (MBP:
helminthotoxin), eosinophil peroxidase, eosinophil cationic
protein, eosinophil derived neurtoin
Structure
Bilobate nucleus
Packed with large eosinophilic granules of uniform size
Granulocyte with bilobed nucleus and large pink cytoplasmic
granules
STAIN RED WITH wright stain (sue to negatively charged eosin
dye bind to positive charged major baiscp ortein in granules)
Note:
Causes of eosinophilia NAACP
Neoplasia, asthma, allergic, parasite (esp by neomatodes), chronic adrenal
insuff
Basophils fcT:
mediate allergi reaction,
type 1 hypersenstivity,
-have receptors on their surface for Fc portion of the jeavu
cjaom pf Ige
- when adjacent IgE molecules are cross linekd by antigen ->
cause release of mediators such as histamine and enzymes (.g
peroxidase and hydrolase) -> thus infl -> thus severe immediate
hyperssentivity reaction (e.g systemic anaphylaxis)
eliminate large extracellular parasite
structure:
densely basophilic granules
contain heparin (anticoagulant), histamine (vascodilator)
granulocyte with bilobe nucleus and large blue cytoplasmic
granules
-STAin BLUE with wright stain (due to positively charged methyl
blue dye bind to negative charge molecuels in grandules)
note:
stain with basic stain
can be sign of myeloprolif diease e.g cml
Mast cell Fct:
Mediate allergic reaction I local tissues
Structure
Contain basophilic granules
Fc proteion of IGE to membrane
-IgE crossl ink upo antigen bind -> degranulation -> release of histamine,
heparin, trypase, eosinophil chemotactic facture
note:
Hsu notes usmle immunology
invive in type 1 Hypersentivity reaction
cromolyn sodium prevent mast cell degrandulation (use for asthma
prophylaxis)
Dendritic cell Locate: epi ttissuee
Constituivey expresss MHC class 2 + costim B7 cell surface receptor
From myeloid
granolyte monocyte progenitor -> dendritic
Structure:
Long cytoplasmic arm
Cd14 postiive
RAQUET SHAPEED intracytoplasmic granule (birbeck granudle) (UWORLD)
Function: antigen caputer, transport remnstaiton, infl
Innate cellular response:
NK cells
Member Innate immunity
Note: -a large granular lymphocyte
Natural = active without prior exposure to virus, not enhanced by exposure and not specific for any virus
-can kill without antibody (but IgG enhances it)(process called ADCC antibody depdent cellular cytotoxicity)
-essentially lymphocyte with some t cel markers
-DONT HAVE TO pas sthrough thyus to mature
-NO memoery, NO t cell repceptor, NO NEED recognition of MHC proteins (just detect number of HM1 )
-viral and tumour cell has dereased number of MHC1 protei thus killed
-ALSO detect MICA (protein on cancer cell)
-clinical: If lack of NK cell, predisposed to infection with varicella zoster and cmv
fct Kill virus infected cells + tumour cells**
Marker CD 16 (FCR), CD 56 ( CAM )
Effector Cytotoxins: Perforin + granzymes
(to induce apoptosis of virally infected cells + tumour eclls)
OR
Antibody depdent cell mediated cytotoxicity (e.g CD16 vubds Fc region of bound Ig, activating the NK cell)
(FAS-FAS ligand mediated apoptosis***)
Enhanced by IL2, IL12, INF alpha, IFN beta
apoptosis can be triggered by number fo mechanism incl deprivation of growth factors, dna damage, intarcellualr acc of
musfiolded protein, mediation by cytotoxic t lymphocyte, activation of recetpors in TNF receptor family such as FAS
fas receptors initate the extrinsic pathway of apoptosis through cytoplasmic component known as death domain
upon binding FAs lingang (FASL), the receptor trimerize thus allow death domain to form a binding site for adaptor protein
cauled fas aw death tdomain (FADD)
receptor bound FADD then stimulate activation of iniator caspases (8 and 10) that begin an activation cascade culminating in the
activation of executioner caspases (3 and 6)
these intiate the terminal process fo apoptosis incl cleavage of dna, fragmentation fo ncuelus, organelle autodigest, plasma
membrane blebbing
FAS receptor is expressed on t lymphocyte and play role in pathogensis of numerous disease incl cancer and autoimmune
Once activated, t lymphocyte begin t oexpress FASL which can bind to FAS on the same cell or adjacent lymphocyte
During intial clonal expansion, activated t lymph are resittant to fas induced apoptosis but after constat stimulation of self
antigen, activated t lymph undergo apoptosis via activation induced cell death
(mutation involve fas or fal impairs this thus result in excess acc of autoreactive t cell and develop of autoimmune diease such as
SLE)
e.g graft reject
-cytotixic t cell recognize foregin mhc1 thus attack
Only recognize polypeptide antigens + in association with MHC protein (AKA mhc restriction)
MHC1 present endogenously synthesized antigen (e.g viral) while MHC2 presnt extracelllar mcorgram (bacterial)
Can bind to sheep erythrocyte (sheep erythrocyte receptor) ** (used as mean of idtnfiyint t cell)
TH cells (subdivision of CD4):
Th 1 Th 2 Th17 T reg
Pathogens Intracellular infections: viruses + Parasitic infections or Extra cellular (arise from Th0)
intracellular bacteria allergens bacteria and fungal
infections
-due to inability to pahgcyte
such pathogen, There is no
significant macrophage or NK
cell stimuatlion
expresses T-Bet GATA-3 ROR-gamma-T Fox P3
transcription factor
(to induce activation)
Secretes IFN gamma + IL 2 IL 2,4,5,6,10,13 IL7, IL22 Inflamatory
-IL2: activate antigen specific t -IL4,5,10: activate b cell inhibitory
helper t cell to produce a clone + -IL4: cause B cell to istype cytokes IL10,
activate cytotixic t cell switch to IgE (Which will bind TGFbeta
-IL2 ALSO stimulate helpter t cell to mast cell, eosinophil +
to multiply into a clone of antigen basophils)
specific helper t cell OR be come -IL13, IL4: enhance
memory cell (capable of rapidly alternative macrophage
activated upon exposure to activation fro tissue repair +
antigen at later time) muscus secretion +
-IFN gamma: activate macrophage peristalissi
+ amplify Th1 response by
Hsu notes usmle immunology
increasing MHC class 2 proteins -IL4, IL10, IL13: promote Th2
on APC+ inhibit th2 response + response while inhibit th1
enhance isotype switching to IgG respponse
-IL5: mature and activate
eosinophils
Activates Macrophages + cytotoxic cells Recruits eosinophils for
parasitic defeces + promote
IgE production by B cell
Differentiation IFN gamma, IL12 IL2, IL4 TGF beta, IL6, IL23 TGF-beta
induced by IL12 secreted by
macrophage*** (thus
increase TH1 thus host
defece against
organisms that are
controlled by a delayed
hyper senstitivity
respne)
IFN gamma from NK cell
Inhibited by IL4, IL10 (from th2) IFN gamma (from th1)
Enhance cell YES NO
mediated immunity
and delayed
hypersentivity
primarily
Enhance antibody NO YES
production primarily
Clinical relevance Kaplan:
Leprosy
Progression of Mycobacterium leprae depends on: balance of th1 and th2
Tuberculoid leprosy
-lipprotein of a certain leprosy -> stimulate toll like receptor on macrophage -> cell to synthesize IL12
IL12 -> cause increase prolif of strong th1 -> which eradicate intracellular pathogen by granuloma formation + secrte IFN gamma
-> which activate macrophage -> thus idisease progress slowly and patient survive
Lepromatous leprosy:
-strong th2 -> AND DUE TO RECIPRICOAL INHIITON THUS CELL MEDIATED RESPONSE IS DEPRESSED (e.g IL10 from th2)-> progress
to lots of infection
Th1 and Th2 development (after thymus and bone marrow)
Hsu notes usmle immunology
Th 1:
(1) microorganisms -> ingested by macrophage -> macrophage release IL12
(2) IL12 -> induces nave TH- cells to -> become Th1 cells
(3) Th1 cells -> gamma IFN (activate macrophage) + IL2 (active cytotoxic t cell) -> THUS CELL MEDIATED IMMUNITY OCURS
TH2:
(1) Microorganism -> ingest by unknown cell
(2) Unknown cell -> release IL4 induce nave th cell to -> become th2 cells
(3) Th2 cell -> secrete IL 4,5 -> activate b cell to -> become plasma cells -> THUS antibodies are pdocued -> ANTIBODY MEDIATED
RESPONSE
(4) TH2 also secrete IL10 -> which inhibit macrophages thus drive ystem toward antbody response and waway from cell mediated
response
Cytokines functions:
Hot T-bone steak
Hot (1), stimulate T cell (2), stimulate bone marrow (3), stimulate IgE (4), stimulate IgA (5), simulate aKute phase protein IL6
Cytokines Major source Important functions
IL1 macrophage Activate helper t cell, cause fever (endogenous pyrogen that act on hypothalamus)
-activate endothelium to express adhesion molecules**
-induces chemokine secretion to recruit WBC
nbme>>>1,2,15>>>impaired snthesis of IL-1>>>impaired function of T lymphocytes
when antigenic peptide (on MHC 2 of macrophages) binds the T-cell receptor on CD4
helper T cells, the macrophages secretes IL-1.
IL-1 stimulates the helper T-cells to proliferate and/or secrete lymphokines
526
IL2 All t cell (th1 also) Activate and stimulate growth of helper + cytotoxic T cell + reg cell, also activate b cell and nk
cell
-*T CELL growth factor
Interleukins-2 (IL-2) receptor is transmembrane protein complex that acts via a
Hsu notes usmle immunology
multipathway system, including a JAK-STAT signaling component, a MAP kinase
pathway, and phosphoinositide 3-kinase
function in an autocrine manner whereby activated T-lymphocytes (Th1 )provide
costimulus to themselves by secreting IL-2 and producing IL-2 receptors
increased activity of T cells and NK cells is responsible for IL-2 antitumors ability
(aldesleukin)
nbme>>>4,2,15
activation of cytotoxic T cells to eliminate virus infected cell require>>>>MHC class 1
and IL-2, NOT interferon-gamma.
explanation
Once activated, the TC cell undergoes clonal expansion with the help of a cytokine
called Interleukin-2 (IL-2) that is a growth and differentiation factor for T cells.
IL3 Secreted by ALL t cell Support growth and diff of bone marrow stem cells
-fincutions like GM-CSF
IL4 Th2 subset of helper th Stimulate B cell growth, increase isotype switching to igE*** (thus increase acute immediate
hypersensitivity) and IgG****
Increase th2 subset of helper t cell
IL5 Th2 Stimulate b cell diff, increase eosinophils + igA**
IL6 Macrophage Fever + production of acute phase protein
(macrophage infect with mycobacteriaproduce Il12 -> stim t cell and nk cell to produce
IFN gamma -> which nthen bind to its receptor thus lead to receptor dimerization and
activate of janus kinase 1 + 2 -> result in neuclear signal via STAT 1 and transcription of
IFN gamma reg gene which promote mycobact kill by phagocyte)(also enhances viral
and parasitic resitance by inc expression of MHC and intrinsic dfefece actor)
Tumor Macrophage -activates endothelium
necrosis -cause wbc recruitment + vascular leak
factor -causes cachexia in malignancy
alpha -maintian granuloma in TB
(TNF -mediate sepsis (IL1, IL6, TNF alpha)
alpha)
Tnf Macropahges Low conetration: activate neutrophils + increase adhesion to endothelial cell
High concentration: mediates septic shock, act as cahectin, causes necrosis of tumour
Other:
IFN alpha + beta Most human cells in response to viral Fct:
infectios Bind to type 1 IFN receptor on infected +
neighboring cells (autocrine/paracrine
signaling) -> transcription of antiviral enzymes
capable of halting protein synteshis
-note: antiviral enzyems active ONLY in
presence of ds RNA (forms in infected cell as
result of viral replication)
Hsu notes usmle immunology
Interleukin by sources
Macrophage IL 1,6,8,12, TNF alpha
All t cells IL 2,3
Th1 cells INF gamma
Th2 cells IL 4,5,10 ,13
Leukocyte Migration (Extravasation)
Note:
First step in acute inflammatory response is activation of vascular endothelium in breached epithelial barrier
Cytokines + other infl mediators released in area as result of tissue damage induce expression of slectin type adhesion molecule on
endothelial cell
Neutrophils are the FIRST cell to bind to infl endothelium and extravasate into tissues, peaking at within 6 hours
Monocyte, macrophage eosinophils may arrive 5-6t hours later in reponse to neutrophil released meidates
(2) O2 dot + NADP -> (superoxide dismutase) -> H2O2 (hydrogen peroxide )
(3) hydrogen peroxide H2O2 + chloride CL- -> (myeloperoxidase) -> HOCL (hydrogen peroxide bleach)
Hsu notes usmle immunology
note:
side oxidative reaction with oxidative burst:
oxidative:
G6P -> (G6PD) -> 6 Phosphoglucolactone -> Ribulose 5P + 2 NADPH + 1 CO2 -> nucleotide puien and pyrimide biosynthesis**** [PRPP]
While G6PD: NADP -> 2 NADPH
NADPH + oxidized glutathione GSSG -> (glutathione reductase) -> NADP + GSH (reduced)
Reduced glutathione (GSH) + H2O2 hydrogen peroxide -> (glutathione peroxidase OR CATALASE***)-> oxidized GSSG + H2O water
Clinical Goljan:
-x linked recessive
-def NADPH oxidase in cell memebrane of neutrophils and monocyte THUS reduced produce of surpoxide THUS absent respiratory burst
-dx:
-organisms are incubated with a colorless NBT dye which is convereted to blue IF RESPIRATORY IS INTACT
-both super oxide and H2O@ are produced BUT ABSENT OF MPO prevent synthesis of HOCL
-G6pd def:
-THUS no NADPH THUS less glutathione THUS more free radicals which damage blood cells and also cause redisposition to infection
note:
o2 indepdent bacterial killing:
e.g lactoferrin (bind iron neccaary for bacterial reproduction) and major basic protein (eosinophil product that is cytotoxic to helminth)
T cell development
initially produced in the bone marrow, but they migrate from that location to mature during the first trimester of gestation in the
thymus.
(1) T cell precursor (or other immature lymphocyte -@ bone marrow
destined to be t cell) leave bone marrow to thymus -first primary lymphoid organ
(2) initially arrive thymus: -@ Thymus
- the T cell precursor -> become -> double negative T -the second primary lymphoid organ
lymphocyte (DO NOT EXPRESS CD4 or CD8 on surface) -bilobed organ consist of: outer cortex (immature cells) +
inner medulla (maturing cells)
(3) double neg T cell travel from thymus cortex ->
medulla
Hsu notes usmle immunology
(4) AT CORTEX:
-double neg t cell rearrange the beta + alpha chain of TCR
(t cell receptor) + coexpress CD3 + CD4 + CD8 co receptor
THUS FORM -> double positive T cell
@ cortex:
double neg T -> double positive T (CD3 + CD4 + CD8)
SELECTION PROCESS: SELECTION PROCESS:
(5) MHC1 + MHC2 each loads with NORMAL self- -note: to remove t cells that would bind to normal self
peptide and presented to double positive T cell antigen and cause autoimmunity OR those with no attraction
-will result in 3 outcomes: at all to APC
Positive selection:
- Where TCR capable of binding with low
affinity to self peptide***
- These T cell will receive signal to divide
and mature into medulla
Failure of positive selection
-those that FAIL to receognize slf MHC
-will not be encouraged to mature
Negative selection
-the T cell that bind too strongly to self MHC
and self peptide will be induced to undergo
apoptosis** (due to potential to cause
autoimmune disease)
(6) - As part of selection in positive selection, those that
bind to MHC1 will be directed to express only CD8 ->
THUS become T helper cell
- those that bind to MHC 2 wil be directed
to express only CD4 -> ths become
cytotoxic t cell
-THUS FORM SINGLE POSTIVE T CELL
minor note kaplan:
-some self reactive t cell -> form T reg cell
-fct t reg cell: inhibit self reactive t cell
-identify self reactive t cell by: CD25, Fox P3
(transcription facor)
-T reg cell release: IL 10 + TGF beta to inhibit
inflammation
Hsu notes usmle immunology
-T reg:
-has exoression of cd3, cd4, cd25, fox p3
-clincal kapalnan:
IPEX (immune dysregulation
polyendocrinopathy enteropathy x linked
syndrome):
-genetic def of FOX P3 -> thus autoimmunity
-Px: enteropathy, endocrinopathy, nail
dystrophy, dermatitis, autoimmuene
dermatological condtion,
-aw diabetes in male infants
(7)
Activation of T cell
(1) dendritic cell samples antigen -> process antigen -> migrate to lymph node
SIGNAL 1:
(2) antigen carrying dendritic cell -> carried on dendritic cell surface by MHC 1 or 2
-Ag-MHC1 or 2 on DENDRITIC CELL-> (interact with) -> TCR + CD4 or 8 on T cell respectively
-IL1 *** from machrogphage required for activation of thcell
signal 2:
(3) B7-1/2 protein (CD80/86) ON DENDRITIC CELL -> interact with CD28 ON T CELL
-IL2 from t helper cell (CD4) to help activate itself***
-under normal condition, B7 is under expressed on APC, but in infection ro infl, expression increase thus enhance activation of the mature
nave t cell (THEN ATERWARDS< preferentially bind to CTLA4 to turn off t cell response)
Note:
If ag presented by signal 2 is not -> state of anergy*
After activation of t cell
(4) CD28 on T cell displaced by -> CTLA protein**
-CTLA protein of T cell -> bind to B7 protein of dendritic cell
- this interaction (of B7 w/ CTLA) -> result in INHIBITION of TCELL -> by BLOCKING IL2 synthesis
-THUS -> RESULT IN T CELL to a quiescent state ******** (homeostasis tcelll)
clinical relevance:
-cells without CTLa-4 THUS CANNOT be deactivated -> resulting in increased freq in autoimmune reaction *** (+ CTLA4 can be
used in treating rejection of organ transplant)
-CTLA4 fct: downreguate th cell response by competitive binding to B7-1 and B7-2 on APC
Agonist CTLA4 Abatacept Use in RA
Belatacept Renal transplant
Antagonist to CTLA4 Ipilumamb melanoma
Clinical relevance number 2:
Super antigen:
e.g staphylococcal enterotoxins, toxic shock syndrome toxin-1 (TSST-1), streptococcal pyrogenic exotoxins
Hsu notes usmle immunology
Definition: viral or bacterial proteins -> that cross link variable beta domain of a t cell R -> AND -> aLpha chain of a
class 2 MHC
Cross link-> result in bypass normal peptide binding grove
THUS activate tcell -> increase IFN gamma -> activate macrophage -> overexpress pro inflammatory cytokeines (IL1,
IL6, TNF alpha) -> thus syteic toicity
Clincia relevance 3:
Normal CD4: CD8 ratio >1.5
(reduced in AIDS/HIV)(where CD4 destroyed by HIV and cD8 increase)
T cell receptor
Structure Alha + beta polypeptide + aw CD3
Recognition of antigen ONLY in conjunction with MHC protein
B CELL
Function:
Humoral immunity
Recognize antigen (undergo somatic hypermutation to optimize antigen specifity)
Produce antibody (differentiate into plasma cells to secrete specific immunoglobins)
Maintain immunologic memory (memory b cells persist and accelerate future response to antigen)
Lifecycle:
Origin: -B cell DO NOT REQUIRE thymus for maturation
(1) B cell precursors start in fetal -B cell precusors:
liver -has u (micro) heavy chain in cytoplasm
st
(2) Migrate to bone marrow (1 - LACK surface IG + lack Light chains
location in adult life)
(3) Maturation of b cell:
- has 2 phases: -B cell surface IgM: serve as receptor for circulating antigen
-antigen independent phase: -surface IgM: monomer
-consist of: stem cell, pre b -circulating igM: pentamer
cell+ b cell
-antigen dependent phase:
Hsu notes usmle immunology
-cellls arise subsequent to
interaction of antigen (e.g
activated b cell and plasma
cell)
-mature b cell: surface IgM
(receptor for antigen) or IgD
B cell activation
(4) Th cell activated first
(5) B cell receptor mediated
endocytosis
-antigen bind to surface IgM
or IgD of B cell -> then
endocytosis of capped
material -> then presented as
MHC2
-> recognized by TCR on Th
cell
(6) CD40 receptor on B cell -> bind to ->
CD40ligand (CD40L) on Th cell
-fct: required for class switching form
IgM to IgG and other ig
(7) CD28 on T cell -> interact with B7 on
B cell ***
-req for activation of T cell to produce
IL2
(8) -Th cell secrete cytokines (IL2, IL4,
IL5)(fct: stimulate growth and diff of
Bcell) that determine Ig class switching
of Bcell
-B cell activate and undergo class
switching, affinity maturation + antibody
production
(8.1) Affinity maturation process occurs
-defintion: B cell strengthen response to
already known Ag (achieved through
somatic hypermutation)
-involves:
-formation of germinal centers in follicls
of secondary lymphoid tissues (clones of
proif antigen specific cells)
-random mutation (somatic
hyerpmuation) -> create single point
mutation in antibody diotype -> if
altered idiotype have increaee affinity fo
antigen then cell will be at slecetive
advanctage in competing to bind to that
antigen
-because binding antigen to cell serve as
first signal for prolif, over time clones of
cells with higher receptor affinity will
begin to predominate in the germinal
center *** (CLONAL
SELECTION***)(AFFINITY MUTURATION)
(8.2) Isotype switching DNA:
-after IL 2,4,5 from t helper cell
-change the heavy chain constant DNA for heavy chain :
domains -> to classes of antibodies Variable (VDJ) + constant region (the rest)
-activate switch region -> excise dna->
rearranging the dna encoding the
constant region of the heavy chain
Hsu notes usmle immunology
-initally, all B cell carry IgM specific for
antigen + produce IgM antibody in
response to exposure to that antigen
-later, gene rearrangement -> allows
elaboration of antibodies of same
antigenic specificity BUT of different
immunoglobin class
(antigen specificity remain the same for (1) recombination in variable region (VDJ)
the lifetime of the b cell and plasma cell +
because the specificity is determined by (2) recombination in constant region
variable region genes (V,D, J genes on
the heavy cahin and V and J genes on
the light chain) no matter which heavy
chain constant region is being utilized
-class switching occurs only with heavy DNA for light chain:
chains
-light chains DO NOT UNDERGO class
switching
-(catalized by switch recombinase):
catalyze rearrangement of vDJ genes
during class switching
-Note: once a B cel has clas switched Variable region (VJ) + constant region (the rest)
pass a certain H-chain gne, it can no
longer make that class of H chain
because the intervening DNA is excised
and discarded
Humoral immunity timeline
(note:
influenza vaccine:
-works by induce neutralizing ab against hemagluttin ag in selct viral strain -> upon subsequent rexposure to influenza virus through natural
infection these ab inhibit binding of hemaglutin to sialyylated eceptor on host cell membrane thus prevent live virus from etner cell via
endocytosis)
Notes:
humoral (antibody mediated) immunity:
-directed primarily against:
-(1) exotoxin mediates disease (E.g tetanus + diphtheria)
(2) infection in which virulence is related to polysaccharide capsules (e.g pneumococci, menigococci, hemophilus influenza)
(3) certain viral infection
evaluation of huoral immunity:
-consist of:
-measuring the amount of each ofh te important ig (ie igG, IgM, IgA) in patient serum
-done by radial immunodiffusion or immunoelectrophoresis
PRIMARY RESPONSE
(1) when antigen is first encountered, -during first encounter, antibodies are detectable In
(2) small clone of B cells + plasma cells specifc for antigen is formed serum after a longer lag period than secondary response
(3) serum antibody coentration rise for several weeks -> then -lag period 7-10 days but can be longer depdening on nature + dose
declines of antigen + route of administration
-FIRST antibody to appear are: IgM
-then: IGG or IgA
-IgM levels decline earlier than igG levels
Secondary response: -when there is second encounter with same antigen OR a closely
(1) second encounter with same antigen related (or cross reacting) one
(2) RAPID antibody response
-lag period = 3-5 days -with each succeeding exposure to the same antigen, antibodies
-DUE to persistence of antigen-sepcific memory cells tend to bind antigen more firmly
after first contact
Hsu notes usmle immunology
-memory cells proliferate to form a large clone of specific -antibody binding improves due to mutations occur in the DNA that
B cells + plasma cells encodes the antigen-binding site (somatic hypermutation)
(3) IgM produced (similar amount) + IgG (LARGER amount of igG
produced + permist much longer than primary response) -some mutations result in insertion of different amino acids in the
hypervariable region that result in better fit thus cause antigen to
bound more strongly
-subset of plasma cells with these improved hypervaraible regions
are more strongly and more freq selected by antigen and therefore
cotnitute an increasingly larger part of population of antoibody
producing cels THUS affinity maturation
-affinity maturation occur in the germinal center of follicles in the
spleen and lymph nodes
-follicle dendritic cells capture antigen antibody complexes on their
surface via Fc receptor
-these complex then interact with an activated b cell bearing the
immunoglobin that best fit the antigen and it is that ba cell that is
stimulated to form a clone of many b cells capable of synthesizing
the improved antibody
clinical:
-one effect of booster dose of vaccine is to improve antibody
binding by enhacing the affinity maturation process
Antibody
definition:
-globular proteins (immunoglobins) that react specifically with the antigen that stimulated their production
-monoclonal (homogenous) if arise from one clone of plasma cell (a single clone of cells)
-polyclonal if arise to typical antigen (thus formed by several different clones of plasma cell)
3 types globulins***:
-alpha, beta, gamma (antibody is GAMMA globulins)
-(types depend on electrophoretic migration rate )
5 types of antibody:
-IgG, IgM, IgA, IgD, IgE
-subdividied based on difference sin HEAVY CHAINS
fct:
neutralize toxins, viruses
opsonize microbes to make it more easily phagocytosed
-occur by two reactions:
-(1) the Fc portion of IgG interacts with its receptor on phagocyte surface to facilitate ingestion
-OR
-(2) IgG or IgM -> activate complement -> to yield c3b -> c3b interact with receptors on the surface of phagocyte
activate complement
Hsu notes usmle immunology
prevent attachment of microbes to mucosal surfaces
catalytic (enzymatic) capability
structure
glycoproteins made of LIGHT (L) and HEAVY (H) polypeptide chain
-L or H refer to molecular weight
e.g Y shape:
-consist of 4 polypeptide chain: 2 H and 2 L
4 chains linked by disulfide bond** (SS)
(any antibody always consist of: identical H chains + identical L chains)
and subdivided into VARIABLE + CONSTANT region
-variable fct: antigen binding (@ amino terminal portion of each L and H chain**)
-antigen antibody binding: involve electrostatic + van der waals fores + hydrogen bond + hydrophobic bonds **
-constant region: various biologic function (E.g complement activation nand bind to cell surface receptor)
each region has DOMAINS
-L region: 1 variable (VL) + 1 constant (CL) domains
-H region: 1 variable (VH) + 3 constant (CH) domains
or
consist of Fab region + hinge + Fc region
fab: 2 fab: antigen binding site
1 fc fragment: placental transfer, complenet fixation,a ttachemnet for various cells etc
Differences Between Antibody Regions
Feature Antibody Binding (Fab) Constant (Fc)
One heavy and one light Two heavy chains
chain Linked by disulfide bonds
Composition
Linked by disulfide bonds Attached to carbohydrate chains
N-terminus of protein
C-terminus of protein chains
Terminus chains
Hsu notes usmle immunology
nbme>>>2,4,18
The immature B cells whose B cell Receptors (BCRs) bind too strongly to self antigens will not be allowed to mature. If B cells
are found to be highly reactive to self, three mechanisms can occur.
1.Clonal deletion: the removal, usually by apoptosis, of B cells of a particular self antigen specificity.
2.Receptor editing: the BCRs of self reactive B cells are given an opportunity to rearrange their conformation. This process
occurs via the continued expression of the Recombination activating gene (RAG). Through the help of RAG, receptor editing
involves light chain gene rearrangement of the B cell receptor. If receptor editing fails to produce a BCR that is less
autoreactive, apoptosis will occur. Note that defects in the RAG-1 and RAG-2 genes are implicated in Severe Combined
Immunodeficiency (SCID). The inability to recombine and generate new receptors lead to failure of maturity for both B
cells and T cells.
3.Anergy: B cells enter a state of permanent unresponsiveness when they bind with weakly cross-linking self antigens that are
small and soluble.
TCR DNA rearrangement is an exceeedingly complex process that results in excess of 10'5 different possible antigen binding
sites.
the process is similar to that of immunoglobulin gene rearrangement in that it involves joininh of V, D, J and C regions of the
TCR gene and the process of junctional flexibility, N and P-region nucleotide addition, alternative joining of genes, and
multiple peptides combining to form the intact receptor.
the mature TCR is formed from joining of an a and a b protein segement, and these proteins are membrane-bound in close
association with either CD4 or CD8 as well as the costimulatory CD28 and CD 45
..............
this TCR gene rearrangement occur in thymic cortex
immunoglobin isotype
(-most nave mature B cell prior to activation express either IgM or IgD on surface)
(-later differentiate in germinal centers of lymph nodes by isotype switching/gene rearrangement mediated by ctyokines
+ CD40L into plasma cells that secrete IgA, E or G)
definition:
-antigenic (amino acid) differences in their CONSTANT REGION of H-chain***
IgG Structure: Notes:
- monomer -most abundant IG in serum
-consist of 2 L and 2 H chain linked by disulfide bond -main AB in 2ndary (delayed) response* to
-divalent**: 2 identical antigen binding site an antigen
-gamma heavy chain -produced in response to IFN gamma
Fct: produced by th1
complement fixation,
-IgM can do activate complement too
transplacental passage (giving infant passive immunity),
-ONLY antibody that cross the placenta
-ONLY its Fc poertion bind to receptors on surface of placenta
opsonization,
-definition: enhance phagocytosis*
-NOT directly, but via
(1) activate complement -> creating C3b
Hsu notes usmle immunology
(2) C3b can opsonize phagocyte**
neutralize bacterial toxins and viruses
IgA Fct: Incdue by secretion of TGF beta by infected
-in secretions (e.g saliva, tears, resp, intestinal, genital tract) cell
-prevent attachemtn of microganism to mucous membrane
found in: colostrum, mucosa, saliva, breast milk first Classical pathway:
- activated by antigen-
structure: antibody complex
-dimer
-two H2L@ units + 1 J chain + secretory component (polypeptide) MALT:
-secretory compoenent: synthesized by epi cell to provide for IgA passage to -mucosal assocaied lymphoid tissue
mucosal surface, protect from being degraded in intestinal tract -a collection of th2 cells dedicated to
providing help for class switching to IgA +
IgA secreting blmphocyte and plasma cell
notes: found here
association of ten distinct protein molecule.
4 IG light chain note:
4 IG heavy chain HSP:
1 J chain (protein) pathogeneiss IgA immune
1 secretory compoanent (protein) complex med
IgA class switching is induced by stimulaiotn of the B-lymphocytes with vasculitis
TGF-beta aw urti
-type 3 HS
mechanism of live oral vaccine (e.g polio): -deposit of thes
upon intestinal exposure to a novel antigen , B cells found in payers complex in walls
patches and mesenteric lymph nodes become activated and preferentially of small vesels
migrate to lamina propia underlying the intestinal mucosa, there they and renal
become fully differentiated plasma cell and begin to synthsize IgA dimers. mesangium ->
these IgA dimer then bind to polymeric immunoglobulin receptor lead to
(PIgR) found on basolateral surface of intestinal epithelial cell and recruitment of
undergo trancytosis. neutrophil and
as linked IgA dimer is released onto intestinal lumen, a portion of PIgR lymphocyte and
remain attached to the antibody (secretory component) forming the activation of
complete secretory IgA molecule complement via
nbme 7,2,37 alternate lectin
movement of dimeric IgA molecules through polarized epithelial cells to pathway -> lead
reach the ductal lumen is>>>transcytosis not endocytosis not to organ
pinocytosis. dysunfction and
explanation. palpabe purpura
Transcytosis is the process by which various macromolecules are
transported across the interior of a cell. Vesicles are employed to intake
px palpable purrua,
the macromolecules on one side of the cell, draw them across the cell, and
arthralgia,
eject them on the other side. While transcytosis is most commonly
abdominal pain,
observed in cells of an epithelium, the process is also present elsewhere.
intussuception,
Blood capillaries are a well-known site for transcytosis, though it occurs in
renal disease
other cells, including neurons, osteoclasts and intestinal cells.
similar to iga
Eg : Insulin and Antibodies
nephropathy
igA protease: (hematuria)
secreted by neisseira and strep pneumonia and h influenza: ft to cleave at dx confirm by skin
hinge ojint of igA and binds and inhibit action of PILLI*** and other cell biopsy showing
surface antigen that normally mediate mucosal adherence and subseqenet iga deposit in
penetration
blood vessels
IGM Fct: antigen binding receptor -primary response
-present as monomer on surfaeo f all B cells
Structure:
-pentamer* (secreted form), MONOMER (if on cell surface) -IgM is the antibody made with the gratest
- 5 H2L2 units + 1 J chain amount in the fetus
-10 antigen binding site ** HTUS most efficient immunoglobin in agglutination, -note: hoever, fetus has more total IgG than
complement fixation, etc IgM because maternal igG pases the
placenta in great amounts
-the first isotype of IG that can be produced
by a B cell DUE to coding for the constant
domains of the heavy chain of IgM (u or
Hsu notes usmle immunology
micro chain) are the first sequences
downstream from the coding for the
idiotype of the molecule
clinical Kaplan:
X-linked hyper IgM syndrome
-characterized by def of IgG, IgA
and IgE and ELEVATED igM
-reach to 2,000mg/Dl (norm 45-
250mg/dl)
-DUE to def in gene encoding
CD40L (in X chr) THUS th cell fail
to express functional CD40L on
membranin THUS fail to give
costim singal needed for the B
cell response to T depdent
antigen THUS only IgM
antibodies produced
-most commonly x linked or
acquired
-dx:
-peripehral blood of patients ahs
high numbers of igM secreting
plasma cells as well as
autoantibodies to neutrophils,
paltlets, rbc
-patients fail to make germinal
centers duringa humoral immune
response
-THUS children suffer resp infect
esp pneumocytitis jiroveci
IgD
IGE Fct: Structure: epsilon heavy chain
-
-bind mast cell, basophils, cross ink when expose to allergen,
-
mediate immediate/anaphlactic (type 1 hyeprsentivity through
relaease of inflamtory mediates eg histamein
- Fc region of IGe binds to the surface of mast cell and basophils ->
THUS bound igE serve as receptor for allergen antigen
- Contribute to immunity to worms by activating eosinophils
- Worms too big to be ingested by phagocyte THUS killed by osinophils
that release worm destroying enzyme + ADCC (antibody depdent
cellular cytotocity)
- Lowest concentration in serum
UWORLD CLINICAL:
Hsu notes usmle immunology
Eosinophils fct:
Parasitic defence: when parasite enter blood, coated
by igG and igE ab that bind to the
Fc receptors on eosinophil cell
surface
- Th2 + mast cell ->
increase IL5 -> increase
eosinophils
- Eosinophis degranulate
-> release cytotoxic
proteins (e.g MAJOR
BASIC PRTEIN) and
reactive o2 > thus
destroy antibody bound
parasite
- HEHNCE ANTIBODY
DEPENDENT CELL
MEDIATED
CYTOTOXICITY ADCC
*****
Type 1 hypersensitivity rxn: eospinphils synthesize =>
prostaglandin, leukotrienes,
cytokines -> late phase type 1
hypersensitivyt
-
-
Immunoglobin allotype
Definition:
-additional antigenic feature that vary due to genes that code for L and H chain are polymorphic
idiotype:
definition: antigenic determinants formed by specific amino acids in the hypervariable region
-each is unique for the immunoglobni produced by specific cone of antibody producing cells
Hsu notes usmle immunology
immunoglobin genes
roughly compose of gene segments: V, D,J,C
Involves specifc genetic mechanism e.g dnarearrangement + rna splicing
Via recombinases (e.g RAG-1, RAG-2)(recombination activation genes)
(clinical: mutatin in RAG1 or Rag2: arrest development of lymphocyte -> SCID**)
ANTIBODY DIVERSITY:
-depends on:
-(1) multiple gene segemnts
-(2) rearrangement into different sequences
-(3) combining of different L and H chains in assembly of IG molecules
-(4) mutations
-(5) junctional diversity (applies to antibody heavy chain)(occur sby adddtion of new nucleotides at splice junctions between genes)
clinical:
Severa lymphoid cancer manifest chromosomal translocations involving VDJ recgion + cellular oncogene
E.g Burkit lymphoma:
-c-myc oncogene on chr 8 is TRANSLOCATED to position adjacent to VDJ region of a heavy chain gene
-the active promoter of the heavy cah in gene increase transcription of c-myc oncogene thus predispose to makginacy
Complement system
Notes:
-made in liver
-heat labile (inactivatd by heating serum at 56 degrees c for 30 min) (Immunoglobins ARE NOT INACTIVATED at this temperature)
Consist of:
-20 proteins that are present in normal human serum
-can COMPLEMENT (ie ability to augment the effects of other componenets of immune system for example antibody)
-important for innate
3 main effects:
-(1) lysis of cells (e.g bacteria, allografts, tumor cells)
-works by insertion of complex on cell membrane result in disturption fo membrane and entry of water and electrolyte into cell
-(2) generation of mediators that participate in inflammation and attract neutrophils
-(3) opsonization (ie. Enhancement of phagocytosis)
- microbes (e.g bacteria + viruses) are phagocytizied much better in presence of c3b because there are c3b receptors on the surface
of many phagocytes
other:
(3) chemotaxis
-c5a, c5,6,7 complex attract neutrophils
-c5a also enhance the adhesive to endotheliam
(4) anaphylatoxin
-c3a, c4a,c5a -> cause degranulation of mast cell
-leads to increase vascular permeability + smooth msucel contraction esp contraction of bronchioles -> bronchospasm
-c5a most potent anaphylatoxins
(5) enhancement of antibody rpdocution
-binding of c3b to its receptor on surface of activated b cell -> enhance antbody production ***
-clincal: patient def in c3b prodce less ab than those with normal amount of c3b
ebg
3 Pathways for activation of complement:
notes:
-all 3 lead to-> production of C3b (the central molecule of complement cascade)
-c3b on surface of molecule marks it as foreign and targets it for destruction
-c3b fct:
-combines with other complement component to -> generate C5 convertase (enzyme that lead to production of the membrane attack complex)
-opsonizes the bacteria because phagocytes have receptors for c3b on their surface
Hsu notes usmle immunology
(1) classical pathway
(1) antigen-antibody complex activates C1 -> to C3a, c5a: anaphylatoxin
form a C1 protease
(2) C1 Protease cleave C4 + C2 -> to form-> C4b +
C2b complex (which is C3 convertase)
(3) C4b + C2b complex (C3 convertase) -> cleave C3
-> to form-> c3a + c3b
(4) C3b + form a complex with c4b2b -> to form C5
convertase (c4b2b3b)
(5) C5 convertase (c4b2b3b) -> cleave c5 -> to form
-> c5a + c5b
(6) C5b -> bind to -> c6 +c7 -> to form a complex
that ineract with c8 + c9 -> to produce
membrane attack complex (c5b, 6,7,8,9)****
(2) alternative pathway
(1) many unrelated cell surface substances (E.g bacterial
lipopolysaccharides (endotoxin), fungal cells wals ,viral
envelopes -> initate by binding c3 (H2O) factor B -> thus
C3+B complex
(2) C3+B complex -> (cleaved by factor D protease)-> form->
c3b Bb
(3) C3b Bb -> become c3 convertase -> to cleave more c3 to
form more c3b
(3) lectin pathway
(1) mannan-binding lectin or mannose binding protein (MBL) -NOTE:
-> bind to surface of microbes bearing manna (a polymer Lectin bypass antibody requiring step
of the sugar mannose) THUS protective early in infection before antibody is
(2) MBL a citvates proteases aw with MBL -> cleaves C2 + C4 formed
-> to actviiate CLASSIC PATHWAY
Regulation of the complement system:
First regulatory step in classic pathway:
-at antibody itself
-the complement binding site on the heavy chain of IgM + IgG is unavaibale to the c1 componenet of complement if antigen is not
bound to these antibodies***
-after antigen is bound to its specific antbody, a conformation change occurs and the c1 componeent can bind and initiate the
cascade
Other:
-@ classic pathway:
(1) c1 inhibitor: important regulator of the classic pathway
-inactivates protease activity of c1
-activation of classic pathway proceed past this point by generating sufficient c1 to overwhelm the inhibitor
-@ alternative pathway
- factor H
-binding of factor H to c3b -> H + c3b complex -> then cleaage by factor I (apreatease) THUS reduce amount of c5 convertase around
-can proceed past if enough c3b created and attach to cell membrane (attachemenet of c3b to cell membrane protect it fro
degradating by factor H and I)
-properidin
-protect c3b and stabilize the c3 convertase
-decay accerlating factor (DAF)
-a glycoprotein located on surface of human cells
Hsu notes usmle immunology
-DAF acts by destabilizing c3 convertase + c5 convertase
-prevents the formation of membrane attack compelx
CLINICAL complement:
Note:
In transfusion mismatch, AB oincompatibiltiy, e.g when type A blood given to mistake to person with type B blood, antbody to type
A antigen in reciepent bind to A antigen on the odnor red cell thus complement is activated thus large amround of anaphylatoxin
and membrane attack complexes are generated and caus red cell hemolysis
In immune comple disease, immune complex bid complement thus compelemnt levels are low in immune complex disease (e.g
acute glomerulonephritis + sle
Pateitn with severe live siease (e.g alcoholic cirrhsos ior chornic hep b thus cannto synthesize sig live ruction and compelenet protein
thus pyogen bacteria infection
Complement protein def
C3 def Increase risk of severe, recurrent pyogenic sinus + resp tract
infection
-increase susceptible to type 3 hyper snestiity reaction
C5-c9 def Terminal complement def -> increase risk to recurrent
Neisseria bactermia
Complement regulatory protein def
C1 esterase inhibitor def Causes hereditary angioedema due to unrega ctivation of
kallikrein -> increase bradykinin
-characteried by decrease c4 level
CI: ACEI
Cd55 def Aka DAF def
Causes complemenet mediated lysis of RBC, + PNH
paroxysmal nocturnal hemogloninura ****
Note:
Eculizumab: prevent conversion of c5 to c5a THUS reduce hemolysis and transfusion req for PNH
PASSIVE vs ACTIVE immunity
Passive Active
Means of acquisition Resistance based on receiving Exposure to foreign antigens
preformed antibodies (antibodies -e.g
preformed in another host) clinical or subclincal infecitons
immunization with lvie or killed
infectious agent or their antigens
or exposure to mircrobial prodcuts (e.g
toxins and toxoids)
Onset Rapid Slow
-
Mediators Antibodies + T cell (hyper and cytotxic)
Duration Short span of antibodies (half life = 3 Long lasting protection (memory)
weeks)
Examples IgA in breast milk, maternal IgG crossing Natural infection, vaccines, toxoid
placenta, antitoxin (diphtheria, tetatnus,
botuism, rabieis, heap a and b virus),
humanized monoclonal antibody
Toxoid vaccines:
-made from exotoxins from toxigenic
bacteria
-prevent disease, NOT infection
-seen in:
-DTaP: diphertia, tetanus, acellular
pertussu
component vaccine:
Hsu notes usmle immunology
-composed of immunodominant protein
from virus that is grown on yeast cell
-e.g
-HBV (hbv surface antigen)
OR
-HPV:
-quadrivalent vaccine with serotype
6,11,16,18
OR
-9 valent vaccine (garasil 9_ ot prevent:
serotype 6,1,,16,18,31,33,45,52,58
Live vs inactivated vaccines FOR VIRAL VIRUSES ****
Live vaccines Killed or inactived
vaccine
notes -composed of LIVE organism which lost capacity to cause disease but still -pathogen inactivated
replicate in the host by head or chimicel
-induces cellular + humoral responses -maintains epitope
structure on surface
antigen important for
immune response
-mainly induces a
humoral response
Examples (In babies, SMALL YELOW VIRUS OR MMR) PAIR
Polio (Salk)
influzna (intranasal), bcg, small pox, yellow fever, varicella, OPV (sabin), Hep A virus
rota virus measule mump rubella Influenza (injection)
Rabies
Pro Induce strong often lifelong immunity Safer than live vaccine
Con May revert to virulent form Weaker immune
Often ci to preg and immunodef response, booster shot
req
Note INDUCES prolonged mucosal IgA secretion
-live vacc colonize natural site of viral entry and produce a greater and
more prolonged immune response there
-pathoegensis U WORDL QUESTION:
-upon intenstinal exposure to novel antigen, B cell in peyers patches +
esetneric lymph node activate and migrate to laminia proprier underlying
intestinal mucosa
-B cell -> diff to plasma cells -> sntehsize IgA dimers (linked by J chain)
-these IgA dimers bind to polymeric immunoglobulin receptor (pIgR)
found on basolateral surface of the intestinal epitheali cell -> undergo
transcytosis
-as linked igA dimer relased into intestinal lumen, oteion of pIgR
(immunoglobulin receptor) remain attached to antbody (secretory
compeonet) THUS forming complete secretory igA
Hsu notes usmle immunology
molecule
Bacterial vaccination
-invovlve administration of characteristic protein:
e.g inactivated toxin (toxioid)
-coat protein from capsule
e.g
DTap: dipheria toxid, tetani toxoid, pertussis toxid
OR
H influenza capsular type B (Hib)
OR
Strep pneumonia: 23 capsular type for adult PPV, 7 capsule type for pediatric PCV
OR
N mengitis with 4 capsular protein (MCV-4, MPSV4)
Extra notes:
CI:
People with egg allergies should avoid: eyellow fever vaccine or other made in eggs
Pregnant owmen: avoid rubella
Immunocompromised: avoid all lvie vaccines
Vaccine schedule:
At birth BE smart: HBV
@ 2,4,6 Dont put her baby at pneumonia risk
Dtap, Polio, hib, HBV, PCV, rota
@ 1 1 monther had passed vaccination
MMR, HAV, Polio, varicella
@ 16 And HID
Hib, Ipv, dtap
4 years DMV inquiry
Hsu notes usmle immunology
Dtap, MMR, varicella, IPV
Hep B:....... 0, 2, 6
HiB: ......... 2, 4, 6, 12 - 15
Pneumo: ... 2, 4, 6, 12 - 15
DTaP:....... 2, 4, 6, 15 - 18, 4 - 6 yrs, Td X 10 yrs
IPV: ........ 2, 4, 6,............ 4 - 6 yrs
Varicella:.............. 12 - 15
MMR: .................. 12 - 15, 4 - 6 yrs
Hep A: ..... 2 yrs
Mening: ... 11 - 12 yrs (or school)
1. are vaccines given according to the gestational age or chronological age? Whats the exception?
3. dirty wound, last tetanus booster was 8 yrs ago. how do you treat?
4. CI to rotavirus vaccine?
Hsu notes usmle immunology
5. Which vaccine is indicated for travelers going to
a. Mecca
b. Subsahara
c. Egypt
Report Abuse
* Re:Vaccinations all in one spot
#3159928
penelope24 - 11/17/14 14:22
1. are vaccines given according to the gestational age or chronological age? Whats the exception?
They are given according to chronological age except in Hep B do not give dosage at birth if they are less
than 2 kg.
3. dirty wound, last tetanus booster was 8 yrs ago. how do you treat?
Tetanus toxoid given to dirty would if booster was more than 5 years ago
4. CI to rotavirus vaccine?
SCID, intussusception, severe allergy to rotavirus components
a. Mecca- meningitis
b. Subsahara- yellow fever
c. Egypt- Hep A, B, typhoid, polio
the pathogenesis of
contact dermatitis
predominantly involves
repeated binding of
small foreign
molecules (haptens)
applied tot he skin
surface to proteins on
the surfaces of
cutaneous cells,
including antigen
presenting
langerhans cells.
LCs with bound
hapten migrate to
local draining lymph
nodes where they
generate circulating
Th1 type memory
cells.
upon cutaneous
reexposure to the
hapten these, Th1 cells
release inflammatory
cytokines at the site of
exposure. the result ia
a type IV, cell mediated
hypersensitivity
immune response in
the dermis and
epidermis.
in scabies has
type 4 against
mite, its egg
and feces
.....
sarcoidosis is a
type IV
hypersensitivity
.
.......
dress
syndrome also
has type 4
Uworld notes:
URUSHIOL INDUCED CONTACT DERMATITIS
note:
puritic skin rash following wilderness exposure is consistent with poison ivy dermatitis
poison ivy, oak, poison sumac all produce -> URUSHIOL (small allergenic substance that causes an immune response hne attached t
oproteins (ie. A hapten)
-following contact with these plants, patient develop a highly pruritic erythematous rash cosnsit of papules, vesicles, bullae that may show
signs of excoriation
rash most freq affect exposed skin and o ften linear streaks as patient walk past the plant,dragging it along the skin
contat dermatitis is a type 4 delayed type occurs in 2 distinct phases
can be either cd 8+ T cell or CD 4 + t h1
Hsu notes usmle immunology
in urushio induced contact dermatitis, cd8 are primary effector cells and destroy keratinocyte express haptenated proteins
(1) sensitization lead to creation of hapten specific t cell and takes 10-14 days
pahse cutaneous dendritic cell take up the haptens and express them on MHC1 and MHC2 molecules as hpaten
conjugated peptides
these dendritic cells travel to the drainging lymph nodes and interact with hapten sensitive cd 4+ and cd 8+ T
cells -> cause activation and clonal expansion
(2) elicitation occur within 2-3 days following REXPOSURE to same antigen (or following sensitization after first exposure to a
phase highly antigenic antigen such as urashiol)
in this phase, hapten is taken up by skin cells and cause ac tivation of hapten sensitized t cell in the dremis and
epidermis
this results in infl response and clinical manifestiation of contact dermatitis
Hsu notes usmle immunology
Immunodeficiency
B cell
Hsu notes usmle immunology
B cell T ell Granulocyte Complement def
..........
aberrant formation
of mandible and
palalate (frequently
associated with
cleft palate) and
low set ear
IL 12 receptor def Decrease TH1 Disseminated non tb Decrease IFN
response (thus cant mycobacterial and gamma
(IL12 fct: cell med immunity limit mycobacterial fungal infection
(maturation of t cell into th1, infect), AR May present after
stim macrophage to secret IFN administration of bcg
gamma, activate NK cell) vaccine
Autosomal Def of TH17 cells due FATED Increase iGE
dominant hyper IgE syndrome to STAT3mutation Course facies Decrease IFN
(job syndrome) (abd JAK STAT Cold staph gamma
pathway) -> impaired abscess(non infl Increase eosinophls
recruitment of abscess on body that
neutrophil to site of is coo lto touch)
infection Retained primary
teeth ( 2 rwos of
teeth)
Increase igE
Dermatologic
problems (eczema)
Chronic mucutaneous T cell dysfunction Non invasive candida Absent in vitro t
candidiasis specifically for albicans infection fo cell prolif in
candidia skin and mucous response to candida
membrane antigens
Absent cutaneous
reactions to
candida antigens
B and T cell disorder SAMW
Severe combined immunodef Several type including Failure to thrive Decrease T cell treatment with retro viral
defective IL-2R Chronic diarrhea receptor excision gene therapy>>>transfer
gamma chain (most Thrush circules (TREC) geentic code for
commn, x linked) Recurrent viral, Absence of thymic adenosine deaminase.
OR bacteria, fungal, shadow (CXR), ..........
-lack gamma chain in protozoalinfections germinal centers ( retroviral vesctor are used
IL2 receptor on T cell lymph node becasie of the ability of
essential for Infections early at 3 biopsuy), retroviridae to
development of T cell months of age incorporate their
because both b and t Absent of t cell ( genome directly into the
Adenosine deminase c ells are defective flow cytometry) genome of infected
def (AR) human cells by the
-cause acc of dATP -> Other: action of the enzyme
inhbit ribonucelotide Eczematous integrase.
reductase -> thus dermatitis, sever
decrease deoxy seborrheic
Triphosphate ofor dna dermatitis, diffuse
aloepica, absent
also defect in MHC lymphatic tissue e.g
class II tonisils and thymus
.......
Null mutations in
Hsu notes usmle immunology
rag1 or rag2 genes Tx: avoid live
No rag enzyme vaccines, give
activity. antimicrobial
AUTOSOMAL prophylaxis + IVIG
RECESIVE Bonem marrow
transplant curative
(no concern for
rejection )
Ataxia telangetisa Defect in ATM gene -> Triad: cerebellar Increase AFP
fail to repair ddna defect (Ataxia, spider Decrease IGA , IgG,
double strand breaks - angioma IGE
> cell cycle arrests (telangctsia), IgA def Lymphopenia,
cerebellar atrophy
autosomal Increase risk of
recessive. lymphoma and
DNA is leukemia
hypersensitive to
ionizing radiation
(X-RAYS) which
causes multiple
chormosomal
breaks
Complement def:
Hereditary Def of C1 inhibitor
angioedema
C1 -> act on C4 to gerneate c4a ->
Leads to capillary permeability and edme,a then laryngeal edema
Tx: e.g oxymetholone, danazol (increase concetriation of c1 inhibitor(
Recurrent infection Def in c1, c3 or c5 or c678
C3 def: susceptible to sepsis with pyogenic bacteria e.g s aureus
C6,7,8: prone to bacteria nwith n mengitis or n goneorrhea
NOTE:
Suprifecia candida in HIV: T lymphocyte ****
Systemic candida in HIV: NEUTROPHILS*
Blood transfusion reaction : AFAT
Hsu notes usmle immunology
Pathogenesis Px Timing
Allergic/anaphylactic Type 1 hypersenstivity against Urticarial Within minutes to 2-3hour
plasma protein in transfused Prurtisis
blood Fever
Wheeze
IgA def indivudals must receive Hyptension
blood products without IgA Arrest
Shock
Febrile non hemolytic Type 2 hypersensitivity reaction Fever, headache, chill flushing Within 1-6 hour s
transfusion reaction
Host antibodies aginst donor
HLA atigens + WBC
Acute hemolytic transfusion Type 2 hypersensitivity reaction Fever, hypotension, tachypnea Within 1 hour
reaction tachycardia, flank pain,
Intra vascylar hemolysis (ABO hemoglobinuria (intravascular
blood group incompatibility) or hemolysis), jaundice
extra vascular hemolysis (host (extravascular)
antibody rxn a gainst foreign
antigen on donor rbc)
Tranfsuio nrelated acute lung Donor anti leukocyte ab against Resp distress and non Within 6 hours
injury receipeient neutrophils and cardiogenic pulm edema
pulm endothelial cell
ABO blood group/ftransfusion reactions:
Note:
All human erythrocyte contain: alloantigens (Antigen that vary among individual members of a species)
A and B genes:
Codominant genes: so people who inherit both are AB
Inherit either homozygous AA or heterozygous Ao are type A
Homozygous BB or heterozygous BO are type B
encode enzymes that add specific sugar to the end of a polysaccharide chain on the surface of man ycells incl red cells
erythrocyte have 3 terminal sgars in common: N acetylglucosamine + galactose + fucose -> all 3 form the H ANIGEN
type A: have N acetylglucosamine added to the galactose of the H antigen
B have galactose added to galactose of the H antigen
Type O DONT HAVE such genes and only have the H antigen
In summary
4 combinations of the A and B antigen:
A, B, AB, O
Determine by mix persons blood with antiserum against A antigen on ONE AREA, antiserum against B antigen on OTHER
If agglutination occur only with A antiserum then blood goru p is A
If it occurs with only B anti serum then blood group is B
If it occurs with btoh and b antisera, the blood group is AB
If occurs with neither A nor b anisero then O
Transfusion reaction noccurs when:
- Incompatiable blood donor (eg group A blood transfuse to group B BECAUSE anti A ab present -> thus red cell
antibody complex- > activate compelemnt -> thus reaction -> shock caused by large amounts of c3A, C5a,
c5,c6,c7,c8,c9 membrane attack compelx
Hsu notes usmle immunology
TO AVOID TRANSFUSION REACITON,
- MATCH:
-defintion: erythrocyte are typed for their surface antigen by specific sera
NOTE:
maternal blood type A and B, isoimmunization does NOT occur as the naturally occurring antibody (ant A and B) are of IGM type which
cannot cross the placenta
type O mothers have ab that are igG type which can cross palcenta and cause hemolsys i
HOWEVER< ABO disease CAN occur with first preg because anti A and anti B ab are formed early in life from exposure to A or B like antigen
present in food bacteria, virus
RH blood type and hemolytic disease of the new born
type 2 hypersenstivity
Definition: destruct of fetal rbc by maternal anti rh (d antigen) igG ab that cross pplacenta
st
1 pregnancy:
-mother is Rh-, fetus is Rh +
-mother exposed to fetal blood at some point during preg or delivery and generate anti rh igG ab
nd
2 pregnancy
mother is RH- and fetus is RH+
maternal anti RH IgG corss placenta and ttach to fetal rbc
fetal splenic macrophage phocytose igG coated rbc
px:
severe eatal anemia after birth
jaundice (kernicterius(
generalized eema (hydrops fetalis due to hypoxic lvier and cardiac injury)
severe anemia (stim release of immature nucleated erythrocyte and lead to persistent extramedullary hematopeosis in liver, spleen,
hepatospelneomgy)
dx:
positive idriect and indirect comb test on cord blood
tx
prevent of initial rh exposure:
th
-rh neg mothers receive anti D globulin during 28 week of pregnancy + at delivery
Hsu notes usmle immunology
-anti D globulin hemolzyes fetal RBC that enter maternal iruclation efore an immune eaction can be mounted against the Rh antigen thus
prevent form of anti rh IgG in mother
note uworld:
rhesus rh antigen is a group of non glycosylated transmembrane protein on surface of rbc
-d antigen is the most immunogenic of the roup and present on erythrocyte of rh positive
-when rh neg mother become pregnant with rh positive, fetal rbc can etner mat circulation and elicit a maternal igG ab response with form
of memory b lymphocyte (rh alloimmunization)
-risk of transplacental fetomaternal blood exchange inc with gestainoal age and higest during delivery
-to prevent mat rh alloimmunize, rh neg mother must be prevented from mounting an immune response against D antigen
-anti RH dD immune globilin is a polyclonal ab product consit of IgG anti D ab collect from pooled donor plasma
-it is routinely administered to Rh neg women at 28 weeks gestatino and in the immed post partum period
-it is administered to rh neg women at 28 weeks gestation and in immediate post partum period
-once gien, anti rhd ab bind to rh positive fetal ertyrhocyte that enter maternal cicurlcation thus preent their interaction with mat immune
system via sequesteration and elimaintino by mothers spleen
-administer of anti D igG ab during preg does not cause sig transplacental fetal hemolysis because the quantitiy of anti rh d admister is very
small compared to that produced in typical immune reaction
Immunosuprresntas
Cyclosporine
Mechanism Use: Toxcity
-Bind to calciphillin Transplant, psoriasis, RA, short and long 5H
-(cytosolic protein) term suppression of organ rejection in hirsutisim , hyperpplsia of gums,
-cyclosporin-cyclophillin complex -> bind transplant of kidney liver heart ( harm to kidney, ht, hyperglycemia
calcineurum inconbination with glucorticoid)
-(calcineurum fct: calcium depddent phosphatase,
activate transcription for il2 via transport NFAT to
nucleus by cleaving phosphate from NFAT-P) -> THUS
inhibit transport to nucleus of the transcription
factor NFAT
-> THUS block IL2
Tacrolimus
Mechnisim
Calcineurin inhibitor Organ rejection transplant (liver) Dm, neurotoxitiy
Bind FK 506 binding protein (FKBP) -> which NO gingivial hyperplasia or hirstuitism***
inhibit calcineurun-> prevent IL2
transcirption
Sirolimus (Rapamune/RAPAMYCIN)
Mechanism
M tor inhibitor Renal transplant only Pancytopenia
(as prophylaxis***) Insulin resistiance
Mtor (mammalian target of rapamycin) + Hyperlipid
bind to FKBP -> interfere with protein
biosynthesis -> delay G1-S transition -> NOT nephrotoxic
block t cell and b cell diff by preventing
response to IL2
Basiliximab/ daclizumab
mechanism
Block CD25 of IL-2R (Expressed on activated NOT FOR ACUTE REJECTION Edema, ht, tremor, sob, hypersenstiviity
t cell) For use as KIDNEY TRANSPLANT REJECTION
PROPHYLAXIIS NLY
Hsu notes usmle immunology
Azathiopirine
Extra note:
-sphase specific
-supress t cell more than b cell, suppres marrow activity
-precusor for mercaptopurine (which is immunosuppressive)
mechanism use
Antimetabolite precursor of 6MP RA, chron, glmeurloenprhtis, autoimmne Pan cytopenia
condition
(6MP degraded by xo)
(toicity increase by allopurinol which
inhibit XO and requires decrease dosage )
Mycohenolate mofetil
Aw invasvive cmv infection
Mech
Inhibit imp dehydrogenase thus prevent Lupus nephritis Gi upset, pancytopenia, ht, hyperglycemia,
purine synthesis of b and t cells less nephrotoxic and less neurotxic
Corticosteroids
Inibit nf kappa B (protein complex that Cusjngoid Cushingoid
control transcritoin of dna, cytokine Cataract
production ) Ulcer
Striae
Hirsutism
Infection
Necrosis fo femoral head
Glucose elevate
Op
Psychosis
Diabetes
Recombinant cytokine and clinical use
Aldesleukin (IL2) Renal cell ca, metastatic melanoma Mechanism:
Inhibit IL2 thus inhibit nk, t, b, cells
Epoeitin alfa (erythropeotin) Anemia (esp renal failure)
Filgrastim (GCSF) Recovey of bone marrow and wbc count by
granulocyte stimulation
Sargramostim GM CSF
Recovery of bone marrow + wbc count y
granulocyte and monocyte
IFN alpha Cytokines which interfere with viral dna HBV, HCV, Kaposi , malig melanoma, hairy
rna synthesis + induce ribonuclease activity cell iekma, rcc, condyloma accuminata
to degrade viral mrna
Part of innate immune repsosne
Beta Ms
Gamma Chronic granulomatous disease
Romiplostim Thrombocytopenia
Eltrombopag Thrombopoetin receptor agaonist
Oprelyekin (IL11) Thrombocytopenia
Therapeutic ab
alemtuzumab Cd52 Cll, MS
Bevacizumab VEGF Colorectal cancer
Rcc
Non small cell lung cancer
Cetuximab EGFR Stage 4 colorectal cancer,head and neck
cacner
Hsu notes usmle immunology
Rituximab Cd 20 B cell non Hodgkin lymphoma, cll, ra , itp
Transtuzumab Her2 neu Breast cancer, gastric cacner