IMM2022 Study Guide - Final Guide: Myasthenia Gravis, Vascular Smooth Muscle, Allergic Rhinitis
4 May 2018
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Hypersensitivity, allergy and autoimmunity
Type 1: immediate hypersensitivity allergy
Th2, IgE, eosinophils and mast.
IgE is the initial response to allergens. IgE
binds to FceR of Mast cells. Repeat exposure
to allergens binds to IgE on mast cells. Cross
linking causes phosphorylation of ITAMs
get activation and degranulation of mast cells.
Get vasoactive amines immediately and
cytokines (late phase). Other things released
from mast cells:
• Proteases tissue damage
• Prostaglandins – vascular dilation
• Leukotrienes smooth muscle
contraction
• Cytokines – inflammation
Immediate response: 1 4 hours: IgE and
mast cells
Late phase: 4 20hours ect: infiltration of
inflammatory leukocytes, swelling:
neutrophils, eosino, baso and Th2
eg. Allergic rhinitis (hay fever) – histamine
(causes dilation of blood vessels) and IL-13
increases mucous production
Food allergies, asthma, anaphylaxis (edema,
vasodilation and bronchoconstriction)
Treatment
• Anaphylaxis epinephrine: causes
vascular smooth muscle to contract to
increase Q, inhibits bronchial
constriction
• Asthma corticosteroids to decrease
inflammation
• Immunotherapy desensitisation
inducing T regs for tolerance.
Type 2: Ab mediated autoimmune disease
contact sensitivity
IgM, IgG, Ab against cell surface or
extracellular matrix antigens (self-antigen)
1. Ab mediated destruction
complement and FcR (neutrophils)
leads to inflammation and tissue
injury. Also see opsonisation and
phagocytosis
2. Ab mediated activation eg Ab
against TSH R Ab stimulates
hormone release by activating R
(mimicking a natural agonist) eg. In
graves disease hyperthyroidism
3. Ab mediated inhibition blocks R
agonsists can no longer bind eg ACH
(neurotransmitter) in myasthenia
gravis causes fatigue, weakness of
muscles.
Type 3: immune complex mediated
autoimmune disease contact sensitivity
Immune complexes of circulating antigens and
IgM or IgG antibodies deposited in vascular
basement membrane. Complexes deposited
complement and FcR recruitment of
inflammatory cells vasculitis. Eg Systemic
lupus erythematosus. Ab against DNA and
nucleoproteins. Causes arthritis, vasculitis and
nephritis. There is no known cure
treatment targets inflammation
• Corticosteroids
• Plasmapheresis (depleting
autoantibodies in plasma)
• Anti CD20 (rituximab monoclonal)
Type 4: T cell mediated diseases
Autoimmune responses and exaggerated
persistent responses to environmental
antigens or chronic infection. T cell mediated
autoimmune diseases tend to be localised to a
single organ rather than widespread, eg T1D
(CD8 killing of Beta cells in pancreas), MS,
hashimotos thyroiditis.
Non-specific excess T cell activation can occur
from superantigens leading to a large release
of inflammatory cytokines cell death and
tissue injury.
Response to environmental antigens (contact
sensitivity( eg Nickle
Responses to chronic infections eg TB see
granuloma formation
Treatments
Document Summary
Repeat exposure to allergens binds to ige on mast cells. Cross linking causes phosphorylation of itams get activation and degranulation of mast cells. Get vasoactive amines immediately and cytokines (late phase). Other things released from mast cells: proteases tissue damage, prostaglandins vascular dilation. Leukotrienes smooth muscle contraction: cytokines inflammation. Immediate response: 1 4 hours: ige and mast cells. Late phase: 4 20hours ect: infiltration of inflammatory leukocytes, swelling: neutrophils, eosino, baso and th2 eg. allergic rhinitis (hay fever) histamine (causes dilation of blood vessels) and il-13 increases mucous production. Food allergies, asthma, anaphylaxis (edema, vasodilation and bronchoconstriction) Treatment: anaphylaxis epinephrine: causes vascular smooth muscle to contract to increase q, inhibits bronchial constriction, asthma corticosteroids to decrease inflammation. Immunotherapy desensitisation inducing t regs for tolerance. Type 2: ab mediated autoimmune disease contact sensitivity. Type 3: immune complex mediated autoimmune disease contact sensitivity. Igm or igg antibodies deposited in vascular basement membrane. Complement and fcr recruitment of inflammatory cells vasculitis.
