(07) Antibody Diversity Flashcards

1
Q
  • Most b-cells screw it up and don’t get out - what’s the percentage chief?
A
  • 95%
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2
Q

What entails the selection of multiple germline genes (1st way)?

What entails H-L chain combinations (2nd way)?

  • LOOK AT PICTURES IN IPAD FOR MORE DETAIL ON WAYS 1 and 3
A
  • choosing VDJ segments (each of which has a different type) for heavy chain and VJ for light (only if both of these chains work will the b cell leave the bone marrow)
  • heavy chain rearranges independenty of light chain - get various specificity by combining different H and L chains (each with their own variable region rearrangements)
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3
Q

(Antibodies - Allelic Exclusion) - the 5th way

  • Rearrangement of the antibody gene DNA in a random event which occurs on ____ chromosome(s) for each each light or heavy chains. This is called _____.

What does allelic exclusion assure?

Does it occur for heavy or light chains?

So for example you have a yellow bunny mating with a blue bunny - their offspring can make either blue or yellow - but for each b cell it only chooses one - doesn’t mix them up - thats allelic exclusion

A
  • one, allelic exclusion
  • That each individual B cell generates only a single antibody molecule rather thatn expressing the genes from both chromosomes.
  • both
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4
Q

Why don’t you want a b cell with two different antibodies (blue AND yellow?

A
  • you want to to have high avidity (strong binding) - if you have mutliple antibodies you have low avidity and therefore weaker binding
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5
Q

(Rearrangement of Antibody Variable Region Genes)

  • The _____ chain gene rearranges first, followed by _____.
  • If the first splice even fails, the chromosome may ______.
  • Does choice of heavy chain VDJ regions influence choice of light chain V and J?
A
  • heavy, light chain
  • attempt to splice further down the gene cluster
  • no
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6
Q
  • _____ proteins/enzymes recognize conserved sequences __________, bend the _______ such that the proteins interact, and _______ the intervening DNA sequences. Animals defincient in Rag activity are _______.

Why?

What are the circular structures calle dthat arve cleaved out?

What do the RAGs recognize on each end?

A
  • RAG (recombination activiated genes), flanking each gene segment, DNA strand, cleave out, severely immunocompromised.

Because they don’t rearrange B and T cell receptors

  • signal joints
  • RSS, recombination signal sequence
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7
Q

(Expression of surface Ig)

  • B cells develop in the ____ and are released with rearranged __ genes.

Which two antibodies are found on mature B cells released from the marrow?

  • Rearrangment occurs in the ____ of Ag
A
  • bone marrow, Ig
  • IgM and IgD
  • absence
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8
Q

Why is IgM the first antibody produced by B cells?

  • IgD is also found on the surface of newly formed B cells due to a ___________
  • look at picture - recognize that antigen a goes up really fast the second time cuase it has already seen it once
A
  • it is encoded immediately adjacent to the VDJ genes
  • mRNA splicing artifact
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9
Q
  • What does antibody RNA code for that allows it to lodge itself into membrane
  • Which is produced more IgM or IgD?
  • Will the binding pocket be different if IgD is made?
A
  • transmembrane regions
  • much more IgM
  • no it will be identical
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10
Q

What will happen to antibodies if they bind to self-antigen in the bone marrow? What is this called?

What if there is no self-reaction?

A
  • they will be deleted, tolerance
  • will be released from bone marrow
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11
Q
  • B cells initially mature in the _____, in the _____ of specific antigenic stimulation
  • Where do they go after this?
  • B cells that encounter Ag (and ____ help) form foci called ______ that contain proliferating B cells\
  • What are b cells called that leave the germinal center, reenter circulation, and secrete Ab called? Where do they sometimes reside?

Where do isotype switching and somatic hypermutation occur? follwoing what?

A
  • bone marrow, absence
  • secondary lymphoid tissues - lymph nodes, tonsils, spleen, and Peyer’s patches
  • T cell, germinal centers
  • plasma cells, bone marrow and spleen
  • in the periphery, specific antigen stimulation
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12
Q

How long will mature be cell live if i doesn’t get into secondary lymphoid tissue?

How long if it gets into there (but has no antigen interaticeion)

  • Mouse bone marrow produces 10*10^6 mature b cells a day - level in periphery stays constant due to cell death. Why does it stay level (3 reasons)
A
  • 2-3 days
  • 3-8 weeks
  • natural turnover, removal of cells that bind self too strongly, or those that fail to enter lymphoid tissue
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13
Q

What happens if a plasma cell receives further activation?

A
  • results in isotype swithcing to secrete IgG or IgA
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14
Q

(Late B Stage Cell Development)

  • Exposure to antigen in the periphery results in
  • activation and cell division
  • differentiation into _____
  • _______ and ______ (introduces AA changes)
  • Selection for receptor specificity with greater affinity (_______)
  • Differention into _____
\_\_\_ activation of B cells and subsequent changes in
 DNA (somatic hypermutation and isotype switching) or
 RNA processing (secretion of antibody) in the periphery
 require exposure to antigen (except for gene conversion
 events).
A
  • plasma cells
  • class swithcing, somatic hypermutation
  • affinity maturation
  • memory B cells
  • ALL
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15
Q

(Germinal center formation)

Germinal centers are specialized areas of _______. If stimulated by _____, the B cells will multiply and start to secrete IgM. They will also undergo ______ and _____ for antigen binding sites in these sites.

Where do Plasma cells migrate to?

How about memory B cells?

A
  • secondary lymphoid organs, antigen specific T cells, somatic hypermutation, selection
  • all the other lymphoid organs
  • continual re-circulation, bone marrow is popular spot - can live a long time (years)
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16
Q
  • What brings antigen into the lympphoid organs to interact with T-cells and B cells?
  • Which t cells are especially helpful to the replication B cells?
A
  • dendritic cells (after phagocytosing something)
  • TH2 (t helper 2)
17
Q
  • What are the first things that happen following B cell activation?
  • what happens to switch the IgM from membrance to secretory?
A
  • proliferation and conversion to secretory IgM (plasma cell)
  • RNA splicing, the membrane binding portions of the code are treated as introns and the S (secretory portion) get spliced in