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.