B Cells + Antibodies Flashcards
Antibodies are composed of
Two identical heavy chains
has one variable site Vh and three constant sections (Ch1, Ch2, Ch3)
two identical light chains
has one variable site Vl and one constant domain Cl
Fab Site
Complex composed of Vl and Cl from light chain and Vh and Ch1 from heavy chain
Fas Site
Complex composed of Ch2, Ch3 from heavy chains
Also known as the effector region
What is different about IgM and IgE heavy chain?
IgM and IgE have Ch4
4th constant domain on their Heavy Chain
How do antibodies on B cells become activated
Antibodies on B Cells need to cross link with antigen in order to become activated
Within each variable domain, there are ______ regions of ________
There are three regions of hypervariablity These regions (Variable Light Vl, and Variable Heavy Vh) can bind with antigen creating 6 sites for antigen interaction
Difference between isotypes and idiotypes
Isotypes are classified by the constant regions of the antibody i.e. Cl and Ch1, Ch2, Ch3 (+Ch4 if IgM or IgE)
Antibodies that bind to Fc region are good ways to identify different isotypes
Idiotype: variable regions of heavy and light chains
i.e. comining sites of Vl and Vh
Idiotypes demonstrate the specific clonal amplification of antibodies
IgM
membrane receptor on B-cell
can be synthesized and secreted as pentamer
Pentamer of IgM is held together by J chain
Potent activator of complement
Immature B cells are marked with _____ and express ______ and ______ when they are fully mature
Immature B cells express IgM
Mature B Cells express both IgM and IgD
IgD is the maturation factor of IgD
IgD
Cannot be secreted
IgG
highest in serum content has longest 1/2 life Complement activator Monmer that is less efficient than IgM Great opsonizer IgG can cross the placenta
When does Macrophage bind to IgG?
Macrophages only bind to Fc portion of IgG after IgG has bound to rorereign substance
Phagocytic cells have FcGamma receptors that accept IgG Fc portion
IgA
involved in mucosal immunity
relatively mild antibody
blocks bacteria from replicating
relies on peristalic action to then clear bacteria and pathogens
IgA is a dimer held together by J chain
IgA prevents damage to epithelia cells in the gut
IgE
sensatizes mast cells, basophills and eosinophills
x-link of IgE causes mast cells to secrete granules of histamines and other contents
IgE works with PARASITES
IgE DOES NOT need to bind to antigen before binding to Fc(epsilon) receptor
i.e. IgE can bind directly to Fc(epsilon) receptor
Cross Reactivity and Example
Cross reactivity is generating antibodies to one substance. That same antibody can then react with another completely different substance
i.e. we generate antibodies to the terminal sugars of bacteria in our gut flora. These same antibodies react with the different antigens found on blood types
T Cells mainly react with ______ moiety while B cells can react with _____ moiety
T cells mainly see polypeptide of bacteria
B Cells can react with carbohydrate moiety of pathogen
NB: T cells with peptide moiety can than activate B Cells
Ig stages and gene expression
Stems Cells: germ line configuration (naive)
Pro-B Cells: D/J begins
Pre-B Cell: VDJ rearangement is complete in cytoplasm but no light chain. VDJ chain is called (u [mew]-heavy chain)
Immature B Cell: VDJ and VJ is complete
Genomic Makeup of Heavy Chain
Beginning
100 V segments (Vh1, Vh2, …, Vh100)
27 D Segments (D1, D2, …, D27)
6 J segments (Jh1, Jh2, …, Jh6)
NB: Only Heavy Chain had D section, so expression of Dh1 is not necessary
1st step of Heavy Chain Rearrangement
DJ rearrangement
one D section merges with one J section i.e. D3 and Jh2
Circular DNA segment between two portions gets removed
Circular excess DNA is called episome
2nd Step of Heavy Chain Rearrangement
VD rearrangement
Hallmark of Pre B Cell
VDJ rearangement is complete
mew-heavy chain is in cytoplasm bound to surrogate light chain
mew heavy chain and surrogate light chain are transported to the surface of the cell.
Transport indicates to stop production of heavy chain and switch over to production of light chain
Enzyme that facilitates recombination of heavy chain
VDJ recombinase
i.e. RAG 1 and RAG 2 are lymphoid specific DNA recombination enzymes
Two isotypes of light chain are _____ and ______
kappa and lambda
Kappa light chain has no D gene segment
Each antibody receptor has a unique _________ (isotype or idiotype)?
Idiotype
Isotype is coded for by constant domain and is a family of antibodies
Diff between Primary transcript, mRNA and protein
Primary Transcript includes portion of V segment and J segment that will be cut out via transcription start site and alternative splicing
i.e. Vh1-Vh2-D3-Jh4-Jh5-Jh6-u1-u2-u3-u4
Vh1 will get removed by choosing a transcription site just before Vh2 and Jh5 and Jh6 will get removed by alternative splicing
mRNA include just what you want and protein is functional antibody.
12 / 23 spacer rule for heavy chain
Certain DNA elements that control recombination process
Rearrangement is only allowed to occur between a spacer of 12 and 23
[Vh] 7 – 23 – 9 ——9 – 12 – 7 [DElement] 7 – 12 – 9 —— 9 – 23 – 7 – [JElement]
12 / 23 rule for lambda and kappa chain
[Vlambda]-7- 23 - 9 ——9- 12- [Jlamda]
[Vkappa]-7- 12 - 9 ——9- 23- [Jkappa]
Generating Idiotype Diversity
- Multiple V regions
- Recombination of VJ (light) and VDJ (heavy)
- Heavy and light combinations
- VDJ recombination is not perfect
Gives rise to junctional diversity
i.e. add/subtract 1 nucleotide between V and D segment - Somatic hypermutation
Principle Enzyme of imperfect VDJ rearrangment
Terminal Deoxynucleotidyl transferase (TDNT)
heavy chain only
Somatic hypermutation only occurs in _____ cells
Principle enzyme of somatic hypermutation
B Cells
Activation-Induced cytomine deaminase (AID)
