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.

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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:

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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.

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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.