Cytokines and their receptors

Cytokines

Messengers and act on other cells by attaching to them and getting them to do something. Draw or elicit from activity from those cells.

Cytokines have ___ molecular wt and are secreted messenger proteins

low

Cytokines regulate

intensity and duration of innate and adaptive immune responses

Cytokines activity is

receptor mediated

Activity of cytokines

• Autocrine

• Paracrine

• Endocrine

Autocrine activity

act on the cell that produced it. Example: IL-12

Paracrine activity

act on another cell nearby. Example: IL-12

Endocrine activity

act at a distant location. Example: IL3, GMCSF

Example of Cytokines

• Monokines

• Lymphokines

• Interleukin

• Interferons

• Chemokines

• Colony stimulating factors (CSF)

• Growth factors

Monokines

those proteins from monocytes

Lymphokines

those proteins from lymphocytes

Interleukin

between leukocytes. Examples: IL-1, IL-2, IL-3, etc.

Interferons

interfere with viral replication, etc.

Chemokines

chemotactic cytokines that attract specific cells to their locations

Colony stimulating factors (CSF)

stimulate colony formation in bone marrow, stimulate stem cell differentiation

Growth factors

stimulate cells to grow in vitro

Pathways that Trigger Cytokine Release

• Antigens → TCR

• PAMPs → TLR

• Antibodies → FcR

Structure of a Cytokine Receptor

When cytokine binds to structure: IL-2 binds to IL-2 receptor that 3 receptors, the whole thing is the assembly of the receptor with 3 chains (part outside and part inside of cell). Creates some type of activity.

Protein Phosphorylation

A key event in signal transduction and cellular activation

Cytokine Function

1. Cytokines that mediate and regulate innate immunity

2. Cytokines that mediate and regulate adaptive immunity

3. Cytokines that stimulate hematopoiesis

Cytokines that mediate and regulate innate immunity

Act immediately and some influence the adaptive immune response that develops

EX: IL-1, IL-6 and TNFα IL-12 Type I interferons

IL-1, IL-6 and TNFα:

Proinflammatory cytokines

IL-12:

i. Produced by antigen presenting cells in response to bacteria and viruses

ii. Activate NK cells to be more efficient killers

iii. Induce IFNγ production

iv. Stimulate differentiation of TH1 cells

Type I interferons:

Antiviral activity

EX: Interferon alpha (IFNα) and Interferon beta (IFNβ)

Type I interferons:

• IFNα and IFNβ

• Part of innate immunity

• Produced by virally-infected nucleated cells

• Make other cells resistant to viral infection

Type II interferons:

• Interferon gamma (IFNγ)

• Role in both innate and adaptive immunity

• Produced by NK cells and activated TH1

• Antiviral

• Activates macrophages, neutrophils and NK cells

• Promotes TH1 development

• Inhibits TH2 development

• Promotes B-cell to produce IgG

• Upregulates MHC expression on APCs

Cytokines that Mediate and Regulate Adaptive Immunity are produced

primarily by T lymphocytes

Cytokines (adaptive)

• Regulate lymphocyte activation, growth and differentiation

• Enhance innate defense

Cytokines that regulate of lymphocyte activation, growth and differentiation:

• IL-2

• IL-4

• IL-13

• IL-10

• TGFβ

• IFNγ

Cytokines that Enhance innate immunity:

• IFNγ

• TNF

• IL-5

IL-2

Lymphocyte proliferation

IL-4

Stimulate TH2, B cell differentiation (IgE)

IL-13

B cell differentiation (IgE)

IL-10

Inhibit TH1

TGFβ

Treg cytokine, B cell differentiation (IgA)

IFNγ

B cell differentiation (IgG) and Activate macrophages, neutrophils and NK cells

TNF

Activate endothelial cells, neutrophils

IL-5

Eosinophil activation and generation

Cytokines that Stimulate Hematopoiesis

Regulate growth and differentiation of bone marrow progenitor cells

Cytokines that Stimulate Hematopoiesis produced

during both innate and adaptive immune responses

Clinically important hematopoietic cytokines:

• Erythropoietin

• Thrombopoietin and IL-11

• IL-3

• IL-5

• GM-CSF

• G-CSF

• M-CSF

Erythropoietin:

stimulate production and differentiation of RBC

Thrombopoietin and IL-11:

stimulate platelet production

IL-3

stimulate bone marrow production of WBCs

IL-5

stimulates eosinophil differentiation during parasite infection/allergic response. Antagonists used in eosinophilia and asthma

GM-CSF

stimulate differentiation of neutrophil and monocyte

G-CSF

stimulate differentiation of neutrophils

M-CSF

stimulate differentiation of monocytes