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Chapter 16 Lecture 3 Cell Mediated Immune Response (T Cell Regulation…
Chapter 16 Lecture 3
Cell Mediated Immune Response
The Perforin-Granzyme Cytotoxic Pathway
The cytoplasm of cytotoxic T cells has vesicles containing 2 key protein cytotoxins - perforin and granzyme.
Perforin- a pore forming cytolytic protein found in the granules of cytotoxic T lymphocytes and Natural Killer cells.
Granzyme- a serine protease released by cytoplasmic granules within cytotoxic T cells and Natural Killer Cells. They induce apoptosis (programmed cell death) which eliminates cancerous or infected cells
Perforin and granzyme are also used by natural killer cells in conjunction with antibody-dependent cellular cytotoxicity.
Antibody-dependent cellular cytotoxicity is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses (disintegrate the cell by rupturing the cell wall or membrane) a target cell, whose membrane-surface antigens have been bound be specific antibodies.
Activation of Cytotoxic T-cell clones and Their Functions
Adaptive initiated response do not initiate at any site of infection but more so in the lymph nodes.
Antigen Presentation - Infected dendritic cells migrate to a lymph node near, which represents virus epitopes in conjunction with the MHC 1 protein. A Tc cell binds to the dendritic cell so that it forms a cell-cell contact. (immunological synapse)
Helper T-cell differentiation - Has improper immune responses due to the Th cells lacking to assist.
Clonal expansion - Dendritic cells give a second signal and it activates the cytotoxic T cell to secrete its own IL-2. The interleukin 2 triggers cell division.
Self stimulation - The daughter Tc cells activate and produce the IL-2 receptors and the IL-2. Now they no longer need the APC or T cell helper they will leave the lymph node and they now are ready to attack virally infected cells.
Cytotoxic T cells kill in two different pathways
The perforin-granzyme pathway
Which is the synthesis of killing proteins
The CD95 pathway
Which is mediated through a glycoprotein found on the body cells
The Perforin-Granzyme Cytotoxic Pathway
When a cytotoxic T cell first attaches to its target, vesicles containing the cytotoxins release their contents
Perforin molecules associate into a channel in the membrane of the infected cell through which granzyme enters, activating apoptosis in the target cell
Having forced its target to commit suicide, the cytotoxic T cell disengages and moves on to another infected cell
The CD95 Cytotoxic Pathway
For cell mediated cytotoxicity
Requires essential glycoprotein CD95, AKA Fas, that is in cytoplasmic membranes in many human body cells.
CD95L is the receptor for CD95 and activated Tc cells insert CD95L into their cytoplasmic membranes
When a Tc cell that is activated comes into contact with its target like a TCR, or the CD95L receptor, it binds to CD95 on the target
It then activates enzymes that trigger apoptosis, killing the targeted cells
Memory T cells
activated T cells
Persist in “suspended animation” for months or years in lymphoid tissues
Become functional immediately
T Cell Regulation
The body carefully regulates cell-mediated immune responses so that T cells do not respond to autoantigens.
T cells require several signals from an antigen- presenting cell to activate.
These signals must be in a specific sequence or they will not respond
When a T cell and an antigen- presenting cell interact in an immunological synapse, the two cell types have a chemical dialogue that stimulates the
T cell to fully respond to the antigen.
If a T cell does not receive the signals required for its activation, it will “shut down” as a precaution against autoimmune responses.
Regulatory T (Tr) cells also modulate cytotoxic T cells by mechanisms that are beyond the scope of our discussion.
Tr cells provide one more level of control over potentially dangerous cell- mediated autoimmune responses.