Hypersensitivity Types Notes

Hypersensitivity

Hypersensitivity or allergy refers to the injurious consequences in the sensitized host, following subsequent contact with specific antigens.

Type-1 Hypersensitivity Reaction

Mechanism

Type-1 Hypersensitivity reaction occurs through two phases:

Read And Learn More: Micro Biology And Immunology Notes

Examples of Type 1 Hypersensitivity Reaction

• Experiments to demonstrate type I hypersensitivity reaction: P-K reaction, Schultz Dale phenomenon and Theobald smith phenomenon
• Systemic anaphylaxis
• Localized anaphylaxis (atopy) such as:
  • Allergic rhinitis (or hay fever)
  • Asthma
  • Food allergy
  • Atopic urticarial
  • Atopic dermatitis (allergic eczema)
  • Drug allergy
  • Wheal and flare reaction.
• Parasitic diseases/tests:
  • Casoni test (hydatid disease)
  • Tropical Pulmonary Eosinophilia (TPE)
  • Loeffler’s pneumonia (Ascaris)
  • Ground itch (Hookworm)
  • Leakage of hydatid fluid
  • Cercarial dermatitis/swimmer’s itch (Schistosoma).

Treatment of Type 1 Hypersensitivity Reaction

• Avoidance of contact with known allergens
• Hyposensitization: Repeated exposure to increased subcutaneous doses of allergens can reduce or eliminate the allergic response to the same allergen.
• Humanized Monoclonal anti-IgE-It can bind and block IgE.
• Drugs: Several drugs are useful in suppressing type-1 response such as antihistamines, adrenaline, cortisone, theophylline, and cromolyn sodium.

Type-2 Hypersensitivity Reaction

In type-II reactions, the host injury is mediated by antibodies (IgG or rarely IgM) which interact with various types of antigens such as:

• Host cell surface antigens (e.g. RBC membrane antigens like blood group and Rh antigens)
• Extracellular matrix antigens or
• Exogenous antigens absorbed on host cells (e.g. a drug coating on RBC membrane).

After Ag-Ab binding occurs, the Fc region of antibody initiates the type-II reactions by the following three broad mechanisms:

Antibody (Fc) Activating Complement System

By complement-dependent cytolysis (due to MAC), inflammation (by C5a, C3a), opsonization (by C3b and C4b)

It is seen in following conditions:

• Transfusion reaction (ABO incompatibility)
• Erythroblastosis fetalis
• Autoimmune hemolytic anemia, agranulocytosis, or thrombocytopenia
• Drug-induced hemolytic anemia
• Pemphigus vulgaris
• Hyper acute graft rejection.

Antibody (FC Portion) Interacting with Fc Receptors on Target Cells

• Antibody-dependent cellular cytotoxicity (ADCC)
• Opsonization.

Antibody-Dependent Cellular Dysfunction or ADCD

Autoantibody Mediated:

• Activation of receptor, e.g. Grave’s disease
• Inhibition of receptor, e.g. Myasthenia gravis
• Other examples of ADCD:
  • Good pasture syndrome (antibody produced against type IV collagen)
  • Pernicious anemia (antibody directed against intrinsic factor)
  • Rheumatic fever (antibody against streptococcal antigens cross reacting with heart)
  • Myocarditis in Chagas disease.

Type-3 Hypersensitivity Reaction

Type-3 hypersensitivity reactions are as a result of excess formation of immune complexes (AgAb complexes) which initiate an inflammatory response through activation of complement
system leading to tissue injury:

• Localized or Arthus reaction
  • In skin: (1) following insect bites or (2) during allergic desensitization
  • In lungs (1) Farmer’s lung (Saccharopolyspora species), (2) Bird-Fancier’s disease
• Generalized or Systemic type III Reactions, e.g. Serum sickness.

Type-4 Hypersensitivity Reaction

Type-4 hypersensitivity reactions differ from other types in various ways:

• It is delayed-type (occurs after 48–72 hours of antigen exposure)
• Cell-mediated: Characteristic cells called TDTH cells are the principal mediators
• Tissue injury occurs predominantly due to activated macrophages.

Mechanism of Type-IV Reactions

• Sensitization phase (occurs 1–2 weeks following Ag exposure): APCs process and present the antigenic peptides to TH cells.
  TH cells are differentiated to TH1 cells which further differentiate to form TDTH cells
• Effector phase: The TDTH cells, on subsequent contact with the antigen, secrete variety of cytokines such as:
  • Interferon γ
    IL-2
  • MCAF (Monocyte chemotactic and activating factor)
  • TNF-β
  • MIF (migration inhibitory factor)
  • IL-3
  • GM-CSF (granulocyte-monocyte colony-stimulating factor).

Cytokines in turn perform various functions which may be either protective type or tissue damage type.