Immune Disorders Study Notes

Chapter 18: Immune Disorders

Hypersensitivity

  • Definition: Any immune response against a foreign antigen that is exaggerated beyond the norm.

  • Four Types:

    • Type I (Immediate)

    • Type II (Cytotoxic)

    • Type III (Immune Complex–Mediated)

    • Type IV (Delayed or Cell-Mediated)

Type I Hypersensitivity: Immediate

Overview

  • Localized or systemic reaction from the release of inflammatory molecules (e.g., histamine) in response to an antigen.

  • Develops within seconds or minutes following exposure to an antigen known as allergens.

Degranulating Cells

  • Mast Cells: Distributed throughout connective tissue, releasing inflammatory chemicals (histamine, kinins, proteases) upon encountering allergens.

  • Basophils: Similar to mast cells, they degranulate when allergens bind.

  • Eosinophils: Released from bone marrow following mast cell degranulation, they release large amounts of leukotrienes.

Histamine Effects

  • Causes strong contractions in smooth muscles (e.g., bronchi, gastrointestinal tract).

  • Causes small blood vessels to dilate and leak, resulting in tissue swelling and redness.

  • Stimulates nerve endings, causing pain and itching.

  • Will also increase bronchial mucus secretion, tear formation, and salivation.

Clinical Signs of Localized Reactions

  • Mild and localized

  • Portal of entry determines the site of reaction

    • Inhaled allergens: Hay fever, asthma

    • Skin: Hives (urticaria)

Systemic Reactions

  • Multiple mast cells degranulate leading to anaphylaxis, characterized by severe allergic responses.

  • Treatment requires immediate administration of epinephrine.

  • Common causes include: bee stings, certain foods.

Common Allergens

  • Environmental: Spores, dust mites, and pollen.

  • Chemicals: Latex from gloves, insect venoms.

Type II Hypersensitivity: Cytotoxic

Mechanism of Action

  • Cells destroyed by an immune response through the combined activities of complement and antibodies.

  • Examples include incompatible blood transfusions (ABO system) and hemolytic disease of the newborn (Rh (+)/Rh (-)).

Blood Group Characteristics

  • ABO System:

    • Type A: Anti-B antibodies; can receive A/O; donate to A/AB.

    • Type B: Anti-A antibodies; can receive B/O; donate to B/AB.

    • Type AB: No antibodies; can receive A/B/O/AB; donate to AB.

    • Type O: Anti-A and Anti-B antibodies; can donate to all; receive from O only.

Hemolytic Disease of the Newborn

  • Occurs when Rh+ fetal antigens enter Rh- mother's blood during delivery; the mother produces anti-Rh antibodies, which can attack future Rh+ fetuses.

Type III Hypersensitivity: Immune Complex–Mediated

Overview

  • Caused by the formation of immune complexes leading to the release of inflammatory chemicals.

  • Localized Reactions: Hypersensitivity pneumonitis, glomerulonephritis.

  • Systemic Reactions: Diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

Disorders Specificity

  • Hypersensitivity pneumonitis: Inhalation of antigens can lead to immune complex formation in lungs especially affecting farmers (farmer's lung).

  • Glomerulonephritis: Immune complexes deposit in kidney glomeruli, leading to failure and death if untreated.

  • Rheumatoid Arthritis: Persistent immune complexes lead to joint damage and inflammation.

Type IV Hypersensitivity: Delayed or Cell-Mediated

Characteristics

  • Inflammation occurs 12-24 hours after contact with the antigen, primarily mediated by T-cells and macrophages.

  • The tuberculin response test (TB test) is a common example; a positive test indicates previous contact with TB antigens.

Manifestations

  • contact dermatitis: Skin rash due to interactions with foreign chemical substances such as poison ivy.

  • Graft Rejection: Foreign grafts are rejected due to immune responses targeting foreign MHC proteins.

Autoimmune Diseases

  • More common in women; characterized by antibodies or cytotoxic T-cells attacking normal cells. Causes include genetic predispositions, environmental triggers, and molecular mimicry.

  • Two Categories:

    • Systemic autoimmune diseases (e.g., lupus, RA).

    • Single-organ autoimmune diseases (e.g., Type 1 diabetes).

Examples of Autoimmune Disease

  • Graves Disease: Leads to hyperthyroidism and features such as exophthalmos.

  • Type 1 Diabetes Mellitus: Resulting from destruction of pancreatic beta cells, leading to elevated blood glucose levels.

  • Multiple Sclerosis: Cytotoxic T-cells damage myelin, impairing neurological function.

Immunodeficiency Diseases

Primary Immunodeficiencies

  • Result from genetic or developmental defects, manifesting in infants and young children (e.g., chronic granulomatous disease, SCID).

Acquired Immunodeficiencies

  • Develop due to external factors (e.g., stress, malnutrition). Most notorious example is AIDS (Acquired Immunodeficiency Syndrome), caused by HIV (Human Immunodeficiency Virus).

HIV Overview

  • An enveloped retrovirus with a complex replication cycle involving a reverse transcriptase stage. It targets CD4 T-cells that are crucial for immune function.

  • Symptoms and Progression: Can lead to opportunistic infections and diseases characterized by a significant drop in CD4 T-cells.

Diagnosis & Treatment

  • Diagnosis typically involves antibody detection through ELISA or Western blot. Treatment includes ART (antiretroviral therapy) to reduce viral replication.

  • Preventive measures include safe sex practices, clean needle usage, and antiviral drugs for pregnant women to reduce transmission risks.

Summary

Understanding hypersensitivity reactions, autoimmune diseases, and immunodeficiencies is crucial for diagnosing and treating various immune system disorders. Awareness of allergens, immune response types, and effective management strategies such as immunotherapy and careful monitoring of patients with autoimmune or immunodeficiency conditions is essential to improving patient outcomes.