B cells and their antibodies Flashcards
what are B cells
-are cells that are produced from fluid called T cells
- and they produce antibodies
what is Ig
they are glycoproteins that binds specifically to the antigen and are important of humoral immunity
they are produced by B cells in response to pathogen
when is Ig called antibody
when they secreted by B cells
when is Ig called B cell receptor (BCR)
when they bound on membrane of B cell
What is the purpose of BCR
is to guide B cells in there development
what is the purpose of antibody
to protect our body against pathogens/ diseases
how does structure of antibody
- 2 alpha and beta chains
-it have 2 antigen binding sites - it have constant and variable region with 2 identical heavy chain and 2 identical light chain
what are the regions of antibody
- variable region : variable aa sequence. VH and VL, forms antigen binding sites
- Constant region : constant aa sequences. determine effector function
what are 3 fragment of antibody
- Fv region : fragment variable
- Fab region: fragment antigen binding
-FC region: fragment crystallizable
important to know that Fc and C region
C region is not Fc region
structure of antibody vs BCR
- BCR has Ig beta and Ig alpha chain used in signaling
- antibody don’t have them
how does structure of antibody relate to it’s function
- variable region: contain antigen binding site and recognize the target antigen.
-constant region: translate the binding of target antigen to the effector function, in few words it ensures proper effective function to antigen take place
how do we get antigen binding sites
how is the shape of antibody binding site
binding site shape depends on the antigen
when is small protein so called hapten it has deep pocket shape but when protein is large it has flat surfaces
how does antibody binds antigen
through non-covalent bonds ( H-bonds, hydrophobic, and Vdw forces)
antigen specificity
-Ab binds specific part of Ag called epitope
-two antibodies can binds one antigen but different two epitopes of antigen
- antigen have different epitopes
two types of epitopes
conformational (discontinuous) and linear (continuous)
what are five class of antibody isotypes
are IgG, IgM, IgD, IgE and IgA, all classes have same variable region but each class have specific constant region with specific effector function
what do B cells produce
-each B cells produce antibodies with one specific aa sequence structure
what kind of antibodies are produced by B cells
- antibodies that recognize appropriate antigen and
- antibodies that generate appropriate effector function
when does antibodies obtain their specific structure
during B cells development
how do B cell develop
what are 7 characteristic of B cells / must and their solutions
- must be able to produce antibodies against antigen they never encounter before
- by creating many different cell that produce antibodies and they will divide and survive
-must avoid producing antibodies that fight against our own body
* eliminating cells that produce unsuitable antibodies
* eliminate T cells that help B cells to produce antibody with unsuitable binding sites
-must know when to initiate response against antigen
*communicate with T cells
-must be able to increase affinity of antibodies to specific target antigen
* somatic hypermutation and selection
-must give antibodies appropriate characteristics to perform specific effector function
* change of immunoglobulin constant region/ class switch which is induced by enzyme A
-must produce large amount of antibodies to fight against antigen
* development of short lived and long lived plasma cells
-must provide body with immunological memory that ensure production of more and better antibodies
*produce long lived memory cells encoding appropriate antibodies
how does B cells be able to produce antibodies for antigen they never encounter before
by creating many different cell that produce antibodies and they will divide and survive
what is negative selection related with must 2
when there is elimination of clones/B cells that produce antibodies with inappropriate binding properties
where is antibody variability more concentrated
in V domain in VH- hyper variable / heavy variable region or in CDR
where do we find 6 CDR that form antigen binding site
3 are found in VH and other 3 on VL
how is antibody encoded
through 4 process or principles:
- somatic recombination: rearrangement of V,D and J gene to form complete V region of antibodies
-junctional diversity: is shown during recombination of VJ and VDJ
-combination of differentVH and VL domain : if 3 VH and 3 VL are combined we can get 9 antibodies
all above 3 take place in bone marrow
- Somatic hypermutation this take place in germinal center
what is irreversible process
when V region of antibody is formed by V and J genes
where does somatic recombination occurs
in bone marrow where B cells precusor are developed
what is non-precised process
recombination of VJ and VDJ segments
how is B cells activated and its first and second signal
- it is required to be stimulated by antigen through BCR which is signal one
-present antigen on MHC class II - talk to CD4+ T helper cells that recognize the same antigen which is signal two
what are two signal of B cells
- antigen binds to BCR
- CD4+ T cells recognize MHC class II- peptide complex on BCR surface
How does the TH-cell know when to communicate with the B cell?
by T cells being activated by dendritic cells (by when TCR bind to MHC class II of dendritic cells) and and T cells will later activate B cells
explain 3 signal of T cells
1.TCR/CD4 that binds to MHC II peptide complex of dendritic cells
2. CD28 that binds to CD286/80 of dendritic cells
3. CD40L that binds to CD40 of dendritic cells
how does second signal of B cells occurs
when T cells is activated by dendritic cells they produce CD40L that bind to the BCR of B cells and activate it
what is linked recognition
is when T cells activate B cells and they can both recognize different epitope of antigen as long as they belong to same antigen
what does B cells do after being activated
- they differentiate into memory or plasma cells
where does antibody proliferate or divide
into primary follicles and they form germinal centra
where in germinal centra do we find cetroblast and centrocytes
cetroblast in dark zone and centrocytes in light zone
cetroblast they proliferate at higher degree than centrocytes
what is somatic hypermutation
process where random mutation is produced while B cells proliferate and can lead to single aa substitutions
what is follicular dendritic cells
capture antigen on their surface in order to make it accessible to B cells.
only B cells with high affinity of CDR will be able to bind
what is positive selection
B cells with low affinity BCR will not be able to bind antigen so they can not bind MHC II of T cells.
and they will be killed by apoptosis
how does antibodies goes from one class to another
- naive B cells : produce IgM and IgD.
so in order for B cells to produce other isotype they have to go through class switch, by replacing constant region (between mouse and human) while retaining variable region
what does it mean class switching process to be irreversible
means once one constant region gene is moved out it can not be included again
where does class switch occure
in germinal centra in dark zone (centrobrust) only for B cells that has been activated by T cells
and once they get activated they receive signal on which class they should switch to
different IgG and IgM
IgG has high affinity and fewer binding site
IgM has low affinity and more binding site
what is avidity
total binding strength of antibody
that why IgM is considered as best antibody to fight antigen due to its more binding site
what is plasma cells
-short-lived plasma cells are B cells that do not enter into the germinal centra to differentiate.
-long lived plasma cells are B cells that enter in germinal centra to differentiate
what antibody does short-lived plasma cells produce
IgM that can act on antigen immediately
what antibody does long-lived plasma cells produce
IgG in large quantity and they reside in bone marrow
what is B cell memory
B cells that are develop in germinal centra can also be differentiated into memory B cells
do study question on slide 81
