Kuby Immunology 6/e

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Transcript Kuby Immunology 6/e

Chapter 19
Cancer and the Immune System
Dr. Capers
Altered self cells
 Unregulated mitosis
○ Produces tumor (neoplasm)
 Benign – does not invade healthy tissue
 Malignant – grows and becomes invasive
- Exhibit metastasis
Malignant cancers are classified according
to embryonic origin of tissue
○ Carcinomas
 Endodermal or ectodermal
 Skin or epithelial lining of internal organs and glands
 Colon, breast, prostate, lung
○ Leukemias and lymphomas
 Tumors of hematopoietic cells of bone marrow
 Leukemias proliferate as single cells
 Lymphomas grow as tumor masses
○ Sarcomas
 Mesodermal connective tissue
 Bone, fat, cartilage
Malignant transformation
 Ability for cell to form cancer
○ Decreased requirements for growth factors
○ No longer anchorage dependent
 What can cause this?
○ Various chemical agents
○ Radiation
○ viruses
Genes that code for
proteins involved in
cell proliferation are
mutations in these
genes can lead to
Chromosomal translocations
 Can lead to movement of proto-
 This can lead to increased
transcription and translation of
the protein
Induction of cancer is a multi-step
 Multiple and subsequent mutations
Tumors of Immune System
Leukemias or Lymphomas
 Lymphomas
○ Solid tumors in lymphoid tissue
○ Include Hodgkin’s and non-Hodgkin’s lymphomas
 Leukemias
○ Proliferate as single cells
○ Lymphoid or myeloid lineage
○ Acute – appear and progress rapidly, tend to rise
in immature cells
○ Chronic – less aggressive and slow, tend to rise in
mature cells, tend to be in adults
Tumor Antigens
Tumor-specific transplantation antigens
○ Unique to tumor cells
○ May arise due to mutation
○ Are presented on Class I MHC
Tumor-associated transplantation antigens
○ Proteins expressed on normal cells
 Inappropriate expression of embryonic gene
 Overexpression of normal protein
Some antigens are tumor specific
Oncofetal antigens
 Found on normal fetal cells
 Only meant to be expressed during embryological
 Suppressed after development of fetus is completed
 If expressed later in adult, could induce
immune response
 Immune system may see these as nonself
 Can lead to cancer
 ~90% of colorectal cancer have CEA
(carcinoembryonic antigen)
Tumor Invasion of Immune System
Anti-tumor antibodies
○ Might actually block sites for CTL to bind
Tumor cells might express less Class I
○ This prevents CTL-mediated death
Tumor cells may provide poor
costimulatory signals
Cancer Immunotherapy
Manipulation of costimulatory signals
 Enhancement of antigen-presenting cells
 Cytokine therapy
○ Interferons
○ Tumor necrosis factors
Monoclonal Abs may be used for some
○ Immunotoxins may be linked to kill specific tumor
cell, still being researched
 Radioactive isotope, drugs