Notes

Hypersensitivity

• Hypersensitivity is defined as injurious consequences in the sensitized host, following contact with specific antigen.
• Hypersensitivity is defined as an exaggerated or inappropriate state of normal immune response with onset of adverse effects on the body.
• Coombs & Gell classifed hypersensitivity reactions into four types based on the different mechanisms of pathogenesis as TypeI, II, III & type IV.
• Depending upon the rapidity, duration, and type of the immune response, 4 types of hypersensitivity reactions are grouped into immediate and delayed type.

Difference between Immediate and Delayed Hypersensitivity

Types of hypersensitivity & their features

Type I Hypersensitivity reaction/ IgE dependent

• These occur in two forms: the acute, potentially fatal, system form called anaphylaxis & the chronic or recurrent, non fatal, typically localised form called atopy.

Anaphylaxis:

• This is the classical immediate hypersensitivity reaction.
• Antigens and hapten can induce anaphylaxis. There should be atleast 2-3 weeks of interval between the sensitising dose & the shocking dose.

Atopy:

• The term atopy refer to naturally occurring familial hypersensitivities of human beings, typified by hay fever & asthma.
• The antigens involved in atopy are characteristically inhalants (for example, pollen, house dust) or ingestants (for examples, eggs, milk).

Mechanism of Type I HSN

1. a. Sensitization phase

Priming dose of antigen (allergen)->processed by APC->antigen peptide presented to T cell->Th2->secretes IL4->Acts on B cell->IgE produced-> Mast cell coated with IgE (Fc).

1. b. Effector phase

Shocking dose->IgE (Fab) binds to antigen-> Mast cell degranulation.

• Tissues or organs predominantly involved are known as target tissues or shock organs.

Type II Hypersensitivity reaction/Cytolytic & cytotoxic

• Type II or cytotoxic reaction is defined as reactions by humoral antibodies (IgG, rarely by IgM) that attack cell surface antigens on the specific cells & tissues & cause lysis of target cells.
• Type II reaction appears generally within 15-30 mins after exposure to antigen.
• In general, type II reactions have participation by complement system, tissue macrophages, platelets, natural killer cells, neutrophils & eosinophils while main antibodies are IgG and IgM.
• Type II hypersensitivity is tissue-specific & reaction occurs after antibodies bind to tissue specific antigens, most often on blood cells.
• Example of Type II hypersensitivity

1. Erythroblastosis fetalis
2. Good Pasteur syndrome
3. Grave’s disease
4. Myasthenia gravis.

Type III Hypersensitivity reaction/ Immune complex diseases

• It results from deposition of antigen-antibody complexes on tissues, which is followed by activation of the complement system and inflammatory reaction, resulting in cell injury.
• The onset of type III reaction takes place about 6 hours after exposure to the antigen.
• Type III reaction is not tissue specific & occurs when antigen-antibody complexes fail to get removed by the body’s immune system.
• Clinical Syndrome: (a) Arthus reaction (b) Serum sickness. 
• There can be 3 possible etiologic factors precipitating type III reaction:

1. Persistence of low-grade microbial infection.
2. Extrinsic environmental antigen.
3. Autoimmune process.

Examples:

1. Hypersensitivity Pneumonitis (Farmer’s lung)
2. Post streptococcal glomerulonephritis.
3. Nephrotic syndrome in Plasmodium malariae.
4. Katamaya fever in schistosomiasis.
5. Connective tissue disorder-SLE, Rheumatoid Arthritis.

Type IV/ delayed or cell mediated hypersensitivity

• Type IV reaction is tissue injury by cell mediated immune response without formation of antibodies but is instead a slow & prolonged response of specifically sensitised T lymphocytes (CD4 &CD8 T cells).
• The reaction occurs about 24 hours after exposure to antigen & the effect is prolonged which may last up to 14

Examples:

1. Tuberculin test-Mantoux/Heaf
2. Lepromin test
3. Montenegro test (Leishmania)
4. Multiple sclerosis
5. Chronic transplant rejection
6. Graft-versus host disease