CELL MEDIATED IMMUNITY (CMI) -

CELL MEDIATED IMMUNITY Pathogen that escapes Ab detection can enter and infect cells,Cytotoxic cells kill infected cell and one has kind of receptor Cell-mediated immunity is an immune response that does not involve antibodies or complement but rather involves the activation of macrophages, natural killer cells (NK), antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen. Activating antigen-specific cytotoxic T-lymphocytes that are able to induce apoptosis in body cells displaying epitopes of foreign antigen on their surface, such as virus-infected cells, cells with intracellular bacteria, and cancer cells displaying tumor antigens;

Types of T cells (Lymphocytes) There are various types T cells Cytotoxic T cells (Tc) or Killer Cell(Tk) Helper T cells (Th) Memory T cells sub types Suppressor T Cells sub types These are main players T lymphocytes the rest are small and regulatory The T cells look alike but can be differentiated by their functions

Types of T cells (T Lymphocytes) Cytotoxic T (Tc)-Killer T cells They attack and destroy cells bearing foreign antigen or misbehaving ie Virus,bacterial infected or cancellous cells etc. How: They have chemical (Perforin )in their storage vacoule as they perforates cell membrane so allows water and salt into the cell leading to eventual burst hence cell death Therefore T cells are responsible for CMI characterized by destruction of Ags bearing cells

Types of T cells (T Lymphocytes) Cont. Helper T (Th) cells they regulate immunity by enhancing the response of immune cells. How: In response to Ag they enlarge and secrete Cytokines (Interferon and interleukins) Cytokines are stimulatory molecules that cause Th cells to clone and other immune cells to perform their functions They stimulate Macrophages to phagocytize Ags and B cells to manufacture Abs Example: HIV infection: the virus attacks Th cells hence inactivate the immune response. Cytokines that stimulate B cell to produce Abs are called Interleukin -4

CELL MEDIATED IMMUNITY (T – CELL) The T cells develop in the thymus gland. Briefly, the stem cells in the thymus undergo differentiations that form two major groups of T cells, the Killer T cell (Tc or Tk) and the Helper T Cells (Th). Each Tk and Th cell responds only to a unique epitope. T cells that react with self antigens die off during the early stages of differentiation. The T cell clones migrate throughout the lymphatic system. When a T cell encounters its coresponding antigen (epitope) it goes through a series of changes that convert it into its final immunological defense posture.

Types of T cells (T Lymphocytes) Cont. When activated Th devides, the clone contains suppressor T (Ts) cells and memory T (Tm) cells sub types Once there is a sufficient number of TS cells the immune response ceases but a population Tm cells persist which are capable of secreting Cytokines in turn stimulation of macrophages and B cells whenever an Ag of the same nature attacks again in the future

Activation of Cytotoxic and Helper Cells T cells have unique receptors like B cells the difference they don’t recognize the Ags in the plasma or blood till when Ags presented by APC such as macrophage. APC enzymatically digests the Ags into peptide fragments which are antigenic The fragments are linked to Major Histocompatibility Complex(MHC) protein and together are displayed to a T cell at cell membrane MHC proteins contribute to specificity at tissue hence difficult to transplant incompatible individuals unless immunosuppressed

Activation of Cytotoxic and Helper Cells cont.. There two types of MHCs(I&II) Most of the body cells display MHC type I protein and only immune cells display MHC type II ie: Macrophages,B cell and some T cells Th express a protein in the CD family known CD4 on their surface TC express protein called CD8 therefore CD4 are helper proteins and CD8 are killer protein T cells recognize peptide fragments which are displayed by specialized molecules(MHC) on the surface of APCs MHC type I are found on healthy nucleated cell in the body and they display peptides antigens that are found within cytoplasm of the cells.

Activation of Cytotoxic and Helper Cells cont. ie: If a cell is infected by the virus that particular cell will display the Viral peptides on the surface which normally are recognized by CD8+ cytotoxic T cells which are better than CD4+ in responding to viral infection. MHC type II are restricted to specialized cells MHC type II display antigens from microbes within the cell vesicles

Steps in CMI Response The Process starts when APC (Macrophage) ingests an Ag Digests it and incorporates pieces of Ag peptides on the surface of cell membrane Wherever macrophage travels in blood or plasma presents the Ag to any T helper cells that it encounters Helper cells have receptors on their membrane(T cell receptors), receptors are proteins with specific shape If Ag on the macrophage matches with T cell receptor The T cell becomes active There are different millions of T helper cells with specific receptors , shapes so when antigen on the macrophage matches with T receptor the process starts(Why response takes longer time)

Steps in CMI Response cont… Once appropriate T helper is activated proceed to stimulate other T cells

CELL MEDIATED IMMUNITY Cellular immunity protects the body by:(Briefly) Activating macrophages and natural killer cells, enabling them to destroy intracellular pathogens; and Stimulating cells to secrete a variety of cytokines that influence the function of other cells involved in adaptive immune responses and innate immune responses. Cell-mediated immunity is directed primarily at microbes that survive in phagocytes and microbes that infect non-phagocytic cells. It is most effective in removing virus-infected cells, but also participates in defending against fungi, protozoans, cancers, and intracellular bacteria. It also plays a major role in transplant rejection

CELL MEDIATED IMMUNITY T- CELL T- Helper Cells Assist other white blood cells in immunologic processes, including: - maturation of B-cell into plasma cell - activation of cytotoxic T cells and microphage, among other functions. These cells are also known as CD4+ T cells because they express the CD4+ glycoprotein on their surface.

CELL MEDIATED IMMUNITY T- CELL Helper T cells become activated when they are presented with peptide ANTIGEN by MHC class II molecules that are expressed on the surface of Antigen Presenting Cell(APC) Once activated, they divide rapidly and secrete small proteins called cytokines that regulate or assist in the active immune response. These cells can differentiate into one of several subtypes, which secrete different cytokines to facilitate a different types of immune response. The mechanism by which T cells are directed into a particular subtype is poorly understood, though signalling patterns from the APC are thought to play an important role.

Cytotoxic T - cell (TC cells, or CTLs) - destroy virally infected cells and tumor cells, and are also implicated in transplant rejection. - These cells are also known as CD8+ T cells since they express the CD8+ glycoprotein at their surface. - These cells recognize their targets by binding to antigen associated with MHC class I , which is present on the surface of nearly every cell of the body.

Activation of Th and B-cell by Antigen A macrophage engulfs a virus or bacterium & breaks(digests) down their proteins. Antigenic fragments of these proteins are presented on the surface of the macrophage. The few Th-cells, which contain receptors on their surface that recognizes a particular peptide presented foreign antigen, INTERACTS WITH that unique-foreign antigen. This interaction triggers a series of events that ACTIVATES the Th-cell.

Activation of Th and B-cell by Antigen The activated Th-cells are stimulated to proliferate, producing a population of this class of Th-cells (clonal selection). The population of activated Th-cells interact physically (via ligand/receptor interactions) with only those rare B-cells that make antibody that recognizes the SAME antigen molecules that have activated the Th-cell.

Activation of Th and B-cell by Antigen During this interaction the Th- & B-cells recognize each other by their common recognition of the unique antigen. The B-cells do not require the macrophage-processed antigen as they react with the whole antigen molecule (e.g. the virus, bacteria, pollen etc.) The B- and Th-cell interaction stimulates the Th-cells to produce chemicals (cytokines) that, in turn, stimulate the appropriate B-cells to proliferate (clonal selection) and to differentiate into Ab-producing plasma cells that produce the Ab that bind the antigen that the Th-cell originally reacted to.

Therefore, the Th helper cell acts as a MASTER CONTROL CELL of the immune system. It is REQUIRED for both the humoral and cellular immune systems to function. When Th cells are not present the host's fate is sealed because the correct B-cells will not proliferate and the correct antibody will not be produced. E,g. HIV infection

exogenous antigen e.g. bacteria, virus MHC II peptide

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