hypersensitivity, allergy and inflammation Flashcards
immunological mechanisms: summarise the mechanisms by which IgE, antibodies, immune complexes and T cells can cause tissue damage and inflammation (the four types of hypersensitivity); clinical disease: list examples of the clinical syndromes associated with each type of hypersensitivity reaction
what do appropriate immune responses occur in response to
harmful agents e.g. viruses, bacteria, fungi, parasites
function and side effect of appropriate immune response
eliminate pathogens, and whilst there may be concomitant tissue damage as a side effect, as long as pathogen is eliminated quickly this will be minimal and repaired easily
what 2 thnigs does appropriate immune response involve
recognition by cells of immune system and antibody production
what does appropriate immune tolerance occur in response to
self and to foreign harmless proteins e.g. food, pollens, other plant proteins, animal proteins, commensal bacteria
what does appropriate immune tolerance involve
antigen recognition and generation of Treg cells and regulatory (blocking) antibody (IgG4) production (antigen recognition in context of danger signals (microbial signatures) leads to immune reactivity, but in absence of danger leads to tolerance)
what 3 things do immune responses mount against to cause hypersensitivity reactions
harmless foreign antigens (allergy, contact hypersensitivty), autoantigens (autoimmune diseases), alloantigens (serum sickness, transfusion reactions, graft rejection)
4 classes of hypersensitivity reactions (many diseases involve mixture of types)
type I: immediate hypersensitivity (IgE), type II: antibody-dependent cytotoxicity hypersensitivity (antibody), type III: immune complex mediated hypersensitivity (complex), type IV: delayed cell mediated hypersensitivity (T cell)
type I: what is immediate hypersensitivity present in
anaphylaxis, asthma, rhinitis (seasonal and perennial), food allergy
type I: immediate hypersensitivity: 3 features and purposes of primary antigen exposure
sensitisation not tolerance, IgE antibody production, IgE binding to mast cells and basophils
type I: immediate hypersensitivity: 3 features of secondary antigen exposure
more IgE antibodies produced, antigen exposure causes cross-linking IgE on mast cells and basophils, IC signalling leading to degranulation and release of inflammatory mediators
type II: antibody-dependent hypersensitivity: what does clinical presentation depend on
target tissue (i.e. organ-specific)
type II: antibody-dependent hypersensitivity: 4 organ-specific autoimmune diseases and what antibodies do to cause them
myasthenia gravis (anti-acetylcholine receptor antibodies), glomerulonephritis (anti-glomerular basement membrane antibodies), pemphigus vulgaris (anti-epithelial cell cement protein antibodies), pernicious anaemia (intrinsic factor blocking antibodies)
type II: antibody-dependent hypersensitivity: what happens in autoimmune cytopenias
antibody mediated blood cell destruction
type II: antibody-dependent hypersensitivity: 3 autoimmune cytopenias
haemolytic anaemia, thrombocytopenia, neutropenia
type II: antibody-dependent hypersensitivity: 2 tests for specific antibodies
immunofluorescence, ELISA (e.g. anti-CCP for rheumatoid arthritis)
type III: immune complex mediated hypersensitivity: 5 stages
formation of antigen-antibody complex in blood -> complex deposition in blood vessels/tissue -> complement and cell activation (e.g. monocytes and neutrophils to cause inflammation) -> activation of other cascades e.g. clotting -> tissue damage (vasculitis)
type III: immune complex mediated hypersensitivity: 2 examples of autoimmune diseases which cause tissue damage (vasculitis) due to immune complex formation
systemic lupus erythematosus, vasculitides (poly arteritis nodosum, many different types)
type III: immune complex mediated hypersensitivity: 4 most common areas affected by tissue damage
glomerulus, skin, joints, lung
type IV: delayed cell mediated hypersensitivity responses: 5 examples of disorders caused by Th1 responses
chronic graft rejection, GVHD, coeliac disease, contact hypersensitivity, most autoimmune diseases
type IV: delayed cell mediated hypersensitivity responses: 3 examples of disorders caused by Th2 responses
asthma, eczema, rhinitis
type IV: delayed cell mediated hypersensitivity responses: 3 main varieties of T cells involved
Th1, cytotoxic, Th2
type IV: delayed cell mediated hypersensitivity responses: 2 mechanisms leading to tissue damage
transient/persistent antigen leading to T cell activation of macrophages, CTLs, fibroblasts and perforin (much of tissue damage dependent upon TNF - released from macrophages - and CTLs)
type IV: delayed cell mediated hypersensitivity responses: common cause of contact hypersensitivity
nickel exposure
hypersensitivity reactions
S19 (image)
common feature of hypersensitivity
inflammation
2 promoters of inflammation in hypersensitivity
immune cells (recruitment and activation), inflammatory mediators (e.g. complement, cytokines)
4 features of inflammation (blood vessels, cells, mediators and outcome)
vasodilation, increased vascular permeability, inflammatory mediators and cytokines, inflammatory cells and tissue damage
4 signs of inflammation
redness, heat, swelling, pain
what 4 things cause increased vascular permeability in inflammation
C3a (complement), C5a (complement), histamine, leukotrienes
5 pro-inflammatory cytokines
IL-1, IL-6, IL-2 (released from Th1 to activate CTLs), TNF, IFN-y
2 pro-inflammatory chemokines
IL-8/CXCL8, IP-10/CXCL10
process by which inflammatory cells infiltrate tissue (cell trafficking)
chemotaxis by cytokines
4 inflammatory cells which infiltrate tissue then activate
neutrophils, macrophages, lymphocytes, mast cells
