Leukocytes

Leukocytes are involved in the ongoing battle against infection by microorganisms. Leukocytes work with plasma proteins and are continuously searching for microorganisms in the tissues and blood. In most cases, invading microorganisms are effectively eliminated by the sophisticated the antimicrobial systems of the blood. Of the total leukocytes, 40-75% are phagocytic cells known as neutrophils.

Neutrophils are usually the most prevalent leukocyte in peripheral blood. These are dynamic cells that respond instantly to microbial invasion by detecting foreign proteins or changes in host defense network proteins. Neutrophils provide an efficient defense against pathogens that have gotten past physical barriers such as the skin. Defects in neutrophil function quickly lead to massive infection and, quite often, death.

Neutrophils are amoebalike phagocytic cells. Invading bacteria induce neutrophil chemotaxis- migration to the site of infection. Chemotaxis is initiated by the release of chemotactic factors from the bacteria or by chemotactic factor generation in the blood plasma or tissues.

Neutrophils express a large number of cell surface receptors that can recognize microorganisms. Those cell surface receptors include G protein coupled receptors, adhesion receptors such as selectins and integrins, various cytokine receptors as well as innate immune receptors such as Toll-like receptors and C-type lectins. The various cell surface receptors trigger diverse signal transduction pathways including activation of G proteins, Ca2+ signaling, protein and lipid kinases and cytoskeletal rearrangement.

Neutrophils express a large number of G protein coupled receptors that participate in host defense and inflammation. Several G protein coupled receptors activate the migration of neutrophils to the site of infection. Many of these ligands trigger neutrophil responses other than chemotaxis, including the production of reactive oxygen species and exocytosis of intracellular granules and vesicles. Neutrophil migration is also mediated by adhesion receptors known as selectins and integrins.

Neutrophils express a number of cytokine receptors including conventional cytokine receptors, members of the Toll-like receptor family, and TNF-receptor family members. Those receptors are involved in intercellular communication regulating various neutrophil functions. Type 1 and Type 2 cytokine receptors trigger the activation of the JAK STAT pathway and regulate gene transcription.

The TNF receptor superfamily is divided into receptors carrying an intracellular death domain such as TNFR-1, Fas, TRAIL-R and those having no death domains (such as TRAIL-R3, LTBR or RANK). TNF-alpha is a major cytokine that mediates neutrophil activation.

In contrast to neutrophils, monocytes and lymphocytes are mononuclear cells and participate in multiple aspects of immunity. The majority of circulating lymphocytes are T lymphocytes or T cells. These cells participate in cell-mediated immune responses that do not depend on an antibody.

T lymphocytes often exert their effects by synthesizing and releasing cytokines. Cytokine activities range from tumor destruction to promotion of blood cell production. Cytokines can limit viral replication in cells (interferons), suppress or potentiate the function of T cells, stimulate macrophages and activate neutrophils. The study of cytokines has opened the door to the development of new agents that have been beneficial in the treatment of diseases such as immune disorders and cancer.


References:
Rhoades R.A. and Tanner, G.A. Medical Physiology. 1994. Little Brown and Company. Boston, MA.

Futosi, K. Fodor, S. and Mocsai, A. Reprint of Neutrophil Cell Surface Receptors and their intracellular signal transduction pathways. Int. Immunopharmacol. 1185-97. 2013.

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