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

Chapter 19 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.

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).

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

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

• Desensitization: Gradual exposure to increasing amounts of allergen to reduce sensitivity.

Type II Hypersensitivity: Cytotoxic Reactions

Type II reactions involve antibody-mediated destruction of cells, often through complement activation.

• Transfusion Reactions: Occur when incompatible blood types are mixed, leading to 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.

  • Thrombocytopenic Purpura: Platelet destruction leading to bleeding.

  • Agranulocytosis: Destruction of white blood cells (granulocytes).

  • 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 damage.

• Glomerulonephritis: Immune complexes deposit in kidney glomeruli, causing 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 important for immune recognition and tissue compatibility.

• Tissue Typing: Matching HLA antigens between donor and recipient to reduce transplant rejection.

Privileged Sites and Tissues

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

• Privileged Site: An anatomical location with reduced immune surveillance (e.g., eye, brain).

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

Tissue Grafts and Transplantation

Grafts are classified based on the genetic relationship between donor and recipient.

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

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

• Immunosuppression: Used to prevent graft rejection but increases risk of infection and cancer.

• Stem Cells in Transplantation: May reduce rejection; pluripotent stem cells can become any cell type, while multipotent stem cells are more limited.

Immune Response to Cancer

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

• Normal Response: Cytotoxic T cells and natural killer cells target abnormal cells.

• Treatment/Prevention: Immunotherapies and vaccines are being developed for certain cancers.

Role of the Microbiome in Immune Health

The normal microbiome helps train and regulate the immune system.

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

• Dysbiosis: Imbalance in the microbiome linked to disease.

• Treatment Options: Fecal transplants and helminth (worm) therapy are being explored to restore balance.

Immunodeficiencies

Immunodeficiencies are conditions where the immune system’s ability to fight infections is impaired.

• 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

HIV is a retrovirus that targets the immune system, leading to acquired immunodeficiency syndrome (AIDS).

• Opportunistic Infections: Infections such as Pneumocystis pneumonia and Kaposi sarcoma were key to the discovery of AIDS.

• HIV Structure: Contains RNA, is a retrovirus with reverse transcriptase, and has gp120/gp41 spikes for cell entry.

• Active vs Latent Infection: HIV can actively replicate or remain dormant in host cells.

• High Mutation Rate: Leads to rapid evolution and immune evasion.

Stage	Description
Stage 1	Asymptomatic or lymphadenopathy (swollen lymph nodes)
Stage 2	Steady decline of T cells
Stage 3	AIDS develops; criteria include very low CD4+ T cell count and presence of specific opportunistic infections

• Immune Evasion: HIV mutates rapidly and hides in reservoirs, making it difficult for the immune system to eliminate.

• Transmission: Spread through blood, sexual contact, and from mother to child; prevention includes safe practices and education.

• Vaccine Challenges: High mutation rate and immune evasion complicate vaccine development.

Key Terms and Definitions

• Hypersensitivity: Excessive immune response to an antigen.

• Autoimmunity: Immune response against self-antigens.

• Immunodeficiency: Impaired immune function.

• Opportunistic Infection: Infection by organisms that cause disease primarily in immunocompromised hosts.

Additional info: The above notes expand on the learning objectives by providing definitions, examples, and context for each topic. Where specific diseases or mechanisms are mentioned, brief explanations are included to ensure the notes are self-contained and suitable for exam preparation.