What is somatic recombination, when does it take place and where does it take place?
somatic cells in bone marrow while the b cell is maturing
What genes need to have somatic recombination take place to make a functional gene?
B and T cells
Why is the first time you encounter a pathogen the most risky? Think about the processes and the amount of time it takes to get those processes going.
Because at this point you haven't built up any specific immunity and there is a 7-14 day lag time between infection on the initiation of the adaptive immunity
Membrane Ig's and the BCR, are they the same thing?
BCR and antibodies, what is the difference between the two?
Antibodies are secreted by plasma cells and BCRs are the membrane bound immunoglobulins of the B cells
Do they have the same binding sites? If one is membrane bound and the other is secreted, how and when is that done?
Difference between membrane bound and secreted antibody lies in the carboxyl terminus of the heavy chain during somatic recombination
5. Are B and T cell receptor genes rearrange by the same mechanism?
No, The B cell rearrangement occur at the heavy and light chains, rearrangement of gene segments. T cell are rearranged DNA segments of the alpha and beta strands
If you looked at mature t cells TCR genes, would the nucleotide sequence be the same as that of neutrophils, TCR genes? Would a B cell receptor gene be configured the same as in a neutrophil when looking at the b cell receptor gene?
In all cells its going to be germ line sequence but in mature t cells and B cells its will have gone through rearrangement
What is the major difference between TCR's and BCR's? Does one need antigen presented to it?
TCRs need the antigen presented to it by dendritic cells and by MHC I. Each BCR will have a different AA sequence in its variable region and TCRs recognize degraded peptides
Look at the different epitopes (linear vs continuous)
Epitopes can be linear or discontinuous when different parts of the antigen are folded together
Mechanism by which adaptive immune responses derive only from individual antigen specific lymphocytes stimulated by the antigen to proliferate and differentiate into effector cells
Proliferation of the particular lymphocytes that have been bound to their specific antigen
Where do the dendritic cells meet the antigen, where do they go after picking up antigen and what do they do with it? (What is their number one job)
They meet at the site of infection and carry the pathogen to secondary lymph tissue (pyer's patch, white pulp of spleen, and lymph nodes) Their number one job is to present the antigen to the T cell. Dendritic cells also degrade pathogen by protease into antigenic peptides that the TCRs can recognize.
What are the lymphocytes?
T cells, B Cells, NK cells
Know which MCH molecules present to CD8 t cells and which ones present to CD4 t cells. What are the other names associated with CD8 and CD4 t cells?
CD8 (cytotoxic cell) MHC I CD4 (helper) MHC II
What is taking place in positive selection and what is taking place in negative selection?
Takes place in the thymus why the T cell is maturing
Which lymphocyte undergoes positive and negative selection or do both go through both slections?
Only T cells go through both and negative selection to become mature T cells, about 1 %
Selects thymocytes bearing antigen receptors that work effectively with MHC I and II and signals them to survive and divide
Selects T cells bearing receptors that bind too strongly to self MHC complexes that are likely capable of attacking healthy cells expressing these proteins and signals them to die by apoptosis
Primary vs secondary immune responses, which use memory cells?
What are two of the things that antibodies do to help our immune system during an infection? What is the goal of vaccination?
Through neutralization of viruses in the extracellular space stopping replication and opsonization by coating pathogen with Ig's and activating the classical complement pathway to coat the pathogen with Cd3. Goals of vaccination is to establish a primary response against that antigen and neutralization. It is essential to incorporate protein sequence in a vaccine that will stimulate a strong response by CD4 to the appropriate B cell
What is the first antibody isotype put on the surface of a niave, mature b cell and which isotype is first secreted?
Affinity of the antigen binding site of an antibody gets better over the course of an infection by introduction of mutations to the variable region by which mechanism?
: (class switch recombination) Changes the isotype of the immunoglobulin but not the antigen binding site, acts in activated B cells
What do CD4 t cells do? (helper)
i. Effector T cells of the adaptive immunity ii. Secretes several types of cytokines iii. All four types of pathogens can effect extracellular spaces iv. In the tissue is where helper cells interact with macrophage that have engulfed the pathogen making them more effect at killing the pathogen v. Helper cells that do not leave the secondary lymph tissue stay and stimulate the B cells to become plasma cells and secrete antibodies vi. Enhance phagocytosis of macrophages and neutrophils
What do CD8 t cells do? (cytotoxic)
i. Kill the infected cell by recognizing the pathogen-derived peptide presented by the MHC I ii. Activation in secondary lymph tissue of niave CD8 cells by dendritic iii. Mature CD8 cells kills the pathogen in the peripheral tissue
What are the five isotypes of antibodies?
IgA IgG IgM IgD IgE
What is the name of the cell that secrete antibody?
Which MHC molecule presents peptide from intracellular origins and which presents peptides from the extracellular origins?
Intracellular= MHC I Extracellular = MHC II
What does the germline configuration of the Ig variable region genes look like in all cells except mature B cells?
In a fragmented form that cannot be expressed. Inherited through the germinal cells so the configuration is the same as it would be expressed in the germ cell. Matuere B cells have gone through somatic recombination and no longer contain all of the orgininal chromosomal DNA sequence.
What gene segments need to come together to make a functional gene ( for the variable region) in b cells for heavy and light chains?
Heavy chain is V D J Light chain is V and J and kappa and lambda
What are the different isotypes of heavy and light chains?
Heavy: All other greek letters beside kappa and lambda Light: kappa and lambda
Which chains isotype confers the antibodies isotype, heavy or light?
Contains two other polypeptide chains: 1) Secretory component is involved in the transepithelia transport of exocrine IgA and stabilizes IgA against proteolytic degradation. 2) Two four chain units composing secretory IgA are held together by the J-chain through the disulfide bridges - First line of defense against microbes entering through the mucosal surfaces -Forms monomers and dimmers -Highest concentration in body
First antibody produced by B cells. - High avidity -Forms pentamers -Antigen receptor of niave B cells -First antibody secreted by clone B cell
Low quantities in the circulaton -Functions primarily as an antigen receptor on B cells -Always a monomer
Very low levels present in serum -Plays roles in inflammation and worm infection -binds to mast cells -Always a monomer
Four different subclasses arising from slight differences in the Heavy chains. -Only Immunoglobulin to cross the placenta. - Found in both vascular and extravascular spaces. -Most abundant Ig in the blood -Always a monomer -Highest concentration in blood -Low affinity -Bacertium coated in IgG are more effectively phagocytized
What do the constant domains do for the Ig's? Do they bind to the antigen?
Make up the C region. C regions are not rearranged during somatic recombination of Igs. No, Fab arms bind to the antigen and the FC portion binds to other immune molecules
Which gene segments provide diversity to CDR1 and 2? Where do the diversity for the CDR3 come from?
From the different amino acid arrangements of Ig molecules. The diversity in Light: determined by the junction between the V and J segments. Heavy: By the D segments and the junctions they make with V and J gene segments
RAG1 and RAG2
only made in lymphocytes. First step in gene rearrangement is the binding of the RAG complex to the RSS
Reccombination sequence signals, ensures that the DNA molecules are brought together in the right order flaking the germ line
12/23 or 1turn-2turn rule
Ensures that the gene segments are joined in the correct order
TDT (terminal deoxynucleotidyl transferase)
an enzyme that randomly inserts N nucleotides into the junctions b/w gene segments
rearrangement of Ig genes resulting in various antibodies in which some have higher affinity
Where does somatic hypermutation take place?
The rearranged V regions of both heavy and light chain genes
When does somatic hypermutation take place?
Which cells does somatic hypermutation affect?
In somatic hypermutation, is there a specific area that is mutated more than other areas?
IN the Hv and CDR
B cells switch from producing one isotype to another
Where are switch regions located?
The V region
What do switch regions allow to happen?
Different effector functions from different isotypes
How do switch regions switch?
Recombination with a cluster of c genes, excising the previous C gene and joining a new c gene with a previously assembled V region
Which cells does switch regions happen in and when does it happen
B cells that are proliferating in response to an antigen
What benefit does switch region provide?
Changes to an Ig with more affinity and binds more strongly to the antigen
For switch regions, What can the antibody isotype be switched to and which isotypes can it not be switched to?
It cant be switched to D because it doesn't contain a switch region IgM/D to A E G
Affinity maturation , what is it and what does this result in?
Though somatic hypermutation the mutant cells will have higher affinity and this better binding sites and these B cells will be selectively matured into antibody secreting cells
Somatic recombination, V gene reassembly from gene fragments, junction diversity, assembly of transcriptional controlling elements, Somatic hypermutation, isotype switch