Immune Disorders Study Notes

Immune Disorders

Immunodeficiency

  • Definition: A state of reduced immune response against pathogens or foreign substances, leading to a greater susceptibility to infections.

    • Categories:

    • Neutrophil disorders: Impairment of neutrophil function which affects the body's ability to respond to infections.

    • Antibody deficiency: Lack of antibody production leading to increased risk of infections.

    • Complement deficiency: Reduced complement proteins leading to diminished opsonization and lysis of pathogens.

    • T-cell dysfunction: Impairs the adaptive immune response and can lead to susceptibility to opportunistic infections.

Hypersensitivities

  • Definition: An exaggerated immune response against a foreign antigen that is beyond normal limits.

  • Types:

    • Type I (Immediate)

    • Type II (Cytotoxic)

    • Type III (Immune Complex-mediated)

    • Type IV (Delayed or Cell-mediated)

Type I Hypersensitivity

  • Characteristics:

    • Response: Immediate reaction occurring seconds to minutes following exposure to an allergen.

    • Mechanism:

    • Multi-step process consisting of:

      • Sensitization: Initial exposure to allergen leads to the activation of T-helper cells (Th2).

    • Degranulation: Upon subsequent exposure, sensitized mast cells and basophils release inflammatory mediators like histamine, cytokines, and leukotrienes.

  • Clinical Examples: Anaphylaxis, hay fever, hives.

Degranulation Process

  1. Initial Exposure:

    • Antigen Presentation: Antigen-presenting cells (APCs) process and present antigens to Th2 cells via MHC-II.

    • Activation of B cells: IL-4 from Th2 cells activates B cells to produce IgE antibodies.

    • Binding of IgE: These IgE molecules bind to mast cells and basophils.

  2. Subsequent Exposure:

  • Degranulation occurs upon re-exposure, leading to the release of substances including:

    • Histamine: Causes smooth muscle contraction and increased vascular permeability.

    • Kinins: Induce inflammation and irritation.

    • Prostaglandins: Mediate prolonged smooth muscle contraction and inflammation.

Type II Hypersensitivity (Cytotoxic)

  • Definition: A form of hypersensitivity where antibodies lead to the destruction of cells.

  • Mechanism: Involves antibodies targeting specific antigens on cell surfaces, leading to cell lysis via complement or phagocytosis.

  • Examples: Hemolytic disease of the newborn, transfusion reactions.

Type III Hypersensitivity (Immune Complex-mediated)

  • Definition: Caused by the formation of immune complexes (antigen-antibody complexes) which can cause localized or systemic inflammatory responses.

    • Examples: Hyper-sensitivity pneumonitis, glomerulonephritis, systemic lupus erythematosus (SLE).

Type IV Hypersensitivity (Delayed or Cell-Mediated)

  • Definition: Inflammatory response that occurs 12–24 hours after contact with certain antigens.

  • Mechanism: Involves the activation of memory T cells and macrophages.

  • Examples: Tuberculin response, allergic contact dermatitis, graft rejection.

Autoimmune Diseases

  • Causes: Autoimmunity arises when the immune system mistakenly attacks the body's own cells, often influenced by genetic, environmental, and hormonal factors.

  • Categories:

    • Systemic autoimmune diseases (e.g., lupus)

    • Single-organ autoimmune diseases (e.g., type 1 diabetes)

  • Examples:

    • Autoimmune hemolytic anemia: Antibodies against red blood cells leading to anemia.

    • Graves’ disease: Overproduction of thyroid hormones due to autoimmune reaction against thyroid gland.

    • Multiple sclerosis (MS): Destruction of myelin sheaths around neurons leading to neurological symptoms.

Immunodeficiency Diseases

  • Types:

    • Primary Immunodeficiency Diseases: Result from genetic or developmental flaws, usually evident in infancy or early childhood.

    • Examples: Chronic granulomatous disease, severe combined immunodeficiency disease (SCID), DiGeorge syndrome.

    • Acquired Immunodeficiency Diseases: Develop later due to environmental factors, infections, or malignancies.

    • Example: Acquired Immunodeficiency Syndrome (AIDS).

  • Opportunistic infections associated with AIDS: Coccidioidomycosis, Kaposi's sarcoma, candidiasis, and others.

Treatment and Management of Conditions

  • Type I Hypersensitivity:

    • Prevent and Treat:

    • Identify and avoid allergens.

    • Use antihistamines to neutralize histamine.

    • Epinephrine for severe reactions.

  • Type II Hypersensitivity: Blood transfusion matching to prevent reactions.

  • Type III Hypersensitivity: Anti-inflammatory medications for conditions like RA.

  • Type IV Hypersensitivity: Corticosteroids for severe allergic reactions and transplant rejection.

Immunosuppressive Drugs

  • Classes:

    • Glucocorticoids (e.g. prednisone): Anti-inflammatory; reduce the activity of the immune system.

    • Cytotoxic drugs (e.g. azathioprine): Kill or inhibit lymphocyte functions.

    • Cyclosporine: Inhibits T cell activation.

    • Lymphocyte-depleting therapies: Monoclonal antibodies targeting T cells.