Hypersensitivity; Definition and classification; Type I, II, III, IV and V hypersensitivity, mechanism, diagnosis and treatment.

 Hypersensitivity is an exaggerated or excessive immune response to a normally harmless substance or antigen. This heightened immune reaction can lead to tissue damage and various clinical manifestations. Hypersensitivity reactions are classified into four main types (Type I, II, III, and IV), with a fifth category (Type V) sometimes mentioned for completeness. Each type of hypersensitivity has distinct mechanisms, clinical presentations, and approaches to diagnosis and treatment.

Type I Hypersensitivity (Immediate Hypersensitivity):

• Mechanism: In Type I hypersensitivity, exposure to an allergen triggers the release of IgE antibodies. These antibodies bind to mast cells and basophils, leading to their activation. Subsequent exposure to the same allergen cross-links IgE on mast cells, causing the release of inflammatory mediators like histamine.
• Clinical Presentation: Immediate symptoms include hives, itching, rhinitis, asthma, and anaphylaxis.
• Diagnosis: Skin prick tests, blood tests for specific IgE antibodies, and clinical history help diagnose Type I hypersensitivity.
• Treatment: Management involves allergen avoidance, antihistamines, corticosteroids, and in severe cases, epinephrine for anaphylaxis.

Type II Hypersensitivity (Cytotoxic Hypersensitivity):

• Mechanism: Type II hypersensitivity involves the binding of antibodies (IgG or IgM) to antigens on cell surfaces. This leads to cell destruction via complement activation or phagocytosis.
• Clinical Presentation: Examples include hemolytic anemia, autoimmune hemolytic anemia, and drug-induced immune thrombocytopenia.
• Diagnosis: Laboratory tests, such as direct and indirect Coombs tests, are used for diagnosis.
• Treatment: Management depends on the underlying condition and may include removing the trigger (e.g., discontinuing the drug causing the reaction) and immunosuppressive therapy.

Type III Hypersensitivity (Immune Complex-Mediated Hypersensitivity):

• Mechanism: Type III hypersensitivity involves the formation of immune complexes between antibodies (usually IgG or IgM) and antigens in circulation. These complexes can deposit in tissues, leading to inflammation and tissue damage.
• Clinical Presentation: Examples include systemic lupus erythematosus (SLE), rheumatoid arthritis, and serum sickness.
• Diagnosis: Clinical evaluation, serological tests, and biopsy may be used to diagnose Type III hypersensitivity.
• Treatment: Management focuses on controlling the underlying condition, often using immunosuppressive drugs.

Type IV Hypersensitivity (Delayed-Type Hypersensitivity):

• Mechanism: Type IV hypersensitivity is mediated by T cells (primarily CD4+ and CD8+ T cells) rather than antibodies. Upon exposure to antigens, T cells activate and release cytokines, leading to inflammation and tissue damage.
• Clinical Presentation: Delayed-type reactions typically occur 24-72 hours after exposure and include contact dermatitis, tuberculin skin tests, and organ transplant rejection.
• Diagnosis: Skin patch tests and clinical evaluation are used to diagnose Type IV hypersensitivity.
• Treatment: Management depends on the underlying condition and may involve topical or systemic corticosteroids, immunosuppressive drugs, or allergen avoidance.

Type V Hypersensitivity:

• Mechanism: Type V hypersensitivity is a less well-defined category that includes diseases where autoantibodies stimulate receptors or other cellular components in an abnormal and chronic manner.
• Clinical Presentation: Examples include Graves' disease, where autoantibodies stimulate thyroid hormone production.
• Diagnosis: Diagnosis is based on clinical and laboratory findings specific to the underlying condition.
• Treatment: Management is directed at controlling the autoimmune condition and may include medications like antithyroid drugs for Graves' disease.

In summary, hypersensitivity reactions are exaggerated immune responses to various triggers. Understanding their classification, mechanisms, clinical presentations, diagnosis, and treatment is essential for managing these conditions effectively. Treatment strategies often focus on reducing the immune response and addressing the underlying cause or trigger.