Term
| what are 2 examples of areas in the body where inflammation is particularly harmful and apoptosis is used to eliminate unwanted or potentially harmful cells/those that have outlived their usefulness? |
|
Definition
| in the eyes and reproductive system |
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|
Term
| are digits formed by apoptosis developmentally? |
|
Definition
|
|
Term
| what is an example of a pathologic event that apoptosis can prevent? |
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Definition
| cells damaged beyond repair, especially concerning DNA will default to apoptosis when p53 comes in and blocks cell replication between the G1 and S phases, and the damage is too much to repair |
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Term
| what are some examples of hormone dependent involution, apoptosis in the human female? are these examples considered physiologic? |
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Definition
| regression of the lactating breast after weaning, endometrial breakdown during menstrual cycle, and ovarian follicular atresia in menopause. all of these examples are considered physiologic apoptosis. |
|
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Term
| what process do implantation, organogensis, developmental involution and metamorphosis have in common |
|
Definition
| apoptosis in physiologic circumstances |
|
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Term
| what are some examples of apoptosis's role in cell deletion in proliferating cell populations? are these examples considered physiologic? |
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Definition
| cells in intestinal crypt epithelia, immune response cells which put up a marker labeling them for apoptosis via the extrinsic pathway, (in the absences of survival signals) -> once the infection is destroyed or limited in it's ability to replicate. neutrophils usually only live for about a week. these examples are considered physiologic. |
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Term
| what is tumor necrosis factor? |
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Definition
| a pro-inflammatory cytokine, that during early events of immune activation, when inflammation is being stimulated, THF promotes cell cycle. in this instance, in the absence of other survival signals, TNF is pro-apoptotic via the extrinsic death pathway |
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Term
| what is autoimmunity? when should this be eliminated for T cells? does apoptosis help regulate this? is this an example of physiologic apoptosis? |
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Definition
| the body recognizing itself, and then attacking it's own tissues. this should be eliminated in T cells during thymic education. elimination of potentially harmful self reactive lymphocytes during or after maturation should occur via apoptosis to prevent this. this is an example of physiologic apoptosis. |
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Term
| how does the body eliminate virally infected cells? is this considered physiologic? |
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Definition
| cell death of virally affected cells induced by cytotoxic T lymphocytes. this is considered physiologic apoptosis |
|
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Term
| how can radiation, like UV light from the sun induce apoptosis in skin cells? |
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Definition
| if the body is exposed to too much sun, (DNA damage occurs), but not enough to cause sun poisoning, (necrosis), apoptosis will be necessary |
|
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Term
| what are the targets of anti-neoplastic drugs? |
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Definition
| highly replicating cells in tumors, but also areas like the lining of GI tract can be affected |
|
|
Term
| what happens if normal repair mechanisms fail? |
|
Definition
| the cell undergoes apoptosis in a default pathway where p53 blocks replication |
|
|
Term
| can heat or hypoxia cause apoptosis? |
|
Definition
| yes, to a small subset of cells. |
|
|
Term
| how do apoptosis and necrosis differ? |
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Definition
| apoptosis usually doesn't take place on a large scale, while necrosis usually does. apoptosis is usually a limited or scheduled event, with no or only a small degree of inflammation involved. |
|
|
Term
| what happens when accumulation of unfolded proteins occurs? |
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Definition
| there is stress on the ER, and induction of apoptosis can follow, however this response is limited and inflammation can follow |
|
|
Term
| how do viruses behave concerning apoptosis? |
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Definition
| viruses can induce or prevent apoptosis |
|
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Term
| what role might apoptosis play in an organ such as the pancreas if it is occuded by some abnormal process? |
|
Definition
| if whatever factor the organ is producing doesn't make it out of it's microenvironment, then it can cause involution of that tissue, in other words a high level of whatever factor is being produced can stimulate apoptosis. in some cases new ducts can be formed. this can also occur in the kidney or parotid gland |
|
|
Term
| how does TNF cause cell death in tumors? |
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Definition
| it can block new vessel formation, (= cell death via ischemic cell injury), or it can to a limited degree, promote apoptosis |
|
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Term
| how do apoptosis and necrosis differ in terms of the cell's shape? |
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Definition
| necrotic cells will swell and organelles will be unrecognizable, (this is not necessarily irreversible damage), while apoptotic cells shrink, and the cell's components maintain proportion and membrane integrity. |
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|
Term
| how do apoptosis and necrosis differ in terms of the cell's genetic material? |
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Definition
| in necrosis, chromatin will break down into mant differently sized fragments; however in apoptosis, the chromatin will condense around the nuclear membrane, and then fragmentation in a "ladder" |
|
|
Term
| how do apoptosis and necrosis differ in terms of the cell's disassembly? |
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Definition
| in necrosis, the cell is a swollen and distended. in apoptosis, the cell is packaged into a series of cytoplasmic blebs full of tightly packed organelles and nuclear fragments, ready to be taken away |
|
|
Term
| what happens to cytoplasmic blebs left over from apoptotic cell disassembly? is there inflammation? |
|
Definition
| phagocytic cells come in an engulf the apoptotic bodies, and there is no inflammation |
|
|
Term
| what characterizes necrotic cells? |
|
Definition
| chromatin clumping and organelle swelling |
|
|
Term
| what are four targets in apoptotic cells for protein cleavage? what enzyme carries this process out? |
|
Definition
| lamins, nuclear scaffold, cytoskeleton, and DNAses are all broken down by caspase |
|
|
Term
| what needs to take place at the plasma membrane in apoptosis? |
|
Definition
| markers for phagocytic recognition need to be presented. ex: phosphatidylserine is flipped from the inside of the membrane to the outside, members of the complement pathway |
|
|
Term
| what are the two ways that apoptosis can be induced in the cell? |
|
Definition
| intrinsicly or exstrinsicly |
|
|
Term
| how does intrinsic induction of apoptosis happen? |
|
Definition
| most of the events start of the exterior surface of the mitrochondria, beginning with the release of cytochrome C, and other pro-apoptotic molecule, forming an apoptosome which initiates caspases in the cytoplasm |
|
|
Term
| how does extrinsic induction of apoptosis happen? |
|
Definition
| immune cells express the FAS receptor which binds to the FAS ligand on cells in places like the reproductive tract where inflammation is problematic. the FAS ligand/receptor is a member of of the TNF family, and when activated, intiate initiator caspases, which initiate executioner caspases which enact apoptosis |
|
|
Term
| how do cytotoxic T lymphocytes initate apoptosis? |
|
Definition
| cytotoxic T lymphocytes introduce release of granzymes through pores made by their porforins that directly activate the executioner caspases |
|
|
Term
| where is the fas ligand located? what is an example of it's use? |
|
Definition
| on the target cell. lymphocytes at the end of an immune rxn will express fas, and the lymphocyte will be eliminated by other cells expressing the fas ligand or free fas ligands circulating |
|
|
Term
| what happens when fasL binds to fas on the surface of a target cell? |
|
Definition
| three or more fas molecules become cross-linked by fasL and their combined cytoplasmic death domains form a binding site for FADD, (sas-associated death domain), an adaptor protein that has it's own death domain. each of these death domains convert procaspase to caspase-8. caspase-8 itself can autocatalytically convert more procaspases into casapase-8 in close proximity. caspase-8 is the initiator caspase that activates the executioner caspase. |
|
|
Term
| can caspase-8 also be activated by TNF in a pathway similar to the fas ligand interaction? |
|
Definition
| yes, however TNF can also promote inflammation and thus potential survival of the cell in the presence of other survival signals. FADD however is replaced by TRADD in this cascade |
|
|
Term
| what does FLIP do? what produces FLIP? |
|
Definition
| FLIP binds to pro-caspase-8 but cannot cleave and activate the caspase because it lacks a protease domain, (takes the place of another active caspase-8, but has no enzymatic activity). some viruses and normal cells produce FLIP or FLIP-like proteins. |
|
|
Term
| is the major function of TNF induction of apoptosis? |
|
Definition
| no, even though TNF can induce apoptosis, it is more commonly important in regulating cell survival and inflammation via activation of NF-kB, (nuclear factor kappa B), and it's inhibitor, (IkB) |
|
|
Term
| how can TNF induce apoptosis and promote cell survival? |
|
Definition
| in isolated situations where there are no other proinflammatory/cell survival stimuli, TNF can interact with TRADD+FADD to induce apoptosis. however in situations where other proinflammatory/cell survival stimuli are present, TRAFs favor activation of NF-kB |
|
|
Term
| how is the intrinsic pathway of apoptosis induced? |
|
Definition
| increased mitochondrial permeability allows leakage of pro-apoptotic proteins such as cytochrome C that bind to a protein called Apaf, (apoptosis-activating factor-1), forming an apoptosome which binds to capasase-9, the initiator for the executioner capsase, (auto-amplification of capsase-9 can then also occur) |
|
|
Term
| how is the intrinsic pathway of apoptosis regulated? |
|
Definition
| the Bcl family of proteins handle most of the regulation. growth factors/other survival signals stimulate production of Bcl-2, Bcl-x, and Mcl-1 which control mitochondrial permeability/prevent leakage of pro-apoptotic proteins. in the absence of survival signals/presence of cell damage or stress, BH3-only sensors Bim, Bid, Bad are tripped and Bax and Bak are activated which create channels in the mitochondrial membrane allowing proteins to leak out into the cytoplasm. BH3-only proteins may also bind to and block the function of Bcl-2 and Bcl-x. |
|
|
Term
| what are IAPs and what role do they play in the intrinsic induction of apoptosis? |
|
Definition
| IAPs are physiologic inhibitors of apoptosis, (block capsase activation), but mitochondrial proteins such as Smac/DIABLO bind to and neutralize IAPs |
|
|
Term
| do death receptors play a role in the intrinsic apoptosis pathway? |
|
Definition
|
|
Term
| where did the Bcl-2 family of proteins get its name from? |
|
Definition
| an oncogene in B cell lymphoma in C. elegans |
|
|
Term
| can the intrinsic apoptosis pathway be induced w/out the mitochondria? what is an example? |
|
Definition
| there is evidence, it may in include overlap between the extrinsic and intrinsic pathways. in hepatocytes Fas signalling can activate pro-apoptotic bid -> activating the mitochondrial pathway |
|
|
Term
| can virally infected cells induce apoptosis in uninfected nearby cells? |
|
Definition
|
|
Term
|
Definition
| cysteine proteases that cleave after aspartic acid residue. |
|
|
Term
| what are the the initiator caspases? executioners? |
|
Definition
| caspase 8, (extrinsic), 9, (intrinsic), are initiators and caspase, 3,4,6 are executioners |
|
|
Term
| what do caspases exist as initially? how are they activated? |
|
Definition
| pro-enzyme or zymogen forms. they undergo cleavage to be activated by death domains/apoptosomes, or autocatalytic events |
|
|
Term
| what happens when p53 blocks the cell cycle at the G1-S phase and the cell is unable to repair the DNA sufficiently? |
|
Definition
| under normal conditions, the executioner capsases will be activated |
|
|
Term
| what are nuclear targets for executioner capsases? |
|
Definition
| proteins involved in transcription, DNA replication, and repair |
|
|
Term
| what are cell structure targets for executioner capsases? |
|
Definition
| the nuclear lamina and elements of the cellular cystoskeleton |
|
|
Term
| what is a direct result of the action of capsase 3? |
|
Definition
| endonuclease action, which translocates to the nucleus and enacts DNA fragmentation |
|
|
Term
| what does endonuclease do in the cell after activation by capsase 3? |
|
Definition
| cleaves in internucleosomal spacer regions, first into large chunks, (50-300kb), then into multiples of 180 bp. this forms a "ladder" on agarose gels. (necrotic cells' DNA would just show up as a smear) |
|
|
Term
| how does phagocytosis of apoptotic cells occur? is inflammation involved? |
|
Definition
| apoptotic cells+their fragments have markers on their surface that facilitate early recognition by phagocytic cells, (via markers such as phosphatidylserine or antibodies like C1Q). inflammation is not involved. |
|
|
Term
| if p53 is absent or mutated what may happen? |
|
Definition
|
|
Term
| what might p53 upregulate in the cell regarding regulation of intrinsic/extrinsic apoptosis? |
|
Definition
| p53 may upregulate Bax, Fas, and APAF-1, activating capsases->apoptosis |
|
|
Term
| how do cytotoxic T lymphocytes communicate with executioner capsases in target cells? |
|
Definition
| CTLs recognize Class 1 MHC presented foreign antigens at the cell surface, and upon recognition, perforins create transmembrane pores through which granzyme B, a serine protease is secreted |
|
|
Term
| how does granzyme B activate executioner capsases? |
|
Definition
| granzyme B cleaves proteins at aspartate residue, directly activating executioner capases, bypassing upstream signalling events |
|
|
Term
| what is another way CTLs can induce apoptosis other than granzyme B? |
|
Definition
| CTLs also express Fas-L on their surface, (target cell must express Fas however) |
|
|
Term
| what might p53 mutation lead to? |
|
Definition
| accumulation of cells giving rise to cancer |
|
|
Term
| what is one way that autoimmunity can occur? |
|
Definition
| certain microorganisms have molecules similar enough to molecules in our own body that the body may end up attacking it's own cells |
|
|
Term
| what are some examples of diseases associated with varying degrees of apoptosis? |
|
Definition
| neurodegenerative diseases susch as spinal muscular atrophies, alzheimers, ischemic injuries such as MIs, and virus-induced lymphocyte depletion such as AIDs. there is a balance of apoptosis and necrosis/inflammation in these conditions however |
|
|
Term
| what can chlamydia do in terms of apoptosis? |
|
Definition
| block apoptosis to a degree |
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