Hypersensitivity

Department of Microbiology

Important terms• Hypersensitivity reactions are exaggerated antigen-specific immune

responses which is harmful to the host.

• Allergen ： The antigens that give rise to immediate

hypersensitivity

• Atopy ： The genetic predisposition to synthesize inappropriate

levels of IgE specific for external allergens

• Types of hypersensitivity: As per Coomb and Gel Classification

hypersensitivity is of four types (Type I, Type II, Type III and Type

IV)

Type I Hypersensitivity

– Mediated by IgE antibodies.

– Also known as “immediate hypersensitivity "or “Allergic response”.

– Antigens that induce type I hypersensitivity are also termed as “Allergens”.

Type I Hypersensitivity

– The IgE antibodies produced against Allergens remain bound to Mast cells.

– Upon exposure to specific Allergens IgE antibodies induce degranulation of Mast cells.

– This leads to release of inflammatory mediators like Histamine, Serotonin, Prostaglandins etc.

– Some common Allergens are Pollen, Dust etc.

– Example: P-K reaction

Type I Hypersensitivity

Type I Hypersensitivity

Histamine: Dilate blood vessel Increase vascular permeability

2. Leukotrienes: Bronchial smooth muscles contract

Asthmas

3. Prostaglandin: High concentration of PGE Inhibit the secretion of histamine

low concentration of PGE promote the release of histamine

4. Platelet activating factor (PAF) :

Agglutinate and activate platelets to release histamine

5. Eosinophil chemotactic factor（ ECF-A） :

6. Bradykinin : Vasodilator function

Type II Hypersensitivity

• Type II Hypersensitivity is mediated by antibodies that are produced against the antigenic determinants present on cell surface.

• As the antigenic determinants are present on cell surface, thus type II reaction is manifested in the form of massive cell destruction.

• The target cells are lysed by: • activation of Complement cascade by the antibody molecules

bound on the cell surface. • antibody dependent cell mediated cytotoxicity (ADCC).

• Transfusion reactions and Hemolytic Disease of the Newborn are examples of type II reaction.

2. Mechanism of Type II hypersentivity

1. Surface antigen on target cells

Target cells: Normal tissue cell, changed or modified self tissue cells

2. Antibody, complement and modified self-cell

Antigen : Blood group antigen, Common antigen,

Self-antigen modified by physical factors or infection

Drug antigen,

Antigen-antibody complex

Activate complement Lyse target cells

Opsonic phogacytosis Destroy target cellsADCCMf 、 NK 、 T

Stimulating or blocking effect Promote /surpress the target cell funcion

Antigen or hapten on cell

Antibody (IgG, IgM)

Activate complement

Lyse target cell

Opsonic phagocytosis NK , phagocyte Stimulate / block

Destroy target cell ADCC

Target cell injury Change the function ofTarget cell

Mechanism of Type II hypersensitivity

3. Common disease of type II hypersensitivity 1)Transfusion reaction

hemolysis : mismatch of ABO blood group, severely destroy RBC nonhemolysis : repeat transfusion of allogenic HLA drug anaphylactic shock： penicillin 2) Hemolytic disease of newborn Mother Rh- : first baby Rh+(Ab), second baby Rh+,

fetal RBC destroyed 3) Autoimmune hemolytic anemia and type II drug reaction i. Foreign antigen or hapten Penicillin RBC hemolytic anemia Quinin Platlet thrombocytopenic purpura Pyramidone Granulocyte agranulocytosis ii. Self-antigen Drug conversion from a hapten to a full antigen induce self antibody autoimmune hemolytic anemia

Auto-Immune Hemolytic Anaemia

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

17

Type II HypersensitivityAntibody-Mediated Cell Disfunction

Example: Myasthenia Gravis

Type III Hypersensitivity

– Mediated by immune complexes (Antigen-Antibody complex).

– During normal immune response only moderate quantity of immune complexes are formed and they are removed efficiently from circulation by phagocytosis.

– In case of production of large quantities of immune complexes, phagocytes fail to remove all the immune complexes from circulation.

– Thus, Ag-Ab complexes are deposited in various tissues. They lead to activation of complement components. Activation of complement may leads to destruction of bystander cells.

Type III Hypersensitivity

– Moreover, under the influence of chemotactic complement components polymorphonuclear cells are recruited at the site.

– These cells, in their attempt to engulf immune complexes, releases lysozymal enzymes in the tissue and thus cause tissue destruction.

– Arthus reaction is an example of localized type III hypersensitivity.

– Serum Sickness is an example of Systemic type III hypersensitivity.

– Blue Eye: Dogs infected or vaccinated with live canine adenovirus I develops anterior uveitis. This lead to corneal oedema and opacity. The blue eye is considered to be an immune complexes mediated condition.

Immunreaktionen der Haut 20

Type III Hypersensitivity

• “Immune complex disease”

• Soluble Ag / IgG or IgM– high titers of each required

• Immune processes involved:– classical complement pathway– phagocytic cells

Soluble antigen Body Antibody

Immune complex

Small molecular soluble Immune complex

intermediate molecular soluble Immune complex

Large molecular insoluble Immune complex

Deposit on the basement of capillaries

Combine and activate complement system

C3a,C5a,C3b

Infiltration of neutrophils

Phagocytose complex

Release the enzymes in lysosome

Tissue injury

Eliminate by phogacytosis

Platelets

Thrombus

Aggregation of platlets

Blood Clotting MechanismsRelease of vasoactive amine

Increase vascular permeability

Bleeding Edema

Basophils and mast cells

Release of vasoactive amine

Increase vascular permeability

Edema

Local or systemic immune complex diseases

3. common disease of type III hypersensitivity 1. Local immune complex disease

Arthus reaction ： Experimental local reaction, Necrotic vasculitis vasculitis, Ulcer Human local reaction: insulin-dependent diabetes mellitus (IDDM) 2. Acute systemic immune complex disease serum sickness Anti-serum Ab+Ag systemic tissue injury ,fever, arthritis, skin rash Pinicillin 、 Sulfanilamide Acute immune complex glomerulonephritis : Streptococcus infection 3. Chronic immune complex disease SLE Rheumatoid arthritis ： RF+IgG Deposit on synovial membrane

Type IV hypersensitivity reaction

– Because of delay in onset of response, type IV hypersensitive reaction is also known as Delayed Type Hypersensitivity (DTH).

– It approx takes 24 to 48 hours from the time of antigenic stimulation.

– Unlike Type I, II, and III response (antibody mediated), Type IV reaction is mediated by Cellular immune components.

Type IV hypersensitivity reaction

– The effector cells of Type IV hypersensitivity response are CD4+ (Th), CD8+ cells and activated macrophages.

Some common examples of type IV hypersensitivity reaction:

– Tuberculin test (used for diagnosis of Tuberculosis),

– Johnin test (used for diagnosis of Johnes disease),

– Mallein test (used for diagnosis of Glanders),

– Brucellin test (used for diagnosis of Brucellosis).

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