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cell cooperation for antibody production
cmbm exam III
71
Chemistry
Graduate
01/16/2010

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Term
what is T cell activation? what else is it called? what is it the first step of
Definition
what happens when a naive T cell encounters its specific antigen and is stimulated to differentiate into an effector T cell. this is also called T cell priming and it is the first step in any adaptive immune response.
Term
what needs to happen as soon as infection begins in terms of T cells?
Definition
the one T helper T cell that is specific for that pathogen needs to be found out of about a million different choices.
Term
is the adaptive immune response initiated at the site of infection?
Definition
no, it is initiated in the secondary lymph tissue
Term
what secondary lymph tissue does T cell activation occur for if infection occurs in the skin/periphery, the blood, respiratory mucosa, and GI tract?
Definition
skin/periphery:regional lymph nodes
blood borne antigens: spleen
respiratory mucosa: tonsils/bronchial associated lymph tissue
GI tract: peyer's patches, GALT, appendix
Term
how does antigen get to secondary lymphoid tissue?
Definition
dendritic cells+macrophages act as sentinels for infection in tissue, upon infection, both cells uptake pathogens and can proces and present antigen
Term
what is the range of function of macrophages? how are they exposed to antigen?
Definition
defense+repair of damage tissue. they are resident in tissues and do not migrate. macrophages in lymphoid tissue can process and present antigen that is carried passively in lymph from infected tissue
Term
what is the function of dendritic cells? how do they know where to go?
Definition
only known function is to trigger T cell response, dentritic cells are migratory and carry their antigen load from site of infection to the nearest secondary lymphoid tissue. they get there because activation induces expression of CCR7, which is a receptor for the chemokine CCL21
Term
why do people think rusty nails give you tetanus?
Definition
the rust has nothing to do with anything, other than the fact that rust is usually in places where clostrium tetani is found.
Term
when the dendritic cell brings antigen to the lymph node how to the T cells come to interact with it? how do they enter the lymph node?
Definition
naive T cells are brought to the lymph node through the blood and bind endothelial cells in thin high endothelial venules, (HEV). they squeeze through the vessel wall and enter the cortical region of the lymph node.
Term
once the naive T cell is in the lymph node, what does it do?
Definition
if the naive T cell sees the antigen, it activates, proliferates and differentiates. if it doesn't, it recirculates out.
Term
what 2 processes control the passage of the naive T cell out of the bloodstream and through the HEV to the cortex of a lymph node?
Definition
the T cells' passage is controlled by contacts made by the cell surface interactions between surface molecules on the T cells and those on the endthelium and it is also influenced by chemokines (CCL21 binds to CCr7 chemokine receptor)
Term
in terms of the T cell interacting with the HEV endothelial cells, what important initial interactions occur?
Definition
the T cell L-selectin with the endothelium CD34 and/or the T cell L-selectin with the endothelium GlyCAM-1. (remember, selectins bind to sugars)
Term
after the T cell L-selectin binds to the CD34/GlyCAM-1 of the HEV endothelial cell, what happens?
Definition
the contact is strengthened by the interactions of LFA-1 (integrin) with ICAM-1 and ICAM-2, (members of the Ig superfamily).
Term
where is homing of T cells into draining lymph nodes significantly enhanced? why?
Definition
at sites of acute inflammation. this is probably due to cytokines produced as part of the innate immune response, (IFNs) that inhibit egress via different lymphatics
Term
once LFA-1 on T cells bind to the ICAM-1 on the endothelial cell, what happens?
Definition
the T cell can squeeze through the HEV and into the node
Term
what does the T cell do once it gets into the lymph node?
Definition
looks around using its TCR. first it binds a dendritic cell through LFA-1/ICAM binding and the cells get close enough to see if its receptor ligates with the antigen in the dendritic cells MHC class II.
Term
if the T cell receptor ligates with the antigen in the MHC class II dendritic cell, what happens?
Definition
the T cell sends a signal to LFA-1 saying it must bind very tightly to keep the two together and start the reaction, and the T cell is activated. the CD4 of the T cell also binds to the invariant region of the MHC class II. this is the FIRST SIGNAL OF T CELL ACTIVATION
Term
what are the cells that can present antigen to CD4+ T cells?
Definition
dendritic cells, macrophages, and B cells
Term
what is the first signal involved in T cell activation?
Definition
engagement of the T cell receptor
Term
what is the second signal in T cell activation? what is one reason for this interaction?
Definition
a CD28 receptor on the T cell binds with B7 on the APC dendritic cell. this is done as a checkpoint b/c only APCs have costimulator B7, (expression goes up with an infection)
Term
what happens if the second signal for T cell activation doesn't occur?
Definition
if CD28 doesn't bind to costimulator B7, this leads to inactivation of the T cell, (anergy) or no response...textbooks differ
Term
what happens if the second signal goes through and T cell activation occurs? are there any other receptors involved in this?
Definition
t cell activates, proliferates and differentiates. CD3 and the zeta chain on the T cell are also involved.
Term
what are the 4 interactions in T cell interaction that we need to know?
Definition
ICAM and LFA, CD28 – binds to B7.1/2, CD4 – interacts with an invariant region of MHC 2, and the T cell receptor – interacts with processed peptide antigen presented in the context of MHC 2 (binds a different region than CD4)
Term
what does activation of the helper T cell induce?
Definition
intracellular signaling, (leading to activation of protein kinase C, tyrosine kinases, and GTP binding proteins), and changes in gene expression, (cytokines/growth factors, cytokine receptors, other activation products such as CD40L)
Term
what is CD40L? what does its expression mean about the T cell?
Definition
the most important surface protein involved in CD4+ effector function, it is a ligand that binds receptors expressed on all APCs. once CD40L is expressed, it is no longer in its naive state.
Term
what does binding of CD40L to CD40 do?
Definition
activates the cell bearing the CD40
Term
what does CD40 activation on B cells do?
Definition
promotes proliferation, antibody secretion and clas switching, particularly to IgG -> VERY IMPORTANT. thus CD40 has an important role in regulating humoral immunity
Term
what does CD40 activation on macrophages do?
Definition
helps turn the "clark kent" macrophage into "superman" macrophage, activates them for cytotoxic function, ultimately for killing phagocytized microbes. thus CD40 has an important role in regulating cell mediated immunity
Term
what is hyper IgM syndrome?
Definition
rar primary immunodeficiency disorder, cannot make CD40L. pts can make a lot of IgM but cannot switch to IgG, thus their humor immunity is defective and their cell mediated immunity is partially defective b/c they cannot activate macrophages by T cells.
Term
after CD40 what is the second activation marker on T cells? what kind of factor is this receptor for?
Definition
IL-2 receptor, (IL-2R). IL-2 is an autocrine growth factor, meaning the the cell that made it can respond to it.
Term
how is the expression of IL-2r regulated since IL-2 is not constitutively expressed in complete form by resting T cells.
Definition
it is composed of 3 peptide chains, alpha, beta, gamma, and it shares the gamma chain with IL-7. the alpha chain is not expressed at all in resting T cells, only at a high level in activated T cells. beta/gamma chain are constitutively expressed though beta chain expression goes up 10x with activation. to get the highest affinity for IL-2, all 3 chains must be present, though beta/gamma chains have some affinity. therefore the alpha chain determines the state of off/on in resting/activated cells
Term
what happens when the IL-2r is stimulated either but its own IL-2 or that from others? why does this happen?
Definition
division and proliferation of T cell clones specific for that pathogen
Term
how do T cells differentiate into TH1 or TH2?
Definition
if there is interferon gamma in the system, it is usually accompanied by IL-12, (often related to microbial infection), these 2 growth factors push the T cell to becoming a TH1 cell. if IL-4 interact with the T cell, it pushes it to become TH2
Term
what do TH1 cells do?
Definition
TH1 make interferon gamma. they are important in host defense against intercelluar pathogens, important in inflammation, (particularly chronic inflammation, which they drive - they bring in macrophages)
Term
what is a difference between acute and chronic inflammation in terms of effector cells?
Definition
acute: lots of PMNs
chronic: many mononuclear cells, disproportionately high TH1 level
Term
what do TH2 cells do?
Definition
make IL-4, IL-5, and IL-13. these are important against helminthes, parasitic infections and allergic reactions - cellularly and molecularly these responses are very similar and driven by TH2 cells
Term
what do TH17 cells do?
Definition
make IL-7 and are involved in host defense against some bacteria and some inflammatory disorders
Term
what cytokines are produced by TH1 cells?
Definition
interferon gamma, IL2, TNF, some IL-10
Term
what cytokines are produced by TH2 cells?
Definition
IL-4 (signature cytokine), IL-5, IL-13, and more IL-10 than TH1
Term
what cytokines are produced by both TH1 and TH2 cells? what are these both involved in?
Definition
IL-3, GM-CSF, these are both involved in hematopoiesis
Term
what is the difference between TH1 and TH2 in terms of microbial killing?
Definition
TH1 activate microbial killing because they make CD40L and interferon gamma
Term
what is the role of B cells in the immune response? are they toxic by themselves?
Definition
production of antibodies, which is important for clearance of organisms present in the extracellular space such as free virus, (which replicate inside cells but move from cell to cell), and bacteria. they are not toxic, they merely bind to neutralize of toxin/enzyme or opsonize via IgG, (further promoted by complement, mostly via C3b), and B cells themselves target bacteria for destruction via complement
Term
what do immature cells express? what do naive B cells express?
Definition
immature B cells express only IgM. naive B cells express IgM and IgD.
Term
do B cells need antigen processing? do they need help from other cells?
Definition
b cells do not need an antigen to be processed, but they do need a helper T cells and other stimuli to work with them
Term
what happens when B cells are activated?
Definition
they proliferate and differentiate
Term
what do B cells differentiate into?
Definition
memory, (so next time antigen is seen, faster and bigger response) and plasma cells, (produce antibodies)
Term
what is affinity maturation in the B cell population? how does it happen
Definition
over time affinity for the antigen will increase, because clones that bind will proliferate more
Term
what is a native antigen? can T cells bind them? can B cells bind them?
Definition
a native antigen is an antigen that is not yet processed by an APC to smaller parts, B cells can bind them, but T cells cannot
Term
what happens when a B cell binds a native antigen via a surface antigen?
Definition
it induces intracellular signaling transduction events involving ryrosine kinase and protein kinase C, resulting in Ig gene transcription changes, readying them for secretion
Term
where do B cells interact with antigens? where do they interact with dendritic cells and T cells?
Definition
B cells interact native antigen in the primary follicle while T cells interact with dendritic cells in the cortex, and both the B+T cells move to the area of delineation at the edge of the follicle and bind to each other
Term
what do you see over time in a lymph node in terms of T cell movement?
Definition
T cells move toward the B cells in the primary follicle
Term
once the B cell and T cell are bound, what does the B cell do?
Definition
the B cell has the native antigen bound to it, which is in a complex 3D state. the B cell thus processes it and presents the peptide by MHC class II to the T cell, (CD4+), and by doing so, activates it
Term
once the B cell and T cell are bound, what does the T cell do?
Definition
the T cells CD40L is bound by the B cell's CD40 receptor, and this connection keeps the B cell activated. the T cell, by staying activated makes IL-2 and upregulates IL-2r -> clonal expansion
Term
other than the TCR/MHC and CD40L/CD40 are there other bindings going on inbetween the T cell and B cell?
Definition
CD28 on T cell surface binds to B7, (B7 is costimulatory, this must happen for T cell activation). there is also integrin/CAM interaction
Term
why do lymph nodes get enlarged and sore?
Definition
clonal expansion
Term
what cytokines do T cells give to B cells depending on their TH1/TH2 status?
Definition
TH1 T cells give off IL2
TH2 T cells give off IL4
(TH1 x 2 = IL2, TH2 x2 = IL4, TH type x 2 = the related interleukin)
Term
how does cytokine stimulation by T cell stimulate B cell most Ig class switching? is there anything other stimulation that affects class switching?
Definition
cytokines mandate through a mechanism where the recombinases are going to land. CD40L/CD40 interaction promotes class switching to IgG
Term
once the B cell recombinases are activated by the T cell cytokines, what do they do?
Definition
looping out occurs of DNA (just like B cell differentiation), and a cleavage and a religation of heavy chain constant regions occur -> new Ig class, (variable region has to stay the same)
Term
if there is still DNA downstream can a B cell switch classes again?
Definition
yes, its not uncommon for IL-4 to come come along later and induce a class switch to IgE.
Term
why does it make sense that IL-4 would induce a B cell class switch at some later point to IgE? can this occur directly?
Definition
TH2 gives IL-4 cytokines, and both TH2 and IgE are involved in allergies/parasites. this can occur directly or through an intermediate subclass step like IgG
Term
what characterizes a secondary immune response in terms of time, size of response, starter antigen need, kind of Ig involved?
Definition
secondary responses are faster (1-3 days), (b/c memory cells are primed), have a bigger peak response, higher avg affinity, only need a little bit of antigen to boost a response, and are almost always more IgG, but IgA/E are seen in certain circumstances
Term
what characterizes a secondary immune response in terms of time, size of response, starter antigen need, kind of Ig involved?
Definition
primary immune responses are slower (5-10 days), have a smaller peak response, have a lower avg affinity, need a larger amount of starter antigen, and IgM is made, and as the primary response matures, class switching will occur. (non specific inflammatory inducers seem to be the key here).
Term
how long should it take to mount ant Ig response in a primary infection?
Definition
~5 days
Term
if someone is sick and you see IgG, what do you know?
Definition
it is a secondary infection
Term
if someone is sick and you see IgM, what do you know?
Definition
it is a primary infection
Term
if it is 2 weeks after an infection and you see IgM and IgG, what does that tell you?
Definition
you can't know if it was a primary or secondary infection at this point – the further out you go in a primary response, the more likely it is that you have class switched.
Term
what are T independent antigens? what are 2 ways antigens can be T independent?
Definition
antigens you can make an antibody response to w/out T cell help either because because the antigen has repeating subunits, (usually polysaccharides, cause extensive BCR cross-linking), or the antigen can directly stimulate B cell @ high conc.
Term
what are examples of T independent antigens that have repeating subunits and thus cause extensive cross-linking?
Definition
pneumococcal polysaccharide, salmonella flagellin
Term
what is an example a of T independent antigen that can directly stimulate B cells at high conc? where do they bind?
Definition
bacterial lipopolysaccharide. they bind to B cell via surface markers other than surface Ig
Term
what kinds of antigens are polysaccharides most of the time? can they be made T-dependent?
Definition
T independent, they can be made T dependent if conjugated to a protein.
Term
do T-independent antigens cause B cell proliferation and IgM secretion? is there class switching?
Definition
T-independent antigens can cause B cell proliferation and IgM secretion, but there is no class switching b/c of lack of T cell help
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