i) give two reasons why the immune system may fail to control infection?
ii) give two ways that the immune system maay cause disease directly
iii) who proposed a system to classify immunol mediated disease? what mechanisms does the classification refer to?
i) pathogen factors have evasion mechanisms
- host factors eg immundeficiency
ii) imm sys can directly cause disease by failure of tolerance (allergy/autoimm)
- or inapprop activation eg IBD/asbestos
iii) Gell and Coombes
- refers to immunol processes that are all normal functions but are inappropriately activated
GELL AND COOMBES CLASSIFICATION
i) what is the mechanism of a Type I hypersensitivity reaction?what Ig is involved? give two examples
ii) what directly causes disease in Type II hypersens? give two examples
iii) what causes disease in Type III hypersens? give three egs
iv) which cells is inflammation directly mediated by in Type IV hypersens? give two examples
i) type I - IgE antibody directeed against an allergen triggers mast cell degranulatin
- seasonal rhinitis and cat allergy
ii) type II - pathogenic antibody directly causes disease
eg autoimmune haemolysis and haemolytic disease of newborn
iii) antibody-antigen complex causes disease
eg serum sickness, hypersens pneumonitis, SLE
iv) type IV - inflamm is directly mediated by T cells
eg contact dermatitis and tuberculin reaction
TYPE I HYPERSENSITIVITY REACTION
i) which Ig mediates this reaction? which cells class switch to allow this?
ii) what process involving the Ig antibody and antigen activates mast cells?
iii) what do mast cells release on activation? (2) what does this lead to in the affected organ? what is this believed to aid in health?
- B cells class switch > secrete IgE which is taken onto surface of mast cells and basophils
ii) cross linking of allergen spec IgE antibody by allergen activates the mast cell
iii) mast cells release histamine > symptoms in affected organ
- in health - assist in parasite immunity
TYPE II HYPERSENSITIVITY REACTION - BLOOD
i) what is this mediated by? give an example
ii) which antibodies to AB antigens on blood cells develop in first year of life? what type of antibody are these an eg of?
iii) where are these antigens also found apart from on red cells? how does the immune system respond to this?
iv) complete diagram
i) mediated by antibodies eg mismatch of blood types in blod transfusion
ii) develop IgM antibodies to antigens on blood cells
- eg of isoantibodies
iii) body develops antibodies to antigens on gut bacteria that are also found on red cells
iv) 1 - anti B
2 - anti A
HAEMOLYTIC DISEASE OF THE NEWBORN
i) what type of hypersensitivity reaction is this?
ii) what is the D antigen?
iii) are the majority of the population D+ or D-? will they have anti-D antibody?
iv) give two instances where a mother may be sensitised to foetal red cells during pregnancy?
v) when may anti-D to fetal cells cause disease?
i) type II hypersensitivity
ii) D antigen is found on the surface of RBCs
iii) most people are D+ so wont have Anti -D antibody
iv) mother can be sensitised during birth or trauma
v) anti-D may cause disease in subsequent pregnancies if baby is rhesus positive - antibods cross placenta and cause disease in baby
HAEMOLYTIC DISEASE OF THE NEWBORN - MECHANISM
i) how can this disease be described? name three consequences for thee baby?
ii) what resus status mother and partners are given Anti-D igG during pregnancy?
iii) what does giving anti-D do? at what week is it given? name three other events it may be given after?
iv) what does giving anti D reduce the risk of maternal sensitisaton from and to?
v) what type of immunisation is this?
i) autoimmune haemolysis
- growth retardation, CV failure, neurotox from high bilirubin levels
ii) rh- mother and rh+ partner - usually given at 28 weeks
- binds to fetal cells entering circulation and prevents sensitisation and production of antibodies
- also given post accident/miscarriage/surgical delivery
iv) giving anti D reduces risk of maternal sensitis from 16% to 0.1%
v) passive immunisation
i) what type of hypersensitivity reaction is it?
ii) what happens in relation to macrophages? (extravascular) (3)
iii) what triggers intravascular AH?
iv) give two clinical signs
i) type II
ii) spontaneous form antibodies against red blood cells
- antibodes bind RBC
- macrophages see opsonised red cell and destory it
iii) intravascular AH can be triggered by activating complement
iv) anaemia and jaundice
TYPE III HYPERSENSITIVITY
i) what is it caused by? is this a physiological process?
ii) what happens to cause a type III hypersens reaction? (3)
iii) name four situations that may cause this reaction
i) caused by complexes of antibody and antigen
- this is physiological and happens all the time but usually soluble and removed by the spleen
ii) in a reaction - the complexes become insoluble, deposit in capillaries and cause disease
iii) large quantity of antigen, large quantity of antibody, interac bet antigen and antibod is v strong, complexes are of a certain size
LOCAL IMMUNE COMPLEX DISEASE
i) what type of hypersensitivity reaction is it?
ii) what happens? why?
iii) name two conditions it may be seen in
i) type III
ii) painful lesions in the fingertip pulp due to depos of circulating immune complexes
- local inflammation and necrosis
iii) may be seen in infective endocarditis (oslers nodes) and SLE
i) what type of hypersensitivity reaction is it? what is it mediated by?
ii) what does it mainly result from? give an example of this?
iii) name four symptoms
iv) is it transient or permanent?
i) type III
- mediated by immune complexes
ii) results from injection of non humanised immunogenic drugs/anti sera produced by animals eg after a snake bits
- inject venom to animal to raise high affinity IgG antibodies to venom > purify and inject
iii) rash, fever, arthritis, glomerulonephritis
iv) transient - once serum is cleared it will go away
i) what is it also known as? what type of hypersensitivity reaction is it?
ii) what happens? what type of Ig is produced?
iii) where do immune complexes form? what does this cause (2)
iv) name two causative organisms
v) is it transient or permanent? what can occur if it repeatedly happens?
i) extrinsic allergic alveolitis
- type III hypersens reac
ii) patient becomes sensitised to an environmental allergen by repeated exposure > prod large amounts of IgG antibod
iii) immune complexes form in the lung upon re-exposure
- causes shortness of breath and cough
iv) caused by mould spores in hay (farmers lung) and pigeon feathers/stool
v) transient but get lung scarring with repeated exposure
TYPE IV HYPERSENSITIVITY
i) what type of hypersensitivity is it?
ii) what are reactions mediated by?
iii) how long does it take for the reaction to develop? why?
iv) what is it known as in the skin?
i) delayed type hypersensitivity
ii) reactions mediated by antigen specific effector T cells
iii) takes at least 24hrs to develop as it takes time to process and present the antigen
iv) contact dermatitis in skin
CONTACT DERMATITIS - SENSITISATION
i) what type of agent is the sensitising agent? give two examples
ii) what does the agent react with and what is created? which cells mediate this?
iii) what is haptensiation? which cells process and present antigen on MHCII?
iv) how do some individuals respond to these complexes? which cells are activated and where do they travel?
i) highly reactive small molecules that can penetrate the skin
eg nickel and molecules in perfume/cosmetics
ii) agents reacts with self proteins to create a protein-hapten complex > picked up by langerhans cells and migrate to regional LNs
iii) haptenisation is when hapten (small molecule) cant produce an immune response by itself byt can bind to a protein to alter its immunogenicity
- langerhans cells process and present complex on MHC II in LNs
iv) some individuals recognise the complexes as foreign
- this activates T cells > migrate to the dermis
CONTACT DERMATITIS - ELICITISATION
i) when does this process occur?
ii) what happens in terms of hapten and langerhans cells?
iii) what is already found in the body? what is subsequently released to cause a reaction?
iv) name three ways the body reacts (3)
v) how can contact dermatitis be tested for? how long does it take for results to be read?
i) when the antigen is met again
ii) agent penetrates the skin > haptenisation > taken up by langerhans cells and presented to a T cell
iii) pre formed Th1 cells that produce IFNy > reaction
iv) cytokines such as IFNy and chemokines cause
- inflammation, vasodilation and infiltration of inflammatory cells
v) antigen impregnated patch test placed on back
- impreg with nickel, chrome, cobalt, epoxy etc
- results read after two days as its a delayed hypersens reaction
TUBERCULIN SKIN TEST
i) what type of hypersensitivity reaction is this an example of? what is it used to determine?
ii) what happens in the test?
iii) what happens if there has been previous exposure to MTB? how long does this take to develop? why?
iv) which cells mediate the reaction?
i) type IV hypersens reaction
- used to determine previous exposure to TB
ii) tuberculin (mixture of antigens from MTB) is injected intradermally
iii) if prev exposure > local inflam response over 24-72 hours
- takes up to 72 hours as its a delayed response that involves T cells
iv) Th1 cells mediate reaction
MECHANISM OF TUBERCULIN SKIN TEST
i) what happens to the tuberculin once its injected to the skin?
ii) what type of cells is it recognised by if there has been previous MTB exposure? what happens in this case? (2)
iii) what happens if there has been no prev exposure to MTB?
iv) is this a specific or non specific test? why?
i) tuberculin is processed by local APCs and presented
ii) if there has been previous MTB exposure then it will be recognised by Th1 cells
- get inflammation and recruit phagocytes
iii) no prev exposure = no reaction as wont have Th1 cells
iv) non specific test has tuberculin has cross reactivity with non TB mycobacteria eg found in soil
DETECTION OF TB SPEC TH1 CELLS BY INTERFERON GAMMA RELEASE ASSAY
i) how is the test set up? which two MTB peptides are used?
ii) if there has been previous TB expsoure - what happens? if there has not been previous exposure - what happens?
iii) which lab technique is then used?
iv) what is the plastic well of the dish coated with? what is added? if there has been exposure to TB - what happens?
v) what is the final step? what does this allow?
vi) name another method that can be used for detection
i) MTB peptides added to blood in the lab
- use ESAT-6 and CFP-10 (unique to MTB)
ii) if prev TB expos > memory Th1 cells recog antigen and release IFNy in short time frame
- if no prev expos then no IFNy is produced in the short timeframe
iii) then use ELISPOT
- plastic well coated with catcher antibod to IFNy
- add blood cells and peptide
- if cells have produced IFNy then it will be captured by the antibody on the plate
v) then add a secondary antibody as a marker to produce a colour change if IFNy has bound to antibody > see spots on plate
vi) can also use ELISA method > look for concentration of IFNy produced
GELL AND COOMBES
i) name two pros
ii) is it useful in clinical practice?
iii) name a con
iv) name three diseases that are not well described in this framework? why?
i) only sucessful attempt to classify disease by mechanism
- useful framework to describe and understand diseases
ii) not very useful in clinical practice
iii) con - oversimplifies immunology (usually there are lots of components of the immune system involved)
iv) Rheumatoid arthritis, chronic asthma, inflam bowel disease
- involve multiple immunol effector mechs that arent well described in this framework