Disorders in Immunity: Hypersensitivity, Autoimmunity, and Immunodeficiency

Chapter 17: Disorders in Immunity

Introduction

This chapter explores the major disorders of the immune system, focusing on hypersensitivity reactions, autoimmune diseases, and immunodeficiency. Understanding these conditions is essential for microbiology students, as they illustrate the consequences of both overactive and underactive immune responses.

The Immune Response: A Two-Sided Coin

Immunopathology

• Immunopathology is the study of disease states associated with abnormal immune responses, including both overreactivity and underreactivity.

• Overreactivity leads to allergy, hypersensitivity, and autoimmunity.

• Underreactivity results in immunodeficiency diseases, where immune function is incomplete, suppressed, or destroyed.

Overview of Disorders of the Immune System

Classification

• Primary Immunodeficiency: Congenital, often genetic, such as Severe Combined Immunodeficiency (SCID).

• Secondary Immunodeficiency: Acquired after birth, e.g., AIDS.

• Hypersensitivities: Overactive immune responses, classified into four types.

Hypersensitivity States

Types and Mechanisms

Type	Systems and Mechanisms Involved	Examples
Type I: Immediate hypersensitivity	IgE mediated; involves mast cells, basophils, and allergic mediators	Anaphylaxis, allergies such as hay fever, asthma
Type II: Antibody-mediated	IgG, IgM antibodies plus complement act upon cells and cause cell lysis; includes some autoimmune diseases	Blood group incompatibility, pernicious anemia, myasthenia gravis
Type III: Immune complex-mediated	Antibody-mediated inflammation, circulating IgG complexes deposited in basement membranes of target organs; includes some autoimmune diseases	Systemic lupus erythematosus, rheumatoid arthritis, serum sickness, rheumatic fever
Type IV: T-cell-mediated	Delayed hypersensitivity and cytotoxic reactions in tissues; includes some autoimmune diseases	Infection reactions, contact dermatitis, graft rejection

Type I Hypersensitivity: Atopy and Anaphylaxis

Mechanism and Clinical Features

• Type I hypersensitivity is an immediate allergic reaction mediated by IgE antibodies.

• Common allergens include pollen, food, insect venom, animal dander, and drugs.

• Atopy refers to chronic, local allergies (e.g., hay fever), while anaphylaxis is a systemic, potentially fatal reaction.

• Genetic predisposition plays a role; family history increases risk.

• Diagnosis involves detection of IgE, skin testing, and blood tests.

• Treatment includes antihistamines, allergen avoidance, and controlled allergen exposure (immunotherapy).

Type II Hypersensitivity: Reactions That Lyse Cells

Mechanism and Examples

• Involves IgG or IgM antibodies binding to cell surfaces, activating complement, and causing cell lysis.

• Examples: Blood transfusion reactions, hemolytic disease of the newborn, autoimmune hemolytic anemia.

• ABO blood group system is crucial in transfusion compatibility.

Blood Type	Antigen Present	Antibody in Plasma
A	A	Anti-B
B	B	Anti-A
AB	A and B	Neither anti-A nor anti-B
O	Neither A nor B	Anti-A and anti-B

• Type O is the universal donor; type AB is the universal recipient.

• Rh factor (D antigen) is another important determinant in transfusion and pregnancy.

Type III Hypersensitivity: Immune Complex Reactions

Mechanism and Examples

• Involves formation of antigen-antibody complexes (IgG, IgM, or IgA) that deposit in tissues, triggering inflammation.

• Requires large doses of antigen; symptoms are delayed (hours to days).

• Examples: Post-streptococcal glomerulonephritis, systemic lupus erythematosus, rheumatoid arthritis.

Type IV Hypersensitivity: Cell-Mediated (Delayed) Reactions

Mechanism and Examples

• Primarily involves T cells responding to antigens on self tissues or transplanted cells.

• Symptoms arise 2-3 days after exposure.

• Examples: Tuberculin reaction, contact dermatitis (e.g., poison ivy), graft rejection.

Type of Graft	Description
Autograft	Tissue transplanted within the same individual
Isograft	Tissue from an identical twin
Allograft	Tissue from a genetically different individual of the same species
Xenograft	Tissue from a different species

Autoimmunity

Mechanism and Examples

• Occurs when the immune system mounts an abnormal response against self antigens.

• Can be systemic (affecting multiple organs) or organ-specific.

• Genetic and environmental factors contribute to susceptibility.

• Molecular mimicry: Microbial antigens resemble self antigens, leading to cross-reactivity.

Disease	Target	Type of Hypersensitivity	Characteristics
Systemic lupus erythematosus (SLE)	Systemic	Type III	Inflammation of many organs; autoantibodies against blood cells, platelets, and DNA
Rheumatoid arthritis	Joints (systemic)	Types II, III, IV	Vasculitis, joint damage, autoantibodies (rheumatoid factor), T-cell involvement
Graves' disease	Thyroid	Type II	Antibodies stimulate thyroid hormone receptors, causing hyperthyroidism
Type 1 diabetes	Pancreas	Type IV	Cytotoxic T cells attack insulin-producing beta cells
Multiple sclerosis	Myelin sheath	Types II and IV	Autoantibodies and T cells damage myelin, leading to neurological symptoms

Immunodeficiency Diseases

Primary and Secondary Immunodeficiencies

• Primary immunodeficiencies are congenital, often due to genetic errors (e.g., SCID, DiGeorge syndrome).

• Secondary immunodeficiencies are acquired after birth, caused by infection (e.g., HIV/AIDS), chemotherapy, radiation, or metabolic disease.

• B-cell deficiencies lead to recurrent bacterial infections; T-cell deficiencies result in severe opportunistic infections and cancer risk.

• SCID involves dysfunction in both B and T cells, often due to absence of lymphocyte stem cells or metabolic defects (e.g., adenosine deaminase deficiency).

• HIV infects helper T cells, monocytes, macrophages, and APCs, leading to profound immunosuppression.

Key Terms and Concepts

• Allergen: Substance that triggers an allergic response.

• Antibody: Protein produced by B cells that binds to antigens.

• Complement: Group of proteins that enhance immune responses and cell lysis.

• Autoantibody: Antibody directed against self antigens.

• Immunodeficiency: Reduced or absent immune function.

Important Equations

• Complement Activation (Classical Pathway):

$ext{C1} + ext{Antigen-Antibody Complex} \rightarrow ext{C4} \rightarrow ext{C2} \rightarrow ext{C3} \rightarrow ext{C5} \rightarrow ext{Membrane Attack Complex}$

• Blood Type Genotype-Phenotype Relationships:

$ext{Genotype:} \quad AA \text{ or } AO \rightarrow \text{Type A}$ $ext{Genotype:} \quad BB \text{ or } BO \rightarrow \text{Type B}$ $ext{Genotype:} \quad AB \rightarrow \text{Type AB}$ $ext{Genotype:} \quad OO \rightarrow \text{Type O}$

Summary Table: Hypersensitivity Types

Type	Antibody/Cell Involved	Onset	Examples
I	IgE	Immediate (minutes)	Hay fever, asthma, anaphylaxis
II	IgG, IgM + complement	Minutes to hours	Transfusion reactions, hemolytic anemia
III	IgG complexes	Hours to days	Lupus, rheumatoid arthritis
IV	T cells	2-3 days (delayed)	Contact dermatitis, graft rejection

Conclusion

Disorders of immunity encompass a wide range of conditions resulting from abnormal immune responses. Mastery of these concepts is essential for understanding clinical microbiology and the impact of immune dysfunction on human health.