Hypersensitivity Reactions: Types and Mechanisms

Previously discussed type one hypersensitivity, which is immediate and mediated by IgE antibodies.
Key symptom of anaphylaxis: vascular permeability.
- This symptom leads to a drop in blood pressure and inadequate oxygen supply to organs, making it the most life-threatening aspect of anaphylaxis.

Discusses the increasing prevalence of hypersensitivity in Western nations.
Central Idea: Overcleanliness reduces childhood exposure to pathogens, commensals, and animals.
- Urban lifestyles limit interactions with farm animals, which contributed to immune development in earlier times.
Vaccination may inhibit the developing immune system's ability to face natural infections due to the following reasons:
- Immune systems that do not encounter infections may not fully develop effective responses.
- Early exposure to specific infections can strengthen immunity.
Excessive use of antibiotics contributes to premature termination of infections, resulting in less immune system training.
Consequences include a poorly educated immune system that targets harmless substances, leading to allergies.
Research indicates that early exposure to food allergens can decrease allergy development (example: peanuts).

Basophils are crucial in initiating T helper 2 (Th2) responses.
- Produce interleukin 4 (IL-4) and interleukin 13 (IL-13).
- Can drive class switching of antibodies to IgE and IgG4 by interacting with B cells through CD40 ligand.

Discusses the role of prostaglandins and leukotrienes.
- Produced from arachidonic acid via COX and 5-lipoxygenase pathways during inflammatory responses.
- These mediators are targeted by NSAIDs, which include medicinal properties for treating allergies and inflammation.
- Aspirin acts by inhibiting prostaglandin synthase, blocking production of prostaglandins.

Focus will shift beyond type one hypersensitivity to type two, three (both involving antibodies), and type four (T cell-mediated).

Caused by IgG antibodies targeting altered cellular structures.
- Commonly involves reactions induced by drugs, notably penicillin.
Mechanism:
- Altered structures on host cells lead to recognition as foreign by the immune system, promoting an antibody response.
- Antigen-bound antibodies activate the classical complement pathway and induce phagocytosis.
Penicillin example:
- Can modify the surface of erythrocytes, resulting in immune recognition and antibody production against penicillin-modified blood cells.
Blood transfusion implications:
- Transfusion reactions can be life-threatening if the antibody against donor blood type antigens is present (e.g., ABO system).
- Universal donor: Type O blood does not have A or B antigens that would be recognized as foreign by other blood types.

Blood groups determined by carbohydrate antigens on erythrocyte surface:
- Type A: terminal residue galNAC (N-acetylgalactosamine).
- Type B: terminal residue galactose.
- Type O: absence of these terminal residues.
Antibodies develop against unlike blood group antigens due to similarities with bacterial antigens.

Mediated by immune complexes formed from antigen-antibody interactions.
Mechanism:
- Immune complexes can deposit in tissues, activating complementary processes.
- Lead to inflammation and variety of diseases (e.g., serum sickness, Arthus reaction).
Examples resulting from exposure to nonhuman proteins:
- Antivenoms derived from horse serum.
- Therapies using monoclonal antibodies from other animals (e.g., mice).

Vasculitis: Inflammation of blood vessels due to immune complex deposition.
Nephritis: Immune complex deposition in renal glomeruli.
Arthritis: Immune complex deposition in joints.
Arthus Reaction: Localized immune complexes causing local reactions (e.g., farmer's lung due to inhaled antigens).

Small immune complexes are formed during a stage of high antigen concentration relative to antibodies.
Large immune complexes arise when antigens and antibodies are in similar concentrations, leading to increased tissue damage due to deposition.

Mediated by antigen-specific T cells (specifically CD4+ Th1 cells).
Mechanism:
- Takes days to develop, with symptoms appearing 24-72 hours after re-exposure to the antigen.
Examples:
- Insect bites.
- Tuberculin skin tests (reactive to Mycobacterium materials).
- Contact dermatitis due to substances like poison ivy (pentadecatechol).
- Celiac disease, where T cell-mediated damage leads to atrophy of the intestinal villi through gliadin (gluten protein).

Characterized by localized skin swelling, redness, and itchiness due to T cell and macrophage activity at the challenge site.
Involves cytokine-driven processes enhancing macrophage recruitment and edema formation.

Granulomas formed in response to bacterial pathogens like Mycobacterium tuberculosis contain infection within a walled-off structure consisting of macrophages and lymphocytes, potentially leading to necrotic tissue in the center (caseous necrosis).

Summary of hypersensitivity types:
- Type Two: antibody responses against altered host molecules.
- Type Three: immune complexes leading to inflammation and tissue damage.
- Type Four: T cell-mediated reactions causing delayed local response compared to immediate hypersensitivity reactions.