Antibody Structure/ Generation of B cell diversity Flashcards
What are the highly variable recognition molecules of the adaptive immune response?
Immunoglobulin (BCR) and T cell receptors
What is active immunity? Passive immunity?
Active is generated in the host (infection, vaccine); Passive is generated elsewhere and transferred to host
True or False: Antigen receptors are unique to the adaptive immune response
True
What is the basic structure of the TCR?
A heterodimer composed of two transmembrane glycoproteins
What is the name of the regions of antigen molecule recognized by the BCR/TCR?
Epitopes
What kind of antigens can B cells recognize? T cells?
B cells can recognize free, surface bound, or degraded antigen; TCRs only recognize processed antigen peptides presented on an MHC
What is an immunogen?
Epitopes that induce an immune response and are recognized by antigen receptors
What are haptens?
Small, non-immunogenic, but antigenic molecules
What are the characteristic of an antigen that favor induction of an immune response?
Size (>10 kDa), Complexity, conformation (accessible), and chemically cleavable
What confers the different functions in different antibody isotypes?
Differences in the Fc region
By what cells are antibodies secreted?
Plasma cells
What polypeptides make an antibody?
2 identical heavy chains and 2 identical light chains
What domains are contained within the immunoglobulin light chain? Heavy chain?
One variable domain and one constant domain; One variable and 3 or 4 constant domains
What makes up the antigen-binding site of immunoglobulins?
The combination of the variable domains from one L chain and one H chain
What are the different H chains? L chains?
Gamma, mu, delta, alpha, and episilon; kappa and lambda
What is the hinge region of an antibody and what is its importance?
The flexible, unstructured portion in the middle of the Ab; allows antigen binding arms to adopt different orientations
What are the two fragments an antibody can be cleaved into by proteases?
Fab (fragment antigen binding=arms) and Fc
Where on the antibody are the hypervariable regions? How many are there per variable domain?
There are 3 HV per variable domains and they are located on loops at the end of the arm
What are complementarity-determining regions?
Hypervariable regions on antibodies
What forms the Ag binding site at the tip of each Fab on an antibody?
Pairing of HV regions from the H and L chains
How many total hypervariable regions are their per antibody? How many different HV regions/ antibody?
12– 2 identical pairs of 6
What dictates the specificity of an antibody?
The different sequences of variable regions which create different antigen binding sites
True or False: An antibody that recognizes one pathogen is also designed to recognize other pathogens
False
What is a multivalent antigen?
An antigen with more than one epitope
What are the different types of epitopes? What is each
Linear epitopes (sequential amino acids) and discontinuous epitopes (amino acids brought together via protein folding
True or False: Not all 6 complementary determining regions may make contact with an antigen
True
What is avidity?
Combined strength between more than one antigen binding site and more than one epitope
What is avidity?
Combined strength between more than one antigen binding site and more than one epitope
What antibody generally has low affinity but high avidity?
IgM
What are abzymes?
A catalytic antibody; a monoclonal antibody that binds and changes the antigen
What are polyclonal antibodies?
Antibodies generated from a mixture of different B cells and recognizes multiple epitopes
True or False: Humoral immunity response to infection is polyclonal?
True
How are monoclonal antibodies generated?
B-cell hybridomas- b cells fused with tumor cells
What is agammaglobulinemia?
The absence of antibodies
What are chimeric and humanized monoclonal antibodies?
Chimeric- mouse variable region + human constant regions; Humanized- mouse CDR replaces human CDR
How is diversity of antigen receptors generated?
Somatic recombination - Gene rearrangement
What segments are in the variable domain?
Heavy chains- V(ariable), D(iversity), and J(oining); Light chains- V and J
What cells in the body undergo somatic recombination?
Only B and T cells
True or False: Somatic recombination must occur before the gene can be transcribed?
True
What is clonal selection and expansion?
Clonal selection is the process by which only B and T cell receptors that recognize a given pathogen are activated to proliferate and form clones of cells with identical receptors (clonal expansion)
What is the order of rearrangements to make the V region in the Ig heavy chain?
D and J and then DJ and V
What is V(D)J recombinase?
A set of enzyme required for V-D-J?
What is the RAG complex?
RAG-1 and RAG-2 form a RAG complex which binds to recombination signal sequences and initiates recombination events
What is junctional diversity?
The RAG compex cleaves RSSs from the D and J (or DJ and V) gene segments to yield DNA hairpins, and then it opens the hairpins generating palindromic P-nucleotides. Terminal deoxynucleotidyltransferase randomly fills in the gaps with non-templated nucleotides (N nucleotides)
True or False: Each B cell will produce hundreds of Heavy and Light chain combinations
False: only one
What kind of Ig is expressed on naive B cells?
IgM and IgD
What is the mechanism by which both IgM and IgD are expressed on naive B cells?
mRNA splicing
What confers the difference between surface-Ig and secreted antibodies? What is the mechanism by which Ig changes from surface to secreted?
Membrane Ig have hydrophobic tails and secreted have hydrophilic tails; Alternative RNA splicing
What is somatic hypermutation?
When a B cell undergoes clonal expansion the clones will accumulate small point mutations in the CDR loops and some mutations will increase the affinity
What is affinity maturation? What enzyme is required?
The process by which the interaction between antibody and epitope improves; Activation-induced cytidine deaminase (AID)
True or False: T cells do not undergo somatic hypermutation?
True
What is the first antibody produced?
IgM
What is the structure or IgM antibodies?
Pentameric– 10 arms total
What is the reason for isotype/class switching? What enzyme is required?
Production of antibodies with different effector functions but same antigen specificity; AID
What is the mechanism of Isotype switching?
Rearrangement of VDJ and C genes
What factors dictate which isotype is needed?
Location and type of infection
What stimulates isotype switching?
T-cell signals
What generates TCR diversity?
Somatic recombination through RAG1 and RAG2- V segment joins to J segment in the alpha chain, and D with J and DJ with V in beta chain
True or False: RAG is required for generation of diversity of both T and B cells?
True
