Cytokines are tiny proteins secreted by immune and non-immune cells to communicate with each other. They bind to receptors and trigger a response in the receiving cell. They often promote activation, proliferation, and differentiation of immune cells

Cytokine Signalling

Cytokines mainly use autocrine and paracrine signalling, and sometimes endocrine

Autocrine

• A cell effecting and being effected by its own cytokine signalling.
• e.g. IL-2 in CD4+ T Helper Cells, promoting proliferation

Paracrine

• A cells cytokine signals affecting nearby cells
• e.g. IL-2 promoting CD8+ T cell proliferation

Endocrine

• Cytokine signals affecting cells that are not nearby
• e.g. IL-1$\beta$ , IL-6 and TNF-$\alpha$ produced by macrophagesand dendritic cells travel to liver and brain during acute inflammation. The liver produces acute phase reactants like C reactive protein and mannose binding lectin. The brain increases body temperature and causes fever. IL-1$\beta$ and TNF-$\alpha$ also recruit other immune cells to the site of injury.

Classes of Cytokines

Interleukins

Numbered in order of discovery and act between leukocytes and non-leukocytes.

Tumour Necrosis Factors

TNFs were discovered by their supposed ability to kill tumour cells. They were in fact eliciting inflammation for leukocytes to kill the tumour cells.

TNF-$\alpha$, TNF-$\beta$ (aka LT$\alpha$) and lymphotoxin $\beta$ (LT-$\beta$) have a wide variety of effects including activating endothelial cells to upregulate expression of adhesion molecules, and increasing vascular permeability

Interferons

IFNs interfere with processes such as viral replication. Separated into type 1 and type 2. Type 1 includes interferon $\alpha$ and interferon $\beta$ and are typically produced by virally infected cells, and some dendritic cells. Type 2 includes interferon $\gamma$ which is a powerful macrophage activator. It also activates CD4+ Helper T cells

Colony Stimulating Factors

They bind to surface receptors of Hematopoietic Stem Cells (HSCs) to induce proliferation and differentiation. e.g. granulocyte-macrophage colony stimulating factor (GM-CSF). GM-CSF is secreted by immune and non-immune cells, stimulating development of granulocytes and macrophages

Transforming Growth Factors

There are over 30 TGFs, the most important being TGF-$\beta$. TGF-$\beta$ is an inhibitory factor that supresses proliferation and differentiation of various cells. TGF $\beta$ helps CD4+ T cells to develop into regulatory cells that can slow or stop overall immune response.

Cytokine Functions and Responses

Some cytokines are:

• pro-inflammatory
• anti-inflammatory
• growth factors
• etc..
  One cytokine can be included in different pathways

Pro-Inflammatory Response

Includes cytokines that enhance innate or adaptive immune response.
For example

• IFN-$\alpha$ and IFN-$\beta$ produced by virally infected cells
• IL-1$\beta$, IL-6 and TNF-$\alpha$ released by macrophages and dendritic cells, inflammatory triad (IL-6 can also be produced by T cells and B cells)
• Assisting CD4+ T cells differentiate into Th1, Th2, or Th17
• IL-12; produced largely by dendritic cells and macrophages to activate NK cells
• IL-12 produced by CD4+ acts on CD4+ as well as CD8+ cytotoxic T cells and B cells
• IL-12 also helps CD4+ differentiate into Th1 cells that produce interferon $\gamma$ and lymphotoxin (LT-$\beta$)
• IL-6, IL23, and TGF $\beta$ help CD4+ Th17 cells which produce IL-17 to recruit neutrophils to site of inflammation.

Parasite Response

IL4, IL5, and IL13 are secreted by Th2 cells and deal with parasites as well as inducing asthma and allergy responses. They induce T cell differentiation, creating Th2 Helper T cells and stimulating mast cells, basophils, and eosinophils.

Regulatory Immune Response

The regulatory immune response is immunosuppressive. It involves IL-10 and TGF-$\beta$ ; the overall mechanism is to regulate response by developing T cells into regulatory T cells, which in turn create more IL-10 and TGF-$\beta$. These cytokines also reduce the expression of co-stimulatory receptors thus inhibiting cell growth.

Growth Factors

GM-CSF, M-CSF and IL-7 are produced by bone-marrow stromal cells where they differentiate bone-marrow progenitor cells. GM-CSF and M-CSF promote the differentiation of granulocytes and mono-cytes. IL-7 promotes the differentiation of progenitor cells into lymphocytes (B cells, T cells, and NK cells)

Chemokines

Chemokines are chemotactic agents that help cells move toward the site of infection. For example, IL-8 is generated by fibroblasts, neutrophils, and macrophages to recruit phagocytes to the site of inflammation. Another example is IL-17 which is an inductor of chemokine production, generated by CD4+ Th17 cells during inflammation.

Summary

Source

#SourceNeeded

next page | back to contents