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26.2 Function of CD8+ cytotoxic T lymphocyte
Cytotoxic T lymphocytes (CTLs) get activated after antigenic recognition over the MHC in the antigen presenting cells. The costimulatory molecules and their close association with other receptors results in the formation of immunological synapse (ICAM-1 to LFA-1). Activated CTLs secrete cytotoxic granules such as granzyme and perforin . Perforin is homologue to complement protein-9 and is known to produce holes and perforation in the target cell. Perforin polymerize to form an aqueous pore in the target cells through which granzyme enters the target cells. Granzyme is serine proteases which is responsible for the cleavage and activation of caspase in the cells leading to the apoptosis of the target cells. In addition, activated CTLs also secrete granules such as serglycin which are known to assemble the granzyme and perforin over the surface of target cells.
CTLs also kill the target cells in granule independent fashion by Fas Ligand mediated pathway. The Fas ligand binds to the death receptors that are expressed in many cell types and activates the caspase mediated apoptosis pathway.
The infection of intracellular microbes to host needs participation of CTLs because it will eliminate the reservoir of infection by killing the infected cell. Hepatitis B and C virus infection to a host activates the CTLs in order to kill the liver cells to eliminate the reservoir.
26.3 γδ T cells
These are clonally distinct cells containing heterodimer of γ and δ chains, which are homologous to α and β chains in αβ T cells. Usually less than 5% of total circulating lymphocytes are composed of γδ T cell receptor. The γδ T cells present in the epithelial surface of bowel are called as intraepithelial lymphocytes . The γδ T cells do not recognize the MHC loaded peptide and are MHC independent. They require protein and non-proteinous antigen that do not require processing by MHC molecules.
26.4 Natural killer cells
T cells population that express the CD56 marker over their surface are called natural killer or NK cells. NK cells recognizes the lipid bound to CD1 receptor (MHC class I homologue). NK cell secretes IL-4 and interferon-γ after activation and help in the production of antibody by B cells. NK cell plays an important role in the protection against mycobacterium infection.
26.5 Points to remember
• Cell mediated immunity is a type of adaptive immune response that is stimulated by microbes and can be transferred to naïve animal by T cells.
• Differentiation and migration of lymphocytes are orchestrated by different cytokines.
• Both CD4+ and CD8+ cells are responsible for cell mediated immunity
• CD4+ cells are comprised of Th1, Th2, and Th17 subsets and have different effector functions.
• CD8+ cells are converted into cytotoxic T lymphocyte upon differentiation and help in eradication of infection by killing the target cells.