Diseases of the Immune System: Hypersensitivities, Autoimmunity, Transplantation, and HIV/AIDS

Diseases of the Immune System

Overview of Hypersensitivity Responses

Hypersensitivity responses are exaggerated or inappropriate immune reactions that cause tissue damage. They are classified into four main types based on the immune mechanisms involved.

• Hypersensitivity: An abnormal immune response to an antigen that results in tissue injury.

• Hygiene Hypothesis: Suggests that a lack of early childhood exposure to infectious agents increases susceptibility to allergic and autoimmune diseases by suppressing natural development of the immune system.

Type I Hypersensitivity: Anaphylactic Reactions

Type I reactions are immediate allergic responses mediated by IgE antibodies. They can be systemic or localized.

• Systemic Anaphylaxis: A severe, rapid allergic reaction that can be life-threatening (e.g., anaphylactic shock from bee stings or peanuts).

• Localized Anaphylaxis: Reactions limited to specific tissues (e.g., hay fever, asthma, food allergies).

• Food Allergies: Allergic reactions to specific proteins in foods, often resulting in gastrointestinal or systemic symptoms.

• Desensitization: Repeated exposure to small amounts of allergen to reduce sensitivity.

Type II Hypersensitivity: Cytotoxic Reactions

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

• Transfusion Reactions: Occur when incompatible blood types are mixed, causing hemolysis.

• Hemolytic Disease of the Newborn: Maternal antibodies attack fetal red blood cells due to Rh incompatibility.

• Drug-Induced Cytotoxic Reactions: Some drugs bind to cell surfaces, triggering immune destruction. Examples include:

  • Thrombocytopenic Purpura: Platelet destruction leading to bleeding.

  • Agranulocytosis: Destruction of white blood cells.

  • Hemolytic Anemia: Destruction of red blood cells.

Type III Hypersensitivity: Immune Complex Reactions

Type III reactions occur when antigen-antibody complexes deposit in tissues, causing inflammation and tissue injury.

• Glomerulonephritis: Immune complexes deposit in kidney glomeruli, leading to inflammation and impaired function.

Type IV Hypersensitivity: Delayed Cell-Mediated Reactions

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

• Contact Dermatitis: Skin inflammation caused by contact with allergens (e.g., poison ivy, nickel).

Autoimmune Diseases

Autoimmune diseases result from the immune system attacking self-antigens. They are classified by the mechanism of tissue injury.

• Cytotoxic Autoimmune Reactions: Antibodies target self-cells (e.g., Multiple sclerosis).

• Immune Complex Autoimmune Reactions: Immune complexes deposit in tissues (e.g., Graves’ disease, Myasthenia gravis, Systemic lupus erythematosus, Rheumatoid arthritis).

• Cell-Mediated Autoimmune Reactions: T cells attack self-tissues (e.g., Type I diabetes mellitus, Psoriasis).

Human Leukocyte Antigen (HLA) and Tissue Typing

HLA molecules are cell surface proteins essential for immune recognition. Tissue typing matches donor and recipient HLAs to reduce transplant rejection.

• HLA: Human version of the major histocompatibility complex (MHC).

• Tissue Typing: Laboratory testing to match HLAs for transplantation.

Privileged Sites and Tissues

Some body sites and tissues are less likely to elicit immune responses.

• Privileged Site: Area where immune responses are limited (e.g., eyes, brain).

• Privileged Tissue: Tissue that can be transplanted with minimal immune rejection (e.g., cornea).

Types of Tissue Grafts

Term	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 Product	Tissue transplanted from a different species (e.g., pig heart valve to human)

Graft-vs-Host Disease (GVHD)

GVHD occurs when transplanted immune cells attack the recipient’s tissues, common in bone marrow transplants.

Immunosuppression in Transplantation

Immunosuppressive drugs are used to prevent graft rejection but increase susceptibility to infections and cancer.

• Unwanted Side Effects: Increased risk of infection, malignancy, and drug toxicity.

Stem Cells in Transplantation

Stem cells may reduce transplant rejection and repair damaged tissues.

• Pluripotent Stem Cells: Can differentiate into almost any cell type.

• Multipotent Stem Cells: Can differentiate into a limited range of cell types.

Immune Response to Cancer

The immune system can recognize and destroy cancer cells, but tumors may evade detection. Immunotherapies and vaccines are being developed to enhance anti-tumor immunity.

Role of the Microbiome in Immune Health

The normal microbiome educates and regulates the immune system.

• Hygiene Hypothesis: Reduced microbial exposure may increase autoimmune and allergic diseases.

• Dysbiosis: Imbalance in the microbiome linked to disease.

• Treatment Options for Dysbiosis:

  • Fecal transplant

  • Therapeutic worms (helminth therapy)

Immunodeficiencies

Immunodeficiencies are conditions where the immune system’s ability to fight infection is compromised.

• Congenital Immunodeficiencies: Present at birth due to genetic defects.

• Acquired Immunodeficiencies: Develop later in life due to infections, drugs, or other causes (e.g., HIV/AIDS).

HIV/AIDS

Discovery and Opportunistic Infections

HIV/AIDS was first recognized due to unusual infections such as Pneumocystis pneumonia and Kaposi sarcoma in immunocompromised individuals.

Structure of HIV

• RNA Virus: HIV contains two copies of single-stranded RNA.

• Retrovirus: Uses reverse transcriptase to convert RNA into DNA.

• gp120 and gp41 Spikes: Surface proteins that bind to CD4 receptors on T helper cells, facilitating viral entry.

HIV Infection: Active vs Latent

• Active Infection: Virus replicates and destroys T cells.

• Latent Infection: Viral DNA integrates into host genome and remains dormant.

HIV Mutation Rate

HIV has a high mutation rate due to error-prone reverse transcriptase, complicating immune response and vaccine development.

Stages of HIV Infection

Stage	Description
Stage 1	Asymptomatic or persistent lymphadenopathy
Stage 2	Steady decline of CD4+ T cells; minor symptoms
Stage 3 (AIDS)	Severe immunodeficiency; opportunistic infections; CD4+ T cell count < 200/µL

Criteria for AIDS Diagnosis

• CD4+ T cell count below 200 cells/µL

• Presence of specific opportunistic infections or cancers

HIV Evasion of the Immune System

• High mutation rate alters viral antigens

• Latency in host cells

• Destruction of immune cells

HIV Transmission and Prevention

• Transmission: Blood, sexual contact, mother-to-child, contaminated needles

• Prevention: Safe sex practices, screening blood products, needle exchange programs, antiretroviral therapy for pregnant women

Challenges in HIV Vaccine Development

• High genetic variability of HIV

• Latency and integration into host genome

• Immune evasion mechanisms

Additional info: This guide expands on the learning objectives with academic context, definitions, and examples for clarity and exam preparation.