Lecture 31 - Autoimmunity, Hypersensitivity and Skin I Flashcards
Immune hypersensitivity - type I?
IgE mediated allergic reaction or anaphylaxis
Immune hypersensitivity - type II?
IgG antibody-mediated (cytotoxic)
Immune hypersensitivity - type III??
IgG immune complex regulated
Immune hypersensitivity - type IV?
T cell mediated (DHT - delayed type)
Mast cell degranulation?
antigen cross links IgE on mast cells (also triggered by C3a, C5a and some drugs) which causes release of mediators - chemoattractants, activators and spasmogens
Allergies & causes?
rhinitis (dust mites, animal hair, pollen), insect stings (proteins in venom), food allergies (wheat and milk proteins, peanuts), small molecules (penicillin, morphine, codeine)
Allergy treatments?
avoidance, antihistamines, corticosteroids, sodium cromoglycate (stabilises mast cells), epinephrine (for anaphylaxis), desenstisation (introduce IgG reaction to compete with IgE)
Type II Hypersensitivity - physiology & e.g.?
antibodies against cell surface antigens, causign ADCC, complement activation, and frustrated phagocytosis e.g. organ specific autoimmunity and haemolytic disease of the newborn
Type III hypersensitivity - physiology?
antibody response to circulating antigen (chronic disease), antibodies appear as antigen circulation becomes high -> immune complex-induced vasculitis and nephritis
Type III hypersensitivity - blood vessel effect?
platelet aggregation -> microthrombus formation -> complement activation of neutrophil -> chemotaxis -> vascular damage
Type IV hypersensitivity e.g.?
Mantoux test - immune (T cell) memory assessment; contact sensitivity - antigen (aka. hapten) uptake, processing and presentation to memory Th1 cells -> cytokine mediated Th1 cytokine-mediated inflammation (lymphocytes and macrophages)
Autoantibodies?
natural IgM low affinity; Anti-nuclear antibodies seen in patients w SLE and in elderly; Anti-thyroid antibody seen in thyroid disease and elderly;
Mechanisms of tolerance?
clonal depletion (central - BM and thymus), clonal regulation (peripheral - no co-simulation, anergy), suppression (peripheral - tregs control self-reactive cells) and ignorance (privileged sites and sequestered antigens)
Molecular mimicry?
HLA presents self-antigen similar to bacterial, T cell thinks they look the same (not are), HLA haplotype dependent
Goodpastures syndrome?
antibodies against type IV collagen in glomerular basement membrane
MG?
antibodies block Ach receptors
Hashimoto’s thyroiditis?
antibodies and T cells destroy thyroid tissue
ITP?
idiopathic thrombocytopenic purpura - antibodies against platelets
Addison’s disease?
destruction of adrenal cortex, hyperpigmentation
Type 1 diabetes?
CD8 T killer cells attacking beta cels of islet of langerhans
Pernicious anaemia?
antibodies against B12 or intrinsic factor preventing B12 absorption
Grave’s disease?
Anti-TSH receptor autoantibody over-activates TSH receptor increasing Thyroxin release -> chronic thyroid stimulation by autoantibody
Systemic autoimmune disease (type III) e.g.?
systemic lupus erythematosus (w butterfly rash) and RA
Genetic predisposition?
antigen receptor genes (immunoglobulin and TCR), antigen presenting genes (associations w class I and II), complement genes (impaired immune complex clearance), regulatory genes (cytokines and co-stimulators)
Treatment?
either replacements (insulin, thyroxin, -corticoid replacement) or suppression (immunosuppresives e.g. corticosteroids)
