Immunology Lecture 4: Allergy & Autoimmunity

Immunology Lecture 4: Allergy & Autoimmunity

• The lecture covered allergy and autoimmunity, including hypersensitivity reactions and disease mechanisms.
• The lecture identified 4-5 types of hypersensitivity reactions, and provided examples of each.

Hypersensitivity

• Hypersensitivity is an excessive or inappropriate immune response leading to tissue damage.
• Gell & Coombs (1963) developed a method for defining and describing harmful immune reactions.
• Types I, II, III, and IV are mediated by antibodies or T cells.

Type I Hypersensitivity (IgE-mediated allergy)

• Characterized as immediate hypersensitivity.
• IgE is produced by B cells in response to allergens.
• Atopy is a tendency to produce IgE in response to allergens.
• IgE binds to mast cell receptors, triggering degranulation and release of allergic mediators such as histamine.
• Atopic conditions include eczema, allergic rhinitis, asthma, and food allergy.

Hypersensitivity Sensitization

• First exposure to an allergen causes IgE to bind to Fcɛ1 receptors on mast cells.
• Second exposure triggers cross-linking of IgE, leading to mast cell degranulation and allergy symptoms.

Mast Cell Mediators

• Pre-formed mediators (histamine, tryptase, serotonin) are stored in granules and released quickly.
• Other mediators (cytokines, lipid mediators) are synthesized de novo and released after a delay.
• These mediators cause vasodilation, increased vascular permeability, and contraction of smooth muscles.

Lipid Mediators in Allergy

• Phospholipid is broken down into arachidonic acid by phospholipase A2.
• Arachidonic acid is processed through 12-lipoxygenase, 5-lipoxygenase, and cyclo-oxygenase pathways to form various lipid mediators in allergy, including leukotrienes and prostaglandins.

Early/Immediate Phase and Late-Phase Reactions

• Early phase reactions occur within minutes, triggered by primary mediators from mast cells.
• Late phase reactions, appearing 4-24 hours later, are caused by secondary mediators such as cytokines and lipid mediators released from eosinophils, neutrophils, and T cells.
• These reactions can lead to long-term tissue damage, evident in asthma.

Symptoms of Allergy

• Allergy symptoms vary depending on the affected tissue.
• Gastrointestinal tract symptoms (diarrhea, vomiting) often involve increased fluid secretion and peristalsis.
• Airways symptoms (wheezing, coughing) result from decreased airway diameter and increased mucus secretion.
• Blood vessel symptoms (increased blood flow, permeability) lead to fluid buildup in tissues.

Type II Hypersensitivity (IgM/IgG-mediated)

• This type involves IgG or IgM binding to antigens on cells or tissues.
• The bound antibody activates complement or binds to Fc receptors on phagocytes, leading to cell destruction and tissue inflammation.
• Goodpasture's syndrome is an example, where antibodies target the basement membrane in lung and kidney tissues.

Type III Hypersensitivity (Immune Complex-Mediated)

• This type results from the formation of immune complexes (antigen-antibody complexes).
• These complexes can deposit in tissues (e.g., blood vessels, joints), activate complement, and trigger inflammation leading to damage.
• Vasculitis is a symptom caused by immune complex deposition.
• Systemic lupus erythematosus (SLE) is an example of systemic autoimmune disease.

Type IV Hypersensitivity (T Cell-Mediated)

• Characterized by delayed-type hypersensitivity.
• T cells drive reactions, causing inflammation and damage to tissues over hours or days.
• Examples include contact dermatitis, multiple sclerosis, type 1 diabetes, and rheumatoid arthritis.
• Contact hypersensitivity is triggered by small molecules (haptens), which combine with larger tissue proteins, leading to an immune response.
• Granulomatous hypersensitivity is caused by a persisting immune stimulus, resulting in granuloma formation in tissues like the lungs, intestines (e.g., Crohn's disease) and in sarcoidosis.

Multiple Sclerosis (MS)

• Characterized by demyelination of nerve tissue, frequently at multiple sites.

Anaphylaxis

• A severe, potentially life-threatening systemic hypersensitivity reaction.
• Allergen entering the bloodstream (e.g., peanuts, insect stings, penicillin) triggers widespread vasodilation, smooth muscle contraction, and rapid drop in blood pressure.

This quiz covers essential concepts from Immunology Lecture 4, focusing on allergy and autoimmunity. It examines the different types of hypersensitivity reactions, their mechanisms, and examples of conditions associated with each type. Test your understanding of IgE-mediated allergies and the associated immune responses.