Disorders of the Immune System

Introduction

• Immune system disorders involve cells and processes critical to the immune response.
• Review common terms and processes before discussing specific disorders.

Hygiene Hypothesis

• Suggests increased exposure to pathogens reduces sensitivity to allergens.
• People in rural areas (e.g., farms, tribal regions) have fewer allergies/asthma than urban dwellers.
• Modern clean environments (e.g., disinfectants, sanitizers) lead to higher allergies/asthma rates by limiting pathogen exposure.

Hypersensitivity

• Refers to an overreaction of the immune system to antigens (allergens).
• Four types: Anaphylactic, Cytotoxic, Immune Complex, Delayed Cell-Mediated.

Type I: Anaphylactic Reactions

• Occurs minutes after exposure to a previously sensitized antigen.
• Involves IgE antibodies, mast cells, and basophils releasing mediators (histamine, leukotrienes, prostaglandins).
• Types of Anaphylaxis:
  • Systemic (Anaphylactic Shock): Whole body involvement, can be fatal, requires epinephrine (EpiPen).
  • Localized: Symptoms depend on the entry route (e.g., ingestion, inhalation).
• Desensitization treatment involves gradual exposure to allergens to reduce sensitivity.

Type II: Cytotoxic Reactions

• Involves the complement pathway leading to cell lysis.
• Example: Blood type incompatibility (A, B, AB, O, Rh factor) and hemolytic disease of the newborn.
• Drug-induced cytotoxic reactions can destroy platelets (thrombocytopenic purpura) or red blood cells (hemolytic anemia).

Type III: Immune Complex Reactions

• Formation of immune complexes that lodge in tissues, causing inflammation.
• Common sites include kidneys (glomeruli) and joints.

Type IV: Delayed Cell-Mediated Reactions

• Involves T-cells and delayed hypersensitivity (e.g., allergic contact dermatitis).
• Direct contact with allergens (e.g., poison ivy, latex) leads to symptoms.

Autoimmune Diseases

• Occur when the immune system attacks the body's own cells due to loss of self-tolerance.
• Can involve cytotoxic, immune complex, or delayed cell-mediated reactions.

Cytotoxic Autoimmune Diseases

• Multiple Sclerosis (MS): T-cells and antibodies attack the myelin sheath of nerves, leading to fatigue, weakness.

Immune Complex Autoimmune Diseases

• Graves Disease: Autoantibodies stimulate the thyroid gland excessively.
• Myasthenia Gravis: Autoantibodies block nerve-muscle communication, causing paralysis.
  • Other Examples: Lupus (kidney involvement), Rheumatoid Arthritis (joints).

Cell-Mediated Autoimmune Diseases

• Type 1 Diabetes: T-cells destroy insulin-producing cells in the pancreas.
• Psoriasis: T-cells target skin cells, causing flaky skin.

Transplants and Grafts

• Importance of blood and tissue typing to prevent rejection.
• Types of grafts: Autograft, Isograft, Allograft, Xenograft.
• Graft versus host disease is when donor tissue attacks the recipient.
• Privileged sites like corneal or heart valve transplants have lower rejection risks.

Cancer and the Immune System

• Immune surveillance usually removes cancer cells, but cancers can evade detection and destroy immune system regulation.
• Tumor antigens mutate and overgrow, making detection difficult.

Immuno-deficiencies

• Congenital: Born with them; missing genes/cells.
• Acquired: Develop later; due to infections, drugs, or cancer.
  • AIDS (Acquired Immuno Deficiency Syndrome): Caused by HIV, attacks CD4+ T-cells.

HIV and AIDS

• HIV is a retrovirus that infects CD4+ T-cells, entering via GP120 spikes and undergoing reverse transcription.
• Three stages of HIV infection: asymptomatic, symptomatic (flu-like symptoms), and AIDS (CD4+ T-cells < 200).
• Transmission through sexual contact, breast milk, blood transfusions.
• Treatment: HAART therapy; targets multiple aspects of the virus.
  • Challenges include high mutation rate and human-only infection.

Conclusion

• Understanding immune disorders aids in devising treatments and preventive measures.