front 1 2/06 | back 1 Types of humoral immune responses and functional diversification of antibodies |
front 2 B cell activation in antibody responses | back 2 division of labor among 3 mature B cell types
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front 3 T cell independent B cell activation
review this | back 3 BCR can activate B cells with non-T help (TLR and BAFFR ligands)
BCR can activate B cells without T cell help or other help
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front 4 role of innate immune signals in TI-type 1 B cell activation | back 4 CR2 complement receptor and CD19 are part of BCR as a whole BCR do not function in isolation - have coreceptors another component like complement can help even in T cell independent antibody response important to keep in mind that T and B cells NEVER work in isolation 2 situations where have coreceptors -> help with B cell activation
so:
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front 5 B cell Ab response requires signals in addition to Ag | back 5 need 2 signals in order to activate and undergo B cell proliferation + differentiation
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front 6 the germline center reaction | back 6 where T cell help is important bc changes in antibodies are much more potently helped by T cells activation of B cells and migration of B/helper T cell complex into germinal center -> B cell proliferation -> somatic mutation and affinity maturation; isotope switching -> exit of high affinity antibody secreting cells and memory B cells |
front 7 sequence of events | back 7
B cell can be anywhere in the body B and T cell must have same specifications to work together to make potent immune response must find each other for tangle to happen this interaction (activation of B cell) not happening to germinal center (interaction occurs outside of germinal center) make antibodies bc new relationship, B cells make IgM isotype antibodies produced help bridge gap btw initial exposure and have not refined binding site of antbodies some T follicular and B cells move to germinal center (like discussed last class) which is important for maturation of B cells and memory cells germinal center does not exist without infection 1. B and T cell activated independently 2. They find each other, B cell can start making antibodies early to cover the gap in time |
front 8 differences in the antibody responses to TD (T cell dependent) vs TI (T cell independent) antigens | back 8 TD
TI
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front 9 polysaccharides conjugated to a protein carrier (TT) can recruit T cells and generate memory B cells | back 9 see pic
shows that can make T cell independent immune response into a T cell dependent immune response, bc B cell can attach to the pathogen (made of biomolecules) complex of molecules has sugars, etc. so there is a mix of things, which B cell can bind bc they see shapes what the B cell interact w/ gets internalized, and the protein in the pathogen gets processed by B cell, which is then presented to T cell -> now will produce long lived plasma cells (very used/handy in vaccine design, to provide longer time of resistance / better immunity) they attach protein piece to a structure, can trick the T cell to help |
front 10 What signals are triggered by TI type-2 versus TI type-1 T cell-independent antigens? What is the stepwise process of T cell-dependent B cell activation and germinal center reaction? | back 10 pause for activity |
front 11 Tfh-CD40L induces AID in B cells via CD40 | back 11 see pic from google: Activation-induced cytidine deaminase (AID) is an enzyme that is predominantly expressed in germinal center B cells and plays a pivotal role in immunoglobulin class switch recombination and somatic hypermutation for antibody (Ab) maturation. |
front 12 AID induces isotype class switching in B cells | back 12 Process where constant region can be switched to other constant region Can switch constant regions without changing binding site Why change binding site of antibody? So constant regions get switched - each clone w/ same specificity has potential to change constant region, so have the same specificity |
front 13 in the geminal centers: Ig isotope class switching | back 13 see pic IgM - standard if have T cell help: can switch to IgG, IgE, IgA IgM - complement activation IgG - Fc receptor dependent phagocyte responses; complement activation; neonatal immunity (placental transfer) IgE - immunity vs helminths; mast cell degranulation (immediate hypersensitivity) IgA - mucosal immunity (transport of IgA through epithelia) overview of isotypes
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front 14 primary antibodies can change their class by class switch recombination (CSR) | back 14 IgM - primary antibody IgG - class switching CH he didn't say anything |
front 15 VDJ recombination creates binding site and class switch recombination (CSR) switches constant region of the Ab molecule | back 15 changing the DNA/genome of B cells to accomplish switch that constant region is changing initially making IgM (constant region mu)
same specificity can be juxtaposed to another constant region constant regions can be switched and keep same specificity HOWEVER, the genome itself obviously changes a LOT with these switches |
front 16 Ig class organization in a naive B cell | back 16 see pic initial transcription of VDJ recombination turned out to be DNA recombination |
front 17 Ig isotype class organization in a naive B cell | back 17 extremely long distances between Ig constant regions longtranscripts or DNA recombination?
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front 18 Ig class organization in a naive B cell | back 18 DNA sequences before each constant regions can be joined together by an enzyme (cuts to where line goes) result - same specificity now to make diff antibody isotype T cell help w/ cytokines can each target DNA areas in chromosomes to make it available for recombination if recombine to alpha, make IgA antibody, etc. remaining DNA sequences are chopped out of genome, so then the isotope change is irreversible (permanent change in B cell clone) |
front 19 fusion of 2 switch regions changes Ab class | back 19 rearranged DNA in IgM producing cells -> signals from helper T cells -> AID signal can make regions switch carried out by AID |
front 20 AID modifies DNA at the switch region to enable CSR | back 20 IgM -> AID -> recombination os Su with Sy -> deletion of intervening C (constant) genes -> transcription; RNA splicing -> translation = IgG region not used -> deleted as a circle = now diff constant region |
front 21 the intervening C regions are lost during class switch recombination | back 21 showing middle regions of C region being cut out during class switch recombination already said this in isotype switching, lose big chunks of genome |
front 22 intervening DNA sequences of Ig CH regions are lost during CSR (class switch recombination) | back 22 same info genes in heavy chain locus of an IgM expressing B cell transcript for IgM -> removal of DNA segment by enzyme activity between switch regions -> non homologous end joining of DNA at switch regions -> genes in heavy chain locus of an IgG expressing B cell transcript for IgG1 |
front 23 SMH and CSR are 2 distinct processes | back 23 SHM (somatic hybrid mutation)
and CSR
are BOTH carried out by the same enzyme, AID |
front 24 V(D)J recombination generates antibody ---------. | back 24 pause for activity *******EXAM QUESTION!!!!******* answer: diversity, affinity, constant region (isotype, IgG, IgA, etc.) |
front 25 T cell cytokines determine CSR to distinct isotopes | back 25 cytokines
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front 26 Ig heavy chain class (isotype) switching | back 26 diff type cytokines made by helper cell allow switching to diff regions (have gone over this a lot already this lecture) |
front 27 diff cytokines regulate the expression of diff antibody class | back 27 Summary to help remember Which cytokines important for what IL4 – IgE important for allergic rxns Interferon gamma produced in immune response by T cells when pathogen is cross cellular - result – antibodies produced help killing of target cells by T cells Cytokines guide switching of antibody |
front 28 major concepts in antibody generation + function | back 28 1. Exquisite specificity of Antibody for its cognate Antigen
2. Adaptability of the Antibody to change its effector functions by changing Ig isotype by Class switch recombination (CSR) 3. Ability of antibodies to increase binding affinity (affinity maturation) by Somatic Hyper mutations (SHM)
4. CSR and SHM take place in specialized structures called Germinal Centers
5. GCs are formed after T and B cells activated by the same antigen meet in extrafollicular spaces 6. GCs produce antibody-secreting plasma cells and memory B cells that produce recall antibody response upon reexposure with the same antigen (pathogen)
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