Disorders Associated with the Immune System: Hypersensitivity, Autoimmunity, Transplantation, and HIV/AIDS

Disorders Associated with the Immune System

Hypersensitivity

Hypersensitivity refers to an exaggerated or inappropriate immune response that results in tissue damage. These reactions are classified into four main types based on their mechanisms and timing.

• Definition: Hypersensitivity is an antigenic response beyond what is considered normal, leading to tissue injury.

• Types: Type I (Anaphylactic), Type II (Cytotoxic), Type III (Immune Complex), Type IV (Delayed Cell-Mediated).

Type I Hypersensitivity: Anaphylaxis

Anaphylaxis is a rapid, severe allergic reaction mediated by IgE antibodies. It can be systemic or localized.

• Mechanism: Upon first exposure, allergens stimulate IgE production, which binds to mast cells and basophils. Upon re-exposure, the allergen cross-links IgE, triggering release of histamine and other mediators.

• Systemic Anaphylaxis: A severe, life-threatening reaction affecting multiple organ systems (e.g., anaphylactic shock).

• Localized Anaphylaxis: Reactions limited to a specific tissue or organ (e.g., hay fever, asthma).

• Allergy Skin Tests: Small amounts of allergen are introduced into the skin to detect hypersensitivity by observing localized swelling or redness.

• Desensitization: Repeated exposure to increasing doses of allergen to induce production of blocking IgG antibodies, which neutralize the allergen before it binds to IgE.

Type II Hypersensitivity: Cytotoxic Reactions

Cytotoxic reactions involve IgG or IgM antibodies directed against cell surface antigens, leading to cell destruction.

• Mechanism: Antibodies bind to antigens on target cells, activating complement and leading to cell lysis or phagocytosis.

• Drug-Induced Cytotoxicity: Some drugs bind to cell surfaces, forming new antigens that elicit an immune response.

ABO and Rh Blood Group Systems

• ABO System: Based on presence or absence of A and B antigens on red blood cells. Incompatible transfusions cause hemolysis.

• Rh System: Presence (Rh+) or absence (Rh-) of the Rh antigen. Rh incompatibility can cause hemolytic disease of the newborn.

• Blood Transfusions: Must match both ABO and Rh types to prevent immune reactions.

Type III Hypersensitivity: Immune Complex Reactions

Immune complex reactions occur when antigen-antibody complexes deposit in tissues, causing inflammation and tissue damage.

• Mechanism: Excess antigen-antibody complexes activate complement, attracting neutrophils that release enzymes and cause tissue injury.

Type IV Hypersensitivity: Delayed Cell-Mediated Reactions

These reactions are mediated by T cells and occur hours to days after exposure to antigen.

• Mechanism: Sensitized T cells release cytokines upon re-exposure to antigen, recruiting macrophages and causing tissue damage.

• Examples: Contact dermatitis (e.g., poison ivy), tuberculin skin test.

Self-Tolerance and Autoimmunity

Self-tolerance is the immune system's ability to avoid attacking the body's own tissues. Failure leads to autoimmune diseases.

• Mechanism for Self-Tolerance: Elimination or inactivation of self-reactive lymphocytes during development.

• Examples of Autoimmune Diseases:

  • Cytotoxic: Autoimmune hemolytic anemia

  • Immune Complex: Systemic lupus erythematosus

  • Cell-Mediated: Type 1 diabetes mellitus

HLA Complex and Transplantation

The Human Leukocyte Antigen (HLA) complex encodes cell-surface proteins important for immune recognition and tissue compatibility.

• Importance: HLA matching is crucial for successful organ and tissue transplants; mismatches increase risk of rejection.

• Transplant Rejection: Occurs when recipient's immune system attacks transplanted tissue as foreign.

• Privileged Sites: Body sites (e.g., cornea, brain) where immune responses are limited, reducing risk of rejection.

• Stem Cells in Transplantation: Used to regenerate tissues and reduce rejection risk due to their ability to differentiate and modulate immune responses.

Types of Grafts

Type	Definition
Autograft	Tissue transplanted from one site to another in the same individual
Isograft	Tissue transplanted between genetically identical individuals (e.g., identical twins)
Allograft	Tissue transplanted between genetically different members of the same species
Xenotransplantation	Tissue transplanted between different species

• Graft-versus-Host Disease (GVHD): Occurs when transplanted immune cells attack the recipient's tissues.

• Prevention of Rejection: Immunosuppressive drugs (e.g., cyclosporine) are used to reduce immune responses against transplants.

Immune Response to Cancer and Immunotherapy

The immune system can recognize and destroy some cancer cells, but tumors may evade immune detection.

• Immune Evasion: Cancer cells may lack antigens, secrete immunosuppressive factors, or induce tolerance.

• Immunotherapy Examples:

  • Monoclonal antibodies targeting tumor antigens

  • Immune checkpoint inhibitors

Immunodeficiencies

Immunodeficiencies are disorders in which part of the immune system is missing or dysfunctional.

• Congenital Immunodeficiencies: Present at birth due to genetic defects (e.g., Severe Combined Immunodeficiency, SCID).

• Acquired Immunodeficiencies: Develop later in life due to infections (e.g., HIV), malnutrition, or immunosuppressive therapy.

Emerging Infectious Diseases

New or increasing infectious diseases can arise due to changes in pathogens, environment, or human behavior.

• Examples: HIV/AIDS, SARS, COVID-19

HIV/AIDS

HIV Attachment and Entry

HIV infects host cells by binding to CD4 receptors and co-receptors (CCR5 or CXCR4) on T helper cells.

• Attachment: The viral gp120 protein binds to CD4 and a co-receptor, allowing fusion and entry into the cell.

HIV Evasion of Immune Response

• Mechanisms:

  • High mutation rate of HIV envelope proteins

  • Latency in host cells

Stages of HIV Infection

• Acute Infection: Flu-like symptoms, high viral load

• Clinical Latency: Asymptomatic period with ongoing viral replication

• AIDS: Severe immunodeficiency, opportunistic infections, and cancers

Effects of HIV on the Immune System

• Destruction of CD4+ T Cells: Leads to impaired cell-mediated and humoral immunity

Diagnosis of HIV Infection

• Methods: Detection of anti-HIV antibodies (ELISA, Western blot), viral RNA (PCR)

HIV Transmission and Epidemiology

• Routes: Sexual contact, blood transfusion, sharing needles, mother-to-child

• Geographic Patterns: Highest prevalence in sub-Saharan Africa; global distribution varies by region and risk factors

Prevention and Treatment of HIV Infection

• Prevention: Safe sex practices, needle exchange, screening blood products, antiretroviral prophylaxis

• Treatment: Combination antiretroviral therapy (ART) to suppress viral replication and restore immune function