Immune Disorders Study Guide

Immune Disorders Overview

14.1 Immune Deficiency

  • Primary Immune Deficiencies

    • Genetic conditions affecting the immune system.

    • Severe Combined Immunodeficiency (SCID)

    • Affects T1 cells and leads to severe vulnerability to infections.

    • Caused by adenosine deaminase (ADA) deficiency and DiGeorge syndrome.

    • Results in recurrent fungal, protozoan, and viral infections.

    • Lymphoid Stem Cell Disorders

    • Disorders that affect T lymphocytes include pre-T cell and pre-B cell lymphoid stem cells.

    • B Cell Deficiencies

    • Deficiencies such as agammaglobulinemia and hypogammaglobulinemia lead to recurrent bacterial infections due to inadequate antibodies.

  • Secondary Immune Deficiencies

    • Acquired immunodeficiencies due to external factors.

    • Examples:

    • AIDS: Caused by HIV that targets CD4+ T cells.

    • Cancer: Can compromise immune function.

    • Aging: Natural decline in immune efficiency.

    • Pregnancy: Physiological changes affecting immunity.

    • Immunosuppressive Therapy: Treatments that weaken the immune response.

14.2 Hypersensitivity

  • Types of Hypersensitivity Reactions:

    • Type I: IgE-mediated responses (e.g., allergies, asthma).

    • Type II: IgG/IgM-mediated cell lysis (e.g., blood transfusion reactions).

    • Type III: Immune complex-mediated reactions (e.g., serum sickness).

    • Type IV: T-cell mediated (e.g., delayed-type hypersensitivity).

Type I Hypersensitivity (Allergy)

  • Mechanism:

    • First exposure does not cause symptoms but creates memory cells.

    • Subsequent exposures trigger activation of memory response leading to:

    • IgE production.

    • Degranulation of mast cells and basophils leading to chemical mediators release (e.g., histamine).

    • Local symptoms: swelling, itching, nausea, vomiting (due to increased peristalsis).

    • Systemic symptoms: airway obstruction, hives, drops in blood pressure.

  • Atopy:

    • Genetic predisposition to develop allergic reactions.

    • Affects 10-30% of the population.

    • Influenced by genetic and environmental factors (e.g., microbiome hypothesis).

  • Anaphylaxis:

    • A severe, systemic allergic reaction.

Mechanism Detail

  • Sensitization Process:

    1. Allergen exposure via dendritic cells.

    2. Activation of allergen-specific Th2 cells, and the release of cytokines (IL-4, IL-5).

    3. B cells produce allergen-specific IgE.

    4. IgE binds to mast cells causing degranulation, releasing mediators:

    • Histamine, leukotrienes, cytokines, prostaglandins, and platelet activating factor (PAF).

  • Symptoms from Chemical Mediators:

    • Histamine: increases blood vessel permeability, leading to swelling and redness.

    • Leukotrienes: cause bronchoconstriction and mucus buildup, complicating asthma.

Therapy for Type I Hypersensitivity

  • Diagnosis:

    • Skin tests for allergens.

  • Common Treatments:

    • Antihistamines (e.g., Benadryl - Diphenhydramine Hydrochloride): provides relief for sneezing, runny nose, itchy throat, and watery eyes.

    • Desensitization/Vaccination: decreasing IgE levels and increasing IgG levels against allergen.

14.3 Types of Hypersensitivity

  • Type II Hypersensitivity (ABO & Rh):

    • Antigen-antibody reactions lead to cell agglutination and lysis during blood transfusion mismatches.

    • ABO Blood Group:

    • Determined by A & B antigens on red blood cells.

    • Type O is universal donor; Type AB is universal recipient due to the absence of anti-A/B antibodies.

  • Rh Factor:

    • Important in pregnancy where an Rh- mother carries an Rh+ fetus, resulting in potential hemolytic disease of the newborn (HDN).

    • Treatment: RhoGAM administration to prevent maternal anti-Rh antibody production.

  • Type III Hypersensitivity:

    • Immune complex formation leads to local inflammation and tissue damage.

    • Examples include Arthus reactions (localized) and systemic serum sickness from animal serum.

  • Type IV Hypersensitivity (DTH):

    • T-cell mediated responses like contact dermatitis from poison ivy and tuberculin skin tests.

Tissue Transplantation

  • Rejection Mechanisms: T cells react against non-self MHC (major histocompatibility complex).

    • Types of grafts:

    • Autograft: from the same individual.

    • Isograft: from genetically identical twin.

    • Allograft: from a genetically different organism of the same species.

    • Xenograft: from a different species.

    • Graft-versus-host disease (GVHD): A severe complication post-transplantation where transplanted immune cells attack host tissues.

  • Critical Thinking Question:

    • How can preimplantation genetic diagnosis (PGD) improve allograft success rates?

Autoimmunity

  • Self-antigens triggering immune response against the body’s own tissues.

  • Understanding autoimmune disorders is essential for recognizing how the immune system can misinterpret body cells as foreign.