Disorders in Immunity: Hypersensitivity, Autoimmunity, and Immunodeficiency

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Chapter 17: Disorders in Immunity

Overview

This chapter explores the major disorders of the immune system, focusing on hypersensitivity reactions, autoimmune diseases, and immunodeficiency states. 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 Allergic Reactions: Atopy and Anaphylaxis

Mechanism and Features

Type I hypersensitivity is IgE-mediated and involves mast cells and basophils.
Atopy: Chronic, local allergy (e.g., hay fever).
Anaphylaxis: Systemic, potentially fatal allergic response.
Both result from excessive IgE production in response to exogenous antigens.
Diagnosis: Detection of IgE, skin testing, and blood tests.
Treatment: Antihistamines, allergen avoidance, and controlled allergen exposure (immunotherapy).

Genetic and Environmental Factors

Genetic predisposition influences susceptibility to allergies.
The hygiene hypothesis suggests that reduced microbial exposure in early life increases allergy risk.

Type II Hypersensitivities: Reactions That Lyse Cells

Mechanism and Examples

Involves IgG or IgM antibodies and complement, leading to cell lysis.
Examples: Blood transfusion reactions, hemolytic disease of the newborn, autoimmune hemolytic anemia.

ABO Blood Group System

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: Universal donor (no A or B antigens).
Type AB: Universal recipient (no anti-A or anti-B antibodies).

Rh Factor

Rh+ (dominant) and Rh- (recessive) alleles determine Rh status.
Rh incompatibility can cause hemolytic disease of the newborn.

Type III Hypersensitivities: Immune Complex Reactions

Mechanism and Examples

Involves IgG, IgM, or IgA antibodies forming complexes with antigens, which deposit in tissues and trigger inflammation.
Requires large doses of antigen; symptoms are delayed (hours to days).
Example: Acute post-streptococcal glomerulonephritis (APSGN).

Type IV Hypersensitivities: Cell-Mediated (Delayed) Reactions

Mechanism and Examples

Primarily involve T cells; known as delayed hypersensitivity.
Symptoms arise 2-3 days after antigen exposure.
Examples: Tuberculin reaction, contact dermatitis (e.g., poison ivy), graft rejection.

Types of Grafts

Graft Type	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

Autoimmune diseases occur when the immune system attacks self-antigens.
Can be systemic (multiple organs) or organ-specific.
Examples: Systemic lupus erythematosus (SLE), rheumatoid arthritis, Graves' disease, type 1 diabetes, multiple sclerosis.

Selected Autoimmune Diseases

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	Systemic	Types II, III, IV	Joint inflammation, vasculitis, autoantibodies (rheumatoid factor), T-cell damage
Graves' disease	Thyroid	Type II	Antibodies against thyroid-stimulating hormone receptors
Type 1 diabetes	Pancreas	Type IV	Cytotoxic T cells attack insulin-producing beta cells
Multiple sclerosis	Myelin	Types II, IV	Autoantibodies and T cells attack myelin sheath, leading to neurological symptoms

Genetic and Environmental Factors

Genetic susceptibility and gender influence risk.
Molecular mimicry: Microbial antigens resemble self-antigens, triggering autoimmunity.
Gut microbiome changes may affect immune system training and tolerance.

Immunodeficiency Diseases

Primary Immunodeficiency

Present at birth; often genetic.
Examples: Agammaglobulinemia (absence of gamma globulin), DiGeorge syndrome (thymic aplasia), Severe Combined Immunodeficiency (SCID).
SCID: Dysfunction in both B and T cells; can be due to absence of lymphocyte stem cells or metabolic defects (e.g., adenosine deaminase deficiency).

Secondary Immunodeficiency

Acquired after birth; caused by infection (e.g., HIV/AIDS), metabolic disease, chemotherapy, or radiation.
HIV infects helper T cells, monocytes, macrophages, and APCs, leading to opportunistic infections and cancers.
Cancers of bone marrow or lymphoid organs (e.g., leukemia, thymus tumors) can impair immunity.

Key Terms and Concepts

Hypersensitivity: Excessive immune response to antigens.
Autoimmunity: Immune response against self-antigens.
Immunodeficiency: Reduced or absent immune function.

Equations and Immunological Principles

Complement activation (Type II hypersensitivity):

Antigen-antibody complex formation (Type III hypersensitivity):

Summary Table: Hypersensitivity Types

Type	Immune Component	Onset	Examples
I	IgE, mast cells, basophils	Immediate (minutes)	Allergy, anaphylaxis
II	IgG, IgM, complement	Minutes to hours	Transfusion reaction, hemolytic disease
III	IgG, immune complexes	Hours to days	Serum sickness, glomerulonephritis
IV	T cells	Delayed (days)	Contact dermatitis, graft rejection

Additional info: These notes synthesize textbook slides and outlines, expanding on mechanisms, examples, and clinical relevance for each immune disorder type. All tables are reconstructed and content is logically grouped for clarity.