Lecture 10 - Regulating immune responses- cytokines and chemokines

Question 1

what is a cytokine?

Answer 1

Immune mediators

Question 2

what are the antiviral mediators known as and how do they work?

Answer 2

Interferon-

interfere with viral replication

Question 3

What IFN alpha, beta and gamma made by?

Answer 3

IFN alpha- lymphocytes
IFN beta-fibroblasts
IFN-gamma-lymphocytes and NK cells

Question 4

Name the immune activators and what do they do?

Answer 4

Lymphocyte-activating cytokines (IL-1)
T cell growth factors (IL-2, -7, -9, -15; they share a co-receptor)
Macrophage-activating cytokines (IFN-gamma)

Question 5

what are cytotoxins and give an example?

Answer 5

identified as products of activated lymphocytes or macrophages that can kill tumour cells- TNF alpha

Question 6

what is X-linked SCID (severe combined immunodeficiency) is caused by?

Answer 6

SCID is caused by the genetic inactivation (by mutation) of one receptor that is a common signalling component of the IL-2, IL-4 and IL-7 receptors

Question 7

what are the cardinal signs of inflammation?

Answer 7

heat
swelling
redness
pain
tissue damage

Question 8

Explain the chain of events when macrophages encounter bacteria?

Answer 8

1) Bacteria trigger macrophages to release cytokines and chemokines- increasing permeability
2) Vasodilation and increased vascular permeability causes redness, heat and swelling
3) Inflammatory cells migrate into tissue, releasing inflammatory mediators that cause pain

Question 9

what are the principle inflammatory cells?

Answer 9

Neutrophils and macrophages

Question 10

which cytokines are important in inflammatory disease and allergic disease?

Answer 10

Inflammatory- Th1

Allergy- Th2

Question 11

Name four T cells that formed from naive CD4 cells and what cytokine they produce?

Answer 11

1) Th1- IFN gamma- INFLAMMATION
2) Th2- IL-4, 5, 9 and 13- ALLERGY AND ANTI-INFLAMMATORY
3) Th17- Inflammation
4) T-Reg IL10, inhibit the activity of other T cells- ANTI-INFLAMMATION

Question 12

What does MCP-1 (CCL2) and IL-8 attract?

Answer 12

MCp-1- Monocytes

IL-8: Neutrophils

Question 13

What does the CLL2 do?

Answer 13

chemotaxis- site of infection

causes macrophages to accumulate at the site of infection

Question 14

What is the therapeutic IFN beta and gamma?

Answer 14

IFN gamma- macrohphage activation

IFN- beta: Immunomodulation

Question 15

What is the therapeutic role of IL2 and IFN alpha?

Answer 15

IL2: melanoma and renal cell carcinoma

IFN alpha- hairy cell leukemia, kaposi and viral hepatitis

Question 16

role of GM-CSF
GCSF
IL-11
EPO

Answer 16

GM-CSF (myeloreconstitution following bone marrow transplant, chemotherapy-induced neutropenia)

GCSF: chemotherapy-induced neutropenia)
IL-11: thrombocytopenia in oncology
EPO- Anaemia

Question 17

Role of cytokines

Answer 17

1) Anti-TNF and sTNFR (R.A., Chron’s, ulcerative colitis, psoriasis)
2) IL-1Ra (rheumatoid arthritis, cryopyrin-associated periodic syndromes, CAPS)
3) Anti-IL-6, IL-6R (rheumatoid arthritis),
4) Anti-IL-17, -12, -23 (psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn)

Question 18

Roles of cytokines

Answer 18

5) Anti-IL-5 (Reslizumab, Mepolizumab; approved FDA 2016-2017) for asthma and eosinophilic granulomatosis
6) Anti-IL-4R (Dupilumab; approved FDA 2017 for atopic dermatitis (eczema)

Question 19

Name three main approaches to block cytokines?

Answer 19

1) antibody to the cytokine
2) antibody to their receptors so that the cytokine can’t bind anymore
3) soluble (decoy) receptors-bind to cytokine

Question 20

what are the side effects of Anti TNF and anti IL17 and anti-IL6?

Answer 20

increased susceptibility to TB, listeria and pneumocytosis