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BIG QUESTION:
What happens when immune system overreacts?
Differentiate between the mechanisms of the four hypersensitivity reactions.
1. Mechanism of Type I hypersensitivity
2. Understand the principle of chronic desensitization
3. Examples of Type I
4. Know the role of ADCC in Type II hypersensitivity
5. Foreign antigen versus selfantigen in Type II hypersensitivity
6. Druginduced hypersensitivity
7. Examples of Type II
8. Mechanism of Type III
9. Foreign antigen verses self antigen in Type III hypersensitivity
10. Examples of Type III
11. Mechanism of Type IV
12. Foreign antigen verses self antigen in Type IV hypersensitivity
13. Examples of Type IV
Hypersensitivities
Type I Hypersensitivity
Most of what we call "allergy" is Type I hypersensitivity, in which
mast cells are activated by IgE produced in response to an allergen
ONE IN 5 PEOPLE HAVE ATOPY - a predisposition towards Type
I hypersensitivity
The risk of developing a Type I hypersensitivity is linked to family
history and IgE levels.
People with higher IgE levels tend to be atopic more often than
people with lower IgE levels, although the linkage is not absolute.
Allergens for Type I fall into groups of molecules, such as grasses,
pollens, animal, and foods that usually reach mucosal surfaces at
very low doses.
They are protein, since only protein molecules can be presented
to T cells and elicit T cell help.
Mast cells
Mast cells are common at sites in the
body exposed to the external
environment, such as the skin.
Mast cells
Type I examples
TYPE I mechanism:
Has two distinct phases:
1. Sensitization phase (the synthesis of IgE
upon initial exposure to Ag)
Sensitization phase
Low Ag dose
Low M.W, soluble
mucosal membranes
Activation phase
Mast cell
2. Rresult: Increased blood flow and fluid released at the mucus membranes
and at the tissues washes away antigen
The chemokines released in early phase attract more leukocytes, such as eosinophils
to the inflammation.
Cytokines from early and late phase stimulate white blood cell production in the marrow,
Skin test
1. Activation of complement
Classical complement activation by IgG releases
inflammation-promoting anaphylatoxins and leads to
formation of membrane attack complex (MAC) and lysis
of the antibody-coated cell.
Autoantigen induced
Myasthenia gravis
Graves disease
Hemolytic anemia
Foreign antigen-induced:
1. Blood transfusion can also result in Type II
Hypersensitivity to blood group antigens such as A, B
and Rh.
Foreign antigen-induced:
2. Drugs like aspirin and penicillin, which often complex with
erythrocyte membrane proteins, may induce synthesis of IgG antibodies
which then bind drug-coated erythrocytes and damage them.
Autoantigens induced
1. Myasthenia gravis Ab against the acetylcholine receptor
Hyperthyroidism is the most common feature of Graves' disease, affecting nearly all patients
Arthus reaction
Serum sickness
Autoantigen induced
Lupus
Rheumatoid arthritis
Autoimmune diseases:
1. Rheumatoid arthritis
Patients develop an auto-IgM antibody against their own IgG that
is thought to contribute to arthritic joint inflammation.
Autoimmune diseases:
2. Systemic Lupus Erythematosis autoantibodies are produced against the
patients own DNA and histones.
Events
required
to trigger
lupus
Ab
Ag
Clearance by
complement
Immune complex
Immune
complex disease
localized
systemic
SLE
Serum sickness
Arthus rxn
Glomerulonephritis
Rheumatoid arthritis
Type IV hypersensitivity
Delayed-type hypersensitivity (DTH)
PPD test
Autoantigen induced
Diabetes Type I
Multiple Sclerosis
Celiac disease
Autoimmune reactions:
Type I diabetes
Multiple sclerosis
Celiac disease
Autoimmune reactions
1. Type I diabetes
In type 1,
pancreatic beta
cells in the islets
of Langerhans
are destroyed,
decreasing
endogenous
insulin
production.
Autoimmune reactions
2. Multiple sclerosis
Demyelination of nerves in CNS, including the optic nerves
which control vision, so vision is affected, but the closure of
eyelid is fine.
Autoimmune reactions
3. Celiac disease
Hapten
Binds cell
Type II
Binds
cytoplasmic
protein
Binds soluble
protein
Stimulate IgG
Stimulate IgE
Type III
Type I
Activates T
cells
(Type IV)