W11L17 - Cytokines

Question 1

What are Cytokines?

Answer 1

Master regulators of the immune system
Critical for lymphocyte development
Regulate innate and adaptive immunity 
Large family of small soluble proteins
Produced by many cell types

Question 2

Cytokine Nomenclature

Answer 2

Interleukins - produced by white cells
Interferons - produced by many cells types and control viral infections
Colony-stimulating Factors - maturation of leukocytes
Chemokines - control migration of leukocytes
Growth factors - stem cell differentiation

Question 3

Cytokine Properties

Answer 3

Low molecular weight proteins or glycoproteins 
Synthesised in active and inactive forms
Rapid secretion
Secretion is brief and self-limiting 
- burst of cytokine release when needed
- short half-life
Active at very low concentrations

Question 4

Cytokines and Target Cells

Answer 4

Autocrine - affects the secretory cell itself
Paracrine - targets only cells nearby
Endocrine - travels through blood to reach distant cell

Question 5

Cytokine Functions

Answer 5

Pleiotropic - have multiple effects and affects multiple cell types
Redundant - several cytokines can perform the same function
Synergistic - combined effect > sum of the individual effects
Antagonistic - regulatory

Question 6

Cascade Effect of Cytokines

Answer 6

For example
INfected cell activates Th cells
Produces interferons
Interferons activate macrophages, NK cells and dendritic cells
NK and dendritic cells produce more cytokines
Macrophages release IL-12 which activates more Th cells prodcuing more cytokines and IFN

Question 7

Function of Cytokines

Answer 7

Direct effector functions
Induce inflammatory responses
Regulate haematopoiesis and immune responses
Induce the process of wound healing
Communicate with the nervous and hormonal systems

Question 8

Cytokine Families

Answer 8

Haematopoietin - bone marrow cells + others
Interferon - anti-viral and activates immune system
Chemokine - cell migration
Tumour necrosis factor (TNF) - inflammation

Question 9

Signal Transduction

Answer 9

The movement of signals from outside the cell to inside
Needs to reach nucleus - changes in DNA
Changes the program of genes expressed
Usually rapid
Small stimulus = large response
Phosphorylation is the primary mechanism for information transfer
Positively mediated by
- JAK (janus kinase)
- STAT (signal transducer and activators of transcription)

Question 10

Pro-inflammatory and Anti-inflammatory Cytokines

Answer 10

Control immune reactions
Pro-inflammatory examples
- Interleukin 1
- Tumor necrosis factor alpha
Anti-inflammatory examples
- Transforming growth factor beta (TGF-b)
- IL-10

Question 11

Release of Cytokines by CD4+ Th1 and 2

Answer 11

CD4+ Th1
- IL-2
- IFN
- TNF-b
- GM-CSF
CD4+ Th2
- IL-3
- IL-4
- IL-5
- IL-10
- IL-13

Question 12

Chronic Th1 and Th2 Stimulation

Answer 12

Th1
- chronic inflammation
- autoimmune disease
- Type 1 diabetes
- Multiple Sclerosis
- Crohn's disease
Th2
- allergy
- failure to respond to infection

Question 13

Cytokine Storm

Answer 13

Inappropriate (exaggerated) immune response
Over activated immune response
- graft versus host disease (GVHD)
- influenza
- smallpox
Rapidly proliferating and highly activated immune cells
Systemic release of >150 inflammatory mediators
Especially TNFa and IL-6

Question 14

Differentiation into CD4+ Helper T cells and the Cytokines that help differentiate

Answer 14

CD4+ Th0 in the thymus and lymph nodes
Th0 when IFN in system, signal tranduction pathway in Th0 to become Th1
Expresses all genes involved in Th1
Th0 when IL-4 in the system, signal transduction pathway Th0 becoming Th2
Expresses all genes involved in Th2