Exam #2 Flashcards
In somatic hypermutation, a B cell that has been activated to proliferate what chemically changes DNA bases to another base, resulting in a new codon?
Enzyme: activation induced cytidine deaminase
What helps this occur and where does somatic hypermutation occur?
T cell help, germinal centers
Define affinity maturation and what happens if this isn’t met.
This is when somotic hypermutation provides better binding of the antibody pocket to the antigen. These B cells are selected for. If this doesnt occur and binding ability is decreased, these B cells die via apoptosis.
The enzyme in somatic hypermutation converts cytidine residues to what?
Deaminates cytosines and what in what two regions of an antibody gene?
Uridine, which is recognized as a thymidine.
adenosines, VDJ and VJ
Affinity maturation only occurs if ????
as a response to antigen stimulation. Multiple rounds of mutation/apoptosis can occur.
On the other hand, the affinity maturation can occur via a different process called what??
This occurs in what species?
Gene conversion
Pigs, cattle, rabbits, horses and chickens. (humans and mice are hypermutation exclusive)
Chickens/birds use gene conversion when? But hypermutation when? Where does gene conversion occur in birds? Ruminants?
During B cell differentiation. During an immune response. Bursa. Ileal Peyer’s patches
In species with gene conversion, there is very little diversity within what? Therefore, what happens in gene conversion? Does T cell stimulation cause this?
V, D, and J gene segments. Short sequences within the exon are replaced by V gene segments from pseudogenes. No!! Unlike somatic hypermutation, this does NOT NEED T cell stimulation.
When a mature B cell traffics to peripheral tissues (including 2ndary lymphoid organs), encounter with its antigen and T cell help (cytokines), the B cell converts to a?
Plasma cell
After encountering antigen and converting to plasma cells, B cells will also go through somatic hypermutation, affinity maturation and isotype switching. After these occur, the B cells that survive will differentiate into 1 of 2 things. Name the 2.
Memory B cells and plasma cells
Remember that somatic hypermutation and gene conversion just changes the what inside of antigen binding pockets?
Amino acids
In comparison to somatic hypermutation, isotype switching causes a change to what in the antibody. Does this change it’s antigen specificity?
The heavy chain region. NO
After stimulation by cytokines, isotype switching occurs how? How is switch back prevented? Does specificity change? Are light chains changed?
The somatic DNA is rearranged ONLY IN THE HEAVY CHAIN REGION. No switch back because the DNA loops out and is lost. Specificity is NOT changed. Light chains are NOT changed.
IgM is the first antibody produced during a primary response. Can be bound on surface or secreted as a pentamer. Plasma cells in what 3 tissues secrete IgM. What function is IgM good at?
Spleen, bone marrow, lymph nodes. Activating complement, (neutralization and opsonization less.)
Isotypes switch to which antibodies?
IgG, IgE, IgA
IgG is secreted by plasma cells in which 3 tissues. What 4 functions are IgG very good at? IgG is often transported across what 2 things?
spleen, lymph nodes, bone marrow. Neutralization, opsonization, sensitization for killing by NK cells and activating complement cascade. Transport across placenta and into extravascular sites.
IgE Fc portion binds to receptors on what 2 cells? Main function?
Mast and basophils. Sensitization of mast cells
IgA is secreted by plasma cells where? Main function? Good at transport across 2 things.
Tissues near body surfaces. Neutralization (a little opsonization). Transport across epithelium and into extravascular sites.
Some immune cells express receptors that recognize the Fc region of an antibody. Interaction between them cause activation of that cell. Which antibodies have receptors and what cells do those antibodies activate?
IgG=phagocytes like macrophages, neutrophils, eosinophils, Nk cells, mast cells. IgE=mast cells and eosinophils IgA (a little)
After the first encounter with an antigen, there is a gradual rise in antibody after a lag phase of how many days? THe second encounter is much stronger due to blank blank. Isotype switches from what to what?
3-7 days. Immunological memory. IgM to IgG.
Does memory involved B or T cells specific for an antigen?
BOTH
Where are memory cells stored? B cells have much larger response in 2nd responses.
Secondary lymphoid tissues. B cells primarily in bone marrow.
Is somatic hypermutation higher at the first or 2nd response?
2nd!!
What are the 3 P’s of MHC and define each.
Polygenic-several genes exist for a given MHC class. Polymorphic-a large umber of alleles exist for a given gene. Promiscuous-will bind a range of similar epitopes.
What is special about the peptide binding cleft of the MHC that makes it able to present almost every possible antigen?
HIGH rate of mutation (many alleles)
Define MHC restriction
T cells will not recognize a MHC allele or an epitope that it is not educated in. Change the MHC allele or epitope and no recognition will occur.
Epitopes are also known as blank blank
antigenic determinant
What are the 3 APCs. What degrades endogenous antigens? Exogenous?
Dendritic cells, macrophages, B cells. Endogenous=proteosomes. Exo=phagolysosomes
Cytosolic pathogens degraded in the cytosol will have peptides bound to what MHC class? Presented to what? Effect on presenting cell? If Exogenous antigen is presented by a dendritic cell in the cytosol, MHC class? Presented to? What happens?
1, Effector CD8 T cells, Cell death.
1, Naive CD8 T cells, dendritic cell ACTIVATES the CD8 T cell.
On the other hand, intravesicular pathogens in an endocytic vesicle in WHAT CELL binds to MHC class what? Presented to? Effect? Extracellular pathogens and toxins in endocytic vesicles IN WHAT CELL bind to MHC class? Presented to? Effect?
macrophages. MHC Class 2, Effector CD4 T cells, Activation to kill intravesicular bacteria and parasites. B Cells, MHC 2, Effector CD4 T cells, activation of B cells to secrete Ig to eliminate extacellular bacteria and toxins.
In the MHC class 1 pathway, endogenous proteins are broken down into peptides via what (2 types)? Name the transporter that allows peptides into the ER. If the peptides find an MHC class 1-calnexin that fits, what happens?
proteosomes (20s and immunoproteosome), TAP protein transporter. It blebs outs of the ER, moves to the golgi and finally to the cell surface=presentation.
The MHC Class 1 is bound to 2 things in the ER. Name them. What happens to these when the peptide binds?
Calnexin protein and beta2 microglobulin. Calnexin is released and the MHC changes conformation before being exported.
Exogenous antigen presentation is blank and blank dependent. Uses what 3 proff APC phagocytes? Connect innate to humoral immunity. This uses the MHC class 2 pathway
time and energy. b cells, dendritic cells, macrophages.
In the MHC Class 2 pathway (exogenous), the antigen binds (non specific receptor mediated) and is brought in by 3 ways. An endosome (or phagosome is formed). What happens to activate proteases? This fuses with blank which contains 2 things. Thus, MHC class 2 now associates with the process antigen. This phagolysosome fuses with the PM and interacts with what kind of T cell?
endocytosis, pinocytosis, phagocytosis, pH decreases to activate the proteases. Lysosome containing more proteolytic enzymes and the MHC class 2 molecules. CD4+ T cells.
Many phagocytes have receptors. Many recognize opsonins like 3!! Without receptors, can still phag. just not as efficient.
Antibodies, complement and acute phase proteins.
How are T cells activated and where does this occur?
by complexing with MHC and occurs in secondary lymphoid organs
Macrophages (myeloid progenitor) are highly phagocytic, highly secretory- can regulate immunocytes, mediate killing of pathogens and stimulate tissure repair. highly activational-respond to changes quickly, like BLANK on bacteria. And highly polymorphic-what does this mean?
LPS, different in different tissues (monocytes, microglia, kupffer, mesangial, langerhans, etc.)
B cells have what on their surface that bind epitopes of antigens. The complex is internalized and processed. Processed peptide complexes with MHC class what–> onto cell surface and interacts with what T cell.
Ig. MHC class 2, CD4+
Which APC stimulates naive T cells the hardest?
Dendritic cells
Dendritic cells are found primarily where, but in low numbers in 3 places. Called what in T cell areas and what in B cell areas. Present with MHC class what?
Lymphoid tissues, skin/spleen/blood, interdigitating cells and follicular cells. MHC class 2
After taking up antigen, dendritic cells become more or less phagocytic as they migrate to what organs? Movement of the dendritic cells is regulated by what?
less towards lymph nodes. Chemokines
Dendritic cells take up immune complexes and shed them in exosomes AKA what? to be taken up and processed by what cells?
iccosomes. B cells.
Even though dendritic cells usually have MHC Class 2 molecules, can use the process of blank blank to present MHC class 1 even with originally exogenous antigens. Same antigens, both pathways!!
cross-presentation
When APCs activate T cells, binding isnt enough. Must 2 other things
cytokines and ligand-receptor engagments
Undifferentiated T helper cells differentiate into different types depending on the BLANK encountered. Name the 4 we must know the the cytokines encountered
cytokine TGF-beta=T reg, IL-12, IFN-gamma=Th1, IL4=TH2, IL-23, TGF-beta, IL6=Th17
What cells does each Thelper cell activate?
Treg (immune suppression=monocytes and T cells), Th1 (systemic immunity)=macrophages, Th2 (barrier immunity)=B cells, Th17 (acute inflamm)=neutrophils
Some of the cytokines from Thelper cells will actually have negative feedback on other T helper cell types in order to increase the pathway towards one kind of T helper. One ex?
IL4 on Th 17
Name the 2 forms of T cell mediated immunity in the cell mediated arm and 2 in the humoral immunity arm. Name what the action of these T cells are.
Cell Mediated/Innate- 1.) cytotoxic T cells due to Class 1 on infected cells. This causes cytolysis. 2.) T helper 1 due to class 2 on infected cells. Causes macrophage activation due to release of things like IFN-gamma. Humoral-Th2 due to class 2 on B cells. B cell activation–> antibodies. 2.) Th17 activated neutrophils for phagocytosis.
T Cell receptors are associated with either blank or blank type of cell. Not both
Cd4, cd8
T cell receptor diversity via what process? Heterodimer receptor is one of 2 types of chains? The TCR complex is associated with what=multi subunit complex that is not variable or antigen specific, but ysed for signal transduction.
somatic recombination of germline DNA, alpha/beta or gamma/delta, CD3
T cell receptor looks a lot like antibody Fab region. Has 3 regions to it
Variable, constant and hinge.
T cell receptor diversity is achieved by a lot of the same steps as antibody diversity. V,D,J regions as well as allelic exclusion, splice sites, insert bases, etc. All of these things things occur where?
Thymus
What has more variable regions to choose from? The alpha or beta chains of the TCR?
Alpha
Of the TCR, which segment is made of V, D, J and which only VJ. Rearrangement can occur multiple times if results are nonfunctional.
beta, alpha
In comparison to antibodies, TCRs do not go through 2 more processes to increase variability.
Somatic hypermutation and isotype switching.
TCR rearranges, self reactive T cells are removed and Ts become Cd4 or Cd8 where? In the presence of?
Thymus, antigen. NOT antigen specific.
T cells are double positive at first in the thymus. What does this mean and what happens?
Both Cd4 and cd8. Which one matures depends on if antigens presented are class 1 or 2.
Immature double negative thymocytes get into thymus via? and start where in the thymus? Move to where as they become double positive and finally to the where when they are mature whats? Enter the bloodstream via what vessels?
HEVs. Subcapsular region of the cortex, deeper in the cortex, medulla as single positives. High endothelial venules or lymph
Define positive selection of thymocytes and negative selection. CD3 is just another protein associated with TCR.
Positive is when the double positive thymocyte recognizes either MHC1 or 2 and receives maturation and survival signals to become Cd8 or 4. Negative is when the thymocytes bind both or none–> apoptosis.
Rearrangement of TCR in thymus is complicated. Do most do it successfully?
No. many die within thymus
After leaving the thymus, T cells end up where? If that t cell encounters their antigen, cytokines and ligand receptor interactions, what happens!
2ndary lymphoid tissues. Activated. Start replicating itself and mature into effector cells as Th or Tc cells.
If a T cell does not encounter antigen OR activated/proliferated T cells go where after lymphoid tissues?
Leave via lymphatics and circulate to other lymphoid organs.
Many activated T cells go where in the end to be apoptosed?
LIver
Remember: which Th activated phags/innate. B cells/humoral. and Neutrophils
1, 2, 17
