Immunology/Heme/Coag Flashcards
Name the TLR that recognizes LPS? Flagellin? DsRNA? Where are they located in the cell (extra vs intracellular)
LPS - 4, Flagellin - 5, dsRNA - 3; TLR-4 and TLR 5 are cell surface, TLR-3 is intra-cellular (recognizes viruses)
High mobility group box protein-1 binds which two TLRs?
TLR-2 and TLR-4
What are the functions of TNF-A?
Adherence, migration, attraction and activation of leukocytes; causes heat/pain/swelling/redness
Which interleukin increases hepcidin in the body? How does this impact blood levels in the body?
IL-6 (and IL-1); hepcidin inhibits Fe transport by binding to the iron export channel ferroportin which is located in the basolateral plasma membrane of gut enterocytes and the plasma membrane of reticuloendothelial cells; this will result in anemia of chronic inflammation
Give the differences between initiation of the complement system in the classical, alternate, and lectin pathway?
Classical - antigen/antibody activates C1
Alternate - bacterial LPS/yeast has C3 undergo spontaneous hydrolysis and combine with Factor B
Leptin - mannose-binding leptin complex binds to mannose-containing carbohydrate on infectious agent
The three complement pathways (classical, alternative, leptin) all end in activation of which complement molecule?
C3 convertase, which cleaves C3 > C3a and C3b
Which two complements result in opsonization?
C3b and C4b
Brittany Spaniels are associated with deficiency in which complement?
C3
IFN-gamma is the primary activator of which white blood cell?
Macrophage
CD45+CD3+CD8+ receptors are specific for which type of lymphocyte?
Cytotoxic T cell (CD45 -all leukocytes; CD3 - T cell; CD 8 - cytotoxic)
IgA functions primarily where, and in what way?
Respiratory tract (also GI); neutralization of pathogens and/or products; particularly good against viruses
Which interleukin is a hematopoietic growth factor and stimulates growth of neutrophils, eosinophils, and macrophages?
IL-3
IL-10 promotes growth of what type of T cell?
Treg
Difference between TNFa, TNFb, and TGFbeta?
alpha - pro-inflammatory; beta - anti-inflammatory; TGF-beta - immunosuppressant
Th2 CD4 lymphocytes are known for what physiologic function?
Defense against helminths/parasites, allergic response; recruit IgE, mast cells, eosinophils
Chronic asthma is an example of what type of hypersensitivity reaction?
Type 4 (delayed)
What is the mechanism of action of cyclosporine?
Calcineurin inhibitor = cannot phosphorylate NFAT > resulting in less IL-2 (and less IL-3, IL-4, TNFa)
Why is azathioprine contraindicated in cats? What dog breed shouldn’t you use azathioprine in?
Cats lack thiopurine methyl-transferase (TMPT), which is the detoxification pathway. Giant schnauzer (same reason)
Azathioprine and mycophenolate inhibit production of what aromatic compound? How do they work differently?
Purines; azathioprine is converted to 6-MP, purine analog that is taken up and thus inhibits S phase of DNA cycle | mycophenolate inhibits inosine monophosphate dehydrogenase, which is an enzyme needed for purine synthesis
Which immunosuppressant specifically targets pyrimidine synthesis?
Leflunomide
Most immune-mediated diseases are from dysregulation of which immune cell?
Th2 (Ettinger 8th ed, p 2046)
Which antibody class is most commonly involved in canine IMHA?
IgG
What causes increase in erythropoietin?
Renal cortical hypoxia
Reticulocytosis should occur after what amount of time?
2-5 (or 7 depending on what chapter of Ettinger you read…) days
Patients on cytotoxic drugs should generally have a CBC rechecked within _ to _ days.
7-21 days
Causes of Heinz body anemia?
Onion, zinc, acetaminophen, methylene blue toxicosis
Collapse following exercise with evidence of hemolysis in English Springer Spaniel is consistent with what disease? What other breed can have this?
PFK deficiency. American cocker spaniels
Breeds affected by pyruvate kinase deficiency? Signs are a result of what pathophysiologic process?
Beagle, Basenji, West Highland White Terrier, Cairn Terrier, American Eskimo Dog, Dachshund, Pug(Pug is included as breed per UCD); signs due to myelofibrosis and hemolytic anemia
What happens to ferritin and transferrin in inflammation? What is transferrin indicated as an iron panel?
Ferritin goes up (positive acute phase), transferrin goes down; transferrin listed as TIBC
Which anti-epileptic agent can cause dysmyelopoeisis?
Phenobarbital
Difference between epoetin and darbopoetin?
Darbopoetin is more heavily glycosylated, which poses less risk of developing anti-EPO antibodies
Other side effects of EPO agents besides development of antibodies
Hyperviscosity (hypertension, seizures); Fe deficiency; for epoetin > fever, injection site irritation, mucocutaneous ulceration
Causes for secondary inappropriate polycythemia?
EPO producing tumor, pyelonephritis, local renal hypoxia, hyperthyroidism, hyperadrenocorticism, acromegaly
EPO production in primary polycythemia is
Low to normal
Low antithrombin III can be secondary to:
Reduced hepatic production, consumption, renal or enteric loss
What are the laboratory markers of DIC? (There are seven)
Thrombocytopenia, prolonged clotting times, elevated FDP, elevated D-Dimer, decreased fibrinogen, decreased anti-thrombin, red blood cell fragmentation
Stored plasma is appropriate to administer to a patient with anticoagulant rodenticide intoxication. T/F?
True - stored plasma does not have factors 5/8 but does have the others
What does cryo-poor plasma not contain?
Cryo-poor plasma doesn’t contain factor 5, factor 8, vWF, fibrinogen, fibronectin (aka what cryoprecipitate contains)
Factor 13 deficiency will result in what change to PT/PTT/ACT?
None
Canine breeds associated with Factor 7 deficiency
colony-bred mongrels, Beagles, Miniature Schnauzers, Alaskan Malamutes, Boxers, and Bulldogs (eClinPath)
Feline breeds associated with Hemophilia B (which factor is this?)
British Shorthair cats and Siamese-cross cats (Factor 9).
Breeds associated with Factor 11 deficiency(hemophilia C)
Springer Spaniel, Great Pyrenees, Weimaraner, and Kerry Blue terrier breeds.
Differentiate the three types of vWD
Type 1 - low plasma concentration, full array of vWF multimers, mild to moderate bleeding
Type 2 - variable concentration, absence high molecular weight multimers, moderate to severe bleeding
Type 3 - no vWF, severe bleeding tendency
Breeds associated with vWD (for which there is DNA testing)
Type 1 - Bernese Mountain Dog, Corgi (Cardigan and Pembroke Welsh), Coton de Tulear, Doberman
Pinscher, Dutch Partridge dog, German Pinscher, Goldendoodle, Irish Setter, Kerry Blue Terrier, Manchester Terrier, Papillon, Poodle, Stabyhoun, West Highland Terrier
Type 2 - German Shorthaired Pointer, German Wirehaired Pointer
Type 3 -
Dutch Kooiker,* Scottish Terrier,** Shetland Sheepdog*** [different DNA mutations in all of these]
What is Glanzman thrombasthenia and how is it different from CalDAG-GEFI
thrombopathia? Breeds?
Both involve fibrinogen receptor, GPIIb-IIIa (this allow platelet activation/connection to vWF and fibrinogen); In Glanzmans’s this is absent or deficient - Otterhounds, Great Pyrenees; in CalDAG this a signal transduction disorder that prevents conformation change that allows binding - BASSETS, Spitz Landseer
A young GSD presents for hemoabdomen following its spay. Coagulation testing is normal. If all surgical steps were followed correctly, what clotting disorder could still be a differential for this dog? What would be the best treatment for this dog?
Scott’s syndrome - platelet procoagulant disorder (platelets cannot externalize phosphatidylserine, which is needed for fibrin formation); give platelets/whole blood
Marked peripheral neutrophilia and hypersegmented neutrophils are consistent with what disease? What breed is known to develop this?
Leukocyte adhesion deficiency. European Irish Setter.
Breeds associated with X-linked severe combined immunodeficiency? What IL receptor is deficient?
Cardigan Welsh Corgis and Basset Hounds; IL-2
You see a Jack Russell Terrier puppy for fever following vaccination. There is severe lymphopenia and decreased serum globulin concentrations. This is consistent with what process?
Autosomal recessive severe combined immunodeficiency.
What breed is associated with cyclic neutropenia?
Gray Collie (insertional mutation in the AP3B1 gene)
Miniature Dachshunds with lymphocyte function deficits can get pneumonia from what organism? What lymphocyte do they tend to lack?
Pneumocystis carinii. Absent B cells.
Cavies have also been reported.
Causes of secondary dysmyelopoiesis in dogs
IMT and IMHA, myelofibrosis, pure red cell aplasia, and lymphoma; drugs, including chemotherapeutic
agents, chloramphenicol, estrogens and phenobarbital; endogenous overproduction of estrogens; heavy metal toxicoses; iron deficiency; adenocarcinoma; and leishmaniasis
Causes of secondary dysmyelopoiesis in cats
immune-mediated hemolytic anemia and thrombocytopenia, pure
red cell aplasia, glomerulonephritis, feline infectious peritonitis (JFMS 2019 review)
Neutropenia is seen in what percentage of cats presenting with FeLV-related illness?
50%
Most common type of bacteria causing septic arthritis (aka Gram positive/negative; anaerobic/aerobic)
Gram positive aerobe
Transient polyarthritis in kittens is associated with:
calicivirus
Most common manifestation of systemic lupus erythematosus in dogs is
Polyarthropathy
Most common manifestation of systemic lupus erythematosus in cats is
Dermatologic lesions (erythema, ulceration, crusts, and depigmentation of the face, ears, and paws) [CNS signs are more common in cats - 24%, than in dogs - 5% but is not the most common overall]
Criteria for diagnosis of SLE?
Two autoimmunity disorders + positive ANA; or three autoimmunity disorders
The ACVIM consensus statement on IMHA describes three infections that can cause Coomb’s positive anemia. What are those three?
Heartworm, Leishamiania, Bartonella
The ACVIM consensus statement on IMHA describes three infections that can cause Coomb’s positive anemia in dogs. What are those three?
Heartworm, Leishamiania, Bartonella
IMHA is more prevalent in which breeds?
Cocker and Springer Spaniels, Old English Sheepdogs, Bichon Frises, Bearded and Rough-coated Collies, Poodles, and Flat-coated Retrievers
ACVIM recommendations for tapering prednisone/immunomodulatory drugs?
Taper pred by 25% q3w if single agent, taper pred by 25-33% q3w OR q2w if using second agent [for first taper: they say can drop pred by 25-50%]
A dog on glucocorticoids should have UA checked how frequently accordingly to ACVIM consensus on IMHA tx?
Every 8-12w
Bloodwork monitoring on azathioprine? (according to IMHA consensus)
CBCs and relevant serum biochemical variables (especially alanine aminotransferase [ALT] activity) be monitored every 2 weeks during the first 2 months of treatment, and then every 1-2 months until treatment is discontinued.
Of the two blood groups Kai 1 and Kai 2, most dogs fall into which group?
Kai 1, 94% of dogs, JVIM 2016
Dogs with severe pulmonary hypertension had higher values of what variable on a hemogram compared to normal dogs?
RDW (related to tricuspid regurgitation pressure gradient), JVIM 2016
Which two gram negative bacteria are most likely to be involved as contaminants in blood bags?
Serratia and Pseudomonas, JVIM 2016
Blood transfusions associated with what in cats receiving dialysis?
increased number of treatments (NOT death - this is only the case in dogs), JVIM 2016
Significance of phosphatidylserine in RBC?
Normally on the inside, but moves to the outside in aged RBC and can be indicator for cell removal by phagocytic cells
Three dog breeds associated with Dal-?
Dalmatians, Dobermans, Shih Tzus, JVIM 2017
Of the following, decreases in which two were associated with well-controlled IMHA? Serum Thymidine Kinase 1, Canine-C-Reactive Protein, Haptoglobin, and Vitamin D Concentrations
TK-1 and c-CRP, JVIM 2017
What is the biological half-life of cell-free DNA?
5.64 hours. JVIM 2018
Congenital methemoglobinemia in Pomeranians can be caused by a variant in what gene?
- ABCB2
- CYB5R3
- COMMD1
- CYB6R2
nonsynonymous variant in the CYB5R3 gene. JVIM 2018 [also associated with sulfonamide hypersensitivty in dobermans]
Transfusion naive cats have a decreased risk of hemolytic reaction if a major cross-matched is performed first. T/F?
False - no change in hemolytic reaction between those cross-matched or not cross-matched in transfusion naive cats. JVIM 2018
Cyclosporine increases which eicosanoid involved in coagulation in normal dogs?
Thromboxane A2, JVIM 2018
What were the characteristics of hemostasis in a study that induced experimental E. canis infection in dogs?
Hypercoagulable (increased MA) and hypofibrinolytic (lower Ly30 and Ly60), JVIM 2018
Dogs with AKI have a phenotype similar to what type of hemostatic disease?
VWF type 2, JVIM 2019
Indications for membrane-based TPE?
Immune-mediated disease, hyperviscosity syndrome, toxicity from highly protein bound substances
What percentage of dogs had complications from TPE? What percentage died from complications?
34%, 2/34 died from complications, JVIM 2019
Prolongation of which values resulted in correlation with therapeutic levels of factor 10a reached from rivaroxaban?
1.5-1.9x delay in PT and R values of TEG 3 hours after rivaroxaban administration, JVIM 2019
What might be a good biomarker to differentiate survivors vs nonsurvivors in SIRS patients?
Angiopoetin-2, JVIM 2019 (significantly higher in non-survivors)
A strong correlation between fibrinogen clauss and what value on rotational thromboelastometry?
Maximum clot firmness, JVIM 2019
What ultrasonographic findings of the spleen were associated with malignant/suppurative inflammation on FNA?
nodules 1-2 cm, peritoneal fluid, >1 target lesions
What percentage of non-ITP thrombocytopenic animals were positive for anti-platelet antibody?
20% JVIM 2020
Dogs on prednisone (2 mg/kg/d) and clopidogrel were how many times more likely to have an excessive effect on platelet function?
11 times JVIM 2020
Dilution at what ratio of saline to blood results in a specificity of 97% (and diagnostic accuracy of 95%) for saline agglutination suggestive of IMHA?
49 (saline) : 1 JVIM 2020
How many dogs became neutropenic when administered vincristine in a study involving dogs with ITP?
19/127 (15%), JVIM 2021
Which feline erythrocyte antigens are most prevalent? Which was associated with higher risk of naturally occurring auto-antibody?
1 (84%) and 5 (95%); 1 was associated; JVIM 2021
Which breeds more frequently presented for nonregenerative immune mediated anemia?
Whippets, Miniature Dachshunds, Lurchers (JVIM 2021)
MST for nonregenerative immune mediated anemia?
277d (JVIM 2021)
What percentage of dogs with immune-mediated disease treated with membrane TPE survived to discharge?
82% (JVIM 2021)
What percent of blood donor bags from Canada tested positive for blood-borne pathogen?
1.1%, JVIM 2021
RBC IgG and phosphatidylserine is more likely to be expressed in IMHA dogs rather than non-IMHA. T/F?
True JVIM 2021
3 breeds that represented 50% of primary splenic torsion
GSD, Bulldogs, Danes (JAVMA 2016)
What breed had the highest risk of aortic thrombosis? What was the most common disease? How many had no underlying disease?
Shetland. Most common disease (in all dogs, not just Shelties) - PLN. 1/3 had no underlying disease (JAVMA 2017)
What RBC abnormality was noted more frequently in dogs with lymphoma than IBD?
Eccentrocyte (JAVMA 2019)
What other physical exam finding is noted in cats with osmotic fragility syndrome? (What breeds are generally affected?)
Splenomegaly (Abyssian, Somali, although this study found that DSH cats and other breeds can also present) - JFMS 2016
What were most common signs of primary erythrocytosis in cats?
Seizures and mentation changes (10/18 cats for each) - JFMS 2018
What are expected changes can be seen with on a CBC post-splenectomy for at least up to 2w weeks following procedure?
Thrombocytosis. Also hypercoagulability (JAVMA 2019)
What is the most common cytological diagnosis for a cat with a honey-comb like spleen? What was the prevalence of lymphoma?
Lymphoid hyperplasia (64%); 24% of cats with honeycomb pattern had lymphoma - JFMS 2020 (two different papers)
Percentage of cats that developed transfusion-related reaction after receiving FFP?
14.8% (JFMS 2020)
Allo-antigen on type A cats? B cats?
N-glycolyl-neuraminic acid - Type A
N- acetyl-neuraminic acid - Type B
AB has both
Breeds of cats more known to have type B?
British Shorthair, Birman, Devon Rex
Why is it recommended to cross-match all cats?
Due to presence of Mik antigen
Feline type I hypersensitivity reactions tend to have clinical signs related to which body system?
Respiratory (upper resp edema, bronchoconstriction) - particularly of relevance in transfusions [but other signs are more likely to happen b/c transfusion reactions are not necessarily hypersensitivities]
Virchow’s triad consists of what?
alterations in blood flow, endothelial damage, and the existence of hypercoagulable states
What is advantage of tissue plasminogen activator compared to other thrombolytic agents (such as urokinase?)
More specifically targets FIBRIN-bound plasminogen as compared to free-circulated plasminogen
Initial use of warfarin can actually result in a hypercoagulable state - why?
Faster drop in protein C levels initially
What populations of dogs/cats are at high risk of thrombosis (according to CURATIVE)
High risk of thrombosis includes: dogs with IMHA or PLN or PLE or heartworm, cats with cardiomyopathy and associated risk factors, dogs or cats with more than 1 disease/risk factor for thrombosis [severe pancreatitis, steroid, HAC, cancer, liver dz, ]
The importance of selectins in the endothelial glycocalyx? What are the two main ones? How are they different?
Allow for adhesion of WBC to endothelial cells (and platelets). P selectin and E selectin. E selectin ONLY on endothelial cells and is inducible. P selectin is on endothelial cells and platelets and is stored (aka readily available).
Delayed hemolytic transfusion reaction occurs only in what scenario reported in dogs/cats?
None in dogs; xenotransfusion of canine blood to cats - 64% incidence
Negative prognostic factors for IMHA in cats?
Age and TBili (JVIM 2016)
Critically ill dogs seem to have significantly decreased respiratory burst capacity despite an increase in monocytes expressing which TLR receptor?
TLR 4 (JVIM 2018)
Prednisone and cyclosporine affected IL-2 and what other cytokine?
IFN gamma. Azathioprine, mycophenolate, leflunomide did not have effects on IL-2 or IFN gamma. JVIM 2020
What percentage of dogs on mycophenolate develop GI effects? What was overall incidence of adverse effects? Was this dose dependent?
24%, 26%, not dose dependent. JVIM 2021
In a study of 13 dogs, what % had erosive IMPA? Where were these lesions? More common in what signalment?
16%; ALL carpal joints; more common in middle-aged small breed JAVMA 2016
Increased/decreased cell-free DNA, increased/decreased mean platelet component, and persistently increased/progressively increasing IL-17 was associated with death in IMHA.
Increased, decreased, persistently increased JVIM 2017, JAVMA 2018, JVIM 2020
What is a characteristic finding in most (92%) of dogs with PIMA on bone marrow cytology (be specific)?
Rubricytophagocytosis (JAVMA 2019)
The median time for PIMA dogs to go into remission (if they did) was how long?
29 days (About 1 month) JAVMA 2019
Major difference between PIMA and non-regenerative IMHA on bone marrow cytologies in cats?
PIMA - erythroid hypoplasia or aplasia
nonregen IMHA - erythroid hyperplasia or maturation arrest (JFMS 2016)
Cyclosporine is not recommended for cats with what diseases?
Probably any kind of infectious lol, But also FIV, FeLV, diabetic, past history of malignant neoplasia (JFMS 2017)
Retrovirus infected cats had the same response to panleukopenia virus vaccine as did normal individuals. T/F?
True - JFMS 2019
Signs and finding typical for pulmonary Langerhans cell histiocytosis in cats?
Mixed restrictive dyspnea, diffuse nodular pattern to lungs, histiocytic infiltration JFMS 2020
E-cadherin biomarker staining on a histiocytic cells confirms that cell as what?
Langerhans cell
Which two coagulation factors are released by DDAVP?
vWF and Factor 8c
Function of IL-8? Who secretes them?
Pro-inflammatory. Attracts neutrophils and other granulocytes, induces angiogenesis, stimulates phagocytosis. Secreted by macrophages and epithelial cells.
what is major acute phase protein in cats?
Serum amyloid A (JFMS 2017 looking at heartworms that noted increase in inflammation)
