CYTOKINES

BY: Ria Fazulbhoy (MSIWM031)

Cytokines are an important group of proteins or glycoproteins which play a major role in cell-to-cell communication between cells like lymphoid cells, inflammatory cells and hematopoietic cells. They are secreted by white blood cells (WBCs) and other cells of the body. They respond to stimuli and assist in the regulation of development of immune effector cells and sometimes have a direct effect of their own as well. The cytokine binds to the target cell by the presence of specific membrane receptors present on the target cell. (very high affinity-cytokines work at picomolar concentrations)

Mode of action

1. Autocrine

The cytokine is released from a cell and binds to the membrane receptor present on the same cell.

• Paracrine

Cytokine is released from the producer cell and binds to the target cell which is in close proximity

• Endocrine

Cytokine binds to the target cell which is in a distant part of the body.

Four major groups of cytokines are Hematopoietic family (interleukins-ILs), Interferons (IFs) family, Tumor necrosis factors (TNF) family and chemokine family.

A variety of cells secrete cytokines, but the major principal producer cells are Th cells and macrophages. Cytokines secreted from these cells activate an entire network of interacting cells.

   Macrophage and Th cells are major producers of cytokines in the body.

Some biological functions of cytokines include:

• Cellular and humoral immunity development
• Inflammatory response induction
• Control of cellular proliferation and differentiation
• Healing of wounds
• Development of innate/acquired immunity
• Hematopoiesis

NOTE: Cytokines have a non-antigen specific mode of action and have very short half-lives.

Functions of some cytokines

Cytokine secretion by Tн cell subsets: Tн1 and Tн2

Difference in the pattern of cytokine secretion amongst Tн cell subsets determines the immune biological response made to a particular antigenic challenge. These two subsets are Tн1 and Tн2, which secrete different cytokines and mediate in different ways. Both these subsets secrete IL-3 and GM-CSF.

Tн1 and Tн2 have the following functional differences:

1) Tн1 subset:

• It is responsible for mainly cell-mediated immune responses like activation of Tc cells and delayed hypersensitivity reactions.
• Helps in promotion of excessive inflammation and tissue injury
• Helps in production of opsonization-promoting IgG antibodies.
• Effective in viral infections and intracellular pathogens.
• IFN-४, IL-12 and IL-18 are responsible for the development of Tн1 cell response.
• E.g.: IFN-४ and TNF-ß mediates inflammation and delayed hypersensitivity.
• E.g.: IL-2 and IFN-४ promote differentiation of cytotoxic cells Tc from CD8 precursors.

2) Tн2 subset:

• Responsible for secretion of antibodies for immune response.
• Stimulates eosinophil activation and differentiation
• Helps B cells
• Promotes production of large amount of IgM and IgG
• Supports allergic reactions
• IL-4 is essential for the development of Tн2 response.
• E.g.: IL-4 and IL-5 induce production of IgE and helps eosinophil attack on helminth or roundworm infections.

Tн2 development is favoured over Tн1. The cytokines produced by the two subsets are cross regulated. The cytokines produced by a subset (Tн1 or Tн2) promote the growth of their subset and simultaneously inhibit the activity and development of the opposite substrate (cross regulation). Two transcription factors known as T- Bet and GATA-3 are important in determining the cross regulation of the two subsets

• T-Bet drives cells to differentiate towards Tн1 cells.
• GATA-3 drives cells to differentiate along Tн2 cells.