Autoimmunity Flashcards
what is autoimmunity
the presence of immune responses against self tissues/cells
when does auto immunity become dangerous
when there is HIGH titres of auto-antibodies or auto-reactive T cells
what can high titres of auto-antibodies or auto-reactive T cells cause
significant tissue/organ damage, chronic inflammation
what is the initiating event of autoimmune diseases
exposure to noxious substance or environmental factor
what determines whether a autoimmune reaction will be driven
genetic susceptibility- build up of many susceptible genes
what occurs after the initiating event
breakdown of self tolerance- loss of immune regulation- generation of auto-reactive B and T cells
what does the breakdown of self tolerance lead to
autoimmune phenomena/disease
what is a monogenic disorder
single gene defect causing autoimmune diseases that are rare
what is IPEX syndrome
a rare monogenic disorder of immune disregulation
what genes are commonly involved in the complex genetic interplay that results in most autoimmune diseases
HLA genes, sex genes, immune response genes
how does ipex syndrome present
overwhelming systemic autoimmunity in early childhood causing a wide range of symptoms
a mutation in what gene leads to IPEX syndrome and why
FOXP3, as essential for the development of regulatory T-cells
why are only males affected by IPEX syndrome
as it is X linked
what are T follicular helper cells
antigen experienced CD4+ T cells that produce interleukins that lead to B cell co stimulation
what is the role of T regulator cells
secrete anti inflammatory cytokines that can act on all of the other T and B cells supressing their activity (ymphocytes)
what does loss of balance of T Reg cells lead to
loss of control of T cell activation- uninhibited; loss of control of adaptive immune response = autoimmune disease
why do healthy T reg cells prevent autoimmune disease
as suppress hyperactive T cells
how do defective T Reg cells affect peripheral tolerance
leads to failure of peripheral tolerance= IPEX
what are tolerance mechanisms
control populations of T and B cells
describe central tolerance
deletion of self-reactive lymphocytes in primary lymphoid tissues
describe peripheral tolerance
inactivation of self-reactive lymphocytes in peripheral tissues that escape central tolerance
why must self reactive lymphocytes be deleted
as healthy T and B cells don’t recognise self antigen
what is HLA
human leukocyte antigen- gene complex coding for MHC proteins in humans
how can each individual express 12 MHC genes
2 variants of each HLA molecule type= 2 copies of chromosome 6 from parents
why is different types of MHC molecules a good thing
as each better at presenting different peptides- able to present T cells with a wider range of peptides- polymorphisms makes all these genes differnt
where do all nucleated cells express HLA class 1
cell surface
how can sex differences affect autoimmune disease
sex bias in predisposing genetic factors, hormonal influences in lymphocyte function, pregnancy
what is molecular mimicry
when pathogenic peptides mimic self antigens triggering a immune response targeting self antigens
what environmental factors can contribute to autoimmune disease
infection- molecular mimicry
give an example of molecular mimicry
acute rheumatic fever after streptococcal infection; strep. M5 protein v similar to cardiac tissue proteins, drives hypersensitivity reaction which targets self antigens
what type of hypersensitivity reaction is acute rheumatic fever after streptococcal infection
type 2 as dealing with immune system vs self antigens bound to surface of cell
what is reactive arthritis and what can it follow
sterile inflammation secondary to bacterial infection
what is antigen sequestration
sequestered antigens are ones that cannot interact with the immune system during development so exposure to them due to damage (e.g to blood brain barrier, testes or eye) could drive autoimmune response
what do super antigens cause
toxic shock syndrome
what are two examples of super antigens
staphylococcal proteins, clostridium endotoxin
why is immune regulation important in autoimmunity
as maintain self tolerance
what is the clinical classification of autoimmune disease
organ-specific or non-organ specific/multi system diseases
what is the pathological classification of autoimmune disease
gel and coombs classification (hypersensitivity reactions)
what type of hypersensitivity reaction is not applicable to autoimmune conditions
type 1- immediate hypersensitivity (allergy)
describe the mechanism of graves disease
mediated by type 2 mechanisms-
antibodies bind to TSH receptor (thyroid stimulating hormone)
what is graves disease the leading cause of
hyperthyroidism
describe goodpasture’s syndrome
mediated by type 2 mechanisms- antibodies bind to glomerular basement membrane in lungs and kidneys leading to bleeding from the lungs and kidney failure
how are type 2 hypersensitivity reactions managed
plasmapheresis (removal of pathogenic antibody) immunosupression (switch off B cell production of antibody)
give two example of type 2 mediated autoimmune diseases (bound anitgen)
graves disease and good pastures syndrome
what is an example of an autoimmune disease mediated type 3 mechanisms
systemic lupus erythematosus (SLE)- auto-antibodies against nuclear antigens
how are type 3 hypersensitivity reactions managed
control symptoms- limit sun exposure, analgesia, hydroxychloroquinine, decrease inflammation and production of auto-antibodies
give three examples of type 4 hypersensitivity mediated autoimmune diseases (delayed hypersensitivity)
type 1 diabetes, coeliac disease, Rh arthritis
what does an overwhelming og clearing mechanism mean
oxygen will not be cleared
