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7.7: Cell Mediated Immunity

Antibodies offer great protection against extracellular pathogens or toxins. But what happens when your cells are invaded by a virus? Is there any hope? Intracellular parasites are targeted by the second arm of our specific immune system, the cell mediated immune response (CMI).

Function of  Cell Mediated Immunity  “CMI

                1. CMI is used to kill intracellular parasites examples:

                                -viruses living within host cells

-intracellular bacteria living within macrophages: Salmonella, Yersinia, Mycobacterium, Brucella, Listeria

                2. CMI is also used to attack helminths/”worms”, tumor cells and transplanted tissue

Vocabulary

                cytokines= chemical messengers produced by cells; permit cells to talk/communicate with one another

                lymphokines= a specfic group of cytokines/chemical messengers produced by lymphocytes

Cells involved in CMI

                1. Monocytes and macrophages: non-specific phagocytes (will eat anything abnormal!)

                2. T lymphocytes/cells

                                a.  2 types : T helper lymphocytes and T cytotoxic lymphocytes

                                b.   T helper lymphocytes =CD4+ T cells

-help “turn-on”/activate macrophages and T cytotoxic lymphocytes by producing lymphokines

                                                -recognize class II MHC (Major Histocompatibility Complex) molecules found on antigen presenting cells (such as macrophages and B lymphocytes)

                                c. T cytotoxic lymphocytes = CD8+ T cells

                                                -cytotoxic T cells:  destroy host cells infected with viruses/bacteria

                                                                -mechanism: “the kiss of death”, produce perforins which insert into target cell membrane and cause it to burst/lyse

                                                -( T cytotoxic cells also kill tumor cells and transplanted cells)

Examples of cell mediated immunity

Delayed type hypersensitivity reactions

“DTH”: turning on macrophages to  kill intracellular parasites

                1. example: Tuberculosis and Mycobacterium tuberculosis         

                                target= macrophages infected with M. tuberculosis bacteria

                2. Mycobacterium tuberculosis bacterium is phagocytized by macrophage

                                -Mycobacterium have evolved defenses to live inside macrophages

                3. Macrophage cannot kill bacterium (macrophage is “resting”,  not “turned on”)

                4. Mycobacterium antigens are displayed on the surface of the macrophage, connected

                                to class II MHC (similar to a  distress flag that says “something is wrong with me!”)

                5. “Patrolling” T helper lymphocytes screen macrophages for unusual surface “flags” (similar to “bouncers” at a party)

                                -specific T helper lymphocytes discover the abnormal macrophage, trigger the Thelper “alarm”

                6. “Alarmed” T helpers  secrete chemical messengers/lymphokines ( example gamma                                        interferon/IFN-gamma)                                 

                                -siren goes off

                7. Some lymphokines (IL-2) attract more white blood cells/defenders to the site of “invasion”

                8. Some lymphokines (IFN-gamma) “awaken”/activate macrophages, turns them into an “angry killers”, (increase in oxidative/respiratory burst)capable of destroying bacteria living inside                                             

                                                -IFN-gamma similar to a several strong cups of coffee

                                                -the activated macrophage produces more lethal substances to kill the invading bacterium  (“sloppy feeders” and tissue damage)

(Sometimes the activated macrophages still cannot kill all the Mycobacterium; the body tries to wall-off” the bacteria, forming a granuloma. Lots of macrophages remain in the vicinity).

B. Virus infected host cells

  1. host cell infected by virus; virus antigens are presented on surface of host cell complexed to MHC-I molecules
  2. Patrolling CD8+ T cytotoxic lymphocytes scan host cells; detect abnormal MHC-I complexed to viral antigen

With Thelper lymphocyte stimulation, Tc lymphocytes releases perforins molecules which create pores in infected host cell membrane. Perforin release (“kiss of death”) leads to osmotic lysis of virus infected host cell, halting virus replication. T c’s also release granzymes which can enter the infected cell through the perforin channels. The granzymes trigger the infected cell to “commit suicide”, a process called apoptosis.