Therapeutic approaches to immune mediated disease Flashcards
List the natural immunosupprives
- Tregs
- Antibodies (neutralisation/ removal of Ag)
- Specific cytokines e.g. IL-10
- HPA axis
Explain how the HPA aaxis have an immunosuppressive effect
- Chronic neurological stress stimulates adrenal cortex to release endogenous glucocorticoids e.g. Cortisol. These have an immunosuppressive function.
How do glucocorticoids work?
- 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)
Compare broad ranging vs specific immunosuppressive control
- Broad: General effects- many aspects of inflammation and/ or IR e.g. glucocorticoids/ NSAIDs
- Specific: targeted- e.g. cytokine inhibitors
How do specific inhibitors work?
- 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)
What is a common haemolymphatic immune mediated disorder?
Immune mediated haemolytic anaemia
What is a common cutaneous immune mediated disorder?
Atopy
What is a common GI immune mediated disorder?
IBD
Are corticosteroids or NSAIDs more potent?
Corticosteroids
How do NSAIDs work?
Block COX enzymes
Describe the mechanism of glucocorticoid action
- 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)
What species of animal is steroid resistant?
Cats
What are the side effects of glucocorticoids?
- Blanket immunosuppression (susceptible to secondary infections)
- Mimic endogenous glucocorticoids (chronic use may lead to iatrogenic hyperadrenocorticism)
- Abrupt withdrawal (adrenal insufficiency, can cause hypoadrenocorticism)
Describe immune mediated haemolytic anaemia (IMHA)
- Causes death through thrombus formation, DIC and marked systemic immune response
- Treatment= corticosteroids
Briefly describe the pathogenesis of canine AD
- 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)
Describe the treatments for AD
- 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
Is inhibition of COX 1 or COX 2 better?
NSAID inhibition of COX 2 is preferable as it has less side effects
(COX 1 inhibition can cause ulceration and bleeding of gastric mucosa)
Describe function of COX1 and COX2
- COX 1: protects intestinal tissue by stimulating mucus production.
- COX 2: induced during IR, an essential component of pathway producing prostoglandins
Briefly describe IL-1b
- Pleiotropic cytokines
- One of the first cytokines produced in inflammation
- Causes maturation of APCs/ production of inflammatory cytokines
What is IL-1Ra?
A competitive inhibitor to IL-1b (works by steric hindrance). Doesn’t stimulate same downstream effects as no signalling capability.
Which neutraceuticals have a possible anti inflammatory effect?
Green lipped mussel and devils claw
