Immunosuppressive Therapy and Immunomodulatory Agents

Question 1

Long term immunosuppressive therapy

Answer 1

Susceptibility to bacterial infections (common)
- ex: cystitis, pyoderma, pneumonia
Overwhelming, unusual infections
- fungal, protozoal, parasitic

Question 2

Mechanisms of immunosuppression

Answer 2

• decrease antibody synthesis by plasma cells (days)
• decrease antibody-cell binding affinity
• impair mononuclear phagocytic system cell destruction of antibody-coated cells (hours)

Question 3

Common therapies

Answer 3

• glucocorticoids
• azathioprine
• cyclosporine

Question 4

Additional medications

Answer 4

• mycophenolate
• vincristine
• chlorambucil
• leflunomide
• cyclophosphamide

Question 5

Glucocorticoids

Answer 5

Prednisone, prednisolone, dexamethasone

- mainstay of immunosuppressive therapy

Question 6

Every animal requires some small degree of _______

Answer 6

Glucocorticoids

Question 7

Corticosteroid mechanisms

Answer 7

Once in the nucleus, binds to specific DNA sequences

• enchance/inhibit transcription of genes
• induce or inhibit protein translation

Question 8

Corticosteroid effects

Answer 8

Effects on complement and rapid down-regulation of Fc receptor expression on macrophages leads to the reduction of phagocytosis of opsonized cells

Question 9

Additional immunosuppressive effects

Answer 9

• decrease egress of cells from the blood
• suppress macrophages and neutrophil bactericidal functions
• inhibit amplification pathways of the complement cascade
• decrease antigen presentation to Th cells
• anti inflammatory properties

Question 10

Glucocorticoid therapy: acute side effects

Answer 10

Polyuria/polydipsia
- increase urination and water consumption
Polyphagia
- increase food intake
Panting
\+/- GI ulcerations

Question 11

Glucocorticoid therapy: chronic side effects

Answer 11

• alopecia
• thin skin
• pot belly
• hepatomegaly
• muscle weakness

Question 12

Local acting steroids

Answer 12

Local effect and fewer systemic side effects

- poor systemic absorption

Question 13

Combination immunosuppressive therapy

Answer 13

Increase immunosuppression

• drugs of different mechanisms of action
• “dose sparing” effect with side effects

Question 14

Immunosuppressive agents are ______ used in dogs

Answer 14

Commonly

• glucocorticoid side effects common
• immunosuppressive agents often well tolerated

Question 15

Immunosuppressive agents are _____ used in cats

Answer 15

Rarely

• can tolerate chronic high doses of steroids
• immunosuppressive agents are poorly tolerated

Question 16

Azathioprine

Answer 16

Interferes with purine synthesis

• does not directly reduce serum antibody production
• indirect reduction in lymphocyte proliferation
• can enter all cells, but only benefits rapidly dividing cells

Question 17

Azathioprine side effects

Answer 17

• myelosuppression
• acute pancreatitis
• hepatopathy
• GI
  Combo therapy with prednisone minimizes side-effects

Question 18

What part of T cell activation directly correlates with B cell activation?

Answer 18

Th1 (IL-2, IFN-y) —> plasma cells –> antibody secretion

Question 19

Cyclosporine

Answer 19

Decreases antibody synthesis
- impairs IL-2
- reduces lymphocyte activation
= reduces T cell and then B cell proliferation

Question 20

Cyclosporine side effect

Answer 20

• myelosuppression
• GI
• refractory cystitis or bladder neoplasia

Question 21

Vincristine

Answer 21

Disrupts assembly of mitotic spindle in mitosis
- IMTP: increases platelet counts = impairs phagocytosis of opsonised platelets by impairing microtubule assembly in macrophages

Question 22

Vincristine binds to ____ and targets_____

Answer 22

Platelets; macrophages

Question 23

Management of immune-mediated blood disorders

Answer 23

High dose intravenous immunoglobulins

Question 24

Human intravenous immunoglobulin

Answer 24

Competitively inhibits binding of canine IgG to monocytes by saturation of Fc receptors
- prevention of phagocytosis of antibody coated RBC and platelets

Question 25

hIVIG

Answer 25

• minimal toxicity, but expensive
• may increase risk of blood clots
• availability is a major issue