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Flashcards in L13 - Autoimmunity 1 COPY Deck (21)
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i) what is auto immunity? what is it also known as?

ii) what are auto immune diseases?

iii) what is tolerance? how does autoimmunity relate to tolerance?

iv) why are some diseases such as sarcoidosis and IBD not classified as autoimmune disease?

i) immune response to self antigens 

ii) adaptive immune responses to self antigens contribute to tissue damage

iii) state of immunological non reactivity to an antigen 

iv) involve immune system but have not been demonstrated to involve adaptive immune response to self antigens




i) how are lymphocyte receptors produced?

ii) what is the purpose of positive selection? what is the purpose of negative selection?

iii) what numbers of cells for each antigen are seen for naive B and T cell receptors? what number of receptors are there overall?

iv) after exposure to infection - what happens to lymphocytes? what do most end up doing? what do some do?

i) by random VDJ recombination

ii) positive selection > ensures reeptors are useful and can recognise self antigen in the form of MHCII
negative selection > deletes T cells with receptors that have a very high affinity for self antigen and reduce autoreactivity

iii) naiive T and B cell receptors > small numbers of cells for each antigen but large number of receptors overall

iv) after infection exposure > expansion of best lymphocyte populations 
- most ie and some stay as memory T cells 



i) what does negative selection do? 

ii) what are the consequences of neg selection is too rigorous? (3)

iii) what are the consequences if neg selection is too permissive? (3) 

iv) what is inevitable? 

v) which mechanisms fail if autoimmunity is produced?

i) neg selection > remove all cells with autoreactivity or bind self antigen too strongly

ii) rigourous negative selec > low risk of AI but poor repertoire of cells an increased suscep to infection 

iii) permissive negative selec > broad repertoire of cells, lower risk of infection but higher risk of autoimmunity

iv) some auto reactive T cell production is inevitable 

v) failure of peripheral tolerance mechanisms 



i) what is immunological heirarchy? what is required for CD4 activation?

ii) what is antigen segregation? give two egs of where this occurs

iii) what is peripheral anergy? 

iv) what is the role of regulatory T cells? what do they express on their surface?

v) what is cytokine deviation? give an eg

vi) what is clonal exhaustion? 

vii) what may failure of these peripheral tolerance mechnaisms allow for? 

i) IH - lots of cells are needed for the immune response
- CD4 will not be activated unless antigen is presented in an inflam context with TLR ligation

ii) antigen segregation - physical barrier that sequester antigen
- eg in eye and CNS

iii) PA - weak signalling between APC and CD4 T cell without co stimulation can cause T cell to be non response

iv) Tregs supress immune responses by cytokine/juxtacrine signalling - express CD25 and FOXP3

v) cytokine deviation - change in T cell phenotype eg Th1 to Th2 to reduce inflam

vi) clonal exhaustion - apoptosis post activation due to activation induced cell death 

vii) fail of peripheral tolerance may allow activation of auto reactive T cells > AI disease 



i) what is organ specific AI disease? give three examples

ii) what is multi system AI disease? give three examples

i) organ specific - antigen and target of damage is in one organ
- T1DM, pephigus, graves, hashimoto, AI cytopenias

ii) multi sys - antigen is distributed
- SLE, RA, sjogrens syndrome 



i) which type of hypersensitivity reaction involves production of auto antibods?

ii) how does the antibody act in this situation? what does it cause?

iii) what are the three criteria for an antibody to be pathogenic? 

i) type II hypersensitivity

ii) antibody is clearly pathogenic > causes disease/tissue damage directly

iii) 1) disease can be transferred between experimental animals by infusion of serum or during gestation (mum to baby)
2) removal of antibod by plasmapheresis is beneficial
3) a pathogenic antibody can be identified and characterised 



i) what happens in autoimmune haemolytic anaemia? give two symptoms of this

ii) what other type of AI cytopenias can develop? 

iii) which is characterised by peticiae and bruises?

i) RBC are recog by pathogenic antibodies > phago or activate complement > autoimmune haemolysis
- anaemia and mild jaundice 

ii) can affect any part of blood compartment

iii) rash and bruises = AT thrombocytopenia (low plats) 



i) what type of autoimmune disease is this? which hormone is targeted?

ii) give four symptoms

iii) what may be seen in the neck? what is seen in the eyes? 

iv) give three reasons it is classfied as this type of AI disease?

v) what does production of the antibody cause in relation to thyroid hormone production? what is the end result?

i) antibody mediated disease - antibodies to TSH

ii) tachycardia, palpitations, tremor, heat intol, anxiety

iii) goitre in neck
- eyes = graves ophalmopathy = proptosis and eyelid retrac

iv) baby gets hyperthyroid if mother affected
- serum transfers disease between animals
- antibod can be detected and charac 

v) auto immune B cell makes antibodies against TSH receptor which ACTIVATE the receptor
- stimulation of thyroid hormone production
- hormones neg feedback to TSH but no effect on antibody action so lots of thyroid hormone continues to be produced 



i) name two symptoms

ii) which five things are most often affected? what can make ptosis more marked?

iii) what is an antibody produced against to cause disease? what does this lead to?

i) muscle weakness and fatigability 

ii) eyelids, facial muscles, chewing, talking and swallowing
- ptosis more marked after asking pt to open and close eyes repeatedly 

iii) antibod against Ach receptor at the NMJ
- AchRs are internalise and degraded
- no Na+ influx and therefore no muscle contraction



i) what type of rash does it produce? 

ii) what causes it?

iii) what happens in relation to mast cells? how does this manifest clinically?

iv) is there an allergen trigger present?

v) what happens if it occurs in a deeper skin layer?

i) raised and itchy rash

ii) antibody is produced against IgE receptor or IgE itself

iii) IgG FceR1 antibody cross links the mast cells receptor 
- causes degranulation > histamine
- manifests as hives and swelling

iv) no allergen trigger present 

v) swelling and angioedema 



i) what does an antibody have to be to be defined to cause AI disease?

ii) how else may antibodies be produced? what are these useful for? 

iii) give two examples of where the above occurs?

i) auto antibody has to be pathogenic and directly lead to disease

ii) antibods can also be produced as a by product of inflamm process > dont fulfil criteria to be 'pathogenic'
- useful in diagnosis

iii) tissue transglutaminase antibod - coeliac disease
- islet cell antibody - diabetes 



i) what type of hypersensitivity reaction is mediated by T cells? 

ii) give two ways in which this can occur? 

iii) how easy is it to demonstrate this in vitro? what do experimental models rely on?

i) type IV hypersensitivity reaction 

ii) T cells can be activated by macrophages/other elements of innate immunity
or CD8 T cells damage tissue directly

iii) hard to demonstrate autoreactive T cells invitro 
- experimental models rely on genetically susceptible animals that are sensitised (by exposure to self antigen with an adjuvant) 



i) what is this mediated by?

ii) what is it the most common cause of? which sex/age are most affected?

iii) what is there autoimmune destruction of? which cells infiltrate? what do they react against?

i) mediated by T cells

ii) most common cause of hypothyroidism in industrialised countries > women 30yrs+

iii) autoimm destruction of thyroid 
- organ becomes infiltrated by CD4 and CD8 T cells 
- T cells react against thyroid antigens 



i) what type of genetic disorders can be associated with autoimmune diseases?

ii) what is enrichment of AI disease in families most attributable to?

iii) in groups of NOD mice with identical genetic background and similar enviro > what is seen in dev of T1DM? what does this indicate?

i) rare monogenic disorders

ii) enrichment in families > HLA associations

iii) NOD mice > variable dev of T1DM
- shows there is more than just genetics at play as they are all genetically identical 



i) what is APACED?

ii) which gene regulates ectopic expression of tissue specific antigens in the thymus? what does this allow?

iii) what do mutations in this gene result in? what is this strongly associated with?

iv) antibodies to which interleukin make candidis a key feature of this disease?

i) autoimm polyglandular syndrome, candidadis and ectodermal dystrophy

ii) AIRE gene reg ectopic express of antigens in thymus which allows T cell exposure to lots of antigens

iii) mutations in AIRE > failure of negative selection
- strong assoc with organ specific AI disease

iv) antibodies to IL-17 = reduced defence to fungi at mucosal surfaces 



i) give four things are seen in the full phenotype

ii) what is it caused by?

iii) which chromosome are there microdeletions in? is it purely monogenic?

iv) how can it present? what is the most common manifestation?

v) do patients have enough T cells? what goes wrong in relation to T cells 

i) absent parathyroids (low calcium > tetany), cleft palate, congenital heart defects, thymic aplasia (low T cell numbers)

ii) caused by failure of migration 3rd/4th brachial arches in embryogen 

iii) microdeletions in chromosome 22 therefore not purely monogenic

iv) can have variable presentation - spectrum of immunodefic
- most common manifestation is autoimmunity

v) patients have enough T cells but not enough pos/neg selection due to thymic aplasia 



i) what is it? which gene does it affect?

ii) what does it cause?

iii) name three key features

i) immune dysreg, polyendocrinopathy, enteropathy, X linked
- affected FOXP3 gene

ii) causes interuption of prod of CD4+CD25+FOXP3+ regulatory T cells

iii) inflamm bowel disease, dermatitis and organ specific immunity 



i) what is it also known as? what does it allow to happen?

ii) which chromosome is it encoded on? which letters encode class I? which encode class II? (3)

iii) how is it classified? 

iv) what do some HLA molecules have a strong association with?

i) aka MHC
- allows APCs to present processed peptide to T cells 

ii) encoded on chromosome 6 
- Class I > A, B, C
- Class II > DR, DP and DQ

iii) classified by what cell expresses on surface 

iv) some HLA molecules have struc association with autoimmine disease 



i) what type of disease is it and which organ does it affect? which other system can also be affected?

ii) what % of UK population is affected? which sex does it affect more?

iii) why is it an unusual autoimmune disease? what triggers it?

iv) what are the main manifestations? (5) what is seen on microscopy? (3) 

v) what HLA do virtually all individuals express? (2) 

i) common inflammatory disease of the small bowel
- also affects GI and extra GI

ii) affects up to 1% of UK population
- affects women more

iii) unusual as it is triggered by an exogenous antigen (gluten) in pre disposed individuals 

iv) main manifestations are malabsorption
- loose stools, weight loss, vitamin defic, anaemia, poor growth in children 
- see total villous atrophy, crypt hyperplasia and lymphocyte infiltration

v) all indivs express HLA-DQ2 or HLA-DQ8 or both



i) what substance found in the diet can trigger the immune reaction? what enzyme is it degraded by in gut tissue?

ii) which two molecules can present the peptides of this molecule to T cells? what must be present?

iii) why are healthy individuals not affected by this peptide?

i) dietary gliadin (wheat rye and barley) 
- degraded in gut tissue transglutamine 2 enzyme > gliadin peptides 

ii) HLA DQ2 and DQ8 can present gliadin peptides to T cells (gliadin gits in the groove of DQ2)
- must have the appropriate T cell receptor present

iii) healthy indivs dont express the DQ2 or DQ8 molecule therefore dont present gliadin peptides to T cells and dont have the reaction 



i) what is needed for gliadin to be presented by an APC? what happens if this occurs?

ii) what type of hypersensitivity reaction is this? what is the damage mediated by? are antibodies produced?

iii) how can inflammation resolve?

iv) what % of europeans express the relevant HLA? does everyone that has these HLAs have coeliac disease?

i) need to have the correct HLA R (DQ2 or DQ8)
- presented to T cells

ii) type 4 hypersensivitiy reaction as irs mediated by T cells
- antibodies are produced but they do not contribute to tissue damage 

iii) inflammation can resolve by strict gluten avoidance

iv) 30-50% europeans have HLADQ2 or DQ8
- not everyone who has these develops CD so there are other factors that play in