Professional Documents
Culture Documents
Contents.
Approximate Duration:
Foreign Invaders
Called Pathogens
Viruses, bacteria or
Antigens
Toxins that pathogens
Nonspecific Defences
= City walls
= Foot soldiers
= Secret Agents
Nonspecific Defenses
Against Infection
Organisms must find a means of defence against
antigens such a viruses described on the previous
page.
If this was not the case, bacteria, fungi and viruses
would replicate out of control inside other organisms
which would most likely already be extinct.
Therefore organisms employ many types of defence to
stop this happening.
Got own3d?
Lysozyme
whites)
Mucus and cilia found in the nose and throat can catch foreign agents entering
these open cavities then sweep them outside via coughing, sneezing and
vomiting.
The cell wall of plants consists of fibrous proteins which provide a barrier to
potential parasites (antigens).
If these first lines of defence fail, then there are further defenses found within
the body to ensure that the foreign agent is eliminated.
Figure 1. Gram stain of a species of Micrococcus, commonly isolated from the skin and nasal membranes of humans.
Contents.
Approximate Duration:
Summary
Tissue injury
mediators
Release of ATP,
Forms prostaglandin E2
= bradykinin release
Bradykinin +
Prostaglandins=
leucocytes to follow.
Neutrophil: (Video)
Pathology:
Hemophagocytosis
Associated with:
EpsteinBarr virus-Tcell lymphoma.
EpsteinBarr virus
(EBV) can infect T
lymphocytes and
manifests as
hemophagocytic
lymphohistiocytosis
(HLH), a distinct entity
of hemophagocytic
syndrome (HPS)
characterized by fever,
hepatosplenomegaly,
cytopenia,
hypercytokinemia, and
systemic macrophage Fukumoto, J. et al. ASH Image Bank 2006;2006:6-00023
activation with
hemophagocytosis.
Copyright 2006 American Society of Hematology. Copyright restrictions may apply.
Figure 1. Histiocytes ingesting red cell precursors may be seen in response to certain
infections
The phagocytes:
Eosinophils
Natural killer (NK) (T
cells)
Monocytes
Neutrophils
Figure 1. Peripheral smear from a 17 year old female with Chediak-Higashi syndrome is
shown
Contents.
Approximate Duration:
Immune Biology
Cytokines
Low molecular weight protein mediators involved
Types
Interleukins (ex. IL-2)
Meaning: They are chemical messengers between (inter)
Leukocytes
Interferons
Intefere with viral reproduction
Secreted by infected dying cells.
Cytokines (chemokines)
Structure of interleukin 2
Fig. 1
Fig. 2
exposed surface
Kappa
hidden surface
Previously
hinge region
hidden surface
carbohydrate
Lambda
Intact Immunoglobulin
Chemokines:
-50 different proteins
-Induces inflammation
-Induces toxin production in lymphocytes
Called
chemo-taxis.
(like taxiing)
Contents.
Approximate Duration:
Antibodies
Y-shaped protein
molecule.
Made up of variable and
constant regions.
Made up of Heavy and
Light chains.
Produced by BLymphocytes
Function: Recognize
antigens, bind to and
deactivate them.
Note: Variable region
Lymphocytes
1. 2 types:
1. B Lymphocyte (B-Cells)
2. T Lymphocyte (T-Cells)
2. Along with their variations:
1. Helper T Cells
2. Cytotoxic T cells
They display specificity only targeting foreign cells
Lymphocytes detect foreign molecule marker
Antigen
Countered with Antibodies.
generator)
Created by B Cells
Video
Origin of lymph
Autoimmune Disease
Autoimmune diseases
Acute disseminated encephalomyelitis (ADEM) yes G04.0 is a form of encephalitis caused by an autoimmune reaction and
typically occurring a few days or weeks after a viral infection or a vaccination. Addison's disease yes E27 is often caused by
autoimmune destruction of the adrenal cortex. Ankylosing spondylitis yes M08.1, M45. is a chronic, painful, progressive
inflammatory arthritis primarily affecting spine and sacroiliac joints, causing eventual fusion of the spine. Antiphospholipid
antibody syndrome (APS) yes D68.8 affects the blood-clotting process. It causes blood clots to form in veins and/or arteries.
Aplastic anemia no D60 is often caused by an autoimmune attack on the bone marrow. Autoimmune hepatitis no K75.9 is a
disorder wherein the liver is the target of the body's own immune system. Autoimmune Oophoritis no N70 is a disorder in
which the immune system attacks the female reproductive organs. Celiac disease no K90.0 is a disease characterized by
chronic inflammation of the proximal portion of the small intestine caused by exposure to certain dietary gluten proteins.
Crohn's disease no K50 is a form of inflammatory bowel disease characterized by chronic inflammation of the intestinal tract.
Major symptoms include abdominal pain and diarrhea. There is also a theory that Crohn's Disease is an infectious disease
caused by Mycobacterium avium paratuberculosis. Diabetes mellitus type 1 yes E10 when it is characterized by a deficiency
or absence of insulin production (Type I), is often the consequence of an autoimmune attack on the insulin-producing beta
cells in the islets of Langerhans of the pancreas. Gestational pemphigoid no O26.4 is a pregnancy-related blistering condition
where autoantibodies are directed against the skin. Goodpasture's syndrome yes M31.0 is a disease characterised by rapid
destruction of the kidneys and haemorrhaging of the lungs through autoimmune reaction against an antigen found in both
organs. Graves' disease yes E05.0 is the most common form of hyperthyroidism, and is caused by anti-thyroid antibodies
that have the effect of stimulating (agonist) the thyroid into overproduction of thyroid hormone. Guillain-Barr syndrome
(GBS) yes G61.0 is an acquired immune-mediated inflammatory disorder of the peripheral nervous system (i.e., not the brain
and spinal column). It is also called acute inflammatory demyelinating polyneuropathy, acute idiopathic polyradiculoneuritis,
acute idiopathic polyneuritis and Landry's ascending paralysis. Hashimoto's disease yes E06.3 is a common form of
hypothyroidism, characterised by initial inflammation of the thyroid, and, later, dysfunction and goiter. There are several
characteristic antibodies (e.g., anti-thyroglobulin). Idiopathic thrombocytopenic purpura yes D69.3 is an autoimmune disease
where the body produces anti-platelet antibodies resulting in a low platelet count Kawasaki's Disease no M30.3 is often
caused by an autoimmune attack on the arteries around the heart. Lupus erythematosus yes L93, M32 is a chronic (longlasting) autoimmune disease wherein the immune system, for unknown reasons, becomes hyperactive and attacks normal
tissue. This attack results in inflammation and brings about symptoms. This is a "Non-organ-specific" type of autoimmune
disease. Mixed Connective Tissue Disease has features of other connective tissues diseases lupus, rheumatoid arthritis,
scleroderma and polymyositis. The presence of a specific antibody called U1-RNP is needed for diagnosis. Multiple
sclerosis yes G35 is a disorder of the central nervous system (brain and spinal cord) characterised by decreased nerve
function due to myelin loss and secondary axonal damage. Myasthenia gravis yes G70.0 is a disorder of neuromuscular
transmission leading to fluctuating weakness and fatigue. Weakness is caused by circulating antibodies that block
(antagonist) acetylcholine receptors at the neuromuscular junction. Opsoclonus myoclonus syndrome (OMS) n/a n/a is a
neurological disorder that appears to the result of an autoimmune attack on the nervous system. Symptoms include
opsoclonus, myoclonus, ataxia, intention tremor, dysphasia,
Allergies
Allergy
- An exaggerated response by the immune system to an allergen.
Allergen: a normally harmless substance that causes an allergic
reaction.
ex: dust, pollen, mould, food, insect stings
Types of Allergic reactions
There are two types of allergic reactions.
a. Immediate occurs within seconds and normally lasts for about
30 mins.
b. Delayed takes longer to react and can last for a much longer
time.
What
happens during an allergic reaction?
During an allergic reaction antibodies cause histamines to be
released from certain cells.
Histamines cause:
a. Swelling of tissues
b. Release of fluids (runny noses and eyes)
c. muscle spasms (some cases)
Anaphylaxis or anaphylactic shock:
This is the sudden and severe allergic reaction to a substance that
can cause death.
Treatments for Allergies
1. Avoidance of material especially food.
2. Epinephrine epi pen
3. Antihistamines -- benadryl
Autoimmune disease - MS
Multiple sclerosis (MS) is typically considered to be a disease of young
adults.
Environmental triggers Environmental exposure to a specific
infectious agent during a window of immunologic vulnerability in
childhood may predispose some individuals to the development of MS
[9] . Many viral and bacterial pathogens have been putatively linked to
demyelination. Of these, the Epstein-Barr virus (EBV) has attracted
much attention.
Exposure to EBV results in persistent B-cell infection, expansion of
EBV-transformed B-cell clones, and the production of antibodies
directed against specific EBV viral antigens as well as lifelong T-cell
surveillance of infected B-cells [10] . EBV nuclear antigen has a similar
structure to myelin basic protein, a major component of central nervous
system (CNS) myelin. T-cells directed against EBV antigens may be
redirected to attack CNS myelin because of similarity between the
antigens, a process termed molecular mimicry.
Treatment of MS
No cure
Only management tehniques
administration of high doses of intravenous corticosteroids, such as
methylprednisolone.
(This will end the attack sooner, and prevent major damage)
Side effects include: osteoporosis, and impaired memory.
Immunosuppressant also used in cancer chemotherapy
(Approved only in the USA.)
Alternative treatments
Different alternative treatments are pursued by many patients
Dietary regimens
Herbal medicine
On the other hand the therapeutic practice of martial arts such as tai chi,
relaxation disciplines such as yoga, or general exercise, seem to mitigate
fatigue and improve quality of life.
Ergo Break~~
5 minutes
Identification
Class I MHC molecules, found in almost all cells,
are poised to present fragments of proteins made
by infecting microbes, usually viruses, to
cytotoxic T cells.
Cytotoxic T cells respond by killing the infected cells.
Because all of our cells are vulnerable to infection by
one or another virus, the wide distribution of class I
MHC molecules is critical to our health.
Class II MHC molecules are made by only a few
cell types, chiefly macrophages and B cells.
These cells, called antigen-presenting cells (APCs)
in this context, ingest bacteria and viruses and then
destroy them.
Class II MHC molecules in these cells collect peptide
remnants of this degradation and present them to
helper T cells.
In response, the helper T cells send out chemical
signals that incite other cell types to fight the
pathogen.
Contents.
Approximate Duration:
Got lazy?...
Immunity
Step 2
Displays portion of Pathogen
on surface
Step 3
Pathogens
Activates B- Cell
Activates Cytotoxic
T- Cell
Memory T-Cell
Memory B-Cell
Antibodies
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Antibody Immunity
Helper T - Cell
Cellular Immunity
Active Cytotoxic T-Cell
Kills Infected Cells
Memory T- Cell
Active B - Cell
Plasma Cell
Antibodies
Deactivates Antigens
Memory B-Cell
Vaccination:
2.
Passive Immunity
This is immunity where antibodies are given to a
person from the blood of another person or animal.
This immunity only lasts for a short period of time.
ex: Breastfeeding mothers pass antibodies to their
children through the milk.
HIV is a retrovirus.
A more specific name is Lentivirus.
Retroviruses have an RNA genome that is
replicated via a DNA intermediate in infected
cells. DNA also integrates in the host
genome to form provirus.
Structure of HIV
Sarcophagus-shaped capsid
contains 2 copies of RNA genome
(SS (+) strand), a reverse
transcriptase, integrase, and
protease.
P7 coats the RNA, and P24 forms
the nucleocapsid structure, which
is enclosed by a lipid bilayer.
Lipid bilayer comes from the host
cell, but contains two viralencoded glycoproteins, gp41 (41
kDa) and gp120 (120 kDa).
gp120 binds the CD4 receptor on
helper T cells.
Infection
gp120 and gp41 associate with one
another. The complete complex is
probably trimeric (3 copies of each
protein).
Beta turns in C3 and C4 regions are
important for binding to the cellsurface CD4 receptor.
1. Autofusion
CD4 and gp120/41 proteins
mediate fusion and intracellular
vesicle formation.
2. Syncytium formation
gp120/41 proteins on
infected cells bind to CD4
receptors on normal cells,
causing cell fusion. The
giant multi-nucleated
syncytium dies before
long.
Infected cell
Normal cell
3.Apoptosis
Current Therapies
1. Nucleoside analogues and other RT
inhibitors.
2. Active site inhibitors of the HIV
protease (part of the Pol gene).
3. Interferon (stimulates anti-viral
response)
4. Cocktails of all 3.
Vaccines?
Whole virus vaccines
Attenuated viruses: Essentially intact, living HIV virions that have
been chemically or genetically damaged.
Whole killed virus: Intact virions that have been damaged so badly
that they are completely nonfunctional (dead).
Subunit vaccines
Clone one gene from HIV, express the protein and use it to vaccinate
patients. The disadvantage is that the person only raises antibodies
against one target. With free virus, the targets are mainly the
envelope proteins; however, these are extremely variable proteins.
Six amino acids of the V3 loop of gp120 appear to be relatively
constant (some variability exists but most antibodies cross react with
the variants). Antibodies against cocktails of different V3's are being
tried.
Nucleic Acid Vaccines
Gene gun, muscle expression.
Effector Cell
Think MichaelisMenton
IL-2 Molecules
Step 1
Tumor
recognition site
Tumor
cells
Ste
p2
IL-2 Receptor
4. Tumor Eating
Site Activated
6. Attack Mode!
Step 6
Step 4
Step 3
Step 5
5. Locates Tumor
Calculus.
Change in
Effector cells
over time
Antigenicity
and size of
tumor
Death
rate
IL-2
Stimulation
Effector Cell
Injection
Logistic
growth rate
of Tumor
Change in
Tumor cells
Killing rate
by Effector
cells
Change in IL-2
Natural
production of IL-2
Death
rate
IL-2
Injection
Lupus
Lupus is a long-term autoimmune disease.
Immune system attacks body
causing inflammation and tissue
Symptoms:
Fatigue, fever, skin rashes, and muscle
and joint pain.
Some people may have severe episodes;
others have a milder form of the disease.
There is no cure for lupus.
More common in women than men.
The Epstein-Barr virus has been linked to lupus in children.
References
References:
1. Kandel ER, Schwartz JH, Jessell TM, editors. Principles of
Neural Science (Fourth Edition). New York: McGraw Hill (Health
Professions Division). 2000;472-491.
2. Millan MJ. Progress in Neurobiology 1999;57:1-164.
3. Dickenson AH. Brit J Anaesthesia 1995;75:193-200.
4. Suzuki R and Dickenson AH. Neuroreport 2000;11:R17-21.
5. Waxman S. Pain 1999;6:S133-140.
www.worldofteaching.com
www.hopkins-aids.edu/hiv_lifecycle/
www.who.int/hiv/en
hivinsite.ucsf.edu/InSite.jsp?doc=kb-02-01-02
Chris Cunningham & Asad Usman Adoptive Immunotherapy
Rosenberg, SA, Yang, JC, White, DE, et al. Durability of complete responses in patients with metastatic cancer
treated with high-dose interleukin-2: Identification of the antigens mediating response. Ann Surg 1998; 228:307.
Rosenberg, SA, Yang, JC, Topalian, SL, et al. Treatment of 283 consecutive patients with metastatic melanoma or
renal cell cancer using high-dose bolus interleukin-2. JAMA 1994; 271:907.
Nicola NA (ed) (1994) Guidebook to Cytokines and their Receptors. Oxford: Oxford University Press.
OstrandRosenberg S (1994) Tumor immunotherapy:the tumor cell as an antigenpresenting cell. Current Opinion
in Immunology 6: 722727.
Rosenberg SA. Lotze MT. Muul LM. Chang AE. Avis FP. Leitman S. Linehan WM. Robertson CN. Lee RE. Rubin
JT. et al. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer
cells and interleukin-2 or high-dose interleukin-2 alone. [Journal Article] New England Journal of Medicine.
316(15):889-97, 1987 Apr 9.
Kirschner D. Panetta JC. Modeling immunotherapy of the tumor-immune interaction. [Journal Article] Journal of
Mathematical Biology. 37(3):235-52, 1998 Sep.
J.C. Arciero, T.L. Jackson, and D.E. Kirschner. A mathematical model of tumor-immune evasion and siRNA
treatment. [Journal Article] Discrete and Continuous Dynamical Systems: Series B. 4(1) 39-58, 2004 Feb.
Dudley ME. Rosenberg SA. Adoptive-cell-transfer therapy for the treatment of patients with cancer. [Review] [97
refs] [Journal Article. Review. Review, Tutorial] Nature Reviews. Cancer. 3(9):666-75, 2003 Sep.
Chang W., Crowl L., Malm E.,Todd-Brown K., Thomas L., Vrable M. Analyzing Immunotherapy and Chemotherapy
of Tumors through Mathematical Modeling. [Book] Department of Mathematics: Harvey-Mudd University, 2003
Summer.
Nonspecific
Defense
Specific
Defense
Immune
Responses
Arising
Immunity
Immunity In
Health and
Disease
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1 pt
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The ingestion of
invading organisms by
certain type of white cells
What is Phagocytosis?
What are
Lymphocytes?
An antigen-binding
immunoglobulin that functions
as the effector in an
immune response.
Lymphoctyes and
Antibodies
A group of at least
20 blood proteins that
cooperate with
other defense mechanisms.
What is the
complement system?
What is perforin?
A localized region
on the surface of an
antigen that is
chemically recognized
by antibodies.
What is a epitope?
What is
neutralization?
What is complement
fixation?
What is an antigen
receptor?
What is vaccination?
A life-threatening reaction
to injected or ingested
allergens.
What is
anaphylactic shock?
What is Passive
Immunity?
What is Human
Immunodeficiency
Virus (HIV)?