Disorders of the Immune System: Hypersensitivity, Immunodeficiency, and Autoimmunity

Disorders of the Immune System

Overview of Immune System Disorders

Disorders of the immune system are classified into three main categories: hypersensitivity, immunodeficiency, and autoimmune disorders. Each category reflects a distinct malfunction in immune regulation, leading to various clinical consequences.

• Hypersensitivity disorders: Immune system overreacts, causing tissue damage.

• Immunodeficiency disorders: One or more components of the immune system fail, increasing susceptibility to infections.

• Autoimmune disorders: Immune system attacks self antigens, damaging the body’s own tissues.

Hypersensitivity Disorders

Types of Hypersensitivity

Hypersensitivity disorders are conditions in which the immune response causes tissue damage. There are four types, classified by the immune components involved:

• Type I: Immediate hypersensitivity (allergies)

• Type II: Antibody-mediated hypersensitivity

• Type III: Immune complex–mediated hypersensitivity

• Type IV: Delayed-type hypersensitivity (DTH)

Type I: Immediate Hypersensitivity (Allergies)

Type I hypersensitivity is the most common and is known as allergies. It occurs when an individual reacts to a foreign antigen (allergen) such as pollen, dust mites, pet dander, peanuts, shellfish, or bee venom.

• First exposure: Allergen binds to B cell, triggering differentiation into plasma cells that secrete IgE antibodies.

• Sensitization: IgE molecules bind to mast cells and basophils, sensitizing them.

• Subsequent exposures: Allergen binds to IgE on sensitized cells, causing rapid response within minutes.

• Degranulation: Cross-linking of IgE triggers release of inflammatory mediators (histamine, leukotrienes, prostaglandins).

• Symptoms: Vasodilation, increased capillary permeability, smooth muscle spasm, runny nose, itchy eyes, hives, asthma, and potentially anaphylactic shock.

Anaphylactic Shock

Anaphylactic shock is a severe, systemic reaction involving widespread release of histamine and other mediators. It causes:

• Severe smooth muscle spasm in the respiratory tract

• Systemic vasodilation and drop in blood pressure

• Increased capillary permeability and body-wide swelling

• Potentially fatal without immediate treatment (epinephrine injection)

Treatments for Allergies

• Antihistamines: Block histamine receptors, limiting symptoms; may cause drowsiness.

• Antileukotriene agents: Block leukotriene synthesis, reducing inflammation.

• Corticosteroids: Inhibit synthesis of leukotrienes and prostaglandins; used for asthma and severe allergies.

• Allergen immunotherapy: Gradual exposure to allergen to induce tolerance and reduce IgE response.

Type II: Antibody-Mediated Hypersensitivity

Type II reactions occur when antibodies produced against foreign antigens also bind to self antigens. Examples include:

• Penicillin binding to erythrocytes, altering antigens and triggering complement-mediated lysis.

• Mismatched blood transfusions (ABO/Rh incompatibility).

• Failure to destroy self-reactive B cells, leading to autoimmunity.

Type III: Immune Complex–Mediated Hypersensitivity

Type III reactions are mediated by immune complexes (soluble antigens bound to antibodies) that are not easily cleared by phagocytes. These complexes deposit in tissues such as kidneys, blood vessels, joints, and brain, causing inflammation and tissue damage.

Type IV: Delayed-Type Hypersensitivity (DTH)

Type IV hypersensitivity is mediated by T cells, not antibodies. TH cells recognize antigens bound to MHC molecules and recruit macrophages, causing tissue destruction. The reaction takes 2–3 days to manifest.

• Contact dermatitis: Skin reaction to allergens like poison ivy, metals, or chemicals.

• Tuberculin skin test: Used to detect exposure to Mycobacterium tuberculosis by observing DTH response.

Immunodeficiency Disorders

Types of Immunodeficiency

Immunodeficiency disorders result from decreased function of immune components. They are classified as:

• Primary immunodeficiencies: Genetic or developmental defects affecting innate or adaptive immunity.

• Secondary immunodeficiencies: Acquired through infection, trauma, cancer, or medications.

Primary Immunodeficiency

• Deficient complement proteins or abnormal phagocytes increase risk for bacterial and parasitic infections.

• Hypogammaglobulinemias: Decreased antibody types.

• Severe combined immunodeficiency (SCID): Failure of lymphoid cell lines, affecting B, T, and NK cells; low lymphocyte levels and thymus development failure.

Secondary Immunodeficiency

• Often induced to combat cancers or prevent transplant rejection.

• Most common cause: AIDS, caused by HIV-1.

AIDS and HIV-1

AIDS is caused by HIV-1, a retrovirus that targets CD4+ cells (mainly TH cells). The virus uses reverse transcriptase to integrate its genome into host DNA, leading to cell lysis and further infection.

• Acute phase: Sharp decline in TH cells, rise in HIV-1 virions, flu-like symptoms.

• Chronic phase: Antibody production, slight TH cell recovery, decline in virions; lasts years.

• Final phase (AIDS): Progressive TH cell loss, increased virions, recurrent infections, and cancers (e.g., Kaposi’s sarcoma).

• Drug therapies: Inhibit reverse transcriptase, block viral enzymes, or prevent viral entry; administered as combination therapy.

Autoimmune Disorders

Mechanisms of Autoimmunity

Autoimmune disorders occur when self-reactive T or B cells attack self antigens, producing autoantibodies. Several mechanisms can lead to autoimmunity:

• Release of sequestered antigens: Trauma or infection exposes antigens not previously encountered by T cells (e.g., myelin protein in multiple sclerosis).

• Molecular mimicry: Foreign antigens resemble self antigens, activating T cells (e.g., rheumatic fever after streptococcal infection).

• Inappropriate expression of class II MHC: Activates T cells against normal self antigens (e.g., type 1 diabetes mellitus).

• Nonspecific activation of B cells: Pathogens induce cytokine production, leading to autoantibody formation (e.g., systemic lupus erythematosus).

Summary Table: Types of Immune System Disorders

Disorder Type	Main Mechanism	Examples
Hypersensitivity	Overreaction of immune system	Allergies, asthma, anaphylactic shock
Immunodeficiency	Failure of immune components	SCID, AIDS
Autoimmunity	Attack on self antigens	Multiple sclerosis, lupus, type 1 diabetes

Additional info: Expanded explanations and examples were added for clarity and completeness.