Natural Killer and K-Type Lymphocytes
المؤلف:
Mary Louise Turgeon
المصدر:
Immunology & Serology in Laboratory Medicine
الجزء والصفحة:
5th E, P62-63
2025-06-30
573
A subpopulation of circulating lymphocytes (≈10%), NK and K-type lymphocytes, lack conventional antigen receptors of T or B cells. These cells are classified as effector lymphocytes that produce mediators (e.g., IL-2).
Although these cells were previously classified as null cells, MAbs demonstrate that NK and K-type cells express a variety of surface membrane markers (Table 1). Most of these cells lack CD3 but express CD2, CD16, CD56, CD57 and, occasionally, CD8.
Table1. Natural Killer Cell Profile
Natural Killer Cells
Natural killer (NK) cells are essential mediators of virus immunity. Their deficiency in humans lead to uncontrolled viral replication and poor clinical outcome. MHC class I (MCH I) is essential to NK and T cell effector and surveillance functions. A total of 70% to 80% of NK cells have the appearance of large granular lymphocytes (LGLs). Up to about 75% of LGLs function as NK cells and LGLs appear to account fully for the NK activity in mixed cell populations.
NK cells destroy target cells through an extracellular non phagocytic mechanism referred to as a cytotoxic reaction, MHC-unrestricted cytolysis. Target cells include tumor cells, some cells of the embryo, cells of the normal bone marrow and thymus, and microbial agents. Studies have suggested that a considerable number of NK cells may be present in other tis sues, particularly in the lungs and liver, where they may play important roles in inflammatory reactions and in host defense, including defense against certain viruses (e.g., cytomegalovirus, hepatitis). NK cells will actively kill virally infected target cells and, if this activity is completed before the virus has time to replicate, a viral infection may be stopped.
Several cytokines affect NK cell activation and proliferation. NK cells are highly responsive to IL-2, IL-7, and IL-12. These cytokines generate high cytokine-activated killer activity in these cells. In addition, NK cells synthesize a number of cytokines involved in the modulation of hematopoiesis and immune responses and in the regulation of their own activities.
Target cell recognition and the molecular identification and analysis of the involved NK cell receptors are undergoing intensive research. These molecules are mainly classified under the family of cell adhesion molecules (CAMs). The main class of effector CAMs shown to mediate NK cell functions is the leukocyte integrins—more specifically, the β2 class of integrins.
Several NK cell surface molecules involved in target cell recognition and binding have been identified. NK cells recognize targets using several cell surface molecular receptors (e.g., CD2, CD69, NKR-P1) and a high density of the Fc receptor CD16 of IgG (FC-R III). They also receive inhibitory signals from MHC class I on potential target cells, transduced by a killer inhibitory receptor on the NK cell. CD56 may mediate interactions between effector and target cells. NK cells are able to bind and lyse antibody-coated nucleated cells through a membrane Fc receptor that can recognize part of the heavy chain of immunoglobulins. This enables NK cells to mediate antibody-dependent, cell-mediated cytotoxic (ADCC) activities. Some, if not all, of the activation of NK cells is mediated by CD16, which exerts a regulatory role in their cytolytic function. NK cells respond to cross-linking of CD16 and CD69 as follows:
• Increasing the rate of proliferation of NK cells
• Elevating the levels of TNF production within 4 hours of stimulation
• Increasing the expression of CD69 on the cell surface of NK cells
• Increasing the cytotoxicity activity against a normally resistant cell line (P815)
K-Type Lymphocytes
K-type killer cells are mononuclear cells that can kill target cells sensitized with antibody, which they engage through their Fc receptors. Most K-type cells are non-T, non-B lymphocytes, but macrophages and eosinophils can also have K cell activity.
K-type cells exhibit a different cytotoxic mechanism than NK cells. The target cell must be coated with low concentrations of IgG antibody, referred to as an ADCC reaction. An ADCC reaction may be exhibited by both K cells and phagocytic and nonphagocytic myelogenous-type leukocytes. K cells are capable of lysing tumor cells. Although morphologically similar to a small lymphocyte, the precise lineage of the K cell is uncertain.
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