TUMOR IMMUNITY – A tumor, or neoplasm, is a collection of the clonal descendants of a cell whose growth has gone unchecked. When a tumor continues to grow and to invade healthy tissue, it is considered to be a cancer. – Cancer cells have unregulated rates of cell growth and invade healthy tissue. – Metastasis is a characteristic of many malignant cells as they become dislodged from the main tumor and travel to distant sites in the body. – Lymphomas and leukemias are tumors of immune cells that are derived from hematopoietic cells. Lymphomas are solid tumors, whereas leukemias grow as dispersed, single malignant cells. – Malignant transformation is the process by which a normal cell becomes a cancerous cell. – Oncogenes are sometimes linked to malignant transformation. Mutations of cellular oncogenes often results in a change in cellular growth. – Tumor antigens include tumor-specific antigens (TSTAs) that result from altered proteins expressed as a consequence of gene mutations within tumor cells and tumor-associated antigens (TAAs) that are not unique to tumor cells but have unusual expression on tumor cells. – The immune surveillance theory suggests that cancer cells frequently arise within the body but are normally eliminated by the immune system before a tumor develops. – Innate immune responses against tumors include NK cell killing of tumors and macrophage production of antitumor cytokines, including tumor necrosis factor and the interferons. – Adaptive immune responses against tumors include generation of antitumor antibodies, CTL killing of tumor cells, and DTH reactions (involve Th1 cells recruiting and activating macrophages, which attack and kill tumor cells). – Immune evasion by tumor cells facilitates survival of malignant cells. – Several mechanisms that facilitate evasion of the immune response by tumor cells have been identified. Page | 1/5
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TUMOR IMMUNITY– A tumor, or neoplasm, is a collection of the clonal descendants of a cell whose growth
has gone unchecked. When a tumor continues to grow and to invade healthy tissue, it is considered to be a cancer.
– Cancer cells have unregulated rates of cell growth and invade healthy tissue. – Metastasis is a characteristic of many malignant cells as they become dislodged from the
main tumor and travel to distant sites in the body. – Lymphomas and leukemias are tumors of immune cells that are derived from
hematopoietic cells. Lymphomas are solid tumors, whereas leukemias grow as dispersed, single malignant cells.
– Malignant transformation is the process by which a normal cell becomes a cancerous cell.– Oncogenes are sometimes linked to malignant transformation. Mutations of cellular
oncogenes often results in a change in cellular growth. – Tumor antigens include tumor-specific antigens (TSTAs) that result from altered
proteins expressed as a consequence of gene mutations within tumor cells and tumor-associated antigens (TAAs) that are not unique to tumor cells but have unusual expression on tumor cells.
– The immune surveillance theory suggests that cancer cells frequently arise within the body but are normally eliminated by the immune system before a tumor develops.
– Innate immune responses against tumors include NK cell killing of tumors and macrophage production of antitumor cytokines, including tumor necrosis factor and the interferons.
– Adaptive immune responses against tumors include generation of antitumor antibodies, CTL killing of tumor cells, and DTH reactions (involve Th1 cells recruiting and activating macrophages, which attack and kill tumor cells).
– Immune evasion by tumor cells facilitates survival of malignant cells. – Several mechanisms that facilitate evasion of the immune response by tumor cells have
been identified.1. Antibody enhancement of tumor growth
Antitumor antibodies may actually enhance the growth of some tumors and may result in decreased detection of some tumor antigens. The antitumor antibodies may bind to the antigens on the tumor cells, masking the antigens and blocking the ability of CTL cells to bind and kill the tumor cell. Antibody bound to tumor antigen may inhibit binding of Fc receptors on macrophages, dendritic cells, and NK cells.
2. Antibody modulation of tumor antigensIn the presence of antibodies directed against tumor antigens, downregulation of expression of certain tumor-specific antigens has been demonstrated. In a process known as antigenic modulation, the antigens disappear for a time and then reappear when the antibody is eliminated. Cells that do not express the antigen are no longer targets of other adaptive immune responses
3. Modulation of MHC I expressionTumor cells often express reduced levels of MHC I molecules, helping the tumors to evade immune detection. If tumor cells express decreased amounts of MHC I, NK cell responses to them may be enhanced, whereas CTL-mediated responses against those tumor cells are decreased.
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– Immuno-editing describes the postulated process by which the developing anti-tumor immune response both identifies and kills tumor cells, as well as participates in selection of cells that have developed immune-evasive mutations.
– Cancer immunotherapy is designed to increase the immune response against cancer cells.– Current cancer immunotherapy: Cytokine therapy, monoclonal antibodies and cancer
vaccines. Cytokines and monoclonal antibodies have proven to have some limited effects in treating certain cancers. Vaccination, either to prevent development of a type of cancer or to inhibit recurrence of a tumor within a patient, continues to be explored. Therapeutic vaccines are aimed at increasing the ability of APCs to activate adaptive cell-mediated tumor eradication.
– Combinations of cytotoxic chemotherapies with selected immunotherapies are yielding promising results against cancer.
REPRODUCTIVE IMMUNITY: PREGNANCY AND FETAL ANTIGENSThe Rh ("Rhesus") antigens
– The Rh ("Rhesus") antigens on erythrocyte surfaces are proteins. When a Rh-negative (Rh-) individual is exposed to Rh positive (Rh+) erythrocytes, he or she can generate antibodies, some of which are of the lgG isotype.
– Rh antigens can be typed prior to transfusion, and Rh-related transfusion reactions can be avoided by avoiding the transfusion of Rh- recipients with Rh+ blood. Rh incompatibility during pregnancy presents a special concern for a Rh- mother who carries a Rh+ fetus.
– Fetal blood immunizes the mother's immune system to make lgG antibodies that may cross the placenta and destroy fetal erythrocytes in utero.
– Rh antigens are encoded by a series of closely linked loci (D and CE) with dominant alleles (e.g., D) and recessive alleles (e.g., d), the most important of which is D. DD or Dd individuals have the Rh+ phenotype, whereas those with dd are Rh-.
– When the father is Rh+, a Rh- mother may carry a Rh+ fetus. The maternal immune system is exposed to fetal blood as early as the first trimester of pregnancy and begins to generate anti-Rh lgG antibodies.
– The first Rh+ fetus is rarely at risk because of the time needed for injurious levels of anti-Rh antibodies to develop. However, subsequent Rh+ fetuses are at risk because maternal anti-Rh antibodies can increase rapidly and enter the fetus. Binding to fetal erythrocytes
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can lead to anemia and damage to other fetal organs. This is called hemolytic disease of the newborn (HDN) or sometimes erythroblastosis fetalis.
– The Rh antigen is a protein and elicits an lgG response. Every conception between a Rh+
male and a Rh- female has the potential to produce a Rh-incompatible fetus. Aborted (spontaneous or induced) conceptions can also lead to the development of an lgG antibody response to Rho (D).
– In HDN, binding of anti-Rh antibodies to erythrocytes activates fetal complement, causing lysis of erythrocytes. The resulting anemia may become so severe that the fetus sustains severe damage or dies in utero. To compensate for the anemia, the fetal bone marrow releases immature erythrocytes (or erythroblasts). The abnormal presence of these erythroblasts in the fetal circulation is the hallmark of the disease (hence the term erythroblastosis fetalis).
– Preventive therapy, especially the use of Rho (D) immune globulin to minimize the risk of the mother becoming sensitized against Rh, is now routinely available for this situation. This involves the injection of a high-titer anti-Rh antibody preparation such as RhoGAM or MICRhoGAM. These preparations contain pooled anti-Rh antibodies, prepared from human serum obtained from mothers who have made antibodies to Rh antigens.
– Rho (D) immune globulin should be administered after the 12th gestational week for ongoing pregnancy as well as for spontaneous or induced abortion.
– RhoGAM and MICRhoGAM remove fetal cells from the maternal circulation quickly enough to avoid sensitizing the mother's own immune system against Rh. Use of Rho (D) immune globulin may also be appropriate after a blood transfusion of an Rh- female.
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