Immune Disorders: Hypersensitivity and Autoimmunity

Immune Disorders

Overview of Hypersensitivity and Autoimmunity

Immune disorders arise when the immune system's response is either exaggerated or misdirected, leading to tissue damage or dysfunction. Two major categories are hypersensitivity reactions and autoimmune diseases. Hypersensitivity refers to inappropriate or excessive immune responses to antigens, while autoimmunity involves immune attacks against the body's own tissues.

Types of Hypersensitivity Reactions

Classification and Characteristics

There are four main types of hypersensitivity reactions, each with distinct mechanisms, time courses, and cellular mediators. Understanding these types is crucial for diagnosing and managing immune-related diseases.

Type	Name	Cause	Time Course	Characteristic Cells Involved
I	Immediate hypersensitivity	Antibody (mainly IgE) on sensitized cells interacts with allergens, causing degranulation	After initial sensitization, seconds to minutes	Previously sensitized mast cells or basophils
II	Cytotoxic hypersensitivity	Antibodies and complement lyse target cells	Minutes to hours	Plasma cells secrete antibodies that act against other body cells
III	Immune complex–mediated hypersensitivity	Nonphagocytized complexes of antibody and antigen trigger complement activation, leading to inflammation	Several hours	Neutrophils
IV	Delayed (cell-mediated) hypersensitivity	T cells attack the body's cells	Several days	Activated T cells

Type I (Immediate) Hypersensitivity

Type I hypersensitivity, also known as anaphylactic or allergic reactions, occurs rapidly after exposure to an allergen. It involves the release of inflammatory mediators from mast cells and basophils that have been sensitized by IgE antibodies.

• Key Point: Allergens are antigens that provoke allergic responses.

• Examples: Pollen, dust mites, and certain foods are common allergens.

Mechanism: Sensitization and Degranulation

• Sensitization: Initial exposure to an allergen leads to IgE production, which binds to mast cells and basophils.

• Degranulation: Upon subsequent exposure, the allergen cross-links IgE on these cells, triggering the release of histamine and other mediators.

Type II (Cytotoxic) Hypersensitivity

Type II hypersensitivity involves the destruction of cells by antibodies (usually IgG or IgM) and complement. This reaction is central to certain autoimmune diseases and transfusion reactions.

• Key Point: Antibodies bind to antigens on the surface of target cells, leading to cell lysis.

• Examples: Hemolytic transfusion reactions, hemolytic disease of the newborn (Rh incompatibility).

ABO Blood Group and Transfusion Reactions

Transfusion of incompatible blood can result in antibody-mediated destruction of donor red blood cells.

ABO Blood Group	ABO Antigen(s) Present	Antibodies Present	Can Donate To	Can Receive From
A	A	Anti-B	A or AB	A or O
B	B	Anti-A	B or AB	B or O
AB	A and B	None	AB	A, B, AB, or O (universal recipient)
O	None	Both anti-A and anti-B	A, B, AB, or O (universal donor)	O

Rh System and Hemolytic Disease of the Newborn

The Rh antigen is present in most humans. If an Rh-negative mother carries an Rh-positive fetus, she may develop antibodies that attack fetal red blood cells in subsequent pregnancies, causing hemolytic disease of the newborn. Administration of RhoGAM prevents this response.

Type III (Immune Complex–Mediated) Hypersensitivity

Type III hypersensitivity is caused by the formation of immune complexes (antigen-antibody complexes) that deposit in tissues, triggering inflammation and tissue damage.

• Key Point: Immune complexes activate complement and attract neutrophils, leading to tissue injury.

• Examples: Systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), glomerulonephritis.

Type IV (Delayed or Cell-Mediated) Hypersensitivity

Type IV hypersensitivity is mediated by T cells rather than antibodies. The response is delayed, typically appearing 12–24 hours after antigen exposure.

• Key Point: T cells and macrophages are the main effectors, causing tissue damage at the site of antigen exposure.

• Examples: Tuberculin skin test, contact dermatitis, graft rejection.

Autoimmune Diseases

Overview and Causes

Autoimmune diseases occur when the immune system attacks the body's own tissues. These diseases are more common in the elderly and in women. The mechanisms underlying autoimmunity are complex and multifactorial.

• Key Point: Autoimmunity may result from the production of autoantibodies or cytotoxic T cells against self-antigens.

• Examples: Type I diabetes, rheumatoid arthritis, lupus, multiple sclerosis.

Hypotheses for the Causes of Autoimmunity

• Estrogen may stimulate cytotoxic T cell activity against self-tissues.

• Maternal or fetal cells crossing the placenta may trigger autoimmunity later in life.

• Environmental factors, such as viral infections, may initiate autoimmune responses.

• Genetic predisposition, especially certain MHC genes, increases risk.

• T cells may encounter self-antigens that are normally hidden from the immune system.

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

• Failure of normal immune regulatory mechanisms.

Criteria for a Good Vaccine

Key Features of Effective Vaccines

• Induces a strong and lasting immune response (immunogenicity).

• Provides long-term protection (memory response).

• Is safe, with minimal side effects.

• Is stable and easy to administer.

• Is affordable and accessible to the target population.

• Does not cause disease in immunized individuals.

Summary Table: Hypersensitivity Types

Type	Mechanism	Example Diseases
I	IgE-mediated, mast cell degranulation	Allergies, anaphylaxis
II	Antibody-mediated cytotoxicity	Hemolytic anemia, transfusion reactions
III	Immune complex deposition	Lupus, rheumatoid arthritis
IV	T cell-mediated, delayed response	Contact dermatitis, graft rejection