Hypersensitivity Types I & II

• Hypersensitivity is an altered immune response to an antigen, leading to host damage or disease.
• Sensitization to antigens can vary in speed among individuals.
• Hypersensitivity reactions can be immediate (minutes to hours) or delayed (hours to days).
• Hypersensitivity is classified by antigen source (allergy, autoimmunity, alloimmunity) and disease mechanism (Types I-IV).
• Hypersensitivity mechanisms are interrelated and can occur simultaneously.

Type I: IgE-Mediated Reactions

• Type I reactions involve tissue mast cells and are commonly associated with environmental allergies.
• Histamine is the most potent mediator, causing bronchial constriction, increased vascular permeability, edema, and vasodilation.
• H2 receptors can decrease histamine release and increase gastric secretion.
• Antihistamines can mitigate Type I responses by blocking histamine receptors.

Type II: Tissue-Specific Reactions

• Type II reactions target specific cells or tissues.
• Symptoms vary depending on the affected tissue or organ.
• IgG or IgM antibodies can trigger the complement cascade, leading to cell destruction via the classical pathway.
• Macrophages may phagocytize target cells, causing destruction.

Type III: Immune Complex-Mediated Reactions

• Type III reactions involve antigen-antibody complexes deposited in vessel walls or tissues.
• Complement activation, particularly the generation of chemotactic factors for neutrophils, is a harmful effect.
• Neutrophils release granules and toxic oxygen products, damaging healthy tissue while trying to phagocytize, especially when combined with toxic oxygen products from target cells.
• Raynaud’s phenomenon, caused by temperature-dependent immune complex deposition, is an example of a Type III reaction.
• Immune complex precipitates block circulation, causing pallor, numbness, cyanosis, and potentially gangrene.

Type IV: Cell-Mediated Reactions

• Type IV reactions are cell-mediated by cytotoxic T lymphocytes and do not involve antibodies.
• Tissue destruction results from Tc cell toxins or factors like lysosomal enzymes and reactive oxygen species from macrophages.
• Graft rejection and allergic contact reactions (e.g., poison ivy) are examples of Type IV hypersensitivity.

Fifth Mechanism

• The fifth mechanism involves antibodies modulating target cell function without destroying the cell.
• Antibodies can prevent ligand interactions, replace ligands, or eliminate receptors.
• Myasthenia Gravis, where antibodies bind to Ach receptors at the neuromuscular junction, exemplifies this mechanism.

Allergy

• Allergy refers to the harmful effects of hypersensitivity to environmental antigens.

Autoimmunity

• Autoimmunity is a disturbance in self-antigen immunologic tolerance.
• Autoimmune diseases often result from a breakdown in peripheral tolerance.
• Systemic lupus erythematosus, where autoantibodies target nucleic acids and other self-components, is an example.
• Lupus can cause congenital heart defects or pregnancy loss.
• Mild lupus is treated with NSAIDs; serious cases use antimalarials, immunosuppressants, or IVIg.

Alloimmunity

• Alloimmunity occurs when one individual's immune system reacts against another's tissues or organs.
• Examples include transplants, skin grafts, blood transfusions, and reactions to a fetus during pregnancy.

Transfusion Reactions

• Type A blood has Type B antibodies; transfusion with Type B or AB blood causes a severe reaction and erythrocyte destruction.
• Type O individuals lack A and B antigens, making them universal donors.
• Type AB individuals lack anti-A and anti-B antibodies, making them universal recipients.

Immune Deficiency

• Immune deficiency is a failure of self-defense mechanisms, increasing infection susceptibility.
• Primary (congenital) immune deficiency is caused by genetic anomalies.
• Secondary (acquired) immune deficiency results from illness or aging and is more common.
• Pregnancy, though immunocompromised, does not significantly alter infection rates.
• Other secondary deficiencies can be caused by psychological stress, dietary issues, chronic diseases, malignancies, physical trauma etc.

Replacement Therapies for Immune Deficiencies

• Gamma-globulin
• Transplantation and Transfusion
• Immune Modulators via Gene Therapy