Mar27 M1-Hypersensitivity disease Flashcards
Coombs and Gell classification of hypersensitivity
type 1 = immediate (IgE): allergies, asthma, dermatitis
type 2 = ADCC (Ab dependent cell mediated cytotoxicity) (IgM, IgG)
type 3 = immune complex mediated (IgM, IgG)
type 4 = delayed type (T cell mediated)
can you have allergic response upon first exposure to an allergen
no. never happens. not possible. always circulating IgE first that binds mast cells, ready for 2nd response
IgE is on surface of what cells
tissue mast cells and circulating IgE
substances released by mast cells when activated (pro inflam substances)
immediate = histamine, TNF-a, proteases, heparin (in the granules)
in minutes = PGs, LTs
over hours = IL4, IL13
lead to local AND systemic effects
different routes for type 1 rx to occur
- skin contact
- injection
- ingestion
- inhalation
in ADCC (type 2), what are the IgG or IgM made against
- intrinsic Ag (normal self Ag) = failure of immune tolerance OR cross reactivity of self ag with foreign one and we recognize both
- extrinsinc Ag (penicillin at surface of RBCs)
ADCC what happens after Ab binds self cell surface
- opsonization
- complement (classical MAC)
- NK cell activation
- activation or blockage of important Rs
effect of ADCC when penicillin rx
- complement or opsonization (MAC)
- get hemolytic anemia
ADCC: how NK cells kill self cells
- recognize Fc portion of the IgG Ab
- release perforin (makes pore) and granzyme (enters cell, causes apoptosis)
examples of ADCC mediated pathologies
- autoimmune diseases like ITP, myasthenia gravis, Grave’s (thyroid), Goodpasture’s
- AB and Rh blood group incompatibilities (transfusion reactions)
- some drug rxs
type III HS rx: immune complex mediated: what happens
- Ag excess compared to amount of Ab
- Ag-Ab complexes form and large amounts in circulation
- deposit in end capillaries of certain organs (skin, joints, kidneys, etc.)
effect of deposited immune complexes in type III HS rx
- encourage neutrophil influx = lead to immune response
- MACs (complement) happen
- aggregation of platelets
- inflammation and vasculitis results
immune complex mediated (type III HS) pathologies: give 3
- serum sickness
- immune complex GN
- extrinsic allergic alveolitis (Farmer’s lung)
serum sickness def
- happens upon 2nd injection of horse serum in the pre-Abx era
- prod of Abs against horse Ags recognized as foreign
- complexes form bc Ags»_space; Abs
- get chills, fever, rash, arthritis, GN sometimes
kid given Ceclor (Abx) for otitis media and comes 7 days later with rash and refuses to walk: what type of HS is that
- type III immune complex mediated.
- Abx known to produce serum sickness like rxs
- stop the Abx
good example of type IV HS rx (delayed)
- PPD test (for M, TB). helps determine previous exposure
- intradermal injection
pathophysiology in type IV delayed T cell HS rx
- APCs see Ag, present through MHC 2 to CD4+
- pro inflam cytokines (chemokines IFN-g, TNF-a, TNF-b, IL-3) released and recruit macrophages, plasma cells etc.
- swelling, redness after hours
type IV HS pathologies
-contact dermatitis (with poison ivy for ex)
how IgE produced by plasma cells (1st exposure is TH2 mediated) binds mast cells
through FceRI receptor expressed on tissue mast cells and circulating baso and eosi
name of a protease released by mast cell + clinical use
- tryptase
- if above 11.5 ng per mL = anaphylaxis or allergic or sensitivty rx
atopy charact
- tendency in certain individuals to mount an increased IgE response to Ags
- genetics involved a lot
2 things explaining increased prevalence of allergic diseases in developed countries
- genetic susceptibility
- hygienic environment
- hygiene hypothesis*
cytokines of Th1 cells
IFN gamma and IL-2
-for pathogens, infectiosn, defense
cytokines of th2 cells
IL-4,5,13. for allergic diseases
stim production of IgE and recruit eosinophils
