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Hypersensivity reaction types

1. Anaphylactic and atopic (type I)
2.Cytotoxic ( antibody mediated, type II)
3. Immune complex (type III)
4. Deleayed ( cell mediated , type IV)


Anaphylactic and atopic (type I ) hypersensvity reaction - mechanism

Antigen induce the formation of IgE through Th2 and IL-4 ---> Reexposure --> Freee antigen cross- links IgE on presenting mast cells and basophils , triggering immediate re release of vasoaactive amines that act at postcapillary venules ( eg. Histamine). Rapidly reaction because of preforemed antibody --> delayed production of arachidonic acid metabolites (e.g Leukotrienes) --> neutrophils and eosinophils


Anaphylactic and atopic (type I) hyperreaction - main vasoactive amine and where it acts

Histamine --> post capillary venules


anaphylactic and atopic (type I) hypersensivity reaction - test

skin test for specific IgE


Type I hypersesnsivity -reaxtion - delayed respond -cell

Neutrophils and eosinophils


Basophil contains

1. heparin ( densly basophilic granules)
2. histamine (densly basophilic granules)
3. synthesis and release leukotriene


Mast cell releases

1. Histamine
2. Tryptase
3. eosinophil chemotactic factor
4. Heparin


Eosinophil produce

1. Histaminase
2. Major basic protein ( a helminthotoxic)


Cytotoxic (antibody mediated ) Hypersensivity reaction- mechanism

IgM, IgG bind to fixed antigen on " enemy " cell --> complement activation --> membrane attack complex (MAC) --> a. opsonization and phagocytosis b. complement and Fc-mediated inflammation c. antibody - mediated cellular dysfunction


Cytotoxic (antibody mediated ) Hypersensivity reaction- disease tends to be specific on

tissue or site where antigen is found


Direct Coombs test - definition and example

detects antibodies that have adhered to patient RBCs eg test an Rh+ infant of an Rh- mother


Indirect Coombs

detects serum antibodies that can adhere to othweR BCs eg test in Rh- woman for Rh+ antibodies


Cytotoxic (antibody mediated ) Hypersensivity reaction- types of antibodies



Immune Complex Hypersensivity reaction- mechanism

Antigen - antibody (IgG) complexes --> activate complement --> attracts neutrophils which release lysosomal enzymes


Type II reaction associated with

1. Vasculityis
2. Systemic manifestation


Serum sickness mechanism

Antibodies formation to foreign proteins (take 5 days) --> immune compexes formation and deposition in membranes --> fix the complement --> tissue damage


MC serum sickness is caused by

drugs (not serum) acting as haptens


Haptens are

Small molecules that elicit an immune response only when attached to a large carrier ( eg. protein ) which may be one that also does not elicit an immune response by itself


Serum sickness - antibodies formation takes ... (time

5 days


Serum sickenss - sx

1. Fever
2. Urticaria
4. Proteinuria
5. Lymphadenopathy
6. Splenomegaly
7. Eosinophilia
OCCURS 5-10 days After antigen exposure


Arthurs reaction mechanism

local subacute antibody - mediated hypersensivity reaction --> intradermal (or subcutaneous) injections into a pre-sensitized (has circulating IgG individual leads to immune complex formation in the skin --> activation of complement --> PMN infiltration and platelet clumbing


Arthus reaction - time

3-6 h


Arthus reaction - sx

edema and necrosis


Arthus reaction vs serum sickness according to time and whic is mc

Arthus reaction --> 3-6 H MC
Serum sickness --> 5days


Arthus reaction - diagnosis

immunofluorescent staining


Arthus reaction - example

tetanus immunization if they are are given at same site with too short interval between immunization (min interval usually 5 years)


Delayed (cell mediated ) Hypersensivity reaction (IV) - mechanism

sensitized T cells encounter antigen and then release cytokene (leads to macrophages activation ) DOES NOT INVOLVE ANTIBODIES (I, II, III)


Hypersensivity rection type II is cell mediated so it is not transferable by



HSR IV - test

1. patch test
2. PPD


• What are the 4 Ts associated with type IV hypersensitivity reactions? How is it tested for?

T-lymphocyte mediation, Transplant rejection, TB skin tests, and Touching (contact dermatitis); with patch test, PPD (for TB)


How does the mnemonic ACID help you remember important features of the four types of hypersensitivity reactions?

Type I = Anaphylactic and Atopic, type II = Cytotoxic, type III = Immune complex, type IV = Delayed


A man has fever, joint pain, enlarged lymph nodes, hives, and proteinuria. He started a new drug 7 days ago. What type of reaction is this?

Serum sickness (type III hypersensitivity reaction


Which type of hypersensitivity reaction does the Coombs test look for? Describe the difference between a direct and indirect Coombs test.

Type II; direct = detects antibodies that are already stuck to RBCs, indirect = detects antibodies that can stick to RBCs


• A mother is Rh- and her infant may be Rh+. Whom do you test with the indirect Coombs test? Whom do you test with the direct Coombs test?

Test the Rh- mother for Rh+ antibodies with the indirect Coombs; test the Rh+ infant for antibodies adhered to RBCs with the direct Coombs


A patient suffers from a type II hypersensitivity reaction. The complement system is activated. How does it destroy the patient's cells?

Antibody and complement lead to formation of the membrane attack complex (MAC) (type II is cy-2-toxic)