Disorders Associated with the Immune System (Chapter 19): Hypersensitivity, Autoimmunity, and Transplantation

Disorders Associated with the Immune System

Introduction

This chapter explores the mechanisms and clinical implications of immune system disorders, focusing on hypersensitivity reactions, autoimmune diseases, and transplantation immunology. Understanding these processes is essential for recognizing how the immune system can malfunction and the consequences for human health.

Hypersensitivity

Definition and Overview

• Hypersensitivity: An antigenic response beyond normal, occurring when an individual is sensitized by previous exposure to an antigen (allergen).

• Four major types: Anaphylactic (Type I), Cytotoxic (Type II), Immune Complex (Type III), and Delayed Cell-Mediated (Type IV).

• Hygiene hypothesis: Suggests that reduced exposure to pathogens may lower immune tolerance and increase susceptibility to harmless antigens.

Types of Hypersensitivity

Type of Reaction	Time Before Clinical Signs	Characteristics	Examples
Type I (Anaphylactic)	2-30 min	IgE binds to mast cells/basophils, degranulation releases mediators (histamine, leukotrienes, prostaglandins)	Anaphylactic shock, hay fever, asthma
Type II (Cytotoxic)	5-12 hours	IgG/IgM antibodies activate complement, causing cell lysis or damage	Transfusion reactions, hemolytic disease of the newborn
Type III (Immune Complex)	3-8 hours	Immune complexes deposit in tissues, activate complement, cause inflammation	Arthus reaction, serum sickness
Type IV (Delayed Cell-Mediated)	24-48 hours	Antigens activate T cells, which target cells	Contact dermatitis, tissue rejection

Type I (Anaphylactic) Reactions

• Occurs minutes after re-exposure to antigen in sensitized individuals.

• Antigens combine with IgE antibodies, which attach to mast cells and basophils.

• Degranulation releases mediators:

  • Histamine: Increases blood capillary permeability.

  • Leukotrienes: Cause prolonged contraction of smooth muscles.

  • Prostaglandins: Affect smooth muscle and increase mucus secretion.

Systemic anaphylaxis (anaphylactic shock): Can result in circulatory collapse and death; treated with epinephrine. Localized anaphylaxis: Associated with ingested/inhaled antigens; symptoms depend on entry route (e.g., hives, hay fever, asthma).

Preventing Anaphylactic Reactions

• Skin tests: Antigens inoculated beneath the epidermis to test for rapid inflammatory reaction (wheal).

• Desensitization: Increasing dosages of antigen injected beneath the skin to produce IgG (blocking antibodies) that intercept and neutralize antigens.

Type II (Cytotoxic) Reactions

Mechanism

• Activation of complement by IgG or IgM antibodies binding to antigenic cells, causing cell lysis or damage by macrophages.

ABO Blood Group System

• Antibodies form against carbohydrate antigens on RBCs: A antigens, B antigens, or both.

• Type O RBCs have no antigens.

Blood Group	Erythrocyte Antigens	Plasma Antibodies	Cells That Can Be Received	Frequency (%)
A	A	Anti-B	A, O	41
B	B	Anti-A	B, O	10
AB	A and B	None	A, B, AB, O	4
O	None	Anti-A, Anti-B	O	45

Universal donor: Type O Universal acceptor: Type AB

Rh Blood Group System and Hemolytic Disease of the Newborn (HDNB)

• Rh factor antigen (Rh+) found on RBCs of 85% of the population.

• Rh+ blood given to Rh- recipient stimulates anti-Rh antibodies.

• HDNB: Rh- mother with Rh+ fetus produces anti-Rh antibodies; subsequent Rh+ fetus is at risk for antibody-mediated RBC destruction.

Drug-Induced Cytotoxic Reactions

• Thrombocytopenic purpura: Platelets combine with drugs, forming antigenic complexes; antibody and complement destroy platelets.

• Agranulocytosis: Drug-induced immune destruction of granulocytes.

• Hemolytic anemia: Drug-induced immune destruction of RBCs.

Type III (Immune Complex) Reactions

Mechanism

• Antibodies form against soluble antigens in serum, creating immune complexes that lodge in basement membranes beneath cells.

• Immune complexes activate complement, causing inflammation.

• Glomerulonephritis: Inflammatory damage to kidney glomeruli due to immune complexes.

Type IV (Delayed Cell-Mediated) Reactions

Mechanism

• Cell-mediated immune responses caused by T cells (delayed hypersensitivity).

• Antigens are phagocytized and presented to T cell receptors, causing sensitization.

• Reexposure to antigen causes memory T cells to release destructive cytokines.

Allergic Contact Dermatitis

• Haptens combine with skin proteins, producing an immune response.

• Common allergens: poison ivy (urushiol), cosmetics, metals, latex.

• Symptoms: Blistering, raised red rash, itching, burning; contact dermatitis tends to burn and be more painful than itchy.

Autoimmune Diseases

Overview

• Immune system responds to self-antigens, causing organ damage.

• Autoimmunity: Loss of self-tolerance (ability to discriminate self from nonself).

• Three types: Cytotoxic, Immune complex, Cell-mediated.

Cytotoxic Autoimmune Reactions

• Multiple sclerosis: Antibodies, T cells, and macrophages attack myelin sheath of nerves, interfering with nerve transmission and forming scar tissue (sclerosis).

• Graves' disease: Abnormal antibodies in the thyroid produce excessive hormones.

• Myasthenia gravis: Antibodies coat acetylcholine receptors; muscles fail to receive nerve signals.

Immune Complex Autoimmune Reactions

• Systemic lupus erythematosus: Immune complexes form in kidney glomeruli.

• Rheumatoid arthritis: Immune complexes form in joints.

Cell-Mediated Autoimmune Reactions

• Insulin-dependent diabetes mellitus: T cell destruction of insulin-secreting cells.

• Psoriasis and psoriatic arthritis: Autoimmune disorders of the skin.

Reactions Related to the Human Leukocyte Antigen (HLA) Complex

Overview

• Histocompatibility antigens: Self antigens on cell surfaces.

• Major histocompatibility complex (MHC): Genes encoding histocompatibility antigens.

• Human leukocyte antigen (HLA) complex: MHC genes in humans.

• Certain HLAs are associated with increased susceptibility to specific diseases.

Disease	Increased Risk with HLA	Description
Inflammatory diseases	HLA-DR2	Rheumatoid arthritis, multiple sclerosis
Endocrine diseases	HLA-DR3, HLA-DR4	Insulin-dependent diabetes mellitus
Malignant disease	HLA-DR1, HLA-DR3	Cancer of lymph nodes

HLA Typing and Transplantation

• HLA typing identifies and compares HLAs using standardized antisera or monoclonal antibodies.

• Donor and recipient must be matched by tissue typing for transplant surgery.

Reactions to Transplantation

• Transplants may be attacked by T cells, macrophages, and complement-fixing antibodies.

• Transplants to privileged sites and privileged tissues (e.g., cornea, heart valves) do not cause immune response.

Stem Cells

• Stem cells: Master cells capable of generating many different cell types.

• Embryonic stem cells (ESCs): Harvested from blastocysts; pluripotent (can generate all cell types).

• Adult stem cells: Found in differentiated adult tissues; can become induced pluripotent stem cells by gene introduction.

Types of Grafts

• Autograft: Use of one's own tissue.

• Isograft: Use of identical twin's tissue.

• Allograft: Use of tissue from another person.

• Xenotransplantation product: Use of nonhuman tissue; must overcome hyperacute rejection (response to nonhuman antigens).

Graft-versus-host (GVH) disease: Can result from transplanted bone marrow containing immunocompetent cells.

Key Terms and Concepts

• Allergen: An antigen that causes hypersensitivity.

• Degranulation: Release of chemical mediators from mast cells/basophils.

• Blocking antibody: Antibody (usually IgG) that intercepts and neutralizes antigens.

• Self-tolerance: Ability of the immune system to recognize self-antigens and not attack them.

• Privileged site: An anatomical location where transplanted tissue is not likely to elicit an immune response.