Tumor Immunology: Definitions: -Tumor (neoplasm): unchecked cellular growth. -Two types: 1-Benign: controlled tumor. 2-Malignant: uncontrolled tumor. -Malignant tumors are characterized by: 1-Progressive growth without exogenous growth signals. 2-Invasiveness of normal tissue boundaries. 3-Metastasis. 4-Mainly of Monoclonal origin.
Classification of malignant tumor: Malignant tumor is classified according to its embryonic origin into different groups: 1-Carcinoma: Malignant tumors develop from endodermal or ectodermal tissues. Examples: Skin carcinoma, Colon and lung carcinoma. 2-Sarcoma: Malignant tumors develop from bone and cartilage. 3- Leukemia: Malignant tumor of hematopoietic lineage that proliferate as individual cells. 4-Lymphoma: Malignant tumor of hematopoietic lineage that proliferate as solid mass.
Malignant transformation: -Malignant transformation is a transformation of normal cellular phenotype into cancerous phenotype due to proto-oncogenes mutation. -Oncogenes: are cancer-producing genes. Examples: 1-Development of sarcoma in tissue culture due to inoculation of Rous sarcoma virus (SV40). 2- Adult T lymphocytic leukemia due to HTLV (Retrovirus) infection.
Oncogenes and cell growth: Types of oncogenes: 1-Stimulators of cell division: -Cellular oncogene- proteins involved in signaling pathway via tyrosine phosphorylation (Ex: Src or Abl ). Function: Regulate cell division. -Cellular oncogene-proteins act as transcription factors (EX: fos and Jun). Function: Regulate gene transcription.
N 2-Tumor suppressor genes: - Cellular oncogene-proteins that suppress cell growth. Mutation in anti-oncogene; loss of function. Examples : -P53: Nuclear protein that suppresses tumor growth. -Rb: Suppressor of retinoblastoma. 3-Regulators of apoptosis: -Bcl-2: Anti-apoptotic oncogene found in B-cell follicular lymphoma. -Bax: pro-apoptotic oncogene. -Bcl-2/ Bax ratio control whether the cell survive or die.
Tumor Antigens: -Cellular peptides presented by MHC that stimulate specific T cell response. Types of Tumor Antigens: 1-Tumor-specific transplantation antigens(TSTA): -Not found on normal somatic cell. -Unique to tumor cell. 2-Tumor-associated transplantation antigens(TATA): -Found on normal cells (not-unique to tumor). -Found in excessive amount. -expressed on a cell where not normally exist.
Examples: 1-Carcinoembryonic antigen (CEA): -Found in fetal liver normally. -Found in serum of patient with colorectal cancer. 2-α-fetoprotein: (AFP): alpha-globulin: -Found normally in fetal liver. - Found in serum of patient with liver cancer. 3-HER2/neu: -Breast cancer.
Immune Surveillance: 1-Innate immunity: A-Role of NK cells in tumor killing:
N B-Cytokines: -Macrophage cytokines: -TNF-α, and TNF-β: Stimulate Tumor necrosis. -TNF- α: Inhibits angiogenesis; growth of new vessels. -INF- α, and INF-β: Up-regulate MHC I expression. -Activated lymphocytes cytokines: -INF-γ: directly inhibit tumor proliferation.
N 2-Adaptive immunity: A -The Antibodies and Humoral response. :See the effector lymphocyte function lecture. B-CTL effect: -Direct cytotoxicity by effector CD8 cells. C-DTH effect: -The effector CD4 function.