| Term | Definition |
|---|
| APC | B cell activation involves two Ag presentation steps 1) DC -> CD4 T cells -> Th2 2) B cell acting as ___ -> Th2 cell delivers co-stim signals |
| specific | B cells that are ______ for Ags that are present (i.e. have BCR's specific for those Ags) are much more likely to receive T cell help than other B cells since they take up and present Ags much more efficiently |
| chemokines | DC's make _____ that attract naiive T cells, allowing many T cells to scan surface of DC for peptide:MHC complexes their TCr can bind |
| IL-4 | B cells have 2 important co-stim signals 1) CD40L which binds to CD40 on B cells and 2) ____ which binds to IL-4R on B cell |
| CD40 | When the B cell gets both AgR signal and co-stim signals from _____ and IL-4R, it becomes activated and can proliferate |
| concentrating | receptor-mediated Ag uptake of BCR is a highly efficient way of _______ the Ag, compared to fluid phase uptake (endocytosis, pinocytosis) |
| more | _____ (more/less) MHC II proteins on surface will present peptides from Ag than Ags presented by direct presentation than those that have been taken up by fluid phase uptake |
| specific | B cells that can activate Th2 cell and induce their exp. of CD40L is likely to be ______ for the same Ag as that Th2 cell |
| Ag | BCR has two functions 1) Delivering __ signal 2) Providing an efficient __ uptake |
| ubiquitin | major way in which proteins get marked for degradation is a polypeptide called _______ gets covalently linked to them |
| proteasome | ubiquitinated proteins are degraded by the ______ complex |
| I | proteasome produces peptides with optimal structure for transport into ER and binding to MHC _ proteins |
| ER | newly synthesized MHCI alpha chain and B2 microglobulin are transported co-translationally into __ |
| calnexin | once the Beta-2m binds to alpha chain of MHC I, ____ is released |
| calreticulin | once calnexin is released, MHCI proteins bind to _____ and Erp57 that assists 1) Folding of MHCI 2) Keeps MHCI partially unfolded until peptide binding 3) Ensures MHCI does not leave ER |
| cassette | TAP-1 and TAP-2 has an ATP-binding ______ (ABC) that uses energy from ATP hydrolysis to transport molecules across ER membrane |
| tapasin | ______ protein forms a physical bridge between MHCI and TAP transporter complex |
| peptide | TAP, tapasin and MHCI referred to as _____ loading complex |
| peptide | binding of _______ to MHC I completes proper folding of MHC I, i.e. the ______ is an integral part of final MHC I folded structure |
| Golgi | once peptide is bound, MHC I:peptide complex is release dfrom TAP/tapasin/calreticulin/Erp57 complex, and transported via vesicles to _____ then to the cell surface |
| hydrophobic | ideal peptides for MHCI are 8-10 aa long, _____ or basic residues at C- terminus |
| interferons | ______ produced by virus infected cells increase synthesis of MHCI and TAP proteins |
| excess | MHC I proteins are present in ______, meaning there will always be an MHC I protein for virus-derived peptides to be loaded onto |
| cross | DC could endocytose extracellular viruses, but peptides derived from viral proteins would end up being displayed by MHC II, which would activate CD4+ T helper cells not CD8+. so DC's and macrophages undergo ____-presentation to deliver peptides derived from extracellular soruces to MHCI and induced activation of CD8+ T cells |
| sec61 | cross-presentation involves ____ protein channel |
| sec61 | _____ is involved on co-translational entry of proteins into ER, but can work in reverse and pump out unfolded proteins, which can then be degraded |
| fuse | in DC's and macrophages, ER may ____ with phagosomes/endosomes, and then pump out viral proteins into cytosol through Sec61 |
| ubiquitin | viral proteins pumped out by sec61 into cytosol gets ______ added by UBC, and proteasome degrades it into peptides which are pumped back into ER by TAP transporter |
| sec61 | controversy to ___ cross presentation theory 1) ER fusing with phagosome 2) Whether phagosomes have Sec61 3) Whether ER breaks off and become phagosomes |
| off | binding of peptide to MHCI has to be irrversible (very low ___-rate) with little or no exchange at cell surface |
| peptide | MHC I protein is not fully folded until it binds a _____ |
| peptide | _____ binding stabilizes structure of MHC I protein |
| side | N-terminal and C-terminal groups of peptide are bound by ____ chains of MHC I amino acids that line peptide-binding cleft |
| anchor | side chains of MHC I make contact with 2-3 aa of peptide called ____ residues |
| C | one anchor residue is always _-terminal aa and usually hydrophobic or basic |
| aa | different MHC I molecules have different __ lining the cleft and therefore bind different subsets of peptides |
| top | ___ MHC molecule will bind wide variety of peptides as long as they have tyrosine of phenylanine at position 5. bottom MHC molecule will bind a wide variety of peptides as logn as they have tyrosine at position 2. |
| cleft | NH3 and COO- groups are always bound to the _____ of MHCI, as is the C-terminal residue which is always hydrophobic |
| proton | lysosomes have a _____ pump and proteases that are active only at low pH |
| proteases | proton pump pumps H+ into lysosome, and lowers pH to activate 'acid' ______ |
| Ii | __ binds to peptide binding groove of MHCII and prevents it from binding peptides |
| Ii | cytoplasmic domain of __ directs MHC II containing vesicle to low pH vesicle where two vesicles fuse |
| CLIP | Ii is cleaved by acid proteases so only small fragment of it remains in the peptide binding groove. This small fragment is _____ |
| CLIP | ____ is removed, allowing MHC II to bind peptides present in low pH vesicle |
| HLA-DM | CLIP is removed by ______ |
| HLA-DM | ______ - catalyzes release of CLIP and stabilizes empty MHC II protein |
| peptide | ______ editing - peptides that bind with higher affinity to MHC II displaces ones that don't bind as tightly |
| HLA-DM | after ______ dissociates, MHC II folds around bound peptide, forming a stable complex |
| II | peptide that binds MHC __ are at least 13 aa long, often much longer |
| are not | unlike MHC I, the ends of peptides for MHC II ____ (are/are not) important |
| peptide | there are multiple interactions between MHC II aa side chains that line _____-binding groove with peptide backbone as well as 1-2 aa side chains of ______ |
| multiple | a single MHC protein can bind _____ (single/multiple) peptides |
| polygenic | genes for MHCI and MHCII are _______ - multiple genes for each class of molecule |
| polymorphic | genes for MHCI and MHCII are _______ - many alleles for each gene -> diff. aa -> diff versions of peptide binding cleft |
| alleic | _______ variants are same genes with different sequences. these different DNA and hence aa sequences result in different _____ variants of MHC proteins having diff. aa forming peptide binding cleft -> bind different sets of peptides |
| codominant | expression of MHC genes is _______, i.e. you have 1 chromosome with MHC gene from mom and dad |
| codominant | ________ expression maximizes number of different MHC molecules an individual expresses |
| polymorphism | MHC ________ extends range of Ags that the population can mount immune responses to |
| MHCI | ___ genes encode 1) _____ alpha chains 2) TAP 3) Inducible proteasome subunits |
| MHCII | _____ genes encode 1) Both chains of ___ 2) Ii invariant chain , which directs _____ to low pH vesicles 3) HLA-DM |
| interferon | in intracellular bacterial infection, APC's activate Th1 cells which produce gamma-_______, which in turn acts on macrophages and increases transcription of genes encoding the MHC II alpha and beta chains, as well as Ii, and HLA-DM. this increases ability of macrophages to present peptides from bacterial Ags |
| interferon | in viral infection, infected cells produce alpha/beta-_______, which increases transcription of genes encoding MHCI alpha chain, Tap1/2, tapasin, and proteasome components |
| N | variation of MHC amino acid sequences occured in _-terminal domains of MHCI and MHC II proteins, and in particular regions that form floor of peptide binding groove and helices that TCR dock onto |
| restriction | MHC _______ - requirement for the right MHC protein to present a peptide to specific TCR |
| peptide | some strains of mice that could immunologically respond - _____ binding cleft could accomodate hapten bound to that peptide |
| peptide | some strains of mice that could not respond - _______ binding cleft has different shape and haptenated peptide does not fit well into the cleft |
| identical | all TCR's on given T cell are _____ and recognize same peptide:MHC complex |
| helices | TCR must first dock onto MHC protein. successfuly docking only if CDR1 and CDR2 regions of TCR alpha and beta chains have shapes that are complementary to that of ______ of the MHC protein |
| peptide | _____ binding determines off-rate |
| peptide | after docking, TCR must then bind to _____ in order to create a stable interaction. |
| CDR3 | ____ of TCR alpha and beta binds to the peptide. a stable interaction will only occur if there is high affinity binding, i.e. ____ can form many bonds with peptide in MHC peptide binding groove |
| FACS | you can use ____ or magnetic beads to purify CTL |
| CTL | in dish 1, you take macrophage from strain B, infect with virus X. same MHC I:peptide complex generated, TCR on CTL able to dock onto MHCI, recognize peptide, bind with high affinity, ___ get activated, and kill infected macrophages |
| MHCI | in dish 2, macrophages from mouse strain D, d alleles for all MHC genes. infect with virus Y. same virus peptide generated, different ___:peptide complex (H-2K^d instead of H-2K^b). TCR will not bind to this ____:peptide complex and T cell will not get activated |
| peptide | in dish 3, macrophages from strain B with virus Y. same MHCI:peptide complex (H-2k^b) but different viral ______. TCR can dock onto MHC protein, but absence of strong interaction between TCR CDR3 regions and _____, TCR dissociates rapidly and T cell does not get activated |
| polymorphism | MHC ________ arose by 1) Recombination 2) Gene conversion |
| recombination | ________ - during meiosis, before 4 copies of each chromosomes are separated, crossing over between maternal/paternal chromosomes |
| alleles | if crossover occurs at a place where there are different _____ of gene, new 'recombined' _____ are generated |
| gene | _____ conversion - occurs when chromosomes are misaligned during meiosis, short stretches of sequence from mismatched gene gets copied to the other. |
| gene | _____ conversion - copying of DNA sequences between two closely related (but different) genes |
| recombination | ________ - exchange of DNA sequences between two different alleles of same gene to generate new alleles |
| identical | organ, skin, cell transplants from one individual to another always rejected unless donor and recipients are genetically ______ |
| thymus | T cells are responsible for much of the damage in transplants. thus, mice lacking a ______ (nude mice) can accept skin grafts from any donor, whether they are genetically identical or not |
| T | Grafts are rejected because your immune system (primarily your _ cells) recognizes proteins from donor tissue's as foreign |
| MHC | everyone except for identical twins has a different set of ___ proteins |
| MHC | graft rejection is caused primarily by differences in ___ proteins |
| haplotype | _______ - mice with same allele of entire MHC ecomplex, can exchange grafts. |
| minor | ______ histocompatability antigens - genetic loci where alleic differences cause a much slower graft rejection |
| T | high % of _ cells bind with high affinity to foreign MHC proteins (called alloreactivity) |
| T | _ cells with high affinity for self MHC are deleted |
| foreign | _____ MHC proteins are not present in thymus during T cell development, so T cells that bind ______ MHC proteins with high affinity have not been deleted and will react against donor cells that bear these ____ MHC proteins |
| privileged | immune _______ area - non-vascularized region that immune systen can't get to, thus grafts are always accepted |
| minimize | strategy for transplants is to ______ immune responses against organ |
| tissue | ______ typing - determining HLA alleles and trying to match donor and recipient HLA alleles get them to be similar as possible |
| xenograft | ______ - using organis from other species |
| natural | people have ____ Abs against cell surface Ags from other species. these _____ Abs are always in blood, so immunosuppressive drugs don't prevent them from causing damage. These Abs activate C' cascade, leading to rapid damage of transplanted organ |
| CCP | ___ - proteins on surface of cells that protects C'mediated lysis. are species specific, i.e. Pig ___ will not protect against human C' |
| CCP | if transgenic pigs can express human ___, this may solve the xenograft problem |
| Ags | another strategy to xenograft is to destroy foreign ___ on surfaces of organ, without damaging organ itself |
| virus | another potential problem for xenograft is transmission of pig _____ to humans |
| superAgs | bacterial ______ - protein toxins that cause fatal responses by activating large numbers of T cells |
| superAg | _____ activates 2-25% of all your T cells |
| superAg | ______ causes TCR to bind MHC proteins, regardless of the peptide |
| superAg | some ______ binds to 2-25% of all V region of TCR beta chain. bridging TCR to MHC II in this manner delivers a very strong signal that causes T cell activation |
| MHC | superAgs bind to ___ molecules outside of the peptide binding cleft |
| TCR | superAgs bind to ___ in regions other than CDR's |
| T | superAgs link MHC and TCR regardless of peptide presented, which results in non-specific _ cell activation |
| beta | Ig-like domain consists of 2-___sheets folded over each other linked by a disulfide bond and HV regions which are the loops between these ____sheets and forms a continuous surface. |
| T | "Ag-specific Tolerance" means to render anergic only the _ cells that recognize donor tissue without interfering with ability of other _ cells to be activated. |
| TLR | Strategies to prevent activation of T cells that recognize donors 1) Removing graft DC's - use Ab to a DC marker conjugated to cytotoxic drug 2) Interfere with ___ signaling - prevent DC maturation and activation of T cells 3) Interfere with danger signals from DC's - soluble form of CD28 that has higher affinity for CD80/86 than CD28 |
| DC | activated ___ cells upregulate 1) Chemokine receptors 2) MHC II 3) Costim molecules (CD80/86) and downregulate Phagocytosis |
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