Lecture Notes on Hypersensitivity

Overview of Hypersensitivity

• Hypersensitivity: Immune system damages the body rather than protecting it.
• Four types of hypersensitivities.
• Type II Hypersensitivity: Known as cytotoxic hypersensitivity, involves antibody-mediated destruction of healthy cells.

Characteristics of Type II Hypersensitivity

• Tissue-specific: Antibodies target specific tissues or organs.
• Contrasts with Type III hypersensitivities, which are systemic.

Immune System Function

• Central Tolerance: Process that destroys self-reactive immune cells in primary lymphoid organs (Thymus for T cells, Bone marrow for B cells).
• Escape of Self-reactive Cells: Leads to autoimmune diseases.

Mechanisms in Type II Hypersensitivity

• Activation of B cells: Produces IgM or IgG antibodies with CD4 positive T helper cells' help.
• Antigens Involved:
  • Intrinsic: Antigen normally produced by host cells.
  • Extrinsic: Antigen from external sources (e.g., infection, medication like penicillin).

Cytotoxic Mechanisms

1. Complement System Activation:

   • Antigen-antibody complexes form.
   • C1 binds to Fc portion of antibody, activating complement proteins (C2-C9).
   • Cleaved fragments (C3a, C4a, C5a) attract neutrophils, leading to cell damage and tissue destruction.
   • Examples: Hemolytic anemia, thrombocytopenia, neutropenia, Goodpasture’s syndrome.

2. Membrane Attack Complex (MAC):

   • MAC forms a channel in the cell membrane, causing lysis and cell death.
   • Example: Autoimmune hemolytic anemia, detected by direct Coomb’s test.

3. Opsonization:

   • C3b binds to IgG-coated cells, marking them for phagocytosis.
   • Phagocytes in the spleen engulf and destroy opsonized cells.

4. Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC):

   • Natural killer cells recognize Fc tail of antibody and release toxic granules.
   • Perforins and granzymes cause apoptotic cell death without inflammation.

Non-cytotoxic Mechanisms

• Antibody-Mediated Cellular Dysfunction:
  • Antibody binding disrupts cell function.
  • Myasthenia Gravis: Antibodies block acetylcholine receptor, weakening muscles.
  • Grave’s Disease: Antibodies cause overproduction of thyroid hormone, leading to hyperthyroidism.

Key Points

• Type II hypersensitivity is antibody-mediated.
• Generally leads to cytotoxicity.
• Tissue-specific reactions.