Lesson 4

Question 1

List some families of cytokines with examples

Answer 1

• Interferons: INF-α, INF-β, INF-γ,…;
• Interleukins: IL1, IL2, …, IL37;
• Tumor necrosis factors: soluble molecules active in the endothelial cells that mediate the necrosis of tumor cells by disrupting the blood vessels (no blood -> no nutrients). They can be divided into α and β.
• Colony stimulating factors: G-CSF (granulocytic –CSF), GM-CSF (granulocytic and monocytic –CSF), M-CSF (macrophage –CSF).
  The first two works to induce the hematopoietic stem cells to differentiate.
• Transforming growth factors: TGF-β, it is one of the most pleiotropic cytokines that usually is released by suppressive cells, it has an anti-inflammatory effect.

Question 2

Which are the features of cytokines?

Answer 2

• Redundant: different cytokines do exactly the same job
• Pleiotropic: can affect different cells or have different effect on the same cells
• Synergic: cytokines can synergize with other cytokines
• Antagonistic: cytokines can antagonize with other cytokines

Question 3

Which are the ways of working of cytokines?

Answer 3

• Autocrine way: a T cell produce cytokines, the same cell has also the receptor the cytokines that has produced
• Paracrine way: a cell produces cytokines for near cells with the correct receptor.
  The cytokines are secreted in a specific zone of the cell near the cell that has the receptor (polarized stimulation).
• Endocrine stimulation: cytokines work very far from the cell that produced them

Question 4

Which are the receptor families sensible to cytokines?

Answer 4

IFN, common gamma chain, common beta chain, IL1, TNF

Question 5

Cytokines receptors: which are homodimers and which heterodimers?

Answer 5

Hetero: IFN, Common gamma chain, common beta chain
Homo: common gamma chain, IL1, TNF

Question 6

Cytokines receptors: Which transduction pathway is used by which?

Answer 6

JAK-STAT: IFN, common gamma chain, common beta chain
TIR domain: IL1
TRADD, FADD: TNF

Question 7

Which is the function of the TNF Cytokines receptors?

Answer 7

induce apoptosis

Question 8

IL2 receptors: structures

Answer 8

They’re made of 2 (α and β) or 3 chains (α, β and γ). The activation signal is transduced by β and γ chain only.

Question 9

What happens at high IL2 concentration? (ILT cytokines receptors)

Answer 9

β changes conformation, bind IL2 and interact with the γ chain. The complex β-γ chains activate the JAK-STAT pathway, this result in an activation of T, B and NK cells.

Question 10

What does it means that cytokines are pleiotropic?

Answer 10

the same cytokine can signal different kinds of cells and the same cell can be affected by different cytokines.

Question 11

Which are the main features of chemokines?

Answer 11

• They’re a huge family
• They’re able to mediate chemotaxis
• they’re pleiotropic
• could be constitutively expressed or inflammatory
• they can be divided in the alfa family, the beta family and other two families with just one member

Question 12

Which are and which effect have the chemokines on the lymphoid tissues?

Answer 12

they attract T cell, B cell and dendritic cell.
CCL19 and CCL21 lead T lymphocites to a certain area while CXL12/12 drive the movement of B cells.

Question 13

Which is the link between chemokines and HIV?

Answer 13

Two chemokines’ receptors, CXCR4 and CCR5, are also recognized by the HIV: after the HIV infection, people display a rapid decrease in CD4 cells. These are the first to contact the gp120 protein present on the viral capsid and allow the adhesion with the lymphocytes.
After that, other capsid proteins bind the chemokines’ receptors (CD4 stops the virus on the cell’s surface) and therefore the infection can occur.
It has been demonstrated that people with a mutation in CCR5 has a lower possibility to be infected by HIV.