Immunodeficiencies, Hypersensitivities, and Transplant Immunology: Study Notes

Immunodeficiencies and the Immune System

Primary vs. Secondary Immunodeficiencies

Immunodeficiencies are conditions in which the immune system's ability to fight infectious disease and cancer is compromised or entirely absent. They are classified as either primary (congenital) or secondary (acquired).

• Primary Immunodeficiencies: These are genetic or developmental defects present from birth. Examples include:

  • Severe Combined Immunodeficiency (SCID): Characterized by defects in both T and B lymphocytes, leading to severe infections early in life.

  • DiGeorge Syndrome: Caused by a deletion in chromosome 22, resulting in poor development of thymus and T cells.

• Secondary Immunodeficiencies: These are acquired due to external factors such as infections, malnutrition, or medical treatments. Examples include:

  • HIV/AIDS: Human Immunodeficiency Virus destroys CD4+ T cells, leading to acquired immunodeficiency syndrome.

  • Chemotherapy-induced Immunodeficiency: Cancer treatments can suppress bone marrow function, reducing immune cell production.

Cancer and the Immune System

Cancer can be considered a failure of the immune system because immune surveillance is responsible for detecting and eliminating abnormal cells. When this process fails, cancerous cells can proliferate.

• Key Point: Tumor cells may evade immune detection by downregulating antigen presentation or secreting immunosuppressive factors.

• Example: Some cancers express PD-L1, which inhibits T cell activity.

Hypersensitivity Reactions

Types and Mechanisms

Hypersensitivity reactions are exaggerated or inappropriate immune responses to antigens. There are four main types:

• Type I (Immediate, IgE-mediated): Allergic reactions such as hay fever and anaphylaxis.

• Type II (Cytotoxic, antibody-mediated): Antibodies target cells, leading to cell destruction. Examples: hemolytic anemia, transfusion reactions.

• Type III (Immune complex-mediated): Antigen-antibody complexes deposit in tissues, causing inflammation. Examples: serum sickness, systemic lupus erythematosus.

• Type IV (Delayed, T cell-mediated): Cell-mediated responses, such as contact dermatitis and tuberculin reaction.

Type I Hypersensitivity (Allergies)

Type I hypersensitivity involves IgE antibodies binding to mast cells and basophils. Upon re-exposure to the allergen, these cells release histamine and other mediators, causing symptoms.

• Examples: Allergic rhinitis, asthma, food allergies.

• Mechanism: Sensitization phase (IgE production) followed by effector phase (mediator release).

Type II Hypersensitivity

Type II reactions involve IgG or IgM antibodies binding to antigens on cell surfaces, leading to cell destruction via complement activation or phagocytosis.

• Examples: Hemolytic disease of the newborn, autoimmune hemolytic anemia.

• Mechanism: Antibody binds to cell, complement is activated, cell is lysed.

Type III Hypersensitivity

Type III reactions occur when immune complexes (antigen-antibody) deposit in tissues, triggering inflammation and tissue damage.

• Examples: Serum sickness, post-streptococcal glomerulonephritis.

• Mechanism: Immune complexes activate complement, attracting neutrophils and causing tissue injury.

Type IV Hypersensitivity

Type IV reactions are mediated by T cells rather than antibodies. The response is delayed, typically 24-72 hours after exposure.

• Examples: Tuberculin skin test, contact dermatitis (e.g., poison ivy).

• Mechanism: Sensitized T cells release cytokines, recruiting macrophages and causing tissue damage.

Autoimmune Diseases

Mechanisms and Examples

Autoimmune diseases occur when the immune system attacks self-antigens, mistaking them for foreign invaders.

• Examples: Type I diabetes mellitus (destruction of pancreatic beta cells), rheumatoid arthritis (joint inflammation).

• Mechanism: Loss of self-tolerance due to genetic and environmental factors.

Transplantation and Graft vs. Host Disease

Transplant Rejection

Transplant rejection occurs when the recipient's immune system recognizes the transplanted tissue as foreign and mounts an immune response against it.

• Types of Rejection:

  • Hyperacute: Occurs within minutes to hours due to pre-existing antibodies.

  • Acute: Occurs within days to weeks, mediated by T cells.

  • Chronic: Occurs over months to years, involving both cellular and humoral immunity.

Graft vs. Host Disease (GVHD)

GVHD occurs when donor immune cells attack the recipient's tissues, commonly seen in bone marrow transplants.

• Symptoms: Skin rash, liver dysfunction, gastrointestinal symptoms.

• Prevention: Immunosuppressive therapy and careful donor-recipient matching.

Summary Table: Hypersensitivity Types

Type	Immune Component	Mechanism	Examples
I (Immediate)	IgE, Mast cells	Release of histamine and mediators	Allergic rhinitis, asthma
II (Cytotoxic)	IgG, IgM, Complement	Cell lysis via complement or phagocytosis	Hemolytic anemia, transfusion reaction
III (Immune Complex)	Immune complexes	Complex deposition, complement activation	Serum sickness, lupus
IV (Delayed)	T cells	Cytokine release, macrophage activation	Contact dermatitis, tuberculin test

Key Equations

• Complement Activation (Classical Pathway):

  • $C1q + IgG/IgM \rightarrow C4b2a \rightarrow C3b \rightarrow C5b-9$ (Membrane Attack Complex)

Additional info:

• Some explanations and examples were expanded for clarity and completeness.

• Table entries were inferred and summarized for study purposes.