Immunology Flashcards
(36 cards)
What are the feature of type I-IV hypersensitivity reactions? (mechanisms, antigen, examples)
ACID!
Type I - anaphylaxis - IgE dependent (mast cells) , soluble antigen, mast cell activation is the effector mechanism. E.g. anaphylaxis, allergic dz , some drug reactions
Type II - cytotoxic- IgG dependent, antigen = cell or matrix, cell surface receptor. Effector mechanism = complement , Fc receptor positive cells (phagocytes, NK cells). E.g. IMHA, ITP, myasthenia graves, some drug allergies
type III - immune complex- IgG dependent, soluble antigen, effector mechanisms: complement, phagocytes. e.g. leishmania, ICGN, systemic lupus
type IV - delayed, 3 types: Th1 cells- soluble antigen, macrophage activation - e.g. allergic contact dermatitis, TB reaction
Th2 cells -soluble antigen, IgE production, eosinophil activation, mastocytosis- e.g. chronic asthma, chronic rhinitis
CTL - cell associated antigen, cytotoxicity - e.g. graft rejection, poison ivy
list the mechanism of actions of cyclosporine, azathioprine, mycophenolate, leflunomide , chlorambucil and IVIG?
Cyclosporine: inhibits calcineurin resulting in inability of phosphorylation of NFAT (NFAT normally translocates to nucleus to promote cytokine production) - decreased IL2 (and IL3,4 and TNFa ) - target cell T cell
Azathioproine: thiopurine analogue- interferes with S phase of cell cycle (DNA) (inhibits purine synthesis)
Mycophenolate: purine analogue, inhibit inosine monophosphate dehydrogenase (IMPDH - enzyme required for de novo purine synthesis )
Leflunomide- pyrimidine synthesis inhibitor
chlorambucil - alkylating agent- cross links DNA (cell cycle non specific)
IVIG - binds to and blocks the Fc R on macrophages - prevents them taking up opsonised components
what are the active, inactive and detoxification metabolites of azathioprine?
Active metabolites: 6-MeMPN and 6-TGN
Inactive metabolite: thiouric acid - this pathway is under influence of xanthine oxidase which is inhibited by allopurinol; therefore allopurinol can enhance effects of azalea and require lower doses
Detoxification pathway requires thiopurine methyl-transferase (TPMT) which forms 6-methyl mercaptopurine. Cats (and giant scnauzers?) lack TMPT - more prone to toxicity and myelosuppression if give aza
what immunosuppressives can you use therapeutic drug monitoring for?
Cyclosporine and lefulonomide (PK only for L - collect peak/ trough blood samples , one lab in USA will do PD monitoring of cyclosporine to assess impact on T cells (the target cells); in dogs with sufficient suppression by CsA , T cells produce little to no IL2 when activated.
what monitoring of azathioprine therapy is advised (in Ettinger/ ACVIM consensus)? how about cyclosporine, mycophenolate and leflunomide?
Aza: CBC and liver enzymes every 2 weeks during first 2 months, then every 1-2 months until discontinuing therapy.
CsA: liver enzymes every 2-3 months (incase of hepatotoxicity)
Mycophenolate: CBC every 2-3 weeks for first month and then every 2-3 months
Leflunomide: CBC and liver enzymes every 2 weeks for first 2 months, then every 1-2 months
what are negative prognostic indicators for death occurring from anaphylaxis in dogs?
Hypoglycaemia within 5 hours of admission (5.7 times more likely to die)
Hypocoagulability; elevations in PT/ APTT >50% RI associated with death
Hyperphosphataemia (? intracellular phosphate release form hepatocellular or mm damage) - dogs 79.6 times more likely to die if serum phosphate >3.9 mmol/L (120 mg/dL)
What pathologies can be associated with split monoclonal gammopathies and restricted oligoclonal gammopathy? What can be performed to better understand the findings on the SPE trace
Performing Radial Immunodiffusion (RID) can help- measures Ig levels
B cell tumours - IgG or IgM
Plasma cell neoplasia - IgG or IgA
1. Split monoclonal gammopathy - 2 monoclonal peaks present - often due to IgA secreting MM which can dimerize , but in rare cases can be due to 2 different Igs (ie a true biclonal gammopathy)
2. Restricted oligoclonal gammopathy - tall narrow monoclonal like peak superimposed upon a broad polyclonal base - if mostly IgG but also with increased or normal IgM and IgA - often due to infectious (e.g. ehrlichia), inflammatory or IM dz. Alternative ddx B cell neoplasia with concurrent antigenic stimulation.
why may the term trapped neutrophil syndrome be a misnomer? what genetic mutation is involved?
case report of a border collie with TNS based on clinical features, blood and bone marrow evaluation (persistent neutropenia with myeloid hyperplasia) and presence of the associated homozygous mutation. Flow Cytometry and storage studies suggested low neutrophil survival time. However, had substantial neutrophilic inflammation in multiple organs, indicating nuts could leave marrow and enter tissues….
Genetic mutation - mutation of the gene for vacuolar protein sorting-associated protein 13B (VPS13B)
Which immune components have been implicated in canine PIMA
IgG and phosphatidylserine may promote nRBC destruction in PIMA (and PS may promote RBC destruction in IMHA)
which urinary thrombotic marker is increased in dogs with IMHA
dehydrothromboxane E2
Which bartonella species has been reported to cause associative IMHA and lymphadenitis in cat
Bartonella henselae
What treatment option could be considered in an ITP dog refractory to immunosuppression, IVIG and TPE?
splenectomy
Which treatment protocol is associated with lower rates of relapse for IMHA?
corticosteroids + second agent (3.1% relapse vs 11.3% on sole agent pred). (NB this paper said dogs on mycophenolate + pred had longer Hosp times)
which dietary amino acids may have immunomodulatory properties for adult cats?
arginine and ornithine
What is mycophenolate mofetil metabolised?
mycophenolic acid
what dose of mycophenolate is best tolerated by cats?
10mg/kg PO BID (vs 15mg/kg BID or TID not tolerated)
Which drug administered alongside ciclosporine may influence results of IL-2 assessment when considering drug efficacy?
prednisone
what adverse events are associated with mycophenolate administration in dogs?
GI (24.4%), neutropenia (4%), anaemia (4%), thrombocytopenia (4%), dermatitis (1.5%)
which immunosuppressive medication could be considered for a dog with chronic hepatitis that cannot receive prednisolone and the owner cannot afford ciclosporin
mycophenolate
which immunosuppressive medication is associated with increased risk of neutropenia when vincristine is used as treatment for ITP?
ciclosporin
what proportion of dogs with IMPA will have death attributable to IMPA? what proportion have complete cure and what proportion relapse?
Death due to IMPA 19%. Complete cure 63%. Relapse 53%
what is the most common associative cause of feline IMPA
GI disease (JFMS paper); neoplasia (other study from 1988)
what is the expected flow cytometric finding of an english bulldog with polyclonal B cell lymphocytosis
Cd21+, low B-cell MHC II and CD25 expression
what percentage of dogs with metaphyseal osteopathy develop immune-mediated condition later in life?
16%
