Autoimmunity Flashcards
what is autoimmunity?
immune system mistakenly attacks its self, targeting the cells, tissues and organs of a persons own body
how many different types of disease are caused by autoimmunity?
more than 80
what is the most common autoimmune disease?
graves disease
which sex is more susceptible to autoimmune disease?
female - not entirely sure why
what factors can lead to an autoimmune condition?
genetic factors
infection and environmental exposure
immune regulation altered
what is the fundamental problem of an autoimmune disease?
imbalance between immune activation and control
what is the type of disease controlled by?
the type of dominant immune response
what is central immune tolerance?
initiation or development of immune system in immune organs, educate immune system
what is peripheral immune tolerance?
cells have matured and can leave to secondary immune systems, mechanisms which can supress immune response but may be lost
what is molecular mimicry?
when a bacterial epitope looks very simiar to something we naturally present, response can be generated but it is actually self
what is an inappropriate activation?
when something happens and sets of an unnecessary response cascade
what is the regulation in the central immune system?
positive selection
negative selection
what is the regulation in the peripheral immune system?
regulatory T and B cells
dendritic cells and danger
co stimulation
ignorance
privilege
what are the genetics of autoimmune diseases?
-complex polygenic traits
-identified by genome wide association mapping
-single gene mutations are useful for pathway analysis
what can some polymorphisms be associated with?
multiple diseases
may control general mechanisms of tolerance and immune regulation
what can other genetic associations which are disease specific influence?
end organ damage
what genetic factors can increase risk of autoimmunity?
-smoking
-pollution
-drugs
-infectous agents
how do we know infection can be linked with autoimmunity?
-cilincal prodomes, animal models
-autoimmunity develops after infection is eradicated
-ie the autoimmune disease is precipitated by infection but is not directly caused by the infection
which autoimmune diseases have been seen to be prevented by infection?
-type 1 diabetes
-MS
-the hygiene hypothesis
what is the hygiene hypothesis?
if we live in clean environment and immune system does not get correct exposure to mature and educate itself in the correct way can make individuals susceptible to infection
what are immune mediated inflammatory diseases?
chronic diseases with prominent inflammation, often caused by failure of tolerance or regulation
-affect 2-5% of people, incidence is increasing
what is the pathogenesis of autoimmune disease?
-susceptible genes
-failure of self tolerance e
-persistence of functional self reactive lymphocytes
-activation of self reactive lymphocytes
-environmental triggers
what may be causing immune mediated inflammatory diseases?
-immune response against self antigens or microbial antigens
-may be T cells and antibodies
-may be systemic or organ specific
what are autoantibodies?
-often present in autoimmune conditions
-may or may not be pathogenic
-specific examples apparantly significant
-may be associated with specific disease states
what are some examples of specific targets of autoantibodies?
graves disease - TSH receptor
myasthenia Gravis - acetyl choline receptor
ITP- platelets
GBS - gangliosides
what causes graves disease?
-thyroid hormones regulated by TSH
-TSH binds to receptor and stimulates synthesis of thyroid hormone
-GD results in non regulated activating auto antibodies that bind to TSH receptor leading to overstimulation of thyroid hormone s
-auto antibodies are long acting thyroid stimulating hormones
what can T cells specific for auto antigens help?
generate anti host response
what is the anti host response in Graves disease?
T cells to thyroid follicular epithelial cells
what is the anti host response in myasthenia Gravis?
T cells to acetyl choline receptor
how is organ specific immune disease characterised?
-widespread self antigens are targets for autoimmune attack can be presented all over body
-damage affects such structures as blood vessels, cell nuclei ect
how is organ specific immune disease characterised?
-autoimmune attack vs self antigens of given organs
-results in damage of organ structure and function
what happens in Guillian Barre syndrome?
-transient autoimmune disease
-example of molecular mimicry
-auto antibody mediated autoimmune disease of peripheral nerves
-triggered by infections including campylobacter jejune
-common cause of acute paralysis
-pathogenesis incompletely understood
what are the stages of evolving pathogenesis of RA?
pre-articular or lymphoid phase
transition phase
articular plase
what happens during pre articular/lymphoid phase of RA?
autoimmunity
CCP- specific antibody rheumatoid factor
collagen-specific response
GP39 specific response
what happens during the transition phase of RA?
microbial insult
bio-mechanical events
neurological events
microvascular dysfunction
