immunology 3: hypersensitivity reactions Flashcards
hypersensitivity reactions
type I = allergic reaction to foreign antigen
type II, III, IV = can be either to host or foreign antigen
type I - immediate hypersensitivity reaction
allergic response only to foreign antigen
IgE mediated degranulation of mast cells + eosinophils releasing histamine
Th2 mediated
type II - direct antibody mediated
direct antibody mediated
caused by antibodies reacting directly through binding with antigen present on the surface of cells or tissues, the binding then triggers complement cascade or activates macrophages
type III - immune complex mediated
complexes of antibody antigen form and cause damage either at the site of formation or travel through circulation and cause damage elsewhere
type IV - delayed hypersensitivity
T cell mediated and can 2 - 3 days to develop
Type I pathway
allergen phagocytosed by dendritic cell which displays the allergen to Th2 cell. T cell will activate B cell.
B cell produces IgE
plasma cell secreting IgE, the IgE will bind to IgE receptor on a mast cell causing it to degranulate and histamine is released
histamine causes downstream cytokine (2 - 4 hours) and lipid mediator activation (minutes after repeat exposure)
Type I allergy
following initial sensitisation where IgE is bound to IgE receptor on mast cell, a subsequent antigen exposure will cause the antigen to bind to the IgE bound to IgE receptor on mast cell triggering its degranulation
Type II reaction to foreign antigens
reaction in response to foreign blood products i.e. haemolytic anaemia and rhesus incompatibility
Type III reaction to foreign antigens
bacterial endocarditis
Type IV reaction to foreign antigens
contact dermatitis
also observed in hard to clear pathogens
e.g. hep B + mycobacterium TB
Hep shuts down MHC 1
autoimmunity
adaptive response to host components leading to chronic immune response
tolerance
does not happen automatically and immunocytes need to be trained to not react to host proteins
maintenance of tolerance
self reactive immature B cells are deleted in the bone marrow
anergic response in the periphery if B cell makes receptor that interacts with host protein by fas - fas ligand pathway on CD4+ T cells causing the B cell to become eliminated by apoptosis
self reactive T cells are deleted at the cortex/medulla in the thymus
mature self reactive lymphocytes are rendered unreactive (anargy) and deleted when they encounter self antigens
breakdown in tolerance
some MHC subtypes are less able to present antigen to developing T cell so some self reactive T cells escape to periphery
molecular mimicry and cross reaction of antibodies
cross reaction with host proteins for antibodies that are targeted towards antigens that are similar
e.g. streptococcus M protein —-> rheumatic fever
MS? diabetes?
antibody cross reacts with protein in cardiac muscle causing calcification of heart valves
immune privilege and release of sequestered antigen
disruption of tissue barrier causes release of sequestered self antigen and activation of non tolerized cells
superantigen
infection triggers massive T cell response causing polyclonal activation of autoreactive T cells causing their expansion
e.g. rheumatoid arthritis
Goodpasture’s syndrome
antibodies directly bind to GBM protein found in glomerulus of the kidneys and trigger complement cascade and activation of macrophages
GBM = glomerular basement membrane
IgG autoantibodies bind to GBM triggering cc cascade and macrophages, producing cytokines and recruiting neutrophils and more B and T cells
results in: progressive glomerulonephritis i.e. progressive decrease in kidney function
inflammation, RBC present due to rupture of capillaries (C9) abnormal crescent shaped accumulation of cells in the urine surrounding glomerulus
Type II hypersensitivity autoimmune diseases
goodpastures syndrome
autoimmune haemolytic anaemia
pemphigus vulgaris (epidermal cadherin)
acute rheumatic fever
Graves’ disease
myasthenia gravis
Graves’ disease
more common causes of hyperthyroidism
antibody binding to receptor modifies the receptor behaviour causing it to produce too much metabolic hormones T3 and T4
Type III autoimmune hypersensitivity
immune complexes of antigen and antibody are formed (precipitate) and are produces as part of normal immune response and cleared via complement cascade which opsonises them
in hypersensitivity the antigen is a host protein which will never be cleared or eliminated and result in chronic inflammatory reaction
the immune complexes can lodge in vasculature: complement cascade occurs neutrophils activated microthrombi formation platelet aggregation
Type III autoimmune examples
subacute bacterial endocarditis
> results in glomerulonephritis
mixed essential cryoglobulinemia
> systemic vasculitis
systemic lupus erythmatosus
> glomerulonephritis, vasculitis, arthritis
SLE
IgG antibodies produces to self antigens most commonly:
antinuclear proteins
self DNA
e.g. UV damage where cells lyse and host DNA antigens, cytosolic proteins are exposed to immune population
characterized by malar (butterfly) rash
type IV autoimmune hypersensitivity
driven by Th1 cells driving inflammatory response mediated by macrophages
cytokine responses
onset by provacations:
> physiological reaction to pathogen e.g. hep B
> in response to innocuous environment (nickel contact dermatitis)
> against autoantigens (diabetes)
hypersensitivity by both CD4 + CD8
