Cancer and the Immune System Flashcards
what are tumors/neoplasms?
cells that have lost control of the cell cycle
what are the two types of tumors/neoplasms?
- benign: unable to invade healthy surrounding tissue, incapable of indefinite growth
- malignant: becomes progressively more invasive and may metastasize
what are the three types of hematological system cancers?
- leukemia
- lymphoma
- myeloma
what causes leukemia?
cells of myogenous or lymphocytic origin in early stage of development in bone marrow
what causes lymphoma?
blood cells in their later stage of development outside the bone marrow spread through lymphatics to lymph nodes
what causes myeloma?
full differentiated plasma cells that mutated, produce antibodies, migrate back to bone marrow and form multiple lesions
how can a malignant transformation of cells be induced?
- chemical substances
- physical agents
- ionizing radiation
- viruses/infectious agents
- genetic predispositions
what are the two ways malignant cell transformations can occur?
through DNA alterations or cancer-associated genes
what are the three cancer-associated genes and how do they cause cancer?
- proto-oncogenes: genes that induce cellular proliferation become unregulated and cause uncontrolled cell growth
- tumor-supressor genes: inhibitors of cell proliferation (pro-apoptotic) mutates and allows cancer cells to survive when they fail
- apoptosis gene problem: abnormal cell survival
how can inflammatory responses promote cancer?
because chronic inflammation
- increases cellular stress signals
- lead to genotoxic stress
- increase mutation rates
- growth factors/ cytokines released by cells often induce proliferation
- inflammation is proangiogenic
what are the two types of tumor antigens?
- tumor-specific antigens
- tumor-associated antigens
what are tumor specific antigens?
unique to cancer cells, not found on normal cells, that arise due to genetic mutations or viral infections that create new, abnormal proteins where the immune system can recognize them as non-self and attack them.
what are tumor associated antigens?
Not unique to cancer cells—these are normal proteins but are expressed abnormally in tumors that are normally present during fetal development but reappear in cancer or proteins usually present at low levels but over expressed in tumors
what are some examples of tumor specific antigens?
Viral
- HPV: L1, E6, E7 - causes cervical carcinoma
- HBV: HBsAg - causes hepatocellular carcinoma
what are some examples of tumor-associated antigens?
Over expression
- HER-2/neu - causes breast, melanoma, ovarian, gastric and pancreatic
- PSA - prostate
- PAP - prostate
Differentiation Stage
- CEA - colon
- AFP - Hepatocellular carcinoma
why is the immune response (immunoediting) to cancer considered a double edged sword?
the immune system both protects against tumor growth and shapes the evolution of cancer cells. It consists of three phases
what are the three phases and the outcome of immunoediting?
- elimination: attacking the cells that can be targeted
- equilibrium: state of balance between destruction/survival of “best” cells
- escape: most aggressive/least immunogenic cells thrive and spread
- outcome: anti-tumor responses select for toughest cells
what are the innate cells that mediate tumor elimination and how?
- NK cells
- M1 macrophages: activated macrophages secrete TNF (strong anti-tumor activity) and bind to antibody coated tumor cells
- eosinophils: role not completely established yet
what are the adaptive cells that mediate tumor elimination and how?
- T cells
- Tumor-infiltrating lymphocytes: combination of T cells, NKT cells and NK cells
- B cells: generate anti-tumor antibodies against tumor specific antigens
how do NK cells regulate innate/adaptive cancer immunity?
cytokine secretion
explain the process of activation for a NK cell?
- cell is missing MHC 1 molecule
- cell is turned on through immunoreceptor tyrosine based activation motifs (ITAMS)
- phosphorylation of protein tyrosine kinases
- production of INF gamma and increase in IL-2 receptors
- lytic machinery
explain the process of no activation for a NK cell?
- inhibitory receptors bind to MHC class 1 molecules
- immunoreceptor tyrosine based inhibitory motifs are activated
- recruitment of phosphatases
- removal of phosphate groups (no protein tyrosine kinase activation)
how do NK cells recognize a target?
- inhibitory NK receptors (KIR3DL1) that binds to ligand MHC
- activating NK receptors (NKG2D): that bind to ligand, NKG2DL = MICA