Hypersensitivity Flashcards
What is T1 hypersensitivity
Immediate hypersensitivity (allergy anaphylaxis and atopy)
What is T1 mediated by
IgE-mast cells
Describe pathway of T1 hypersensitivity
DC->antigen activates Th2 cells->expresses Il-4, IL-13, Il-5íIgE class switching in B cells->binds to IgE receptor on mast cells->sensitisation Cross-linking of 2 adjacent IgE molecules->degranulation
What does Il-13 do
Increases mucus hypersecretion
What does Il-5 do
Activate eosinophils
What is the role of prostaglandisn
Increase vascular permeability
What is the role of leukotrienes
Smooth muscle contraction
What is the role of cytokine
Vasodilation, systemic anaphylaxis
What is the role of histamine in mast cells
increased vascular permeability, smooth muscle contraction, vasodilation, vascular leak (wheal +flair), bronchoconstriction, intestinal hypermobility
What is the role of tryptase
tissue remodelling, increased mucus secretion
List common allergens
Inhaled: pollens, spores, dander, dust mite
Ingested: peanut, egg, fruits, sesame
Venoms: bees, wasp stings and bites (Hymenoptera) - proteins present in venom and saliva
Drugs: abx, chemotherapeutics
How are allergen responses different to microbe responses
Do not induce macrophages/dendritic cells
What is the role of eosinophil
Activated by IL-5->release granules->tissue damage
What are the symptoms of T1 hypersensitivty
Lung - asthma ,wheezing
Nose - rhinitis, sneezing, runny nose
Eye - conjunctivitis
Skin - atopic dermatitis
Gut - food allergy
Skin prick test >3mm wheal through leakage of plasma and protein, vasodilation and congestion
Lab: total IgE (>100 IU/mL), specific IgE raised (e.g. radio-allergosorent test), tryptase levels but these are transient
What is T2 hypersensitivty
Antibody mediated
What causes T2 hypersensitivity
IgM, IgG antibodies against cell surface/ECM
Complement-mediated
Binding of Ab to Ag on cells->activate complement and recruit immune cells
What are the 3 types of T2 hypersensitivty
Complement activation and opsonisation -> phagocytosis
Complement and Fc receptor mediated inflammation
No cell/tissue injury
What are examples of complement action, opsonisation T2 hypersensitivity
Autoimmune haemolytic anaemia, autoimmune thrombocytopenic purpura, haemolysis in transfusion reaction
What are examples of complement and Fc receptor mediated inflammation
neutrophil and macrophages binding of phagocytes to complement receptors and Fc receptors. Glomerulonephritis, vasculitis caused by ANCA
What are examples of no cell/tissue injury T2 hypersensitivity
Grave’s disease (TSH receptors - increases production of TSH)
Insulin resistant diabetes
Myasthenia gravis (Ab binding to Ach receptor, creating muscular weakness)
What is T3 hypersensitivty
Immune complex mediated
Soluble immune complexes antigen-IgM or antigen IgG
Activation of complement, recruit of neutrophils and macrophages
Pathologic features reflect the site of deposition -> multiple tissues
What is the serum sickness modle
As antigen goes down in blood, antibodies start being produced. Complexes are produced. These small complexes are not phagocytosed can accumulate
What are examples of T3 hypersensiviity
SLE, nephritis, arthritis, vasculitis Polyarteritis nodosa (HepB Ag-Ab): vasculitis Poststreptococcal glomerulonephritis (Streptococcal Ag-Ab): nephritis
What is T4 hypersensitivity
Cell mediated (delayed)
CD4 and CD8 cells. Cell killing and cytokine mediated inflammation
24-48 hour
Antibody-independent
What are the two types of T4 hypersensitivtiy
Cytokine mediated inflammation and T cell mediated cytotoxcicity
What is cytokine mediated inflamamtion
APC presents Ag to T cell -> activation (Th1, Th17, Th2 -> T cell secrete cytokines -> inflammation
What are examples of cytokine mediated inflammation
IBD: Crohn’s (Th1/Th17), UC (TH2)
Contact sensitivity (ni2+)
Asthma
What is T cell mediated cytotoxicity
CD8 T cell directly kill tissue cells
What are examples of T cell mediated cytotoxicty
Autoimmune myocarditis: myosin heavy chain protein
T1DM: destruction of islet cells
