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| 6114237100 | In terms of SOMATIC HYPERMUTATION, describe: 1) What type of cell undergo this uniquely 2) When does this happen 3) Where does it happen 4) What does it require 5) What does it generate | 1) B-cells 2) AFTER B-cell undergoes rearrangement and when it is MATURE (bound to antigen) 3) Secondary lymphoid organ 4) Presence of antigen 5) Generates mutations FAVORING the host | 0 | |
| 6114245961 | What is the name of the process that happens to MATURE B-CELL that generates BENEFICIAL MUTATIONS? | Somatic hypermutation | 1 | |
| 6114247107 | Describe the SOMATIC HYPERMUTATION experiments | 30 MICE ALL INJECTED WITH ANTIGEN (haptin which is very small) - 7 days later, 10 of the animals had B-cells taken out and sequence VARIABLE DOMAIN of heavy and light chain to look for different amino acids ----> Little heterogenity at these cites (so same genes essentially bind to this haptin) ----> Release IgM - Another 7 day wait and see other 10 animals which have MORE HETEROGENITY at those variable domains ----> Release IgM AND IgG - The last 10 mice were re-injected with the SAME haptin and wait 7 days ----> ADDITIONAL heterogenity at CDR ----> Mostly IgG created | 2 | |
| 6114264797 | What do NAIVEE B-cell release first? ** VERY IMPORTANT ** | - IgM | 3 | |
| 6114266937 | - AT FIRST, the antigen is being cleared by the antibodies - OVER TIME, there is SOMATIC HYPERMUTATION to allow for the BEST ANTIBODIES to be selected for (once the antigen is scarce) and this allows very RAPID RESPONSE second time the antigen is exposed | What is happening here? |  | 4 |
| 6114271911 | In terms of SOMATIC HYPERMUTATION, describe: 1) Its rate compared to normal mutation rate 2) What mediates it and how 3) What happens to most 4) Why is this useful | 1) 1 million times greater than normal mutation rate 2) Activation induced cytidine deaminase (AID) and Uracil-DNA N-glycosylase (UNG/APE1) - AID scans VARIABLE region to convert any "C" to "U" - UNG/APE1 comes to repair the "U" and will randomly place a nucleotide (A, T, G or C) 3) MOST are negatively affected 4) SOME have HIGHER AFFINITY and therefore are preferentially activated and selected | 5 | |
| 6114285175 | What are the two enzymes involved in SOMATIC HYPERMUTATION? How do they work? | - AID (activation induced cytidine deamniase) makes any "C" a "U" in the variable region - UNG (uracil-DNA N-glycaolse) replaces all the "U" with random A, T, C or G | 6 | |
| 6114288236 | What are the two hypothesis for generating antibody diversity? Which one is correct and how? | DREYER AND BENNET HYPOTHESIS - Correct when thinking of recombination events occuring since ONE Ig gene does make one polypeptide HYPERMUTATION HYPOTHESIS - There is constant mutation that plays a role in increasing mutation in a positive manner | 7 | |
| 6114301624 | At what stage does the B-cell undergo GENE REARRANGEMENT? What about SOMATIC HYPERMUTATION? | - GENE REARRANGEMENT when it is immature cell - SOMATIC HYPERMUTATION when it is mature cell (bound to antigen) | 8 | |
| 6114303668 | An immature B-cell will release ______ | IgM | 9 | |
| 6114305795 | Describe the HEIARCHY OF REARRANGEMENT EVENTS in terms of events until it leaves the bone marrow | 1) HEAVY CHAIN rearrangement with D to J on BOTH strands 2) HEAVY chain rearrangment of V to DJ on ONE strand and if successful, causes ALLELIC EXCLUSION on the other allele 3) HEAVY CHAIN associates with invariant surrogate light chain (looks like light chain but it is now) 4) LIGHT CHAIN rearrangement on the kappa gene and if this doesn't work then lamda light chain 5) LIGHT CHAIN expressed pairs with HEAVY CHAIN 6) Immature B-cell displays IgM on membrane 7) Negative selection occurs to exclude self-reactivity 8) Before leaves bone marrow, it "matures" to express IgD as well | 10 | |
| 6114319434 | When in the process of bone marrow development does negative selection happen? | After the membrane bound IgM receptor is expressed but BEFORE IgD receptor is expressed | 11 | |
| 6114320537 | What is considered to be a "mature, naivee B cell?" | A newly emerged B-cell from the bone marrow that CO-EXPRESSES IgM and IgD on its membrane | 12 | |
| 6114323769 | What is the MARKER of a NAIVEE B-CELL that has EXITED THE BONE MARROW? *VERY IMPORTANT * | - IgM AND IgD co-expressed on membrane | 13 | |
| 6114326917 | What must happen BEFORE light chain rearrangement but AFTER heavy chain rearrangement? | - HEAVY CHAIN association with INVARIANT SURROGATE LIGHT CHAIN (not light chain itself but similar to it) | 14 | |
| 6114331607 | What terminates immunoglobulin gene rearrangement (2)? | - Mu heavy chain expression - Membrane bound IgM expression | 15 | |
| 6114406949 | What two things are B-cells dependent on for development? | - Stromal cell - Cytokines | 16 | |
| 6114407883 | What does B-cell development require in terms of gene? | Coordination of expression of large number of genes | 17 | |
| 6114424733 | In the bone marrow, describe the TWO interactions that are necessary for B-cell development (and what order) | 1) B cell rolls along STROMAL BONE MARROW CELLS and has COGNATE INTERACTION 2) This allows for INCREASE IN RECEPTOR FOR CYTOKINES IN B-CELL so it can be receptive to soluble cytokines | 18 | |
| 6114427433 | What are the COGNATE INTERACTIONS that are important for B-cell development? Why is it important? | - Interaction between the B-CELL and STROMAL EPITHELAIL CELL in the bone marrow - Allows for INCREASE IN RECEPTORS in the B-cells for CYTOKINES | 19 | |
| 6114430583 | What allows for increase in RECEPTORS for CYTOKINES in the B-cell? | Cognate interactions between the B-CELL and the STROMAL BONE MARROW EPITHELIAL CELLS | 20 | |
| 6114432664 | RAG complex enzymes are involved in ______ function and are turned ______ with optimal ______ | - sloppy nuclease - on and off - expression with heavy and light chain expression | 21 | |
| 6114434214 | What is Tdt? When is it optimally expressed? | - Terminal deoxyribonucleotide transferase - Heavy chain rearrangement | 22 | |
| 6114435265 | What is optimally expressed during HEAVY CHAIN rearrangement? | Tdt (terminal deoxyribonucleotidyl transferase) | 23 | |
| 6114436990 | What two general class of interactions are important for B-cell development? | - Cognate - Cytokines | 24 | |
| 6114441458 | What is the phenotype for a MOUSE with RAG mutation? Specify for humans. WHy does this happen? | - No acquired/adaptive immunity because NO B-CELLS - SCID - Every B-cell developing in these people can form correct structure but RAG never cuts it so there is no mu chain and there are no T-cells | 25 | |
| 6114448252 | Describe the overall purpose of NEGATIVE SELECTION for B-cells | Remove the B-cells that SELF-REACTIVE (react to self-antigens) | 26 | |
| 6114449952 | Where is the site of NEGATIVE SELECTION for B-cells? | Bone marrow | 27 | |
| 6114451333 | What receptors do B-cells usually end up with before exiting the bone marrow? | mIgM and mIgD | 28 | |
| 6114453200 | Describe what happens to a B-cell that recognizes a SELF-ANTIGEN in the bone marrow generally | - It will CROSS-LINK IgM receptor and will signal RECEPTOR EDITING PHENOMENA | 29 | |
| 6114454871 | Describe what happens to B-cell that recognizes a SOLUBLE PROTEIN generally | Triggers IgM on Bcells and induces ANERGY (paralysis of the cell) | 30 | |
| 6114456267 | Describe what happens toB-cell that has low affinity interaction with a self-molecule generally | Probably a high off-rate so no stable engagement and becomes CLONALLY IGNORANT | 31 | |
| 6114457226 | Describe what happens to B-cell that has no self reactivity | Normally is released from bone marrow to find antigen | 32 | |
| 6114459442 | Describe what is IDEAL SITUATION for a B-cell developing in the bone marrow | Get a B-cell that has IgM that doesn't react to anything "self" and then acquires IgD that then allows it to go out and find its non-self antigen | 33 | |
| 6114460507 | Describe the FOUR possibilities of a B-cell in the bone marrow and what happens generally | SELF-REACTIVE TO PROTEIN - Cross-links IgM and undergoes receptor editing and if this doesn't work then apoptosis SELF-REACTIVE TO SOLUBLE SUBSTANCE - Links to IgM and undergoes anergy LOW AFFINITY TO SELF MOLECULE - Links to IgM but has HIGH OFF-RATE so becomes CLONALLY IGNORANT NO SELF-REACTIVITY - Undergoes normal, ideal situation where goes to periphery to find antigen | 34 | |
| 6114465596 | What type of cell becomes CLONALLY IGNORANT? | B-cells that have LOW affinity for self-antigens | 35 | |
| 6114466384 | What type of cell undergoes ANERGY? | B-cells that bind to soluble self-antigen | 36 | |
| 6114466998 | What type of cell undergoes RECEPTOR EDITING? | B-cells that bind to protein self-antigen | 37 | |
| 6114468202 | In terms of RECEPTOR EDITING, describe: 1) What type of cell this happens for 2) What happens and caveat 3) What happens if it works or doesn't work | 1) B-cells in the bone marrow that bind to a self-antigen protein 2) - Use the UNUSED upstream V segments and UNUSED downstream J segments to allow for SECOND REARRANGEMENT - ONLY at light chain because HEAVY CHAIN has D segment but all other D segments were eliminated 3) - If it WORKS, then it is a normal B-cell released to find antigen - If it DOESN'T WORK, then it undergoes apoptosis for elimination | 38 | |
| 6114476003 | Does receptor editing work for heavy and light chains? Why or why not? | - ONLY light chains - Light chains still have unused upstream V and unused upstream J but heavy chains do NOT have anymore D segments to use | 39 | |
| 6114478014 | What is ANERGY essentially? What cells is it related to? | - Cellular paralysis - B-cells that bind to soluble self-antigen | 40 | |
| 6114479448 | An anergic cell is _______ but ______ | - physically present - cannot be activated even if it encounters its antigen | 41 | |
| 6114480833 | True/False: An anergic cell can be activated if it encounters its antigen | False (CANNOT be activated) | 42 | |
| 6114482473 | What is the ideal situation for a B-cell after it is released from the bone marrow? | It goes to SECONDARY LYMPHOID ORGANS to be activated and then PROLIFERATE and DIFFERENTIATE into either effector cells or memory cells | 43 | |
| 6114484935 | What are the different fates for a non-self-reactive B-cell when it interacts with an antigen? | - Either becomes EFFECTOR CELL (PLASMA) or MEMORY CELL | 44 | |
| 6114488989 | What is very stunning about a PLASMA CELL under a microscope? What does this mean? | - TONS of endoplasmic reticulum - Specialized for PRODUCTION and SECRETION of proteins | 45 | |
| 6114490820 | In terms of differentiation, a plasma cell is _____ meaning that ______ | - end-stage differentiated - it will never become something else | 46 | |
| 6114491923 | In terms of a PLASMA CELL, describe: 1) Differentiation 2) Life-span 3) Main job | 1) End-stage differentiated 2) Short 3) Produce a lot of soluble antibodies | 47 | |
| 6114494070 | What are the antibodies that plasma cells generate specific for? | The ORIGINAL antigen that activated the B-cells | 48 | |
| 6114496169 | Does a resting B-cell have a surface immunoglobulin? Does a plasma cell? | - Yes for resting - No for plasma cell | 49 | |
| 6114498095 | What does a PLASMA CELL not have on its membrane that its precursor did have? | A membrane bound immunoglobulin | 50 | |
| 6114500084 | A plasma cell is present for _______ but tries to ______ | - a small amount of time - produce a lot of soluble antibodies | 51 | |
| 6114500906 | Is there isotype switching associated with plasma cells? | No | 52 | |
| 6114500907 | Is there growth with plasma cells? | No | 53 | |
| 6114501322 | Is there somatic hypermutation with plasma cells? | No | 54 | |
| 6114502459 | What determines when an antibody molecule will be EMBEDDED in a membrane or RELEASED as a soluble protein? | Alternative splicing | 55 | |
| 6114503862 | Describe how a TRANSMEMBRANE vs SOLUBLE immunoglobulin is produced | TRANSMEMBRANE - Short series of exons SPLICED into mRNA with HYDROPHOBIC RESIDES at carboxy end of heavy chain to anchor it in the membrane SOLUBLE - Alterantive splicing allows carboxy end of heavy chain to NOT be hydrophobic residues | 56 | |
| 6114510620 | What happens to immunoglobulin that has hydrophobic residues at the carboxy end? | Becomes transmembrane immunoglobulin | 57 | |
| 6114512694 | What type of cells are created by B-cell activation? | - Plasma cells OR memory cells | 58 | |
| 6114527156 | In terms of MEMORY CELLS, describe: 1) What they essentially are 2) What is interesting about them | 1) They are copies of the initial cells that were activated 2) They have undergone CLASS-SWITCHING so they display an immunoglobulin that has a different heavy chain (with different constant domain) compared to the original cell | 59 | |
| 6114530339 | In terms of CLASS SWITCHING, describe: 1) What it refers to 2) What it require | 1) Ability of a B-cell to produce antibodies with SAME ANTIGEN SPECIFICITY (no change in Fab or VDJ organization) but DIFFERENT CONSTANT REGION (Fc) 2) Antigen stimulation | 60 | |
| 6114532567 | A B-cell that has undergone class switching will still _____ but _____ | - recognize the same antigen - has a different Fc region (different constant domain of the heavy chain) | 61 | |
| 6114533453 | True/False: Class switching also causes changes in the Fab region of antibodies | False (only in the Fc region) | 62 | |
| 6114533893 | What does CLASS SWITCHING require? | Antigen stimulation | 63 | |
| 6114535778 | What are the two immunoglobulins that are expressed in naivee B-cells? Why? | - IgG or IgD - RNA polymerase first does the VDJ region and then gets to Cdelta or Cmu (constant for IgD and IgM) but then is unable to continue because it is "exhausted" to go to the rest of the classes so only does delta and gamma exons | 64 | |
| 6114540495 | Describe how CLASS SWITCHING happens molecularly | DNA REARRANGMENT - Conserved regions between exons (i.e switch regions) that can ALIGN and when they do, they create LOOP OF DNA that can be cut and degraded by nuclease so we have DNA JOINING EVENT to create PRIMARY TRANSCRIPT and mRNA that has RNA POLYMERASE go to VDJ and the new class | 65 | |
| 6114544680 | What are "switch regions" and why are they important? | - These are CONSERVED regions between exons in heavy chain that help with CLASS SWITCHING - They can align and cause a DNA LOOP that can be EXCISED and then primary transcript and mRNA can be created for NEW CLASS of ANTIBODY | 66 | |
| 6114545962 | What is a common class switch we see? | IgM to IgA | 67 | |
| 6114546497 | In terms of the nuclease used for CLASS-SWITCHING, is it high or low fidelity? | High | 68 | |
| 6114547883 | If a naivee, mature B-cell undergoes activation to become a MEMORY cell, what is the likely class-switch that will happen? | - mIgM/mIgD will become mIgA | 69 | |
| 6114550019 | What is example of POINT MUTATION of genomic DNA for B-cells that is irreversible but beneficial? | Somatic hypermutation | 70 | |
| 6114551590 | Is ISOTYPE SWITCH irreversible or reversible? | Irreversible | 71 | |
| 6114552334 | What is the ADVANTAGE of class switching? | Can switch to more effective antibody (increase biological effector functions) WITHOUT changing antigen specificity | 72 | |
| 6114553176 | What does not change during class switching? | Antigen specificity | 73 | |
| 6114555409 | What is LARGEST immunoglobulin? | IgM | 74 | |
| 6114556043 | What is the PREDOMINANT immunoglobulin in the bloodstream circulation? | IgG | 75 | |
| 6114558723 | True/False: IgM is the largest and most predominant antibody in the bloodstream | False (IgM is the largest but IgG is the most predominant) | 76 | |
| 6114560102 | What is the FIRST antibody class secreted on initial encounter with an antibody? | IgM | 77 | |
| 6114560940 | Describe the effectivity of IgM to diffuse into extravascular spaces | Not very good because it is so large | 78 | |
| 6114562058 | What is IgM very effective at activating? | Complements | 79 | |
| 6114562867 | In terms of IgM, describe: 1) How early it is made 2) Structure on surface and secreted | 1) First antibody made 2) MONOMER on the surface but PENTAMER when secreted | 80 | |
| 6114563979 | In terms of SOLUBLE IgM, describe what shape it is and how? What type of geometry does it have? How many Fab regions does this have and what does this imply? | - Pentamer via J (joining) chain interacting with Fc region - It is PLANAR - 10 Fab regions so can bind to 10 antigens | 81 | |
| 6114567518 | Describe the ability of IgM to form immune complexes. Describe why this is useful and why this can be bad? | - IgM, soluble form, is a PENTAMER with 10 Fab regions so can bind 10 ANTIGENS and therefore get to cross-link antigens - This is useful for CLEARING since macrophages can easily take this up - IgM cannot really get out of bloodstream and go to peripheral tissue | 82 | |
| 6114572306 | True/False: Soluble IgM cannot easily access peripheral tissue | True (since it is pentamer) | 83 | |
| 6114576635 | List the two conformations IgM can form when it is soluble | - Planar and staple | 84 | |
| 6114577230 | Describe the non-planar form of soluble IgM and why this is important? | STAPLE FORM - Since it has 10 Fab (as it is a pentamer) it can move its J chain to have multiple Fab regions bind to one microbe and have Fc sticking up - This is a GOOD ACTIVATOR of complement cascade (specifically C3b) so that it can come in and create PORE or INDUCE PHAGOCYTOSIS | 85 | |
| 6114579527 | What form of IgM allows for complement activation increase? What does this lead to? Which complement specifically? | - Staple form - Leads to INCREASE PHAGOCYTOSIS or PORE FORMATION - C3b | 86 | |
| 6114580901 | What antibody is effective at complement cascade activation? Why? | - Soluble IgM - It uses its multiple Fab to crowd a microbe and have Fc regions sticking up to make STAPLE CONFORMATION that recruits C3b to pore creation or increased phagocytosis | 87 | |
| 6114582403 | What is the role of soluble IgD? | Not really known | 88 | |
| 6114582966 | What immunoglobulin has a relatively unknown function when it is soluble? What is its membrane bound function? | - IgD - Important receptor for NAIVEE, MATURE B-cells (ones that just come out of the bone marrow) | 89 | |
| 6114584506 | Describe IgD in terms of amount in circulation and half-life | - Low amount in circulation - Relatively short half-life | 90 | |
| 6114585250 | In terms of IgG, describe: 1) Effectiveness for neutralizing specific things 2) Phagocytosis help 3) Specific cell it helps 4) What soluble proteins it can activate 5) What it can cross 6) Where it can go 7) Form as soluble protein | 1) Effective at neutralizing bacterial products and toxins 2) Opsonization increase 3) Helps NK cells 4) Complements 5) Placenta 6) Extravascular spaces 7) Monomer | 91 | |
| 6114588182 | What antibody is important for neutralizing bacterial products and toxins? | IgG | 92 | |
| 6114588777 | What antibody is important for crossing the placenta? | IgG | 93 | |
| 6114589423 | What antibody is made to be "lost?" | IgA | 94 | |
| 6114590022 | What is the MAJOR ANTIBODY class in the bloodstream? | IgG | 95 | |
| 6114590874 | What antibody is a very effective opsonizer and can neutralize bacterial toxins? | IgG | 96 | |
| 6114591827 | Describe how IgG acts as an OPSONIN | - IgG binds via its Fab region to the microbe - The IgG Fc has HIGH AFFINITY for Fc receptors on macrophages - There is ZIPPERING EFFECT that allows phagocyte to engulf the microbe and the IgG bound to it | 97 | |
| 6114593395 | What is important for the macrophage to have in order to work with IgG for opsonizatioN? | Macrophage must have high affinity Fcgamma receptor | 98 | |
| 6114595424 | What antibody is capable of mediating ANTIBODY-DEPENDENT CELL MEDIATED CYTOTOXICITY (ADCC)? What is this? | - IgG - Mechanism by which a cell infected by virus/that has been transformed has FOREIGN ANTIGENS that IgG recognizes and helps recruit NATURAL KILLER CELLS (which have high affininty Fcgamma receptor) to allow NK cell to put GRANULAR CONSTIEUENTS into target cell and cause apoptosis | 99 | |
| 6114597514 | What is ADCC? How does it work? What antibody is important for it? | - Antibody dependent cell-mediated cytotoxicity - IgG binds to a specific cell that has been TRANSFORMED or infected with VIRUS and then it recruits NK cells via its Fc receptor to allow NK cell to deliver its GRANULAR CONSTITUENTS into the target cell for apoptosis | 100 | |
| 6114599549 | What two major processes does IgG help mediate? What is important in both? | - Opsonization and ADCC (antibody-dependent cell mediated cytoxocitiy) - The non-IgG component to have a HIGH AFFININTY Fcgamma RECEPTOR | 101 | |
| 6114600787 | When humans are born, they are born with ______ in terms of antibodies | complete antibody titers | 102 | |
| 6114601053 | What antibody is TRANSPORTED across the PLACENTA? | IgG (G for go) | 103 | |
| 6114601961 | What is important about the IgG a baby has right before they are born? | It is the SAME TYPE as the mom (i.e if it there is IgG in mom for tetanus then the baby also has that) | 104 | |
| 6114602861 | What is the difference between the IgG in mom and baby right before baby is born? | None (they are the same since IgG crosses placenta) | 105 | |
| 6114603421 | What is the half-life of most IgG molecules? | 3 weeks | 106 | |
| 6114604805 | Describe what happens in general for antibodies when a baby is born | - AT FIRST, has all IgG from mother because it was transferred via placenta - IgG has half-life of 3 weeks so starts to decrease BUT normal flora colonizes newborn so there is INHERENT IMMUNE SYSTEM growing and eventual class-switching | 107 | |
| 6114607303 | For a baby between three months to a year, there is a low _______ | amount of anitbodies (hypoglammaglobulinemia) | 108 | |
| 6114608051 | Describe what HYPOGAMMAGLOBULINEMIA of the newborn is. What this implies? | - First three months to year a baby has LOW serum IgG - Very susceptible to infections, especially for those pathogens that are difficult to phagocytozie (like encapsulated ones) | 109 | |
| 6114609753 | What type of pathogens are 6 month year olds most susceptible to? Why? | - Pathogens that are hard to phagocytosize (like ones that have capsules) - 3mo - 1 years have HYPOGAMMAGLOBULINEMIA so low IgG amount in the serum | 110 | |
| 6114611837 | What is key to OPSONIZATION and ADCC for IgG in terms of the antibody itself? | Must have MULTIPLE IgG since need multiple Fcgamma for the macrophages and NK cells, respectively, to bind to | 111 |
