Lymphokines

The T lymphocytes, as well as some other cells such as macrophages, secrete a number of polypeptides that serve in an autocrine fashion (chapter 11) to regulate many aspects of the immune system. These products are generally called cytokines; the term lymphokine is often used to refer to the cytokines of lymphocytes. When a cytokine is first discovered, it is named according to its biological activity (e.g., B cell-stimulating factor). Since each cytokine has many different actions (table 15.7), however, such names can be misleading. Scientists have thus agreed to use the name interleukin, followed by a number, to indicate a cytokine once its amino acid sequence has been determined.

Interleukin-1, for example, is secreted by macrophages and other cells and can activate the T cell system. B cell-stimulating factor, now called interleukin-4, is secreted by T lymphocytes and is required for the proliferation and clone development of B cells. Interleukin-2 is released by helper T lymphocytes and is required for activation of killer T lymphocytes, among other functions. It is now used in the treatment of certain cancers. Granulocyte colony-stimulating factor (G-CSF) and granulocyte-monocyte colony-stimulating factor (GM-CSF) are lymphokines that promote leukocyte development and are now available for use in medical treatments (discussed in chapter 13).

Current research has demonstrated that there are two subtypes of helper T lymphocytes, designated TH1 and TH2. Helper T lymphocytes of the TH1 subtype produce interleukin-2 and gamma interferon. Because they secrete these lym-phokines, TH1 cells activate killer T cells and promote cellmediated immunity. The lymphokines secreted by the TH1 lymphocytes also stimulate nitric oxide production in macrophages, increasing their activity. The TH2 lymphocytes secrete interleukin-4, interleukin-5, interleukin-10, and other lymphokines that stimulate B lymphocytes to promote humoral immunity. The lymphokines secreted by TH2 cells, particularly interleukin-4, can also activate mast cells and other agents that promote an allergic immune response.

Scientists have discovered that "uncommitted" helper T lymphocytes are changed into the TH1 subtype in response to a cytokine called interleukin-12, which is secreted by macrophages and dendritic cells (discussed shortly) under appropriate conditions. This process could thus provide a switch for determining how much of the immune response to an antigen will be cell-mediated and how much will be humoral.

Table 15.7

Some Cytokines That Regulate

the Immune System

Cytokine

Biological Functions

Interleukin-1 (IL-1)

Induces proliferation and activation of

T lymphocytes

Interleukin-2 (IL-2)

Induces proliferation of activated T lymphocytes

Interleukin-3 (IL-3)

Stimulates proliferation of bone marrow stem

cells and mast cells

Interleukin-4 (IL-4)

Stimulates proliferation of activated B cells;

promotes production of IgE antibodies; increase

activity of cytotoxic T cells

Interleukin-5 (IL-5)

Induces activation of cytotoxic T cells; promotes

eosinophil differentiation and serves as

chemokine for eosinophils

Interleukin-6 (IL-6)

Stimulates proliferation and activation of T and

B lymphocytes

Granulocyte/monocyte- Stimulates proliferation and differentiation of

macrophage colony

- neutrophils, eosinophils, monocytes, and

stimulating factor

macrophages

(GM-CSF)

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  • NEAVE
    What do lymphokines stimulate?
    8 years ago

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