Autoimmune disease Flashcards
what attacks the body during an autoimmune disease
T & B cells
what is the humeral response of an autoimmune disease mediated by
B cells
in a humeral response, what is the target against
microbes which are outside of the cell & they produce antibodies against those microbes
what is the cellular response led my in an autoimmune disease
T cells & T lymphocytes
how does the cellular response take place by T cells in an autoimmune disease
T helper cells, which when detect an e.g. microorganism or detect something is wrong, will release cytokines in order to recruit neutrophils, macrophages, B cells into the area
what do cytotoxic T cells do when it finds the infection
it will induce apoptosis
what does an autoimmune disease cause
immune reactions against self antigen (the body itself becomes foreign)
how many % of the population has an autoimmune disease
1-2%
what three prerequisites/evidence is there that there is an autoimmune disease
- presence of an immune reaction specific for a self antigen or tissue
- evidence that the immune complex is the primary cause
- absence of any other aetiology
what is self tolerance
the lack of responsiveness to an individuals own antigens (i.e. own proteins/DNA)
our immune system can tolerate ourselves, we don’t usually attack ourselves so autoimmune is breakdown of self tolerance
which cells that recognise our cells as ‘the self’ that are constantly being produced, must be eliminated
lymphocytes - T & B cells
what does removal of auto reactive T & B cells result in
autoimmune disease
which cells need to be eliminated if they recognise the body as foreign
T & B cells
where are T cells produced
thymus
where are B cells produced
bone marrow
what is central tolerance
when T cells that recognise ‘self’ are removed in the thymus and B cells that recognise ‘self’ are removed in the bone marrow
however the process is not 100% fool proof and some T or B cells which are non tolerant/that recognise ‘self’, escape to the periphery and are auto reactive
when central tolerance is not 100% effective, by what other means can the T or B cells (that are non tolerant) which have escaped to the periphery be removed
via peripheral tolerance
what is peripheral tolerance
Anergy: prolonged or irreversible functional inactivation of lymphocytes (when cleared in peripheral part of body)
many interactions between CD28 and B7 and regulatory T cells that can induce anergy apoptosis (in periphery) in auto reactive T cells (to destroy T cells)
when do we induce a T cell response in relation to the peptide
if it is non self
when do we induce apoptosis in relation to the peptide
when it is self
what induces anergy
tissue cell or APC lacking B7
what causes the non up regulation of B7
when auto reactive T cell comes along & binds to the self peptide cell on the MHC protein, because the cell is not infected, it is not going to up regulate B7, so the cell hangs around and becomes anergic/inactive as it doesn’t get co-stimulation from B7, so lack in B7 induces anergy
what causes the up regulation of B7
bacteria inside a cell
what is one way of muzzling the T cell
by moving B7 = don’t get activation of the T cell
a breakdown of what mechanisms produces an autoimmune disease
- central tolerance
- peripheral tolerance
- induction of immunity
what are the possible causes of an autoimmune disease
a combination of:
- inheritance of susceptible gene
- genes which may contribute to breakdown of self-tolerance
- environmental/infective triggers that activate self-reactive lymphocytes
what does the inability to produce T cells cause and in return, an increase of what cell causes this
autoimmune disease, caused by an increase in auto reactive T cells/self reactive lymphocytes
what can serious trauma or stress cause
autoimmune disease via overload of self infecting T cells
what are the two possible roles in infection of autoimmune disease
- induction of co-stimulators on APCs
- molecular mimicry
what happens during induction of co-stimulators on APCs, as a possible role in infection of autoimmune disease
when a microbe is picked up by an APC, it up regulates B7, but because there is a self reactive T cell, it is co-stimulated with B7/CD28 & self peptide, so we start creating more and more T cells which are reactive against itself
in other words…
it induces APC & up regulation of B7, the APC is presenting self peptide which wants to trap the T cell, making it anergic, but the bacteria up regulates B7, but to produce anergin, we use the autoimmune response = increasing number or T cells
what happens during molecular mimicry as a possible role in infection of autoimmune disease
it is the other a microbe may result in activation or T cells.
the microbial agent produces an antigen & mimics its own self antigen of tissue, so T cells rather than acquiring immunity against the microbe, they acquire immunity against ourselves so this tricks the APC to present a bit of ourselves & T cells go and attack us
what are the two types of clinically varied diseases of an autoimmune disease
- organ specific e.g. diabetes
- systemic diseases eg SLE
give examples of what occurs in organ specific autoimmune diseases
auto reactive T cells and antibodies are specific to beta cells in diabetes
or
MS - in which auto reactive T cells target myelin in CNS
give examples of what occurs in systemic autoimmune diseases
eg in SLE (systemic lupus erythematosus), a diverse range of antibodies are directed against DNA, platelets, erythrocytes and protein phospholipid complexes
what is the ratio of females:males who suffer from SLE (lupus)
1:2500 so more common in females
what two types of onset can trigger SLE
acute or insidious (more common)
what is an insidious onset
periods of remitting and relapsing/inflammatory event in one organ then cessation
i.e. where someone may first present with a cardiac myopathy which goes away, then after have uveitis, and after have dermatitis etc, it is a sequence of inflammatory events which when all put together can be lupus
what are the main injuries to in SLE
- skin
- joints
- kidney
- serosal membranes (ie gut, pericardium, lung)
explain the mechanism of how UV damage + sunlight damages cells and apoptosis causes lupus
components found inside a cell e.g. DNA, ribosome etc don’t normally see the T cells as they’re inside the cell, so theres no reason for the T cell to be looking for stuff inside a cell, but only when a cell is damaged e.g. by apoptosis and suddenly all the components e.g. proteins come out and T cells see this as foreign as they usually only recognise the MHS cell receptors etc found on the cell surface, so the T cell makes antibodies against stuff from the inside of the cell which = lupus (a build up of antibodies against antigens inside the cell)
what are antinuclear antibodies (ANA)
immunoglobulins/antibodies, that are directed against the cell nucleus
what does a antinuclear antibodies (ANA) staining show
antibodies attaching to ribosomes, DNA, RNA, i.e. things that shouldn’t be auto reactive as they should be inside a cell & safe
list the main clinical manifestations and their prevalence of systemic autoimmune diseases
arthritis 80-90%
skin 85%
myalgia 35%
ocular 15%