Notes on Tumor Immunology

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Tumor Cells:

• Tumor cells multiple abnormally, spread throughout the host and interfere with normal organ function.

Benign neoplasms:

• characterized by slow growth and restricted anatomic location. These are non-lethal.

Malignant neoplasms:

• grow slowly or rapidly. Characterized by anaplasia - cells losing their differentiating features. Invade the body and may be lethal.

Immunesurveillance

• The immune system continuously surveys the body for the presence of abnormal cells. These cells are then quickly destroyed.

• Post mortems suggest there are more tumors than clinically revealed.

• Tumors occur frequently in neonatal period and old age. More common in immunosuppressed individuals.

Features of Tumor Immunity:

• Tumors express antigens that are recognized as foreign.

• Tumor responses fail to stop growth of tumors: Tumors are weakly immunogenic and tumors are moving targets.

Tumor Antigens:

• Two groups: TSA and TAA.

• The ideal tumor antigen is recognized by Ag specific CTL and thus destroyed by the immune system.

7 classes of Tumor Antigens:

• Products of mutated oncogenes and tumor suppressor genes.

• Products of other mutated genes with unknown functions.

• Aberrantly expressed normal cellular proteins.

• Tumor antigens encoded by genomes of oncogenic viruses.

• Oncofetal antigens.

• Altered glycolipid and glycoproteins antigens.

• Tissue specific differentiation antigens.

Detection of Tumor Antigens:

• Detected by immune cells or antibodies.

• Many viruses also cause tumors.

• Sera from tumor bearing patients contains antigens.

• Most tumors originate from a single cell.

• Some proteins produced by tumor infested cells include: Oncofetal Ags (fetus), AFP (liver), and CEA (colon).

Tumor Immune Responses

• Tumor cells have marked infiltrate of inflammatory cells.

• Lymphocytes and macrophages dominate the infected area.

• Other cells: dendritic cells, granulocytes and mast cells.

• Monoclonal abies have been used to detect lymphoid cell subtypes in Tu (IL2 receptor,MHC classII,other activation markers).

Tumors Evade Detection

• Tumors are non-immunogenic.

• Tumor cells are poor antigen presenting cells.

• Induction of immune responses require costimuli which may be cell surface molecules or cytokines secreted by APC.

• B7 molecules present on specialized APCs is key stimulus acting via its counter receptor CD28 on the T cell surface.

• Cancer patients have decreased immune response.

• Tumor cells lack LFA1 and 3 or ICAM-1 required for adhesion of lymphocytes.

• Tumor cells express mucin molecules (antiadhesive).

• Tumor cells secrete immunosuppressive cytokines as TGF-beta.

• Loss of MHC Ag-MHC class I allele.

Role of Natural Killer cells

• These play a bog role in tumor suppression.

• Tumors sensitive to NK killing.

• NK stimulated by IL2, IL12 and gamma interferon.

Diagnosis

• Antibodies to tumor cells are useful.

• Radiolabelled antibodies against tumor associated molecules have been detected.

• Other methods include: MRI and Immunoscintigraphy.

• Fluids are taken from bone marrow, cerebrospinal fluid and lymphoid organs.

• Immunoassays detect: CEA and AFP.

Additional Readings:

Basic Immunology

1. Introduction to Immunology
2. Cells of Immunology
3. Selection of Lymphocytes
4. Primary Response to Antigen
5. Antigen Processing and Presentation
6. Humoral Effector Mechanism Generator
7. Cell-Mediated Effector Mechanism Generator
8. Vaccination and Immunotherapy
9. Immunodeficiency Diseases
10. Acquired Immunodeficiency Syndrome
11. Hypersensitivities and Autoimmunity Diseases
12. Immunology of Transplantation
13. Immunology of Cancer
14. Immunology Laboratory Technology
15. Acquired Immunity
16. Type II Hypersensitivity Reaction
17. Hypersensitivity Reactions
18. Primary Immunodeficiency
19. Secondary Immunodeficiency
20. Type III Hypersensitivity Reaction
21. Type IV Hypersensitivity Reaction
22. Type V Hypersensitivity Reaction
23. Tumor Immunology
24. Images of Antibodies
25. Th1 vs Th2 cells

Related Topics

1. Histology of Lymphoid Tissue

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