Cell Mediated Immunity is the type of immunity mediated by T lymphocytes , and is
the defense mechanism against microbes that survive within phagocytes or infect
non-phagocytic cells. Microbes in these locations are inaccessible to antibodies. In
CMI, the effector phase is initiated by the recognition of peptide-MHC antigens by T
cells. Defects in CMI result in increased susceptibility to infections by viruses and
intracellular bacteria. Cell-mediated immune reactions are also important in graft
rejection and tumor immunity. In this lecture, we will discuss the induction and
effector mechanisms of cell-mediated immune reactions. We will also briefly cover
Natural Killer (NK) cells, which are effector cells of the innate immune system that
share many properties with a one type of effector T cell.
Types of cell mediated immunity: o CD4+ helper T cell responses to microbes
residing within the phagosomes of phagocytes
T cell cytokine and CD40-ligand expression, which activate the phagocytes to kill
the microbes and stimulate inflammation. o CD8+ cytolytic T lymphocyte (CTL)
responses to microbes (e.g. viruses) that infect and replicate in the cytosol of various
cell types, including non-phagocytic cells
CTL killing of the infected cells.
CTL secretion of cytokines • CD4+ T cell mediated macrophage activation: In CMI
against phagocytosed microbes, the specificity of the response is due to T cells, the
effector functions are provided by phagocytes, and the communications between
lymphocytes and phagocytes are mediated mainly by cytokines and CD40
ligand:CD40 interactions. The steps in the process of CD4+ T cell and macrophage-
mediated CMI include: o Induction of cell-mediated immunity: Activation of CD4+
TH1 cells by microbes and protein antigens
Antigen recognition by naïve T cells in lymph nodes. Requires costimulation by
professional APCs.
Clonal Expansion: driven by activated T cell IL-2 and IL-2 receptor production,
leading to increase in numbers of T cells of a particular specificity, as much as 100-
fold.
Differentiation of CD4+ T Lymphocytes into effector cells
Th1 and Th2 subsets of effector CD4+ T cells are defined by cytokines they
produce. • Th1 differentiation is stimulated by IL-12 produced by microbe-activated
phagocytes • Th2 differentiation stimulated by IL-4
Th1 cells produce IFN-γ and are the effectors that activate macrophages in CMI.
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