Natural killer (NK) cells are responsible for the destruction of cells with decreased or absent MHC class I proteins on their surfaces.  Such changes in MHC I antigen expression occur in virus-infected cells and tumor cells.  Natural killer cells are derived from lymphoid stem cells and comprise approximately 10% of all circulating lymphocytes.  They are large cells with cytoplasmic granules containing perforins, which produce holes in target cell membranes, and granzymes, chemicals that induce target cell apoptosis.  Granzymes gain access to the target cell via membrane holes created by perforin.  The target cell subsequently undergoes apoptosis. NK cells do not directly lyse cells.

NK cells:

1. Do not express CD4, CD8 or CD3 molecules on their surface.  They do express either CD16 or CD 56.
2. Do not require the thymus for maturation and are present in athymic patients.
3. Have no antigen-specific activities, do not require exposure to antigen for activation, and do not possess antigen memory ability.
4. Are activated by interferon-γ and IL-12.

(Choice A)  Neutrophils do not directly kill malignant cells.

(Choice B)  The functions of macrophages include phagocytosis, antigen presentation to T-helper lymphocytes in association with MHC class II molecules, and secretion of immunomodulatory cytokines, like TNF and IL-1.

(Choice C)  Dendritic cells are avid antigen presenting cells that constantly sample their environment by endocytosis and become activated upon encountering a foreign antigen.  When activated, dendritic cells migrate to the lymph nodes and spleen where they display antigen with MHC II and co-stimulatory molecules to activate T-cells and B-cells.

(Choice D)  CD4+ T-lymphocytes (T_H cells) are activated by antigen presented in association with MHC II molecules and can promote cell-mediated (macrophages and CD8⁺ cells) and/or humoral (B-cells) immune responses.

(Choice E)  B-cells transform into plasma cells under the influence of activated T_H cells.  Plasma cells secrete antigen-specific immunoglobulins.

Educational Objective:
NK cells recognize and kill cells with decreased MHC class I antigen cell surface expression, such as virus-infected cells and tumor cells.  They are large lymphocytes that contain perforins and granzymes in cytoplasmic granules.  NK cells kill target cells by inducing apoptosis.