Lit Immunology Flashcards
What is urinary 11-dehydrothromboxane B2 (u11-dTXB) an indicator of in dogs with primary IMHA?
Any differences in [ ] between IMHA & healthy dogs?
Any associations with prognostic indicators?
Conway JVIM 2021
Prothrombotic risk - potential biomarker of platelet activation
*NB: TXA2 is highly unstable in serum, but urinary metabolites are more stable so easier to measure.
*Has been used in various studies to assess impact of anti-thrombotic & IS drugs on platelet function in normal dogs.
IMHA dogs had increased [u11-dTXB] vs normal dogs –> prothrombotic state
No associations with survival or suspected thrombosis in this study cohort.
a) What does human IVIG comprise of?
b) What are the potential benefits of human IVIG in the treatment of canine primary IMHA?
c) Differences between IgG and IgM in immunomodulatory effects?
d) What were the differences in outcomes between dogs receiving Ig-enriched human IVIG vs controls?
Bestwick JVIM 2021
a) Predominantly IgG, variable IgA, CD4, CD8, human leukocyte antigen molecule, minimal IgM.
b) Multiple - MOA not completely understood.
- hIVIG binds to canine lymphocytes and monocytes, inhibits Fc-mediated phagocytosis of autoantibody-opsonized erythrocytes –> controls haemolysis secondary to autoantibody opsonization.
- Also binding to inhibitory and activating fragment crystallizable (Fc) receptors, downregulation of cytokine synthesis, eradication of autoantibodies, complement inhibition, mediation of Fas-Fas ligand interactions.
c) IgG is associated with longer term humoral immunity, but provides more specific immunogenic functions to particular diseases.
IgM is associated with polyreactivity, which allows B lymphocytes that can produce IgM to rapidly respond to many antigens.
d) No significant advantage was found with IgM-hIVIG use (no sig diff in survival, time to remission, vol pRBC transfused) but note small sample #s.
a) Which of the following immunophenotypes were associated with a non-neoplastic process? B cell, heterogeneous, CD4+ T cell, CD4−CD8−, T cell, CD5-low-expressing T cell.
b) What other characteristics were associated with non-neoplastic immunophenotypes?
c) Which neoplastic phenotype was associated with the shortest MST? CD4+ T cell, DN T cell & CD5 low T cell.
d) Which 3 characteristics were associated with shorter survival in CD4+ T cell cats?
e) List the top 3 most common immunophenotypes in cats with lymphocytosis.
Rout JVIM 2020
a) B cell & heterogeneous
b) Polyclonal antigen receptor gene rearrangements, younger age at presentation, lower lymphocyte counts, prolonged survival.
c) CD5 low T cell (27.5d) - vs CD4+ T cell (752d), DN T cell (271d).
d) Abdominal lymphadenopathy, intestinal involvement, females
e) CD4+ T-cell lymphocytosis > heterogeneous > B-cell phenotypes.
Polyclonal (small-sized CD21+) B-cell lymphocytosis in English bulldogs is characterized by low ….expression. Associated clin path findings include…. (list 3)
Rout JVIM 2020
Low B-cell class II MHC and CD25 expression.
Splenomegaly/splenic masses (57%)
Hyperglobulinemia (71%) consisting of increased IgA ± IgM
+/- Lymphadenopathy (11%)
What is the utility of measuring serum IL-17 concentration in the management & prognostication for IMHA dogs? Answer in terms of:
- Concentrations at time of admission
- Trends in concentration during hospitalisation
- Correlation with clinicopathological parameters
Cuq JVIM 2020
- No sig diff between mean serum [IL-17] between survivors & non-survivors on admission.
- Serum IL-17 significantly decreased by D2 & D4 during hospitalization in survivors, but remained significantly higher in non-survivors.
- No correlation with TBIL, lactate, or CBC parameters.
Pathogenesis of makaloplakia?
What diagnostic test should be considered on tissue biopsies in a patient with suspicion of this condition?
Brückner JAVMA 2021
Makaloplakia = granulomatous disease characterized by impaired histiocytes that are unable to completely digest phagocytized bacteria.
- Case reports in dogs affecting the urinary bladder –> LUT signs (well reported in humans).
- FISH (identify intracellular & subendothelial bacteria) - also guide abx treatment.
Mortality rate for dogs with severe anaphylaxis?
Clin path findings associated with death?
Smith JAVMA 2020
15% (10/67)
Lower body temp on presentation
Sig higher serum P (>12.0mmol/L)
Sig higher PT & APTT >50% upper RI
Hypoglycemia within 6hrs of admission
Need for supplemental dextrose
NB: coagulopathy (?) (85%) & peritoneal effusion (66%) were v common but NOT associated with survival.
What clinical biochemical and/or imaging abnormalities may allow differentiation between dogs with anaphylaxis vs sepsis?
Walters JAVMA 2017
None specifically - lots of overlap (CSx - GI signs, lethargy,
mentation change, bleeding abnormalities. AUS - effusion, thickened/gas/fluid-filled GIT, thickened GB)
Anaphylactic dogs - higher Eos & ALT, lower blood pH
Septic dogs - higher band Np, higher glob, ALKP & lower glucose
Consider anaphylaxis if unable to identify septic nidus. Early differentiation impt due to marked difference in prognosis & tx.
What adverse effects were reported with intraperitoneal injection of adipose tissue-derived autologous mesenchymal stem cells in cats? Proposed indication for these injections?
Reported serious complication of injections that was not observed in this study?
Parys JVIM 2016
Well tolerated. Mild self-limiting SE. Transient lethargy in two cats. Jejunal LN enlargement at weeks 1 & 5.
Chronic inflammatory conditions (immunomodulatory effects)
Pulmonary thrombosis (MSC retention in pulmonary vasculature)
What CD expression do Treg cells have?
VCNA review 2017 (paper?)
CD4+ CD25+
What are the differences between the CT findings of abdominal LNs in older vs younger cats?
Perlini JVIM 2018
Older cats have smaller abdo LNs & less sacral LNs.
Which of the following markers has/have been found to be prognostically significant in dogs with SIRS?
* IL-6
* CRP
* Serum alpha1-proteinase inhibitor
* NT-proBNP
* Cardiac troponin T (cTnT)
Gommeren JVECC 2017
* Serum CRP increased with SIRS; decreases during tx & hospitalisation.
* CRP, IL-6 & TNF-a were not predictive of survival.
Heilmann JVECC 2017
* Serum alpha1-proteinase inhibitor = negative acute phase protein in dogs. Negative correlation with IL-6. Overall not useful to differentiate between sepsis & non-infectious SIRS, but may be useful to stratify these 2 diseases early on (lower [ ] in SIRS/sepsis dogs vs healthy dogs). No diff between survivors & non-survivors.
Gommeren JVECC 2019
* NT-proBNP & cTnT both significantly increased in dogs with SIRS. Higher cTnT in non-survivors.
Which biochemical parameter is prognostically significant in dogs with sepsis?
Hardy JVECC 2018
* Low cholesterol was associated with cardiac arrest. Cutoff of 4.5mmol/L had Sn 75% & Sp 50% for predicting in-hospital mortality.
* Plasma cholesterol + no. of dysfunctional organs = significant predictors for survival. In combination had 94% Sn & 63% Sp for predicting survival.
Heilmann JVIM 2017 (see previous flashcard)
* Serum alpha1-proteinase inhibitor higher in septic dogs, but did not predict survival.
What drug is associated with opportunistic, invasive fungal infections in dogs? Name 2 fungal species & another risk factor.
McAtee JVIM 2017
Cyclosporine (OR 7.1). 13% prevalence in cyclosporine-tx dogs in this study.
Phaeohyphomycosis, hyalohyphomycosis.
Males more at risk.
(2 papers)
What is mycophenolate the pro-drug of? MOA?
Do cats biotransform this drug in a reliable way?
What % of cats had adverse drug effects?
Mycophenolic acid (MPA).
Non-competitive, reversible inhibitor of Type II inosine monophosphate dehydrogenase (IMPDH) isoform in activated lymphocytes. Inhibits guanosine nucleotide production & suppresses B and T cell responses –> inhibits both cell-mediated & humoral immune responses.
Slovak JVIM 2017
All cats in this study biotransformed MMF to MPA (IV form given), but plasma levels were highly variable.
Slovak JVIM 2019
Similarly found that all cats biotransformed MMF. 50% cats had adverse effects within 1 week of MMF administration (at 10mg/kg BID). Efficacy of MMF as an immunosuppressant & long-term safety in cats with this dosage regimen is unknown.
