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29 Cards in this Set
- Front
- Back
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Characteristics of Tumor Ag
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1. Products of mutated genes (you've changed!)
2. Abnormal expression of normal genes (you're acting strangely!) 3. Oncogenic virus genes (you've been infected!) 4. Oncofetal ag (you're acting immature!) 5. Altered glycolipids and glycoprotein ag (you're dressed differently) 6. Tissue-specific diff ag |
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Innate Immune system responders
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NK
Macs |
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Adaptive Immune System Responders
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CD8 T cells
B lymphocytes |
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Why the immune system may not respond to tumor?
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1. Tolerance (got used to tumor)
2. Regulatory T cells (Tregs recognize tumor as self) 3. Loss of MHC I (hiding from CTL) 4. Loss of tumor ag (hiding - losing what it can be identified as) 5. Suppressive secretions by tumor cells: inh immune system (TGFb) |
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How the immune system may promote a tumor?
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Chronic inflammation: macs release angiogenesis factors for tissue remodeling, promotes DNA damage (O2 free rads)
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Immune therapy techniques
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1. Tumor vaccination (exposes tumor ag to APCs)
2. Augmentation of tumor response (seed tumor w/ ILs for better recognition) 3. Blocking inh pathways (CTLs can't rest until tumor is gone) 4. Non-specific stimulation (hail mary pass) 5. Passive immunotherapy |
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Passive Immunotherapy
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1. Adoptive cell culture - lymphocytes removed --> activated --> expanded in vitro --> returned (kinda like autologous BMT)
2. Graft vs. Leukemia rxn - alloreactive T cells administered 3. Anti-tumor Ab - Anti-tumor markers injected (like Ig admin to better fight off Hepatitis, malaria) |
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Problems w/ chemotherapy
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Apoptosis mediated death doesn't cause inflammation -- need inflammation for a better immune reaction
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Produts of mutated genes MOA
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Mutation can occur at level of self peptide or self protein
1. protein can bind to new peptides and present them 2. peptide can be recognized as a new epitope for recognition |
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Abnormal expression of normal genes
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1. Overexpression --> increased density (>10k MHC:peptide complexes) of peptide presentation (via MHC I) for T cells to respond to -- doesn't need co-receptor stim
2. Reactivation of (fetal) genes --> presentation of peptides not normally expressed to immune system (like seeing an old friend from elementary school but totally forgot about them) |
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Altered glycolipid and glycoprotein ag
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Abnormal forms or too much expressed on tumor cell surfaces
- gangliosides on melanoma - blood group ags - mucins |
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Tissue-specific differentiation ag
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CD10/CD20 - B cell lymphomas
Tyrosinase - melanomas CD4 - T cell leukemias |
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Ex of gene product silent in normal tissues - Melanomas
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Cancer/testis ag in melanomas
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Oncogenic virus product - ex: Cervical carcinoma
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E6 and E7
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Oncofetal ag ex
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CEA, AFP
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Differentiation ag on normally present in tissue EX
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PSA
Lymphocyte markers |
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NK MOA
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MOA of recognition: altered cell-surface gp*, loss of MHCI*, bound ab
MOA of killing: cytotoxic granules NKG2 - inh (A,B), act (C,D) Ly49 - inh (A,G), act (D,H) |
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Macrophage MOA
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MOA recognition: bound ab, receptor interactions
MOA of killing: phagocytosis, NO, reactive oxidative pathway |
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CTL MOA
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MOA recog: tumor ag on MHCI
MOA killing: cytotoxic granules, FasR ligation (tumor gets rid of FasL - so not effective) |
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B lymphocytes MOA
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MOA recog: tumor ag, Tcell help
MOA kill: ADCC, ab-dep CM cytotoxicity, complement activation |
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Tolerance - "i'm one of you"
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lack of costimulation --> anergy
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Reg Tcells - "i'm one of you"
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CD4/CD25 autoreactive T cells - inhibit autoreactivity - low immunogenicity
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Loss of MHCI - "laying low - don't look suspicious"
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loose expression of this --> hides from CTL
BUT NK goes up!!! not sufficient though :-( |
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Loss of Tumor Ag - "laying low - don't look suspicious"
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loose expression of ag it was once identified as (if not essential in growth)
Best tumor ag - if it played a role in tumor progression (2fer - identifies whats making it grow... and attack that because it needs it) |
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Augmentation of tumor response
IL2 |
bring lymphocytes and neutrophils -- works against RCC, melanoma
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Augmentation of tumor response
IL4 |
brings eosinophils, macs -- melanoma and RCC
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Augmentation of tumor response
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like sticking a red flag on a tumor so immune cells can recognize them
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Blocking inh pathway
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(CD152) CTLA4 - ab block this receptor to upregulate CTLs/immune system
CD28 delivers costim signal during activation --> expression of CTLA4 (binds B7 better) --> stronger and better signal w/ both CTLA4 AND CD28 to B7 |
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Non-specific stimulation
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IL2 - melanoma, RCC, CRC
IFN-a - melanoma TNF IL12 Anti-CD3 ab GM-CSF |
