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PNS
o Endocrine syndrome: ectopic hormone production
o Neuromyopathic syndromes: progressive destruction of neurons throughout the nervous system
without evidence of metastasis; possibly mediated by immunologic mechanisms. The changes may
effect muscles as well.
o Effect on osseous, joints and soft tissue
o Haemotologic and vascular syndrome
o Gastrointestinal syndromes: malabsorption; hypoalbuminaemia
o Renal syndromes
o Cutaneous syndromes
o Amyloidosis
Tumors are not entirely self; seen as foreign by the host immune system
Cancer occur implies that immune surveillance (recognition and destruction of newly appearing tumors) is
imperfect; some tumors escape from such policing
Tumor antigens
o Tumor specific antigens: present only on tumor cells
o Tumor associated antigens: present on tumor and some of normal cells
o Based on their molecular structure and source
o Cytotoxic T Lymphocytes recognized tumor antigens, in which in its techniques of identifying may
undergo a development; CTLs are responsible for the major immune defense mechanism against tumor.
o CTLs recognize peptides derived from cytoplasmic protein that displayed bound to class I MHC
molecules.
o Antigens: Products of Mutated Oncogenes and Tumor Suppressor Genes:
Neoplastic transformation caused by genetic alterations, some of which may lead to the
expression of cell surface antigens.
Antigens in this category are drive from mutant oncoproteins and tumor suppressor proteins;
unique antigens: arise from on with encoding genes frequently mutated in tumors.
CTLs do not appear to elicit protective responses in vivo
In some cases, unmutated oncogenes are overexpressed and appear as antigens in tumor cells.
o Products of Other Mutated Genes
Tumor cells have unstable gene result in mutation in these cells, including genes whose products
are not related to the transformed phenotype and have no known function. These product are
potential tumor antigens and are diverse (since carcinogens may randomly mutagenize virtually
any host cells).
o Overexpressed or Aberrantly Expressed Cellular Proteins
Tumor antigens may be normal cellular proteins that are abnormally expressed in tumor cells
and elicit immune responses. i.e. melanomas caused overproduced of tyrosinase, In which is
some of the antigens.
o Tumor Antigens Produced by Oncogenic Viruses
Some viruses that are associated with cancers produce proteins that are recognized as foreign
by the immune system.
Most potent: protein produced by the latent DNA viruses; HPV and EBV. Vaccines against HPV
antigens have been found in effective prevention.
o Oncofetal Antigens
o Altered Cell Surface Glycolipids and Glycoproteins
o Cell Type-Specific Differentiation Antigens
Antitumor Effector Mechanisms
o Cytotoxic T Lymphocytes
CD8+ CTLs have a clear protective role against virus associated neoplasms.
o Natural Killer Cells
First line of defense: destroying tumor cells without prior sensitization
After activation with IL-2 and IL-5, NK cells can lyse a wide range of human tumors.
o Macrophages
Active macrophages exhibit cytotoxicity against tumor cells in vitro.
Interferon gamma secreted by T cells and NK cells is a potent activator of macrophages.
Immune Surveillance and Escape
o Selective outgrowth of antigen-negative variants
o Loss or reduced expression of MHC molecules
o Activation of immunoregulatory pathways
o Secretion of immunosuppressive factors
o Induction of regulatory T cells