organ specific autoimmunity Flashcards
what is a type 1 hypersensitivity reaction
immediate reaction and involves immunoglobulin E (IgE) mediated release of antibodies against the soluble antigen -> atopy and allergies
what is a type 2 hypersensitivity reaction
antibody-mediated immune reaction in which antibodies (IgG or IgM) are directed against cellular or extracellular matrix antigens
what is a type 3 hypersensitivity reaction
immune-complex mediated -> immune response in which antigen-antibody complexes accumulate in the tissues and cause inflammation and tissue damage
what is a type 4 hypersensitivity reaction
cell-mediated reaction that can occur in response to contact with certain allergens -> it does not involve the participation of antibodies but is due primarily to the interaction of T cells with antigens.
what are the immune effectors of autoimmune disease
- T cells -> cytotoxic and T helper
- B cells -> make autoreactive self antibodies
what are the 2 parts of the antibody fragement
- Fab (light chain)
- Fc (heavy chain, constant region)
what antibodies are normally involved in autoimmune reactions (2)
IgG and IgE
what does the complement cascade ultimately lead to
formation of the membrane attack complex
function of membrane attack complex
creates pores in the pathogen leading to lysis
how to natural killer cells attack pathogens
Fc region of antobodies that have been bound to pathogens can bind to NKCs leading to the release of cytotoxic granules onto the pathogen leading to it lysing
how does type II autoimmunity wrok
antibodies (IgG and IgM) bind self antigens on tissue -> complement activation, NKCs, etc. -> tissue damage and inflammation
examples of type II autoimmune diseases (10)
- haemolytic anaemia
- thrombocytopenia
- goodpasture’s syndrome
- pemphigus vulgaris
- acute rheumatic fever
- guillian barre
- grave’s disease
- myesthenia gavis
- RA
- T2DM
what types of autoimmunity hypersensitivity does RA have
type 2, 3 and 4
how does type 3 autoimmunity work
antibodies bind soluble self antigens and form immune complexes -> get stuck in small vessels -> immune cells recruited in response to blockage
examples of type III autoimmune diseases (5)
- SLE
- RA
- post strep glomerulonephritis
- Reactive arthritis
- henoch-schonelin purpura
how does type 4 autoimmunity work
cell mediated i.e. does not involve antibodies -> self-reactive cytotoxic T-cells released due to evasion of thymus selection -> these will release cytokines and perforin leading to cell tissue death
examples of type 4 autoimmune conditions (3)
- T1DM
- RA
- multiple sclerosis
why is type 4 hypersensitivity sometimes known as “delayed” hypersensisitivity
delay in processing -> antigen taken up but APCs but it takes a few days for the antigens to be presented to T helper cells and produce cytokines -> these are required for the self cytotoxic T-cells to bind
how does type 1 autoimmunity work
allergy (not strictly autoimmunity) -> immediate reaction to allergen presentation in the body, histamine release
what cell secretes IgE and where does it bind
secreted by B cells and binds to IgE receptors on mast cells and eosinophils -> histamine release
what does the release of histamine in T1 reaction lead to
local inflammation -> vasodilation and porus epithelial lining to allow other immune cells to reach the pathogen
how can T1 hypersensitivity lead to anaphylaxis
large scale release of histamine leads to airway narrowing and reduction of blood pressure through vasodilation -> breathing disfficulties, feeling lightheaded, confusion etc.
what type of autoimmune reaction is anti-glomerular basement membrane disease
type II -> release of cryptic antigens due to damage to the lung from smoking, antibodies released which also bind to the BM in the glomerulus
what happens in goodpasture’s syndrome
auto antibodies bind in the kidney and lung -> leads to haemorrhage so haematuria/ coughing up blood
what does glomerulonephritis often result from
immune complex deposition e.g. by Hep B, C, malaria etc. -> type III reaction (also seen w SLE leading to lupus nephritis)
what is IgA made in response to
infection of mucosal srufaces
how does IgA nephropathy occur
IgA with unusual sugars made -> these sugars trigger auto-antibody reactions and causes immune-complex formation -> T3 reaction
frequent colds and infections increase IgA produciton
what are the antigens presented on to the T helper cells
MHC/HLA
what is central tolerence
the destruction of T cells that recognise self antigens when being educated in the thymus
where do immature T cells differentiate
in the thymus
what is negative selection (central tolerance)
when an immature T-cell binds strongly to a self MHC peptide they are negatively selected and destroyed in the thymus
is there a genetic link to autoanitbody formation
yes e.g. AnkSpn - HLA B27; goodpasture’s - HLA DR2 etc.
why might an infection trigger and autoimmune disease
normally self reactive T cells dont last long, however, is there is a infection then cytokines are made to combat this but these can also cause the proliferation of the self reactive T cells
examples of autoimmune conditions that tend to arise post infection (5)
- guillian barre
- myocarditis
- grave’s disease
- rheumatic fever
- ank spn
5 methods of treatment for autoimmune diseases
- removal of antibodies by plasmapheresis or IgG therapy
- anti inflammatory drugs - NSAIDs, steroids, biologics
- immunosuppressives
- restore/reverse specific damage e.g. insulin for T1DM, carbimazole etc.
- DMARD
