Immune Disorders: Hypersensitivities, Autoimmunity, and Immunodeficiency

Immune Disorders

Overview of Immune Disorders

Immune disorders arise when the immune system malfunctions, leading to exaggerated, insufficient, or misdirected immune responses. These disorders are broadly categorized into hypersensitivities, autoimmune diseases, and immunodeficiencies.

Hypersensitivities

Definition and Types

Hypersensitivity refers to an exaggerated immune response against a foreign antigen, resulting in tissue damage. There are four main types:

• Type I (Immediate): IgE-mediated, rapid onset (allergies)

• Type II (Cytotoxic): Antibody-mediated destruction of cells

• Type III (Immune Complex-Mediated): Immune complex deposition and inflammation

• Type IV (Delayed or Cell-Mediated): T cell-mediated, delayed response

Type I (Immediate) Hypersensitivity

Type I hypersensitivity develops within minutes of exposure to an allergen and is commonly known as an allergy. It involves the production of IgE antibodies, which bind to mast cells, basophils, and eosinophils, leading to the release of inflammatory mediators upon re-exposure to the allergen.

• Allergens: Antigens that trigger allergic reactions

• Genetic predisposition: Susceptibility to allergies is often inherited

• Hygiene hypothesis: Reduced early-life immune stimulation increases allergy risk

Mechanism of Type I Hypersensitivity

1. Sensitization: Initial exposure leads to IgE production

2. Degranulation: Re-exposure causes release of histamine and other mediators

Inflammatory Molecules Released from Mast Cells

Molecule	Role in Hypersensitivity Reactions
Histamine	Causes smooth muscle contraction, increased vascular permeability, and irritation
Kinins	Cause smooth muscle contraction, inflammation, and irritation
Proteases	Damage tissues and activate complement
Leukotrienes	Cause slow, prolonged smooth muscle contraction, inflammation, and increased vascular permeability
Prostaglandins	Some contract smooth muscle; others relax it

Clinical Manifestations

• Localized reactions: Hay fever, asthma, hives (urticaria)

• Systemic reactions: Anaphylactic shock, requiring immediate treatment with epinephrine

Diagnosis, Prevention, and Treatment

• Diagnosis: Detection of allergen-specific IgE (e.g., ImmunoCAP test), skin testing

• Prevention: Allergen avoidance, immunotherapy (allergy shots)

• Treatment: Antihistamines, glucocorticoids, bronchodilators, epinephrine for severe reactions

Type II (Cytotoxic) Hypersensitivity

Type II hypersensitivity involves the destruction of cells by antibodies and complement. It is responsible for transfusion reactions and hemolytic disease of the newborn.

• ABO blood group incompatibility: Transfusion of incompatible blood leads to hemolysis

• Rh incompatibility: Rh-negative mothers may develop antibodies against Rh-positive fetal cells

Type III (Immune Complex-Mediated) Hypersensitivity

Type III hypersensitivity is caused by the formation of immune complexes that deposit in tissues, activating complement and causing inflammation and tissue damage. Examples include hypersensitivity pneumonitis, glomerulonephritis, rheumatoid arthritis, and systemic lupus erythematosus (SLE).

• Localized reactions: Hypersensitivity pneumonitis, glomerulonephritis

• Systemic reactions: Rheumatoid arthritis, SLE

Type IV (Delayed or Cell-Mediated) Hypersensitivity

Type IV hypersensitivity is mediated by T cells and occurs 12–24 hours after antigen exposure. It includes contact dermatitis, the tuberculin skin test, and graft rejection.

• Tuberculin test: Used to diagnose exposure to Mycobacterium tuberculosis

• Contact dermatitis: Skin rash caused by contact with allergens (e.g., poison ivy, latex)

• Graft rejection: Immune response against transplanted tissues or organs

Autoimmune Diseases

Overview and Causes

Autoimmune diseases occur when the immune system attacks the body's own tissues due to a breakdown in self-tolerance. They can be systemic or organ-specific and are influenced by genetic, hormonal, and environmental factors.

• Systemic: Affect multiple organs (e.g., SLE)

• Single-organ: Target specific organs (e.g., type 1 diabetes, Graves disease, multiple sclerosis)

Examples

• Autoimmune hemolytic anemia: Antibodies against red blood cells cause anemia

• Type 1 diabetes mellitus: Immune destruction of pancreatic islet cells

• Graves disease: Antibodies stimulate thyroid hormone production

• Multiple sclerosis: Cytotoxic T cells destroy myelin in the nervous system

Immunodeficiency Diseases

Types and Causes

Immunodeficiency diseases result from defective immune mechanisms and are classified as primary (congenital) or secondary (acquired).

• Primary immunodeficiencies: Genetic or developmental defects present from birth

• Secondary immunodeficiencies: Result from external factors such as infections (e.g., HIV), malnutrition, or immunosuppressive drugs

Acquired Immunodeficiency Syndrome (AIDS)

AIDS is caused by infection with the human immunodeficiency virus (HIV), which targets CD4+ T cells, leading to severe immune suppression and susceptibility to opportunistic infections and cancers.

• HIV characteristics: Enveloped, +ssRNA retrovirus; uses reverse transcriptase

• Transmission: Blood, semen, vaginal secretions, breast milk

• Diagnosis: Detection of HIV antibodies (ELISA, Western blot), low CD4+ T cell count, presence of opportunistic infections

• Treatment: Antiretroviral therapy (ART) reduces viral replication but does not cure infection

• Prevention: Safe sex, clean needles, screening blood products, pre-exposure prophylaxis

Summary Table: Characteristics of Hypersensitivity Types

Type	Name	Cause	Time Course	Characteristic Cells
I	Immediate hypersensitivity	IgE against soluble antigen	After initial sensitization, seconds to minutes	Mast cells, basophils, eosinophils
II	Cytotoxic hypersensitivity	IgG or IgM against cell surface antigen	Minutes to hours	Phagocytes, NK cells
III	Immune complex-mediated hypersensitivity	Immune complexes of antibody and antigen	Several hours	Neutrophils
IV	Delayed (cell-mediated) hypersensitivity	T cells attack body cells	Several days	Activated T cells