|
CELL-MEDIATED IMMUNITY
The immune system is able to effectively eliminate infective agents (bacteria, viruses, parasites, fungi) that have by-passed the barriers of innate immunity and are present both inside the cells and in the extracellular fluids especially thanks to cell-mediated responses.
Cell-mediated immunity (Réaction immunitaire à médiation cellulaire/ Risposta immunitaria cellulo-mediata/ Inmunidad celular) is also of fundamental importance in the study of tumors.
• Cell-mediated immunity against extracellular bacteria
• Cell-mediated immunity against intracellular bacteria
• Cell-mediated immunity against viruses
• Cell-mediated immunity against parasites
• Cell-mediated immunity against tumors
Cell-mediated immunity against extracellular bacteria
Extracellular bacteria are able to replicate in extracellular environments like the blood circulation, the connective tissue, the respiratory tract and the lumen of the intestinal tract: they cause disease by two mechanisms: inflammation and production of toxic substances called toxins (toxines/ tossine/ toxinas). Some of the diseases caused by extracellular bacteria are: diphtheria (diphtérie/difterite/difteria) [E1/F1], [F2/E2/ES], [I], meningitis (méningite/meningite/meningitis)[E],[F], cholera (choléra/colera/cólera) [E1/ES1],[E2/ES2] and tetanus (tétanos/tetano/tétanos)[E/ES], [F], [I]. Escherichia Coli [F/E/ES/I]is also an important bacterium involved in intestinal function, but is also capable of triggering infection in certain circumstances.
The adaptive immune response allows to eliminate bacteria and neutralize the effects of toxins. First of all, APCs can capture circulating bacteria and toxins, then they can engulf them, process them and expose them in association with class II MHC molecules. T-helper cells recognize these non-self components and activate B lymphocytes. Activated B lymphocytes divide, differentiate into plasma cells and produce antibodies. Antibodies opsonize bacteria, promote phagocytosis by macrophages, neutralize toxins and activate the complement system.
The primary consequences of the immune response against extracellular bacteria are inflammation [E], [F1], [F2] and septic shock (Choc septique/Shock settico/Coque séptico)[E/ES], [F], [I]. Septic shock is a syndrome characterized by the fall of blood pressure, the alteration of metabolism and blood vessel coagulation. Extracellular bacteria are able to bypass immune defences, inactivating phagocytosis of macrophages and the complement system and varying the membrane proteins so that they are no longer recognized by memory cells if a second invasion occurs. Vaccinations [E1], [E2], [FR] are fundamental to prevent infections caused by extracellular bacteria and the best therapy is represented by antibiotics.
Cell-mediated immunity against intracellular bacteria
Natural immunity is practically ineffective against intracellular bacteria, that are capable of surviving and replicating inside the cells of our organism, even inside phagocytic cells. It is possible to completely eliminate these invaders only by cell-mediated responses.
Any cell from our body may be infected by a bacterium and may expose a fragment of a bacterial protein in association with class I MHC molecules; the MHC class I- antigen complex activates cytotoxic T cells, which directly lyse the infected cell. Then, cytotoxic T cells proliferate differentiating into memory cells and effector cells capable of eliminating other cells infected by the same bacterium. Further, cytotoxic T cells release cytokines capable of activating macrophages. A macrophage may engulf an intracellular bacterium which is resistant to phagocytosis and therefore may not be able to kill it; if the macrophage is activated by cytokines, though, it produces oxygen reactive species and enzymes that eliminate the engulfed bacterium. The immune response triggers a local inflammation .
Individuals with immune system defects, like HIV patients, are particularly sensitive to infections by intracellular bacteria and viruses. Some intracellular bacteria, which have developed resistance to phagocytosis, may survive for as long as years inside the host cells and continuously stimulate the immune system: in this way, prolonged or chronic infections occur. Examples of diseases caused by intracellular bacteria are tuberculosis (tubercolose/ tubercolosi/ tuberculosis) [F1/E1/I1/ES1], [E2/ES2], [E3], [I2] and leprosy (lépre/lebbra/lepra)[F1/E1/ES1], [F2], [I1].
Cell-mediated immunity against viruses
Viruses are intracellular micro-parasites, that replicate at the expenses of the host cell, taking over the replication machinery of DNA and protein synthesis. Some viruses do not allow normal protein synthesis of the infected cell leading to its death; others are able not to interfere with cellular activities and may remain silent for years. As in the case of intracellular bacterial infections, the major response mechanism against viruses concerns cytotoxic T cells, which recognize MHC class I-antigen complexes and directly eliminate the infected cells. Actually, the primary physiological function of cytotoxic T cells is surveillance against viral infections. When viruses lead the host cell to death, they exit from it to infect new cells. In this phase, they may also be captured by APCs and be exposed with MHC class II molecules: in this way T-helper cells are activated and in turn activate B lymphocytes. Antibodies bind viruses to avoid their entrance in other cells of the body and also to promote their elimination by phagocytosis.
Examples of common human viruses are HIV-1 (Human Immunodeficiency Virus Type 1), responsible for AIDS [E1], [E2], [E3], [E4], [I/E5/ES]and rhinovirus, which causes common colds (rhume/ raffreddore/ frio). Vaccinations are useful in the case of viral infections.
Cell-mediated immunity against parasites (parasite/parassita/parásito).
Animal parasites that may attack humans are unicellular organisms (protozoa), like Plasmodium malariae responsible for malaria [E1/ES], [E2], [F], [I] or pluricellular organisms, like Taenia [E/ES], [F], [I] or Schistosoma mansoni [E1/ES], [F], [E2]; these organisms can live at the host’s expenses both inside and outside the human body and represent the category responsible for the greatest number of diseases in the world. Parasites are indeed able to easily bypass immune mechanisms and escape or resist adaptive immunity; moreover many anti-parasite antibiotics are toxic or relatively poorly effective. Infections by parasites are therefore chronic.
In general, pathogenic protozoa have evolved to survive inside the host cell; immune mechanisms are identical to those described for intracellular bacteria and viruses. On the other side, pluricellular organisms survive in extracellular environments and may be eliminated thanks to the production of particular antibodies, that stimulate degranulation of eosinophils.
Cell-mediated immunity against tumors (cancer/tumore/tumor)
When the physiology of one cell or of a small number of cells is altered, the formation of tumors may take place: cells divide in an uncontrolled manner and, if the tumor becomes malignant, they may enter the blood stream and invade the whole body reproducing at a distance from the tissue of origin [E], [F].
Tumoral cells often synthesize proteins from mutated or deregulated genes; these proteins, like normal ones, may be degraded and exposed in association with MHC class I molecules: in this case they are named tumoral antigens. Therefore tumoral antigens may trigger an immune response against self cells, which are although abnormal. In particular cytotoxic T lymphocytes activated after interaction with the MHC class I-antigen complex, may directly eliminate tumoral cells by lysis. Fragments of dead tumoral cells may be internalized by APCs, processed and associated with MHC class II molecules; in this way T-helper cells also participate to the anti-tumoral action. T-helper cells activate macrophages and B lymphocytes: macrophages, as well as cytotoxic T cells, are able to selectively destroy tumoral cells, without acting against normal ones; B lymphocytes produce antibodies which opsonize tumoral cells, rendering them visible and distinguishable form non-tumoral ones. If the tumor spontaneously regresses, the immune system’s action has been effective; this, though, occurs rarely. In the majority of cases, tumors manage to elude the immune surveillance adopting different mechanisms. For example, occasionally APCs are not able to reveal the presence of tumors and the action of cytotoxic T cells is not sufficient; or the tumor produces a substance capable of switching off the immune response, like TGF-b.
8/11
|
