Therapeutics for Overactive Immune Response

Question 1

When are therapeutics for an overactive immune response necessary?

Answer 1

• When there is inappropriate or extreme triggering go the immune system
• leading to generation of antibodies/T cells directed against self antigens
• leads to tissue destruction and clinical disease

Question 2

Treatment for primary immune mediated disease

Answer 2

Control the overactive immune response

Question 3

Treatment for secondary immune mediated disease

Answer 3

Be directed against the trigger factor

Question 4

Immunomodulatory drug

Answer 4

Substance which stimulates or supresses the immune system
Used to modify immune response to help with managing immune mediated disease

Question 5

Specific immunomodulatory drug

Answer 5

Drug targeted against a specific component of the immune system

Question 6

What determines specificity of a specific immune modulatory drug?

Answer 6

○ Ability to bind to:
An immune protein to prevent interaction with a receptor
A receptor without activating it - blocks receptor
○ Ability to specifically inhibit inflammatory cytokines

Question 7

Why is specific immunomodulatory treatment less relevant in veterinary?

Answer 7

• Lack of pharmalogical data to support use of drugs in people
• No licensed drugs

Question 8

Immune suppressive drugs

Answer 8

• Traditionally high dose glucocorticoids as first line treatment against immune suppression
• Other non-specific immunomodulatory drugs are often used in combination

Question 9

Why are non-specific immunomodulatory drugs used in combination with a glucocorticoid?

Answer 9

Reduced the side effects of steroid treatment by lowering the dose of steroid required
* Steroids have some serious adverse effects

Question 10

Most common oral glucocorticoid

Answer 10

Prednisolone

Question 11

Anti-inflammatory dose of prednisolone

Answer 11

• Inhibits release of pro-inflammatory cytokines
• Stabilises granulocyte cell membranes

Question 12

Immune suppressive dose of prednisolone

Answer 12

○ Targets macrophage function
○ Decreases antigen processing

Question 13

How does prednisolone target macrophage function?

Answer 13

Down regulates Fc receptor expression
Reduces phagocytosis of opsonised red blood cells and platelets
□ Rbcs coated with antibody or complement in IMHA
□ Reducing impact of immune mediated disease

Question 14

How does prednisolone decrease antigen processing?

Answer 14

Suppresses T cell function and induces apoptosis of T cells
Might inhibit B-cell antibody production in longer term

Question 15

Clinical uses of prednisolone

Answer 15

1st line treatment for most immune mediated diseases in small animals
Rapid onset of action
Cheap and available
Licensed in dogs and cats
Most vets are familiar with drug - comfortable prescribing

Question 16

Adverse effects of prednisolone

Answer 16

• Inevitable due to widespread GC receptors in body
• Immune suppression increases risk of bacterial infection
• Increased risk of thrombosis and thrmboembolic disease
• Iatrogenic hyperadrenocorticism (Cushing’s)
• Can lead to iatrogenic hypoadrenocorticism (Addison’s) if treatment is stopped abruptly

Question 17

Naturally occurring supplements and the immune system

Answer 17

• Vitamin D
• Omega 3 fatty acids
• Glutamine
• Arginine

Question 18

How is vitamin D involved in immunity?

Answer 18

○ Involved in:
Enhancing and potentiating immune response against pathogens (innate immunity)
Modulation of adaptive immune system
□ T cell activation
□ Function of antigen presenting cells (dendritic cells)

Deficiency is a risk factor related to development of immune mediated diseases in people

Question 19

How are omega 3 fatty acids involved in immunity?

Answer 19

○ Reduce production of inflammatory mediators
○ Incorporation in synthesis of anti-inflammatory factors attenuates the inflammatory and innate immune responses

Question 20

How are omega 3 fatty acids currently used in veterinary?

Answer 20

Managing inflammatory conditions and protein losing nephropathy in dogs and cats rather than Immune mediated disease

Question 21

How are omega 3 fatty acids currently used in veterinary?

Answer 21

Managing inflammatory conditions and protein losing nephropathy in dogs and cats rather than Immune mediated disease

Question 22

How is glutamine involved in immunity?

Answer 22

○ Important roles:
Preferred energy source for enterocytes
Vital roles in nitrogen metabolism, immune modulation and anti–oxidant function

Arginine has similar properties in people with critical illness