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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
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
- host cell infected by virus; virus antigens are presented on surface of host cell complexed to MHC-I molecules
- 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.
B and T Cells
Lymphocytes, which are a subclass of white blood cells, are formed with other blood cells in the red bone marrow found in many flat bones, such as the shoulder or pelvic bones. The two types of lymphocytes of the adaptive immune response are B and T cells (Figure 1). Whether an immature lymphocyte becomes a B cell or T cell depends on where in the body it matures. The B cells remain in the bone marrow to mature (hence the name “B” for “bone marrow”), while T cells migrate to the thymus, where they mature (hence the name “T” for “thymus”). During the maturation process, each B or T cell develops unique surface proteins that are able to recognize a unique set of very specific molecules on antigens (discussed below). In other words, each B or T cell can recognize only a very few different molecules, but together the entire lymphocyte population in a healthy person should be able to recognize molecules from most pathogens. The specificity of these unique surface proteins, or receptors, on the lymphocytes is determined by the genetics of the individual and is present before a foreign molecule is introduced to the body or encountered. Except in certain immune system diseases called autoimmune diseases, no mature B or T cells are able to recognize and bind to molecules that are found on healthy human cells, but only to molecules found on pathogens or on unhealthy human cells.
B cells are involved in the humoral immune response, which targets pathogens loose in blood and lymph, and B cells carry out this response by secreting antibodies.T cells are involved in the cell-mediated immune response, which targets infected cells in the body. T cells include the Helper T cells and the Cytotoxic, or Killer, T cells. Cytotoxic T cells directly kill human cells that are infected or unhealthy. Helper T cells do not directly kill infected cells, but secrete molecules that are crucial for the function of all other cells in the immune response to a pathogen.
Figure 1. This scanning electron micrograph shows a T lymphocyte. T and B cells are indistinguishable by light microscopy but can be differentiated experimentally by probing their surface receptors. (credit: modification of work by NCI scale-bar data from Matt Russell)