Therapeutic approaches to immune mediated disease

Question 1

List the natural immunosupprives

Answer 1

• Tregs
• Antibodies (neutralisation/ removal of Ag)
• Specific cytokines e.g. IL-10
• HPA axis

Question 2

Explain how the HPA aaxis have an immunosuppressive effect

Answer 2

• Chronic neurological stress stimulates adrenal cortex to release endogenous glucocorticoids e.g. Cortisol. These have an immunosuppressive function.

Question 3

How do glucocorticoids work?

Answer 3

• Bind to glucocorticoid receptor on cells and become internalised.
• Enters nucleus and bind to promote release of anti inflammatory cytokines e.g. IL-10
• Also binds to transcription factors e.g NFkB which prevents them entering nucleus (inflammatory cytokines are transcribed)

Question 4

Compare broad ranging vs specific immunosuppressive control

Answer 4

• Broad: General effects- many aspects of inflammation and/ or IR e.g. glucocorticoids/ NSAIDs
• Specific: targeted- e.g. cytokine inhibitors

Question 5

How do specific inhibitors work?

Answer 5

• Binds to the immune protein preventing it from interacting with its receptor
• Binds to the receptor but doesn’t activate it. Prevents it interacting with the immune protein.
• Inhibiting inflammatory cytokines (IL-10, TNFa)

Question 6

What is a common haemolymphatic immune mediated disorder?

Answer 6

Immune mediated haemolytic anaemia

Question 7

What is a common cutaneous immune mediated disorder?

Answer 7

Atopy

Question 8

What is a common GI immune mediated disorder?

Answer 8

IBD

Question 9

Are corticosteroids or NSAIDs more potent?

Answer 9

Corticosteroids

Question 10

How do NSAIDs work?

Answer 10

Block COX enzymes

Question 11

Describe the mechanism of glucocorticoid action

Answer 11

• Absorbed through cell membrane
• Bind to intracytoplasmic receptors forming a complex
• Results in reduction of pro inflam proteins and increase of anti inflam proteins

(In cytoplasm a protein binds to complex to reduce cells response to external inflammatory proteins. In nucleus complex binds to DNA and alters conc of pro/ anti inflam proteins being translated)

Question 12

What species of animal is steroid resistant?

Answer 12

Cats

Question 13

What are the side effects of glucocorticoids?

Answer 13

• Blanket immunosuppression (susceptible to secondary infections)
• Mimic endogenous glucocorticoids (chronic use may lead to iatrogenic hyperadrenocorticism)
• Abrupt withdrawal (adrenal insufficiency, can cause hypoadrenocorticism)

Question 14

Describe immune mediated haemolytic anaemia (IMHA)

Answer 14

• Causes death through thrombus formation, DIC and marked systemic immune response
• Treatment= corticosteroids

Question 15

Briefly describe the pathogenesis of canine AD

Answer 15

• Occurs when allergens bind to langerhans cells. IgE antibodies produced. Crosslink with circulating basophils/ mast cells. Inflammatory mediators released causing pruritis and erythema.

(can treat with hypimmunisation (expensive)) or prednisolone (cheap) or shampoo/ antihistamines)

Question 16

Describe the treatments for AD

Answer 16

• Systemic or topical corticosteroids (inflam cytokine reduction)
• Cyclosporine (inhibits T Lo function
• Apoquel (Inhibits part of the itch/ inflammation signalling pathway
• Monoclonal anti-canine IL-31 antibody

Question 17

Is inhibition of COX 1 or COX 2 better?

Answer 17

NSAID inhibition of COX 2 is preferable as it has less side effects
(COX 1 inhibition can cause ulceration and bleeding of gastric mucosa)

Question 18

Describe function of COX1 and COX2

Answer 18

• COX 1: protects intestinal tissue by stimulating mucus production.
• COX 2: induced during IR, an essential component of pathway producing prostoglandins

Question 19

Briefly describe IL-1b

Answer 19

• Pleiotropic cytokines
• One of the first cytokines produced in inflammation
• Causes maturation of APCs/ production of inflammatory cytokines

Question 20

What is IL-1Ra?

Answer 20

A competitive inhibitor to IL-1b (works by steric hindrance). Doesn’t stimulate same downstream effects as no signalling capability.

Question 21

Which neutraceuticals have a possible anti inflammatory effect?

Answer 21

Green lipped mussel and devils claw