adaptive immunity: immunoglobulin proteins Flashcards
immunoglobulin proteins
antibodies: large glycoproteins that recgonize a specific Ag
B cell receptor (BCR)
membrane bound
Antibody (Ab)
non-membrane bound
A B cell can only produce ____kind of ___ chain and ____ chain
one; heavy; light
heavy chain
larger chains that attached to each other and light chains via disulfide bonds
light chains
smaller part of the antibody
Fab region of antibody
fragment where antigen binds to; many variations
Fc region of antibody
constant region; has a few isotypes that can affect site or charge; can bind to Fc receptors on innate immune cells
both light and dark chains have a _____ region
Fab and Fc
Papain
enzyme (one of many) that digests and antibody by cleaving the disulfide bonds
why are immunoglobulins flexible
so they can get into contact with antigens
hypervariable regions
amino acid sequences that demonstrate extreme variability between different Ig molecules; gives rise to the enormous antigenic diversity associated with Ig molecules. takes place on light and heavy chains
length of hyper variable regions
5-7 amino acids long
which hypervariable region has the most amino acid variability
CDR3
Light chain isotypes
kappa or lamda; helps contribute to diversity but not function
heavy chain isotypes
IgM, IgD, IgG (subclasses), IgE, igA (subclasses)
when a naive B cell first encounters Ag it will produce what?
IgM
genetic rearrangement of ______ can lead to class switching
constant hey region (or isotype switching design on the type of pathogen)
membrane-bound Ig
have cytoplasmic domains and transmembrane domains to help them attach to cell. Found on B cell plasma membrane and also called BCR (b cell receptor)
Secreted Ig
contains a tailpiece at the end because it doesn’t have to attach to a cell. Found in the blood
Secretory Ig
contains a secretory component that protects it since its found in secretions (tears, mucus) and a J chain that binds them together with other antibody chains. these help neutralize antigens
what are the polymeric immunoglobulins (secreted forms)
IgM pentamer (5 immunoglobulins bound together) 10 binding sites IgA dimer (2 immunoglobulins bound together) 4 binding sites
what do B cell receptor complexes do
they help induces signaling cascade when a antigen binds to an antibody near by. since the antibodies aren’t big enough to initiate a signaling cascade the Ig alpha and beta complexes uses ITAM to initiate it
ITAM
attached to Ig alpha and beta complexes that induce signaling cascade
immunoglobulin genes
the variable regions are made up of many small DNA garments called gene segments
the segments of immunoglobulin gnes
- variable-v
- diversity-d
- joining- j
(light chain doesn’t have d)
V(D)J recombination
somatic recombination that is a radom rearrangement of V D and J segments of the variable region
where does VDJ recombination occur
occurs in every naive B cell and is permanet
this process allows the large antigenic diversity of Ig
VDJ recombination (doesn’t involved the Ig isotype)
epitope
antigenic determinant. area that antibody likes to bind to
induced fit
last minute conformational changes in order for antibody to form a better bond. (more spacial)
which region of recombination removes introns which contributes to antibody diversity
the variable region
which Ab would have the greatest avidity
IgM (most binding sites)
where does B cell development occur
begin in bone marrow and ends in a secondary lymph organ
2 stages of B cell development
maturation, differentiation
b cells in the maturation stage are still ___?
naive
differentiation
begins once b cells recognize its specific Ag,ends with the generation of Ag-specific plasma cells and memory B cells
what are the 7 developmental stages of B cell maturation
- hematopoietic stem cell
- multipotent progenitor cell
- common lymphoid progenitor cell
- progenitorr b ciel (pro-b cell)
- precursor B cell (pre b cell)
- immature naive b cell
- mature naive b cell
bone marrow _____ cells are very important for b cell maturation
stromal
what keeps developing stem cells in the bone marrow
adhesion molecules
kit
found on early pro-b cells that attaches it to the SCF of bone marrow stromal cells to keep it in the bone marrow
IL-7
cytokine that is involved in lymphoid lineage helps development of b and t cells in bone marrow
progenitor b cells
most immature form of b cells. first recognizable b cell. immunoglobulin genes are still in their gremlin configuration
precursor b cells
VDJ recombination has occurred and is complete for both chains (unlike pro b cells) . Late pre-b cells will produce membrane bound IgM plus Ig alpha and beta
how can you distinguish between pro and pre b cells
pre b cells begin to express a membrane immunoglobulin
immature b cell
development of central tolerance. immature b cell get one last change to rearrange the Ig loci. 2-5%of immature b cells survive
central tolerance
b cells can ignore antigens
receptor editing
where immature b cells get one last change to rearrange the Ig loci
in NEGATIVE SELECTION the immature b cell will go through
apoptosis (after it has reacted too strongly with antigens of the body 2x)
when don’t immature b cells survive
when they are too self reactive
transitional b cells are filtered by the?
spleen
how to distinguish between a transitional b cell and an immature b cell
- location (bone marrow vs blood, pulp, pals, and spleen)
2. transitional b cells make more Igm on its surface
transitional type II b cells
BOTH IgM and IgD are expressed on cell surface
mature b cell
express both IgM and IgD. cannot undergo further VDJ rearrangement. are still considered naive
what are the b cell antigens
t- dependent (Td) (follicular b cells)
t-indepdent (Ti1 and Ti2) (marginal zone b cells)
dendritic cells regonize antigen and _____
internalizes it
which cells cut and present antigen specific helper t cells
dendritic cells
t dependent antigen process
- b cell recognizes the antigen with its receptor
- internalizes antigen and presents it to a helper t cell
- isotype switched, now has high affinity for this antibody and is a memory b cell thats long lived in plasma cells
t independent antigen process
polysaccharide antigen is presented to b cell other signals (complement protein
mainly IgM; low affinity antibodies and short lived plasma cells
isn’t ideal if you come in contact with same illness later on, antibodies won’t be present anymore
T- inepdnet antigen (TI-2)
only binds to the b cell antigen receptor and creates BCR cross-linking
T-indepdent antigen (TI-1)
binds to b cell antigen receptors but also to other receptors on the cell
3 steps of b cell activation
- antigen binding
- costimulaition
- cytokines help
(these steps occur in secondary lymphoid tissues; doesn’t happen at active site)
step one of b cell activation
finding of multiple ag to BCR. signal transmitted via Ig alpha and beta. internalizes Ag.
step 2 of b cella activation
integration with activated, ag specific t helper cell
t cell receptor is peptide-MHC II
primary follicle
begins b cell activation. in cortex area
secondary follicle
b cell colonial expansion. becomes germinal center. has light area and dark area. dark area is where all mitosis occurs
germinal centers
sites within secondary lymph organs where mature b cells proliferate and differentiate. 9-12 days after exposure colonial expansion
hyper somatic mutation
b cell mutation happening in germinal centers where DNA mutates to increase affinity
what cells facilitate negative selection on b cells
follicular dendritic cells
isotype switching
happens in germinal centers for b cells. changing heavy chain
3 things that happen in germinal centers
somatic hypermutation, affinity maturation, isotope switching
two types of cells b cells can differentiate into
- plasma cells
2. memory cells
short lived plasma cells
(6-10 days)
secrete low affinity IgM
made in response to Ti or Td antigens
long lived plasma cells
low affinity IgM
what do antibodies do
- neutralization (block antibody attachment to cell)
- classical complement activation (IgM, IgG)
- ozonization
- antibody decent cell mediated cytotoxicity
