HYPERSENSITIVITYSAYAN BANERJEE

1

General descriptions of the 4 types of hypersensitivity

2

3

Type-I Hypersensitivity:

Animation IProduction of IgE in Response to an Allergen

4

Type-I Hypersensitivity:

Animation IIAllergen Interaction with IgE on the Surface of Mast Cells triggers the Release of Inflammatory Mediators

5

Anaphylactic-type Degranulation of a Mast Cell

6

Intervention for Type I Hypersensitivity

Animation: Treatment with monoclonal anti-IgE antibody

Type I :

7

THE MECHANISMS OF A TYPE I

HYPERSENSITIVITY REACTION:

SENSITIZATION

Allergen (antigen)

Antigen-presenting cell (APC)phagocytizes and processesantigen.

APC presentsepitope to Th2 cell.

Th2 cell

B cell

Plasmacell

IL-4 IL-4 from Th2cell stimulates selectedB cell clone.

B cells become plasma cellsthat secrete IgE.

IgE against allergen

IgE stem binds tomast cells, basophils,and eosinophils.

EosinophilBasophilIgE

Mast cell

Sensitization8

THE MECHANISMS OF A TYPE I HYPERSENSITIVITY REACTION: DEGRANULATION

Subsequent exposureto allergen

Degranulation

Sensitized mast cell,basophil, or eosinophil

Histamines, kinins,proteases, leukotrienes,prostaglandins, and otherinflammatory molecules

9

10

11

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.

12

Treatment for Type I Effect of allergy shots Allergen Specific Antibodies

13

Change in amount of each isotype from more IgE to more IgG.

14

Type II HypersensitivityAntibody-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.

Type II (Cytotoxic) HypersensitivityDrug-induced cytotoxic reactions○ Some drug molecules bind larger molecules

Stimulate the production of antibodies○ Can produce various diseases

Immune thrombocytopenic purpuraAgranulocytosisHemolytic anemia

15

EVENTS LEADING TO HEMOLYSIS

Type A antigens on redblood cells of patient

Anti-Bantibody

Donated red blood cellswith B antigen

Complement

Hemoglobin

Transfusion

Hemolysis

Agglutination andcomplement binding

16

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.

17

EVENTS IN THE DEVELOPMENT OF

HEMOLYTIC DISEASE OF THE NEWBORN-

OVERVIEW

18

19

20

Type II HypersensitivityAntibody 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

EVENTS IN THE DEVELOPMENT

OF IMMUNE THROMBOCYTOP-ENIC PURPURA

Platelet

Drug

Drug-plateletcomplex

Drug molecules bind to platelets,forming drug-platelet complex.

Complexes are antigenic,triggering a humoralimmune response.

Antibodies bind to drug molecules; complementbinds to antibodies.

Complement

Membrane attackcomplexes of complementlyse platelet, which leakscytoplasm.

21

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

22

THE MECHANISM OF TYPE III (IMMUNE-COMPLEX MEDIATED) HYPERSENSITIVITY-OVERVIEW

Antigens combine with antibodies to formantigen-antibody complexes.

Antigen

Antibody (IgG)

Antigen-antibody complex

Phagocytes remove mostof the complexes, butsome lodge in the wallsof blood vessels.

There the complexesactivate complement.

Inactive complement

Active complement

Antigen-antibody complexesand activated complementattract and activateneutrophils, which releaseinflammatory chemicals.

Neutrophil

Inflammatory chemicals

Inflammatory chemicalsdamage underlyingblood vessel wall.

23

24

Arthus Reaction

A Dominant Role for Mast Cell Fc Receptors in the Arthus Reaction

25

Fever, rash, joint pain, lymphadenopathy, occasionally glomerulonephritis.

Time course: days to weeks after introduction of foreign antigen.

Causes: allogeneic serum, drugs, infections, autoimmune disorders.

26

Serum sickness

Serum Sickness Reactions

27

28

Serum Sickness

29

TH1-mediated Type IV Hypersensitivity

Stages of Type IV DTH

30

31

Granuloma Formation from DTH Mediated by Chronic Inflammation

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.

32

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.

33

34

CONTACT DERMATITIS BY POISON OAK

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.

35

36

Patch testing for contact dermatitis

37

38

Drug reactions can be any Type of Hypersensitivity

39

ANYQUESTIONS???