(08) B cell development Flashcards
1
Q
(Somatic Hypermutation)
- When a b cell has been activated to proliferate (ag specific), and enzyme (called what?) chemically changes DNA bases to a different base, resulting in what?
- This occurs with help of what and where?
A
- activation induced deaminase; a new codon
- T cell help; in germinal center in lymphoid tissue
2
Q
(Somatic Hypermutation cont)
- If the mutation provides better binding of the Ab pocket to the Ag, what happens? What is the pocress called?
- What happens if the binding is decreased?
A
- these b cells are selected; affinity maturation
- these b cells do not successfully compete for Ag and die via apoptosis
3
Q
(Somatic Hypermutation Mechanism)
- What is the enzyme responsible for mutations in somatic hypermutation events?
- What is the major change? What can this change?
A
- activation-induced cytidine deaminases (AID)
- conversion of cytidiine residue to a thymidine residue; the amino acid encoded
4
Q
- Affinity maturation occurs only in response to what?
- Where does this take place?
- What is the end result?
A
- antigen stimulation
- within germinal centers in secondary lymphoid organs
- increased antigen recognition and binding efficiency
5
Q
- Somatic Hypermutation leads to _______ where the “quality” of the antibodies produced gradually increases.
- This process occurs where during what?
- An enyzme deaminates what and what in the VDJ and VJ region of the antibody gene? Causing what?
- Does it occur on heavy chain or light chain?
A
- affinity maturation
- germinal center in secondary lymphoid organs during B cell proliferation
- adenosines and cytosines; the wrong base to be incorporated when that stretch of DNA is copied
- both
6
Q
(Somatic Hypermutation mechanism)
- What is another way some species do to achieve the same thing as somatic hypermutation? What happens?
- Which species use hypermutation exclusively?
- Which use mostly gene conversion? Do they have a lot of variable region genes?
- Which species use gene conversion during B cell differentiation, but hypermutation during an immune response?
A
- Gene conversion; rather than repair by translesion syntehsis (as in hypermutation), gene conversion just inserts a gene segment
- humans and mice
- pigs, cattle, rabbits; no
- chicken
7
Q
(Gene Conversion)
- Which species exhibit little diversity in V, D, and J?
- How is diversity in the binding pocket generated? explain it!
- Does gene conversion occur with or without T cell stimulation?
- Where does it occur in birds? in ruminants?
A
- horses, rabbits, birds
- gene converstion; short sequences within the exon are replaced by V gene segments from pseudogenes (genes that used to be functional at one point evolution)
- without
- bursa; Peyer’s patches
8
Q
- A mature B cell traffics to what tissues?
- If it encounters an Ag which fits into the Ab pocket, and receives T cell assistance - it will do what?
- What occurs during this stage?
- This B cell maturation leads to formation of what? which do what?
A
- peripheral tissues (including secondary lymphoid organs)
- proliferate to make many copies of itself
- Somatic hypermutation
- plasma cells; secrete large amounts of Ab (some will become memory cells)
9
Q
(Somatic Hypermutation vs. Isotype Switching)
- Does switching from IgM to IgG affect the binding site?
- Somatic hypermuation changes what?
- Are these both occuring in germinal center?
A
- no
- the codon sequence in the VDJ, which changes the binding pocket
- yes
10
Q
(Class (isotype) Switching)
- Activated B cells will rearrange their somatic DNA to produce antibodies of a different isotype following what?
- The switch only involves what region?
- Does specificity of the B cell change?
- What happens to the intervening DNA?
- Do Light Chains switch classes?
A
- appropriate stimulation by cytokines
- the heavy chain constant region
- no
- is looped out and lost (preventing switching back)
- no
11
Q
(Cytokine favorites)
- Which isotype is favored by IL-4
- IFN-gamma?
- TGF-beta?
- Can isotype switching more than once?
- What is the order of isotype? Can you go back upstream?
- when you have a large immune response against something like a worm - initial reaction produces - IL-4 - promotes IgE production - IgE activates mast cells an eosinophils which are good at fighting worms
A
- IgG1, IgE
- IgG2a, IgG3
- IgA, IgG2b
- yes
- IgM (IgD), IgG, IgE, IgA; nope
12
Q
(Antibody Isotypes)
- Isotype or class switching has a major impact on the immune response based on the properties of each isotype. Escpecially important for what?
- Which isotypes are secreted by plasma cells in the spleen, lymph nodes, and bone marrow?
- What is the major Ab isotype produced during a primary response?
- Which can be surface bound or secreted as a pentamer?
- Which is secreted by plasma cells found in tissues near body surfaces?
- Which has an Fc portion that binds to receptors on mast cells and basophils?
- Which one gets out on mucosal surfaces?
- Which have longest half life in blood?
+ look at the table a little bit
A
- phagocytes
- IgG and IgM
- IgM
- IgM
- IgA
- IgE
- IgA
- IgG
13
Q
(Ab receptors)
- Many immune cells express receptors thatn recognize the what on an antibody?
- What does this interaction cause?
- Is there a whole family of Fc receptors?
- What does Fc stand for again?
- Most Fc receptors bind which type?
- Mast cells and eosinophils have receptors for which type?
- IgG receptors are primarily on what?
A
- the Fc region
- activates the cell, including phagocytosis or expulsion of granules
- yes
- constant fragment
- IgG1
- IgE
- phagocytes
14
Q
(Antibody Memory)
- When the immune system again encounters antigen A, a more rapid and stronger Ab response occurs due to what?
- The isotype will swith from what to what?
- So if you have mostly IgM? Been around for awhile?
A
- immunological memory
- and IgM (primary response) response to IgG (more in secondary response)
- early response; IgG
15
Q
(Immunological Memory)
- When are these long-lived cells generated? Where distributed?
- Have memory B cells usually undergone affinit maturation such that the binding to specific antigen is much greater in a second response to antigen?
- Memory B cells reside where?
A
- following initial exposure to and antigen; throughout secondary lymphoid tissue
- yes
- the bone MARROW