B Cells Flashcards
Fab region
the variable region and first constant region
Fc region
the bottom two constant regions
papain
will cleave antibody into monovalent parts –> 2 Fab regions and 1 Fc region
pepsin
will cleave antibody into bivalent Fab regions
monomeric antibodies
IgG, IgD, IgE
dimeric antibodies
IgA (4 antigen binding sites)
pentameric antibodies
IgM (10 antigen binding sites)
light chains contain _
variable region, junction region, and constant region
heavy chains contain _
variable region, junction region, constant region, and diversity region
How is secreted IgM generated?
alternative splicing of the transmembrane regions
IgM vs IgD
controlled by alternative splicing
IgM splicing
contains the mu constant region, the delta constant region is spliced out (mu = M)
IgD splicing
contains the delta constant region, the mu is spliced out (delta = D)
production of isotypes other than IgD
dependent on DNA recombination
What determines what isotype is made by B cells?
which cytokines are secreted by T cells
What cytokine stimulates IgE?
IL-4
two types of light chains
kappa and lambda
RAG1/2
binds recombination signal sequence to cause a hairpin loop to form, aligning the V RSS and J RSS
Ku70:Ku80
joins the DNA ends (V and J) where the RSS was cleaved
TdT
processes DNA ends and adds random nucleotides to achieve additional diversity
artermis:DNA-PK
opens DNA hairpins to generate palindromic sequences
hyper-variable region is also known as _
complementarity determining (CDR) region
Where are the CDR regions located?
on the variable regions of the antibody, each with 3
CDR1 and CDR2 regions
encoded in the germline
CDR3 regions
product of VDJ and VJ recombination
antigen-independent diversity of antibodies
caused by recombination
antigen-dependent diversity of antibodies
caused by somatic hypermutation after antigenic contact
somatic hypermutation
causes changes in the CDR regions after antigen contact causing increased affinity
antibody functions
neutralization of toxins, blocking virus entry, blocking bacteria binding, activation of classical pathway of complement, facilitating uptake by macrophages, working with complement, facilitate killing by NK cells, triggering degranulation of mast cells
activation of classical pathway by IgM
IgM will bind to antigens on bacterial surface and adopt “staple” form –> C1q binds to bound IgM –> activation of C1r –> activates C1s protease
activation of classical pathway by IgG
IgG molecules bind to antigens on bacterial surface –> C1q binds two IgG molecules –> activation of C1r –> activations of C1s protease
antibody facilitation of macrophage uptake
free immunoglobulin will bind bacterial surface, allowing Fc region to bind FcR on macrophages
antibody facilitation of NK cells
antibody binds antigens allowing the Fc receptors on NK cells to recognize the bound antibody –> signals NK cells to kill target cell
antigen specificity determined by _
CDR 1,2,3 regions on variable regions
function of antibody
determined by Fc portion of heavy chain
pro-B cells
stage when D to J rearrangements are carried out
pre-B cell receptor
composed of a mu-chain and a surrogate light chain and the signaling molecules Ig-alpha and Ig-beta
pre-BCR signaling
halts heavy chain rearrangement and initiates light chain rearrangement
immature B cells are all_
IgM
central tolerance
induction of tolerance in primary lymphoid organs as a consequence of immature self–reactive lymphocytes recognizing self antigens
peripheral tolerance
induction of unresponsiveness in peripheral sites as a result of self-reactive lymphocytes encountering self-antigens at the transitional B cell stage
T cell independent antigen
have multiple repeating subunits recognized by B cells; polysaccharide antigens
T cell dependent antigens
most common; full B cell response requires the participation of CD4 + T cells (CD40, CD40L)
passive immunity
monoclonal antibodies, anecdotes, and maternal to fetus antibodies
active immunity
natural infection, vaccines, toxoids
production of monoclonal antibodies
take primed B cells after injecting mouse with antigen and fuse to myeloma cells –> expand hybridomas
humanized monoclonal antibodies
fragment human variable region and insert mouse hybridoma CDR regions
xenomouse
knockout heavy and light chain genes in embryo –> put in human heavy and light chain genes –> chimeric mouse will be born –> breed
bi-specific antibodies
have two regions on antibody (i.e. anti-tumor and anti-hapten) –> anti-tumor will bind to tumor –> radiation can bind to anti-hapten –> radiation is concentrated
magic bullets
adding a toxin to antibody constant region causes endocytosis of the antibody with toxin attached –> blocks translation
