Immune System Disorders: Deficiencies, Autoimmunity, and Hypersensitivities

Immune System Disorders

Immune Deficiencies and Autoimmunity

Immune system disorders encompass conditions where the immune response is either insufficient or inappropriately targets self-tissues. These disorders are classified as immunodeficiencies or autoimmune diseases, each with distinct etiologies and clinical manifestations.

• Primary Immunodeficiency: Congenital, often genetic, defects affecting immune factors. Over 300 disorders exist, ranging from manageable to life-threatening. Examples include DiGeorge syndrome (chromosome 22 deletion, impaired thymus development).

• Secondary Immunodeficiency: Acquired due to aging, chronic disease, infectious agents, or medical interventions (e.g., chemotherapy, corticosteroids). More common than primary forms.

• Therapies: Bone marrow transplants, antibody administration, cytokine therapies, and experimental treatments (e.g., gene therapy).

• Immune Deficiency and Cancer: The immune system also surveils for abnormal cells. Deficiencies increase cancer risk (e.g., HIV patients, transplant recipients).

Autoimmune Disorders

Autoimmunity arises when the immune system attacks healthy self-tissues, leading to chronic conditions. Etiology involves genetic predisposition and environmental triggers, such as infectious agents.

• Examples: Celiac disease, Lupus, Diabetes mellitus, Rheumatoid arthritis, Multiple sclerosis, Graves’ disease.

• Systemic vs. Localized: Systemic disorders affect multiple tissues; localized disorders target specific tissues.

• Diagnosis: Detection of autoantibodies or self-reactive immune cells, supported by hematological tests.

• Management: Immune suppression and anti-inflammatory therapies; no cures or preventions currently exist.

Hypersensitivities

Definition and Classification

Hypersensitivities are inappropriate immune responses, including allergies and autoimmunity. They may be localized or systemic. The Gell and Coombs classification system divides hypersensitivities into four types, remembered by the mnemonic "ACID":

• Type I (Allergy/Immediate): IgE-mediated, rapid onset (e.g., allergic rhinitis, atopic asthma).

• Type II (Cytotoxic): IgG/IgM-mediated, targets cell-surface antigens (e.g., hemolytic anemia, Goodpasture syndrome).

• Type III (Immune Complex): IgG/IgM-mediated, immune complexes deposit in tissues (e.g., serum sickness, lupus).

• Type IV (Delayed): T cell-mediated, manifests 12–72 hours after exposure (e.g., contact dermatitis, transplant rejection).

The Hygiene Hypothesis

The hygiene hypothesis suggests that reduced microbial exposure in developed nations alters immune development, increasing allergy and autoimmunity risk.

Type I Hypersensitivities (Allergy and Atopic Asthma)

Mechanism and Clinical Features

Type I hypersensitivities involve IgE production in response to harmless antigens (allergens). Sensitization leads to IgE binding mast cells; subsequent exposure triggers degranulation and symptoms.

• Risk Factors: Family history, route of exposure, and IgE levels.

• Symptoms: Respiratory distress, skin manifestations (hives, pruritus), gastrointestinal symptoms.

• Anaphylaxis: Systemic, life-threatening reaction requiring epinephrine.

Diagnosis and Management

Diagnosis relies on clinical history, blood tests for IgE titers, and skin tests (wheal and flare lesions). Management includes allergen avoidance, antihistamines, steroidal drugs, and desensitization immunotherapy for severe cases.

Type II Hypersensitivities (Cytotoxic and Noncytotoxic)

Mechanism and Examples

Type II reactions occur when IgG or IgM bind to cell-surface antigens, leading to complement activation, cell lysis, or receptor modulation.

• Cytotoxic: Complement-mediated cell lysis (e.g., hemolytic transfusion reactions).

• Noncytotoxic: Antibody-receptor interactions (e.g., Myasthenia gravis, Graves’ disease).

Blood Groups and Transfusion Compatibility

Blood type is determined by surface antigens (A, B, O, Rh). Incompatible transfusions cause hemolytic reactions, which are potentially fatal.

Hemolytic Disease of the Newborn (HDN)

HDN occurs when an Rh-negative mother develops antibodies against Rh-positive fetal blood cells, leading to fetal anemia. Prevention involves Rh immunoglobulin administration.

Type III Hypersensitivities (Immune Complex)

Mechanism and Clinical Features

Type III reactions result from excessive antibody-antigen complexes depositing in tissues, triggering complement activation and inflammation.

• Autoimmune Examples: Lupus, rheumatoid arthritis.

• Nonautoimmune Examples: Serum sickness from antivenoms or antitoxins.

• Treatment: Anti-inflammatory drugs and antihistamines.

Type IV Hypersensitivities (Delayed, T Cell-Mediated)

Mechanism and Examples

Type IV reactions are mediated by T cells, manifesting hours to days after antigen exposure. They are responsible for tissue-specific destruction in autoimmune diseases and nonautoimmune reactions.

• Autoimmune: Guillain-Barré syndrome, Hashimoto thyroiditis, Type 1 diabetes, Multiple sclerosis, Celiac disease.

• Nonautoimmune: Tuberculin skin test, contact dermatitis, transplant rejection, graft-versus-host disease.

• Therapies: Corticosteroids, cytokine blockers.

Transplant Rejection and Immune Privilege

Transplant rejection is mediated by T cytotoxic cells. Grafts are classified as autografts, isografts, allografts, or xenografts. Immune-privileged sites (eye, brain, uterus, testicles) are less likely to be rejected. Graft-versus-host disease may occur in bone marrow transplants.

Clinical Case Example

Latex Allergy Progression

A case study illustrates the progression from contact dermatitis (Type IV hypersensitivity) to systemic anaphylaxis (Type I hypersensitivity) and the development of cross-reactive food allergies. Diagnosis involves clinical history, allergen testing, and management through avoidance and medical therapy.

Summary Table: Hypersensitivity Types

Type	Immune Mechanism	Examples	Key Features
I (Immediate)	IgE-mediated	Allergy, atopic asthma, anaphylaxis	Rapid onset, mast cell degranulation
II (Cytotoxic)	IgG/IgM-mediated	Hemolytic anemia, Goodpasture syndrome	Cell lysis, complement activation
III (Immune Complex)	IgG/IgM + soluble antigen	Lupus, serum sickness	Immune complex deposition, inflammation
IV (Delayed)	T cell-mediated	Contact dermatitis, transplant rejection	Delayed onset, tissue-specific destruction