B Cells And Antibodies Flashcards
What are the classes of antibodies?
IgG IgM IgE IgA IgD
What is the basic antibody structure ?
2 heavy chains and 2 light chains linked by disulfide bonds
Chains have variable (V) and constant (C) regions
Heavy chains determine the isotypes
Fab=fragment antigen binding-contain antigen binding sites
Heavy and light chains contribute to Fab structure
Fc= fragment constant
Only heavy chains contribute to Fc structure
Fc binds to complement C1q and CRP
What is the characteristic of IgG?
4 subclasses in humans: IgG1, IgG2, IgG3 and IgG4
Major isotype in serum
Has a valence of 2 (2 antigen binding sites)
Only class that crosses the placenta
Provide fetus and newborn with passive protection
Dissipates by age 5-6 months
Major isotype synthesized during the secondary immune response
What are the functions of IgG?
Complement activation Toxin and virus neutralization Opsonization Agglutination ADCC
What is the indication of an elevated serum IgG to an infectious agents in persons older than 6 months?
Past infection or the convalescence phase of a current infection
Prior vaccination
Chronic infection
What are the characteristics of IgM?
First antibody class made to all antigens Major class of the primary immune response Great agglutinator-10 binding sites Elevated levels=acute phase of infection Only class produced by the fetus
What are the characteristics of IgA?
IgA1 and IgA2
Found in seromucous secretions (saliva,breast milk, sweat, mucus)
Dimeric IgA contains a J chain and secretory component
Has a valence of 4
Secretory component protects IgA from proteases
Oral and intranaasal induce IgA synthesis
Secretory component synthesized by epithelial cells
What are the characteristics of IgE?
Similar to IgG in structure Has a valence of 2 Binds to basophils, mast cells and eosinophils, cross linking and causing degranulation Interact with worms and allergens Involved in hypersensitivity reactions
What are the characteristics of IgD?
Similar to IgG in structure
Valence of 2
Co-expressed with IgM on surface of mature, naive B cells
Antigen binding to surface IgD triggers B cell differentiation into plasma cells
What is the genetic basis of antibody diversity?
Antibodies are encoded by multiple exons that undergo rearrangement in the B cell DNA to generate a multitude of combinations
Example of k light chains
DNA coding of kappa light chain variable regions contains 40 variable regions gene segments and 5 joining region.
RAG-1 and RAG-2 components of the VDJ recombinant generate loops in the DNA which bring together the ends of randomly selected V and J exons
The loops containing unused exons are removed by exonucleases
The ends of the V and J exons are lighted together
Persons lacking RAG genes cannot makes antibodies or TCR molecules and suffer from SCID
After rearrangement of segments RNA copy is made
What is the process of the heavy chain gene expression?
Variable region of the heavy chain is encoded by V,D and J exons that are randomly selected and joined together by the action of the VDJ recombinase?RAG enzymes
The DJ construct is formed first
Then the VDJ construct is formed
After VDJ construct is formed the B cell transcribes man exact copy of the rearranged DNA to yield a primary RNA transcript
The NA transcript can undergo alternative splicing
How does class switching occur?
The AID enzyme is required for class switching to IgG, IgA or IgE AID recognizes switch regions preceding heavy chain constant regions exons Unused constant region exons are looped out and excised during class switching Cells that class switch from IgM cannot go back to producing IgM because the Mu exon is gone AID is activated when B cell receives T cell help CD40 on B cell interacts with CD40L on Th cell
What determined the class switching?
Class switching is determined by the cytokines made by the T helper cell
TH2 derived IL-4 and IL-13–>IgE
TH2 derived IL-5—>IgA
TH1 derived IFN gamma—>Ig3
Person deficient in CD40, CD40L or AID sufffer from hyper-IgM syndrome
