Immune Disorders: Hypersensitivity and Autoimmunity

Immune Disorders

Overview of Immune Disorders

Immune disorders arise when the immune system malfunctions, leading to exaggerated, misdirected, or uncontrolled immune responses. These disorders include hypersensitivity reactions and autoimmune diseases, which can cause significant tissue damage and pathology.

Hypersensitivity Reactions

Definition and Classification

Hypersensitivity refers to any immune response against a foreign antigen that is exaggerated beyond the norm. There are four major types of hypersensitivity reactions, each with distinct mechanisms, time courses, and clinical manifestations.

Type	Name	Cause	Time Course	Characteristic Cells Involved
I	Immediate hypersensitivity	Antibody (mainly IgE) on sensitized cells interacts with antigen, 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, inflammation, and neutrophil damage	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 hypersensitivity, is a rapid, localized or systemic reaction resulting from the release of inflammatory molecules in response to an antigen. The antigens that trigger this response are called allergens. Common examples include pollen, dust mites, and certain foods.

• Mechanism: Develops within seconds or minutes after exposure to an allergen.

• Two-step process:

  1. Sensitization: Initial exposure to allergen leads to IgE production and binding to mast cells or basophils.

  2. Degranulation: Subsequent exposure causes cross-linking of IgE, leading to release of histamine and other mediators.

• Clinical manifestations: Allergic rhinitis, asthma, anaphylaxis.

Examples of Allergens

• Pollen grains

• Mold spores

• House dust mites

Type II (Cytotoxic) Hypersensitivity

Type II hypersensitivity occurs when antibodies target and destroy cells, often with the help of complement. This type is involved in several autoimmune diseases and transfusion reactions.

• Mechanism: Antibodies bind to antigens on cell surfaces, leading to cell lysis via complement activation or antibody-dependent cellular cytotoxicity.

• Examples:

  • Destruction of blood cells after incompatible blood transfusion

  • Hemolytic disease of the newborn (Rh incompatibility)

ABO Blood Group Compatibility

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

Type III (Immune Complex–Mediated) Hypersensitivity

Type III hypersensitivity is caused by the formation of immune complexes (antigen-antibody complexes) that are not efficiently cleared. These complexes deposit in tissues, triggering inflammation and tissue damage.

• Mechanism: Immune complexes activate complement and attract neutrophils, leading to inflammation and tissue injury.

• Examples:

  • Hypersensitivity pneumonitis

  • Glomerulonephritis

  • Systemic lupus erythematosus (SLE)

  • Rheumatoid arthritis (RA)

Type IV (Delayed or Cell-Mediated) Hypersensitivity

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

• Mechanism: Antigen-presenting cells activate T cells, which then mediate inflammation and tissue damage.

• Examples:

  • Tuberculin response (e.g., Mantoux test for tuberculosis)

  • Contact dermatitis (e.g., poison ivy)

  • Graft rejection

Autoimmune Diseases

Overview and Causes

Autoimmune diseases occur when the immune system mistakenly targets and attacks the body's own tissues. These diseases are more common in the elderly and in women. The exact causes are complex and multifactorial, involving genetic, hormonal, and environmental factors.

• Possible causes:

  • Estrogen may stimulate cytotoxic T cell activity

  • Maternal or fetal cells crossing the placenta

  • Environmental triggers (e.g., viral infections)

  • Genetic predisposition (e.g., certain MHC genes)

  • Exposure of hidden self-antigens

  • Molecular mimicry by microorganisms

  • Failure of immune regulation mechanisms

Examples of autoimmune diseases: Type I diabetes, rheumatoid arthritis, multiple sclerosis, lupus, inflammatory bowel disease (IBD), and possibly Alzheimer's disease.

Criteria for a Good Vaccine

Key Features of Effective Vaccines

A good vaccine should provide long-lasting protection with minimal side effects. It should be safe, stable, and easy to administer.

• Induces strong and long-lasting immunity

• Safe with minimal adverse effects

• Stable and easy to store/transport

• Cost-effective and accessible

• Capable of inducing both humoral and cellular immune responses

• Minimal risk of causing disease in immunized individuals

Summary Table: Hypersensitivity Types

Type	Mechanism	Time Course	Examples
I	IgE-mediated degranulation of mast cells/basophils	Seconds to minutes	Allergies, anaphylaxis
II	Antibody-mediated cell destruction	Minutes to hours	Transfusion reactions, hemolytic disease of the newborn
III	Immune complex deposition and inflammation	Several hours	SLE, RA, glomerulonephritis
IV	T cell-mediated tissue damage	12–24 hours or more	Contact dermatitis, graft rejection