This document provides an overview of the 4 main types of hypersensitivity reactions: Type I is an immediate allergic reaction mediated by IgE antibodies and mast cells. Type II involves antibody-complement binding on host cells leading to cell lysis. Type III occurs when soluble immune complexes are formed in blood and tissues causing inflammation. Type IV is a delayed type hypersensitivity mediated by T cells against antigens like bacteria or drugs.

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2. General descriptions of the 4 types
of hypersensitivity
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Type-I Hypersensitivity:
Animation I
Production of IgE in Response to an Allergen

4. 4
Type-I Hypersensitivity:
Animation II
Allergen Interaction with IgE on the Surface of Mast
Cells triggers the Release of Inflammatory Mediators

5. 5
Anaphylactic-type Degranulation of
a Mast Cell

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Intervention for Type I
Hypersensitivity
Animation: Treatment with monoclonal anti-IgE antibody

7. Type I :
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8. Allergen (antigen)
Antigen-presenting cell (APC)
phagocytizes and processes
antigen.
APC presents
epitope to Th2 cell.
Th2 cell
B cell
Plasma
cell
IL-4 IL-4 from Th2
cell stimulates selected
B cell clone.
B cells become plasma cells
that secrete IgE.
IgE against allergen
IgE stem binds to
mast cells, basophils,
and eosinophils.
EosinophilBasophil
IgE
Mast cell
Sensitization
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9. Subsequent exposure
to allergen
Degranulation
Sensitized mast cell,
basophil, or eosinophil
Histamines, kinins,
proteases, leukotrienes,
prostaglandins, and other
inflammatory molecules
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12. Treatment for Type I
 Pharmacotherapy:-
 Drugs:
 Non-steroidal anti-inflammatories
 Antihistamines block histamine receptors.
 Steroids
 Theophylline OR epinephrine -prolongs or increases cAMP
levels in mast cells which inhibits degranulation.
 Immunotherapy:-
 Desensitization (hyposensitization) also known as allergy shots.
 Repeated injections of allergen to reduce the IgE on Mast cells
and produce IgG.
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13. Treatment for Type I Effect of
allergy shots Allergen
Specific Antibodies
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Change in
amount of each
isotype from
more IgE to more
IgG.

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Type II Hypersensitivity
Antibody-Complement Dependent Mediated
Lysis
Animation: IgG or IgM reacts with epitopes on the host cell membrane
and activates the classical complement pathway. Membrane attack
complex (MAC) then causes lysis of the cell.

15.  Type II (Cytotoxic) Hypersensitivity
 Drug-induced cytotoxic reactions
○ Some drug molecules bind larger molecules
 Stimulate the production of antibodies
○ Can produce various diseases
 Immune thrombocytopenic purpura
 Agranulocytosis
 Hemolytic anemia
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16. Type A antigens on red
blood cells of patient
Anti-B
antibody
Donated red blood cells
with B antigen
Complement
Hemoglobin
Transfusion
Hemolysis
Agglutination and
complement binding
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17. Hemolytic disease of newborn(Rh
factor incompatibility)
 IgG abs to Rh an innocuous RBC antigen
 Rh+baby born to Rh-mother first time
fine.2nd time can have abs to Rh from 1st
pregnancy.
 Ab crosses placenta and baby kills its own
RBCs.
 Treat mother with Ab to Rh antigen right
after birth and mother never makes its own
immune response.
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Type II Hypersensitivity
Antibody Dependent Cell Mediated Cytotoxicity
Animation: Antibodies react with epitopes on the host cell membrane
and NK cells bind to the Fc of the antibodies. The NK cells then lyse
the cell with pore-forming perforins and cytotoxic granzymes

21. Platelet
Drug
Drug-platelet
complex
Drug molecules bind to platelets,
forming drug-platelet complex.
Complexes are antigenic,
triggering a humoral
immune response.
Antibodies bind to drug
molecules; complement
binds to antibodies.
Complement
Membrane attack
complexes of complement
lyse platelet, which leaks
cytoplasm.
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22. Type-III Hypersensitivity: Immune
Complex
Animation: Large quantities of soluble antigen-antibody complexes form in the blood
and are not completely removed by macrophages. These antigen-antibody complexes
lodge in the capillaries between the endothelial cells and the basement membrane. The
antigen-antibody complexes activate the classical complement pathway and
complement proteins and antigen-antibody complexes attract leukocytes to the area.
The leukocytes then discharge their killing agents and promote massive inflammation.
This leads to tissue death and hemorrhage
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23. Antigens combine with
antibodies to form
antigen-antibody complexes.
Antigen
Antibody (IgG)
Antigen-antibody complex
Phagocytes remove most
of the complexes, but
some lodge in the walls
of blood vessels.
There the complexes
activate complement.
Inactive complement
Active complement
Antigen-antibody complexes
and activated complement
attract and activate
neutrophils, which release
inflammatory chemicals.
Neutrophil
Inflammatory chemicals
Inflammatory chemicals
damage underlying
blood vessel wall.
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Arthus Reaction

25. A Dominant Role for Mast
Cell Fc Receptors in the
Arthus Reaction
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26.  Fever, rash, joint pain, lymphadenopathy,
occasionally glomerulonephritis.
 Time course: days to weeks after introduction
of foreign antigen.
 Causes: allogeneic serum, drugs, infections,
autoimmune disorders.
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Serum sickness

27. Serum Sickness Reactions
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Serum Sickness

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TH1-mediated Type IV
Hypersensitivity

30. Stages of Type IV DTH
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Granuloma Formation from DTH
Mediated by Chronic Inflammation

32. Sensitization stage
 Memory Th1 cells against DTH antigens are
generated by dendritic cells during the
sensitization stage.
 These Th1 cells can activate macrophages and
trigger inflammatory response.
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33. Effector stage
 Secondary contact yields what we call DTH.
 Th1 memory cells are activated and produce
cytokines. IFN-γ, TNF-α, and TNF-β which cause
tissue destruction, inflammation.
 IL-2 that activates T cells and CTLs.
 Chemokines-for macrophage recruitment.
 IL-3, GM-CSF for increased monocyte/macrophage
 Secondary exposure to antigen
 Inflamed area becomes red and fluid filled can
form lesion.
 From tissue damage there is activation of clotting
cascades and tissue repair.
 Continued exposure to antigen can cause
chronic inflammation and result in granuloma
formation.
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CONTACT DERMATITIS BY POISON OAK

35. Contact dermatitis
 The response to poison oak is a classic
Type IV.
 Small molecules act as haptens and
complex with skin proteins to be taken
up by APCs and presented to Th1 cells
to get sensitization.
 During secondary exposureTh1 memory
cells become activated to cause DTH.
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37. Patch testing for contact
dermatitis
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Drug reactions can be any Type of Hypersensitivity

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