MD137 Immunology - Lecture 4: Allergy & Autoimmunity

MD137 Immunology - Lecture 4: Allergy & Autoimmunity

• The lecture covers allergy and autoimmunity, hypersensitivity reactions (types I-V), and disease examples.
• Hypersensitivity is an excessive or inappropriate immune reaction causing tissue damage.
• Gell & Coombs (1963) defined and described harmful immune reactions.
• Types I, II, III, and V are antibody-mediated, while Type IV is T cell-mediated.
• Type I Hypersensitivity (IgE-mediated allergy): Immediate hypersensitivity, IgE is produced by B cells, Atopy is a tendency to produce IgE in response to allergens. IgE binds to mast cells, triggering degranulation and release of allergic mediators (e.g., histamine).
• Atopic conditions include eczema, allergic rhinitis, asthma, and food allergies. An allergic trigger might not always be identifiable.
• Sensitization is required for Type I hypersensitivity: First exposure to allergen causes IgE binding to FcεRI receptors on mast cells. Second exposure causes cross-linking of IgE, mast cell degranulation, and allergy symptoms.
• Mast cell mediators include pre-formed mediators (released quickly), enzymes (e.g., tryptase, serotonin, histamine), causing vasodilation, increased vascular permeability, and smooth muscle contraction. Other mediators (e.g., cytokines, lipid mediators) are synthesised later.
• Lipid mediators in allergy include products from Phospholipase A2, Arachidonate, 12-HETE, 12-lipoxygenase, 5-lipoxygenase, 5-HPETE, Lipoxin A, and B, Cyclo-oxygenase, Leukotrienes, PGI2, TXA2, PGF2a, PGD2, PGE2.
• Early/immediate phase of allergy can occur within minutes, caused by primary mediators from mast cells, followed by late phase (occurring 4-24 hours later) due to eosinophils, neutrophils, and T cells, and the release of secondary mediators (e.g., cytokines, lipid mediators). This late phase can be responsible for long-term tissue damage (e.g., tissue remodelling in asthma).
• Allergy symptoms depend on the affected tissue. For the gastrointestinal tract, symptoms include increased fluid secretion and increased peristalsis (e.g., diarrhoea, vomiting), while symptoms in airways include blockage leading to wheezing, coughing, and phlegm. Blood vessels experience increased blood flow and permeability.
• Type I hypersensitivity (also called IgE-mediated allergy) is a common immune response in which B cells produce IgE antibodies. These antibodies bind to allergens, leading to activation and degranulation of mast cells.
• Type II Hypersensitivity (IgM/IgG-mediated): Caused by IgG or IgM binding to antigens on cells or tissues. Bound antibodies activate complement or bind to Fc receptors on phagocytes leading to tissue damage. Goodpasture's syndrome is an example (autoantibodies against a type IV collagen component in the basement membrane of lung and glomeruli leading to inflammation, tissue necrosis, and pulmonary haemorrhage, eventually glomerulonephritis).
• Type III hypersensitivity (Immune complex-mediated): Caused by IgG binding to soluble antigens, forming immune complexes. Clearance mechanisms may become defective, leading to immune complex deposition in tissues, activating complement and releasing inflammatory substances (anaphylatoxins). Vasculitis is an example of this.
• Type IV hypersensitivity (T cell-mediated): Delayed-type hypersensitivity. T cells, and T-cell-driven responses, are responsible for contact dermatitis and chronic diseases like multiple sclerosis (demyelination and sclerosis of nerve tissue). Contact hypersensitivity involves small molecules (haptens, like nickel or chromate) combining with larger tissue proteins; these converted self-antigens become highly immunogenic antigens, resulting in sensitization. Examples include contact dermatitis, multiple sclerosis, Type I diabetes mellitus, and rheumatoid arthritis.
• Granulomatous hypersensitivity develops in response to persistent immune stimuli as collections of macrophages accumulate with intracellular antigens. Examples include Crohn's disease and sarcoidosis.
• Multiple sclerosis (MS) is characterized by demyelination followed by sclerosis of nerve tissue, typically at multiple sites. T cells specific for myelin basic protein in the CNS are implicated.
• Grave's disease (Type V) is a common autoimmune disease, occurring in approximately 1-2% of white Europeans and Americans. Antibodies to the thyroid-stimulating hormone (TSH) receptor cause unregulated stimulation of hormone synthesis, leading to excess thyroid hormones. Common symptoms include goitre, weight loss, and exophthalmos.

This quiz explores key concepts from Lecture 4 of MD137 Immunology, focusing on allergy and autoimmunity. It covers hypersensitivity reactions, types I to V, and their implications in various diseases. Understand the mechanisms of IgE-mediated allergy and the definition of sensitization in allergic responses.