L14 - Autoimmunity 2 COPY Flashcards Preview

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Flashcards in L14 - Autoimmunity 2 COPY Deck (19)
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i) what is it? what does it lead to?

ii) which MHC are viral peptides presented on? which T cell recognises this? what does this cause in the T cell?

iii) what do the viral peptides resmble in MM? what does this cause the T cell do do?

iv) what does the MM process depend on? (2) 

i) epitopes relevant to the pathogen are shared with host antigens leading to an immune response in the host due to cross reactivity

ii) viral peptides presented on MHC II and recognised by CD4 T cells > activates the T cell

iii) viral peptides resemble host derived peptide > causes the T cell to now strongly react to self peptide and initiate inflammation 

iv) process dep on having correct MHC to present the epitope common to the host and virus (inherited) and also having the correct T cell to recognise it (bad luck) 



i) what can occur after mycoplasma pneumoniae? what is the myocoplasma antigen homologous to in the host?

ii) which Ig is released to mycoplasma and can also cause response to host tissue? how long does this last?

iii) what can occur after streptococcal infection? name three areas it can affect 

iv) what do anti strep antibodies cross react with? 

i) autoimmune haemolysis can occur post mycoplas pneumoniae as mycoplas antigen has homology to I antigen on RBCs

ii) IgM to mycoplas can cause hameolysis = transient response and settles when infection is cleared

iii) rheumatic fever post strep infection
- affects heart, joints, skin, brain

iv) anti strep ABs cross react with connective tissue 



i) which cells undergo autoimmune destruction? what does this lead to a lack of? name three symptoms seen

ii) when is antibody detectable in relation to onset of clinical disease? what does this mean we can do?

iii) what does an early pancreatic biopsy show? is there active inflammation when the patient presents? why?

iv) are autoantibodies thought to be responsible for destruction of pancreas?

i) beta cells in islets of pancreas > lack of insulin
- polyuria, polydipsia, polyphagia, weight loss 

ii) islet cell antibody is detectable for months to years before the onset of clinical disease > track blood of those at risk

iii) early panc biopsy shows CD4/CD8 T cell infiltration 
- there is not active inflam when the patient presents as it has already been destroyed

iv) no 



i) what molecules confer genetic suceptibility?

ii) what can trigger progression to autoimmune disease?

iii) what event happens before clinical onset? what cells are seen in the pancreas?

iv) which protein is lost after clinical onset? what % of the pancreas has been destroyed when overt diabetes has developed?

v) label diagram 

i) HLA molecules

ii) enviro trigger can cause progress to AI disease

iii) autoantibod insulinitis pre clinical onset
- see T cell infiltrating the pancreas 

iv) loss of C peptide after clinical onset
- 90% of panc destroyed at this point

v) A - genetic suscep, B - enviro trigger, C - auto antibod infiltrate panc, D - clinical onset, E - loss of C peptide 



i) what is the approx concordance in monozygotic twins? what does this show?

ii) what type of HLA alleles are the major defined risk factor? having one of which two alleles give relative risk of 6? what is the relative risk of having both?

iii) what are the HLA molecules thought to be responsible for? what other disease is this seen in?

iv) which two things may be required for an AI response?

i) almost 100% concordance > genetic background is important

ii) HLA class II alleles most important
- DR3 or DR4 = RR 6
- DR3 and DR4 = RR 15 

iii) HLA molecules thought to be responsible for presenting relevant islet cell antigens to CD4 T cells (also seen in coeliac)

iv) need appropriate T cell receptors and other genetic/enviro cofactors 



i) how long before diagnosis can autoantibodies to islet cells be detected? why is it difficult to identify triggers?

ii) what can viral infection with coxsackie virus cause in mice and humans? what does this precipitate to in mice?

iii) which protein does protein 2C from the coxsackie virus have homology with? what mechanism may be mediating the reaction  

i) autoantibods present months-years before clinical onset
- hard to identify triggers as there is a gap between init of disease and presentation 

ii) coxsackie virus infection can cause pancreatitis > ppt to autoimmune diabetes in mouse models

iii) protein 2c from coxsackie has homology with islet cell antigen glutamuc acid decarbox (GAD)
- may be through molecular mimicry mech 



i) what is critical for determining which peptides can be presented? what arm of the immune system is AI disease always about?

ii) which part of the T cell repertoire is inherited? which part involves random recombination 

iii) what may influence T ad B cells to be autoreactive?

i) MHC background > AI always involves adaptive immunity

ii) gene segments for the TCR are inherited by production of the receptors is done by random recomb so will differ even between identical twins

iii) infection can cause T and B cells to be autoreactive 



i) what type of AI disorder is it?

ii) what type of rash is commonly seen in skin? what two other things can be seen in skin? how are the kidneys/lungs/joints affected

iii) what group of people is it most common in (sex and age) which ethnic group?

iv) what is it associated witht the presence of? what do these do?

v) give two other things that can precipitate the disease?

vi) which proteins may some patients be deficient in?

i) multi system AI disease

ii) see butterfly lupine rash + photosensitivity and hives
- nephritis, pulm fibrosis, joint pain

iii) most common in women of reproductive age and asian/african descent 

iv) associated with presence of anti nuclear antibodies 
- collection of antibodies that react with cell nuclei/cell div apparatus

v) immune complex deposition and disordered apoptosis can also ppt disease

vi) some patients may deficient in classical complement components eg c1,c4,c2



i) name three complement proteins that can be implicated in lupus?

ii) what do these proteins usually do? what happens when they are absent?

i) C1q, C2 and C4 > deficiency can predis to lupus

ii) these prots usually enhance phagocytosis of immune complexes > deficiency may mean that immune complexes arent removed by spleen 



i) give three roles of autoantibodies in immune disease

ii) what are the three methods for detection? which two detect AB in the blood? which one detects AB bound to tissue in a biopsy?

i) Abs can have diagnostic value, be pathogenic or just have a bystander effect 

ii) detect by indirect immunofluoresc/solid phase immunoassay (det AB in blood) or direct immunofluro (biopsy)



i) where are antibodies detected from?

ii) what is the glass slide covered with? what is added to the well?

iii) what secondary antibody is added? why? 

iv) how is the test read

i) ABs detected in the blood

ii) glass slide covered with tissue of interest from animal etc
- add patient serum to the well (if antibodies are pres they will bind)

iii) detection antibod labelled with a fluorescent marker

iv) looking for fluoresence under microscope using UV light 



i) give three reasons why its important to detect T1DM

ii) which tissue is used to coat the wells? what does positive staining indicate?

iii) is this technique the best way to detect T1DM? what is better?

iv) are the antibodies in T1DM pathogenic?

i) risk of ketoacidosis, requires insulin and monogenic/T2DM req a different approach

ii) coat wells with monkey pancreas > positive staining indicates presence of islet cell autoantibodies

iii) this method is now being replace with immunoassays for specific antigens eg GAD 

iv) antibods are not pathogenic 



i) where are antibodies detected? name a technique used

ii) what is the well coated in? what is added to the well?

iii) why are enzyme linked antibodies then added? what is added after this? 

iv) how is the amount of antibody present quantified?

v) name a technique this is now being replaced with

i) in the blood - ELISA

ii) well is coated in pure source of relevant antigen
- add patient serum that may/may not contain antibodies 

iii) enzyme linked antibody then added to bind the specific antiody in the patient serum
- then add a substrate and the enzyme converts this to a coloured product

iv) amount of specific antibody is proportional to the rate of colour formation 

v) being replaced with newer more automated methods eg particle bead suspension



i) what are wells coated with and what is added to wells?

ii) what type of Ig is the secondary antbody that is added? what does this bind to? what is it cov linked to?

iii) what is needed to make the experiment valid?

iv) what is produced from the readings from each well?

i) coat wells with antigen of interest and add patient serum 

ii) secondary antibody is IgA which binds to IgA Fc regions 
- cov linked to an enzyme eg horseradish peroxidase > colour change when substrate is added

iii) need wells with known concentrations of antibody - pos and neg controls

iv) produce a standard curve from readings 



i) where does it detect antibodies? 

ii) what is put on the slide? in what situation will antibody already be present? 

iii) what is added next? how is the result visualised?

i) in tissue biopsy

ii) put the tissue on a slide
- if damage is mediated by an antibody then antibody will already be stuck to the antigen in the tissue

iii) then added detection antibody with fluoresecent marker and look under MS 



i) what is seen? 

ii) what does it fulfil the criteria for?

iii) where is the target antigen found? what is it 

iv) how is antibody deposited? what does this activate? what is therefore produced?


i) thick walled bullae on skin/mucus membranes 

ii) fulfils criteria for antibody mediated disease

iii) target antigen is at dermo epidermal junction 
- intercellular cement protein desmoglein 3 in superficial skin later 

iv) linear deposition of antibody > activates complement prodiceing skin splitting (dehiscence) and tense blister 



i) where were antibodies found to bind and have a strong disease association with coeliac in 1990s?

ii) what is the target antigen? how is this tested?

iii) what else can be utilised to diagnose? the absence of which protein makes CD very unlikely?


i) antibodies binding to endomysium of smooth muscles fibres

ii) target antigen is tissue tranglutaminase (tTG)
- now expressed in recombinant systems to provide antigen for immunoassays

iii) HLA typing can be used in diagnosis 
- absence of HLA-DQ2/3 makes coeliac disease dx unlikely 
(high negative predictive value - can have antigen and not have CD but if you dont have antigen you probably done have CD)



i) where is vitamin B12 absorbed? what does this absroption require? what cells secrete it?

ii) what is destroyed in PA? what does this lead to in relation to B12 absorption?

iii) how many years supply of B12 does the liver store?

iv) name three manifestations once B12 is depleted

i) abs in terminal ileum - abs requires intrinsic factor which is secreted by gastric parietal cells 

ii) PA = autoimmune destruction of gastric parietal cells therefore no intrinsic factor release and no B12 abs

iii) liver holds 2 years of B12 supply

iv) PA can manifest as anaemia, neurological, subfertility 



i) what is usually managed? why is the immunology not treated? (2)

ii) give three examples of treatment for AI disease 

iii) which type of AI diseases is immunomodulation useful for? give two examples 

iv) what does plasmapheresis involve? what can it be used for? give a pro and con 

i) usually manage the consequences 
- preferable to treating the immunol as immunosupp drugs are toxic and damage is usually already done by time of dx

ii) thyroxine for hypothyroid, carbimazole/sx/drugs for hyperthyroid, insulin for diabetes, B12 for pernicious anaemia

iii) immunomod is useful for multi system non organ specific disease eg give systemic corticosteroids or small molecule immunosupp eg methotrexate

iv) plasmapheresis removes antibodies from blood of healthy donor to give to patient w albumin
- pro = safe as doesnt cause immunosuppress and con it needs specialist technology