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225 Cards in this Set

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  • Back
what causes bare lymphocyte syndrome? what are the symptoms?
it's caused by a defect in CIITA and RFX. defects in these transactivators leads to a lack of MHC II. No Th is activated and severe immunodeficiency results.
how do cytokines regulate MHC expression?
IFN alpha and beta can increase class I expression.

IFN gamma (made by Th1) can increase class II expression on macrophages. (while decreasing class II on B cells)
IL-4 (made by Th2)can increase class II on B cells
how do viruses affect MHC expression?

cancer cells?
viruses decrease MHC expression.

cancer cells decrease MHC expression.
what is the determinant selection theory?
an individual's MHC must bind to a particular antigenic peptide to activate T cells.
what is the 'holes-in-the-repertoire' theory?
absence of the correct TCR to bind the Ag (even with appropriate MHC present).
what is the association between disease and MHC expression?
some haplotypes may be disease associated. inbreeding reduces diversity and therefore increases disease susceptibility.
how is Ig gene processing similar to other genes? how is it different?
as in other eukaryotes, the Ig undergoes mRNA processing, introns are removed, 5' cap and 3' poly A tail are added.

Ig genes have differential RNA processing of H chains. this determines whether the protein will be membrane bound or secreted.(IgM and IgD)
where is the secreted Ig assembled? how does it get secreted?
the protein is assembled along the RER. h/l chains assemble in the ER. the Ig travels in vesicles to the golgi (where you have glycosylation of the h chain). the vesicle leaves the golgi and fuses with the membrane, Ig is secreted.
where is the membrane bound Ig assembled? how is it fused into the membrane?
the protein is assembled along the RER, h/l chains assembled in the ER. Ig travels in vesicles to the golgi, its then anchored to vesicle membrane. (h chain is glycosylated) vesicle fuses with plasma membrane. Ig is bound.
what is unique about IgM and IgD expression? How is one selected?
mature (naive)B cells express both IgM & IgD on its surface. it's primary transcript contains both sequences (on heavy chain constant regions). the mRNA is processed to remove one or the other.
What happens to the Bcell when it binds its antigen?
it can develop into a plasma cell OR a memory cell.

plasma will secrete and then die within days.

memory cell will usually class switch depending on cytokines.
what happens to the memory cell upon second infection?
via class-switching, the B cell can turn into a plasma cell secreting another Ig isotype.

somatic hypermutation will also occur within the CDR regions.
where does class switching occur?

what is it controlled by?
it occurs in the constant region of the H chain.

it is controlled by cytokines: 'switch factors' mostly produced by Th cells
which cytokines cause proliferation?
which cytokines cause differentiation?
differentiation via IL-4 can cause production of which Ig? why is this important?
IgE or IgG1 can be stimulated. IgE is the source of allergic rxns.
how is class switching physically accomplished? in which direction are 'switchable' sequences found?
the DNA of one class is looped and cut out via enzymatic activity. the newly expressed class sequences (isotypes) are only found DOWNstream of original.
Which Ig is needed in secretory areas? to cross the placenta? against multicellular pathogens?
what cells produce the cytokines which induce the class-switching?
Th1 and Th2
how do Ab-Ag interact?
Ag presents protuberance (epitope) which fits into the depression (binding cleft) of the Ab.
what are the non-covalent binding forces between Ag-Ab?
ionic: via charges
hydrophobic: leu, ile & val interact to keep water out.
hydrogen: unequal e- sharing
van der waal (weakest): e- clouds make dipoles
define affinity:
the combined strength of non-covalent interactions between a SINGLE Ag binding site on an Ab with a SINGLE epitope.
define avidity:
sum of interactions between combined sites of Ab and all epitopes of Ag. (not simple sum)
how does affinity affect cross-reactivity?
Ab may bind Ag with v.similar epitope, but it usually has less affinity for it - there may be no biological activity even.
what type of Ab are more effective due to lower incidence of cross-reactivity? why?
monoclonal Ab have less chance of cross reactivity since they only have one epitope specificity.
what is the biological significance of cross-reactivity?
glycoproteins are expressed on RBCs. there are subtle differences in the terminal sugar residues to determine 'type'.
We carry Abs against non-self type stimulated by GI bacteria. these Abs have been created by cross-reactions with a microbial antigen.
how are monoclonal antibodies generated? why would you need to generate them?
fuse Ag specific b cell with myeloma to yield a hybridoma that could grow in vitro and secrete the Ab from the B cell.

Ag specific plasma cells only live for a few days, and rarely survive outside the body.
what types of Ags can generated mAbs act against?
many other non-immunogenic proteins
what is needed to create a precipitation?
what is created?
at least a bivalent Ab is needed, along with multiple epitopes on the Ag. ppt rxns occur best with polyclonal Abs.

a large lattice is formed from the Ab-Ag binding. it leads to increased turbidity and eventually, ppt.
what is the Equivalence Zone?
The graphic range at which most precipitation occurs - indicating that the concentrations of Ab & Ag are correct for that pair.
what is Neutralization ability?
Ab binds to epitopes of infectious Ag, preventing it from attaching to host cell receptors.
How is neutralization related to HIV infection?
Pt has a vigorous immune response against HIV, but the Ab produced are NON-neutralizing and do NOT stop HIV from binding to CD4+ T-cells
What is radial immunodiffusion (RID)?
What are two of the methods?
it's a ppt rxn in a gel to check for the presence of specific Abs to an antigen. the tested presence can be compared to known, relative concentrations.

there is the mancini method and the ouchterlony method.
what is the difference between the mancini and the ouchterlony method?
the mancini method tests one variable, while the ouchterlony method tests numerous variables.
what does the ppt signify in RID tests?
the ppt ring of the mancini test and the lines of ppt of the ouchterlony test indicate the zone of equivalence.
what does circumference of ppt ring in the mancini test indicate?
The diameter of the precipitin ring is proportional to the concentration of the antibody (or antigen) present in the test sample. By comparing the diameter of the test specimen precipitin ring to known standards, a relative estimation of the concentration of specific antibody or antigen can be achieved.
what are agglutination assays used for?
cell bound Ags (surface, soluble)
describe hemagglutination.
agglutination test specific for erythrocytes. Ab bind to the carbs on RBCs and cause clumping. cells do NOT form 'button'. can be used to check relative concentration of Ab (if Ab binds RBC).
what is the titer of Ab?
the last dilution to cause clumping.
if a patient has had exposure to a virus, what will the agglutination results be using the viral Ag?
clumping WILL occur. The pt already has Ab against the virus.
what is another example of an agglutination test? what are these tests used for?
latex beads can be coated with Ab/Ag or immobilized onto cards. samples are incubated, then look for clumping.

test for pregnancy, drugs, autoimmune dz (rheumatoid arthritis and SLE)
What does the direct coombs test check for? how does it work and how are the results interpreted?
Rh incompatibility. add anti-human IgG to babies RBC. +(clumping), baby has hemolytic dz b/c mother's anti-Rh Ab is bound to the babies RBC.
how does the indirect coombs test work?
add the mother's serum to Rh+ RBCs, then anti-human IgG and check for clumping. this tests the mother's serum for anti-Rh Abs.
what is immunoelectrophoresis (IEF)?
a method of determining the blood levels of three major immunoglobulins, IgG, IgM and IgA. it combines separation of antigens by electrophoresis with immunodiffusion against an antiserum.
what indicates a positive IEF test?
a zone of equivalence tells if the patient has the Ab in serum.
what can IEF be used for?
patient serum for a specific Ab can be compared to NHS (normal human serum) to determine whether a patient is producing normal amts of said Ab.
how is immunoblotting performed? (aka western blotting)
1.electrophoresis of pr (Ag) of interest.
2.transfer to nitrocellulose
3.incubate nitrocellulose with Ab
4.add enzyme-linked Ab(secondary)which will bind first Ab
5.add substrate to view bands
when is immunoblotting used instead of IEF? what is the difference?
when the concentrations of Ag are too low. the catalytic enzyme will color the Ab, amplifying it's signal.
how is the western blot used for HIV detection?
1st, lyse HIV with detergent.
2nd, run on gel & t-fer to nitrocellulose.
3rd, add pt samples (potential anti-HIV Abs) to nitrocellulose.
4th, detect patient antibodies by adding enzyme-linked anti-human Ig.
how often must one be tested to ensure a negative HIV test?
twice: first after initial exposure, then 6 months later to give the immune system time to synthesize Abs.
what does ELISA stand for?
enzyme-linked immunosorbent assay
how does the ELISA test work?
A sensitive immunoassay that uses an enzyme linked to an antibody or antigen as a marker for the detection of a specific protein, especially an antigen or antibody.
when is the ELISA test useful? what does it detect?
it is useful when the Ag is in low concentration. It detects serum proteins (ex.cytokines)
how does an indirect ELISA work? A sandwich ELISA?
indirect is used for quantification of Ab levels specific for an Ag.
The sandwich ELISA requires two antibodies that bind to epitopes that do not overlap on the antigen. It quantifies Ag levels.
how does an immunoflourescence test work?
a flourochrome is attached to Ab, this is added to sample with Ag in question. the sample (cells/tissue) is visualized via microscope or FACS.
what is the immunoflourescence test used for? give a specific example.
it can quantify the number of Ag positive cells. ex: CD4 levels in HIV+ patients (CD4 decrease).
it can also be used to isolate/purify cells of interest (research).
what is a flourocytometer?
it excites the flourochrome which attaches to the Ab.
what is a radioimmunoassay? what is it useful for?
it uses radiolabelled Ab to detect Ag (similar to ELISA). it's good for detecting v.low concentrations of Ag.
what is the ELISPOT assay used for?
it detects cells which produce a specific substance (ie cytokines)
how does the immunoelectron microscopy test work?
an Ab is conjugated to a metal to detect the density/location of Ag.
Describe the Antibody microarray and it's purpose.
hundreds of mAbs (multi-specific) are coated onto a plate. Ag in question is added, and post-incubation the presence of bound Abs are detected.
what are the two phases of B-cell development?
Ag-independent and dependent phase.
where does the Ag-independent phase take place? what occurs during this phase?
it occurs in the bone marrow (fetal liver/spleen). Ig gene rearrangement occurs. (making the B cell Ag specific)
what occurs during the Ag-dependent phase?
2.differentiation into either memory or plasma cell
3.class switching.
what happens to the majority of B cells?
90% never encounter their Ag and die without ever being activated.
what is 'clonal deletion'?
the process by which self-reactive cells apoptose.
define 'affinity maturation'.
The higher the affinity of a B-cell for pathogens present, the more likely it is that the B-cell will clone. the highest affinity B-cells are the "fittest" and hence replicating the most. those that replicate the most undergo Ig gene rearrangement the most. the greatest amount of hypermutation provides the most opportunity for pathogen recognition.
what are the early stages of B-cell development?
1.stem cell cell
3.pre-B cell
4.immature B-cell
5.mature B-cell
what does the stem cell combine with to create the B-cell?
cytokines (growth factors)
when does IgH chain rearrangement occur? interaction with BM stromal cells?
D-J occurs during early pro-B. V+ D-J is during LATE pro-
B. this is when interaction with BM stromal cells occurs.
what is present during the pro-B stage?
1.CD45R is present as a surface marker of the B-cell.
2. RAG1/2
3.Ig alpha and beta
which cytokine is associated with pre-B cell? what produces this cytokine?
IL-7, produced by stromal cells
which chain needs gene rearrangement in the pre-B cell stage? which chain has already been rearranged?
the light chain needs to be rearranged. the m-H chain was rearranged during pro-B cell stage.
how is the light chain rearrangement began?
A surrogate Lc joins the Hc and moves to the cell surface. this signals for rearrangement.
what is the surrogate Lc shorthand?
what components are present for Lc rearrangement?
1.pre-B cell
****NO Tdt (only for Hc)****
what is the Ig status of the large pre-B cell?
1.m Hc
2.surrogate Lc
3.pre-B cell receptor on surface
what is the Ig status of the SMALL pre-B cell?
m chain in ER
which Ig is expressed on the immature B-cell? What is different about the immature B-cell vs pre-B cell?
IgM is expressed. The immature B-cell is Ag specific.
what are the final stages of immature B-cell?
receptor editing 'rescue' self-reactive B-cells. the B-cell can rearrange the remaining V region genes.
IgM and IgD are co-expressed. finally, the B-cell leaves the BM.
how is the initiation of the Ag-dependent phase determined?
when the B-cell leaves the bone marrow.
what are Ig alpha/beta?
signaling molecules adjacent to Ig.
what happens if the IgH and IgL bind?
the B-cell will rearrange the Lc V region genes.
why are Lc rearranged if B-cell is found to be self-reactive?
the Lc only joins together the V-J genes.
self-reactive cells in the periphery should become ____ if Lc rearrangement is succesful.
anergic (non-responsive)
how is Hc rearrangment concluded? what is the consequence of this conclusion? what is this called?
When IgH associates with the surrogate Lc and binds the stromal cell marker, IgH stops and Lc rearrangement BEGINS. the other Hc allele cannot be rearranged. this is ALLELIC EXCLUSION.
how is B-cell diversity increased?
B-cell proliferates, yielding 32-64 progeny all with IgH arranged. Each one can rearrange it's Lc differently, giving 32-64 antigenic specificities.
how do interactions with the BM stromal cells affect B-cell maturation? give examples.
various receptor-ligand interactions control the sequential process.
adhesion molecules: VLA-4/VCAM-1
cytokines/GF: IL-7
what is c-myc? it's location where causes what dz?
a chromosome fragment and a 'cell-cycle regulatory' gene.
next to an Ig enhancer, it can cause Burkitt's lymphoma
name three regions associated with Ig genes and their general function.
promoters, enhancers and silencers. they control expression of the Ig genes (within B-cells)
how is cancer caused in B-cells? give an example.
the movement of cell-cycle regulatory gene next to an Ig promoter/enhancer causes over-expression of that gene (cancer).
ex: c-myc translocated next to IgH or IgL enhancer = Burkitt's lymphoma
how does a thymus dependent Ag work? what types of B-cells are produced in this rxn?
the T cell recognizes the Ag and makes cytokines which mark the Ag, making it more susceptible to B-cell recognition via it's epitope. memory cells are produced.
what are the differences between thymus independent Ag #1 and #2?
#1: NOT Ag specific. B-cell interacts with bacterial cell wall components (ie LPS)

#2: Ag specific (crosslinking of mIg with polyvalent Ag). B-cell interacts with repetitious cell wall component(ie polysacch, flagellin)
describe Signal #1 activation. list it's requirements.
Ab binds to Ag via crosslinking of mIg (therefore single epitope Ags are not effective). the binding causes a conformational change in Ig-alpha & beta which sends signals to the nucleus.
what makes up the BCR signaling complex?
mIG + Ig-alpha and beta.
how does signal #2 work? what can serve as a 2nd signal?
signal molecule CD40 (on B-cells) interacts with CD40L found on T-cells. T-cell cytokines can act as a second signal.
which Igs does T-cell cytokine IL-4 inhibit?
which are induced by IL-4?
what indicates an 'unusual' B-cell? what are they called and why?
CD5 markers indicate 'unusual'. they are called B1 cells b/c they develop before B2 (normal).
what makes B1 cells faster developers?
during gene rearrangement they only select the V regions closest to the D regions. this leads to lesser diversity.
where are B1 cells most commonly found?
pleural and peritoneal cavities.
what is the reactivity of B1 cells in comparison to B2s? what do they typically react with?
They often have a low affinity and high rate of cross-reactivity (polyspecific).
polysaccharide Ags on bacteria.
when are B1 cells first produced? What isotype do they secrete the most? Do they undergo class-switching? why or why not?
during fetal development
no, b/c they receive no T-cell help.
B1 cells can self-renew. what affect does this have on repetition of Ag specificity?
there is a higher chance of repetition. B1 cells are often the origins of B-cell chronic lymphocytic leukemia due to this.
what characterizes the PRIMARY B-cell effector response?
1.IgM production.
2.slower (7-10 days)
3.during/after, get B-cell class switch.
4.T-cell help not required (but it's helpful)
How is the SECONDARY B-cell effector response described?
1. production of IgG (or other isotype)
2. affinity maturation (somatic hypermutation)
3. quick (1-3 days)
4. T-cell help required
which Ig is present in vastly greater numbers during the secondary Ab response?
in which tissue is the B-cell activated (generally & specifically)?
g: secondary lymphoid tissue

s: cortex of ln, proliferation at germinal center.
describe activation of B and T-cells within a LN.
Ag is taken in via afferent vessels to the T cell area. B-cell is activated in the cortex and proliferation occurs in the germinal center. plasma cells move into the medulla and Abs leave via efferent vessel/bloodstream.
which immune cells HAVE to leave the lymph node?
what is a germinal center? where are they located?
area where mature B-cell development occurs (they develop upon activation).
they develop in lymph tissue near the site of the antigen.
what are follicular dendritic cells? what is an example of a FDC? how does it work?
they present the Ag to the B-cell. TLRs and other recognition molecules hold the Ag in place and don't internalize it so the B-cell has longer exposure.
***they do not express MHC II.
what are the functions of an Ab?
1.neutralization (cells, virus & toxins)
2.agglutination (cells) and ppt (soluble Ags)
3.ADCC and opsonization (recognition and destruction by phag + NK)
4.complement activation (lysis, opsonization & inflammation)
5.inflammation (allergic response)
what discovery led to an understanding of complement?
there is a heat stable and heat labile fraction of the immune serum.
stable = Ab
labile = complement
what is the mechanism of complement? where are these proteins synthesized?
a cascade of enzymatic-like activity stimulates up to 30 pr-. most are made by liver cells, some by WBCs.
what happens upon activation of MOST complement pr-? how is this signified in nomenclature?
pr- split into smaller 'a' fragment which diffuses and larger 'b' which remains and may bind target cell.
a bar over top indicates enzymatically active.
name an exception to the a/b rule of complement activation.
C2a is larger than C2b
the varying complement cascades differ via their ____? their _____ is the same.

end result
what happens when MAC is activated?
cell lysis
how is the classical pathway initiated? what is required for initiation?
C1 interacts with Fc region of antibodies (IgG - not IgG4 - and IgM).
MULTIPLE Fc regions must be in close proximity to C1. **one IgM v. 2 or more IgG**
what happens after the Ag binds in the classical complement path?
Fc conformation changes, exposing where C1 binds.
what are the components of the C1 complex?
C1q, C1r and C1s (r & s are in dimers: C1qr2s2)
what happens when C1 binds Fc? where does it specifically bind?
1. C1q binds Ch2 domain of Ig. (can be one IgM but need about 1000 IgG for proximity)

2. upon binding, C1r activates C1s.
how is C3 convertase synthesized?
1. C1q binds Ch2 of Ig
2. upon binding, C1r activates C1s.
3. C1s activates C4 and C2.
4. C4 cleaved
5. C4b binds cell surface.
6. C2 binds C4b, is activated by C1s.
7. C2a binds C4b, making C3 convertase.
how is C5 convertase synthesized?
C3 convertase (C4b2a)cleaves C3. C3b binds the convertase, making c4b2a3b, aka C5 convertase.
What is unique about C3a? how does it work?
it's an important inflammatory mediator. it's an anaphylatoxin which causes degranulation of mast cell/basophil.
name two anaphylatoxins.
C3a and C5a
what is the fate of C5?
it is cleaved by C5 convertase into C5a (anaphylatoxin) and C5b which binds it's target cell.
how is the membrane attack complex synthesized? what is it's mode of action?
C5b binds C6-9. the MAC displaces membrane lipids to form a pore by which ions and molecules can pass. this causes lysis.
how is the alternative pathway different from the classical path? what is it critical for?
it activates complement without Abs.
it is critical for opsonization.
what types of cells does the alternative pathway utilize?
it calls in macrophages and B-cells, etc. those which can bind complement pr- via their complement receptors.
how is the alternative pathway activated?
via C3b binding to cell surface components which are foreign to the host (bacterial lps, cell wall components).
how is C3 convertase synthesized in the alternate pathway?
Bound C3b binds Factor B on the Ag. Factor D activates the release of Ba and Bb binds the complex, making C3bBb (C3 convertase).
how is C5 convertase synthesized in the alternate path?
C3bBb is stabilized by properdine to keep it active. Additionally cleaved C3b binds giving us C3bBb3b, AKA C5 convertase.
how is the MAC made in the alternate path?
C3bBb3b, C5 convertase, cleaves C5. C5b binds to the antigenic surface.
name 9 initiators of the alternative pathway.
1. LPS
2.teichoic acid
3.zymosan (fungal/yeast cell wall)
4.viruses, viral-infected cells
6.human IgG, IgA and some IgE in complexes
7.cobra venom factor
8.anionic polymers (dextran sulfate)
9.pure carbs (agarose, insulin)
why is the MBP pathway useful?
it's another way to activate complement without Ag-Ab recognition.
what is a lectin? what is a collectin?
a protein that binds carbohydrates.
C-type lectins which have been implied to play an important role in the innate immune defence against microorganisms.
what are the components and functions of the collectin?
a lectin binding domain (to bind microbe) and a collagen domain (opsonin). there is also a c' activating portion.
what is an example of a collectin? what does it's activation emulate and what results?
mannan-binding protein. after activation it acts like C1 and activates C2 and C4. the rest of the path is similar to classical.
what are the biological functions of complement? what is responsible for each one?
lysis (MAC), opsonization (C3b and C4b) and inflammation (C3a, C4a and C5a).
how do C3b and C4b participate in opsonization?
they bind to Ags and to c' receptors on host defense cells.
they increase phagocytic cell recognition/destruction of Ag.
How do C3a, C4a and C5a participate in inflammation? which is strongest?
they cause the degranulation of mast cells, basophils and eosinophils. they extravasate WBCs and release neutrophils from bone marrow. they cause increased expression of c' receptors on neutropils. C5a is most potent.
what is the fourth function of the immune response?
removal of immune complexes. c' pr- will tag the smaller, non-ppt complexes for macrophage recognition.
where are CR1s (CD35) found and what do they bind? what is their fxn?
erythrocytes, neutrophils and lymphocytes. they bind C3b and C4b. they transport and opsonize immune complexes.
what is an example of CR1 (CD35) activity?
RBC bind an immune complex via C3b or C4b, bring it to the spleen/liver where macrophages can grab the complex for destruction. RBC returns to circulation.
which cells have CR2 (CD21)?what is the action of CR2(CD21)?
B-cells, they bind C3d, iC3b (inactivated). they take up immune complexes and activate B-cells. *memory cell activation*
what types of cells have CR3 receptors? what is their fxn?
monocytes, neutrophils and NK cells. they fxn in uptake of immune complexes and opsonization (iC3b).
what can CR3 (CD11) binding regulate?
cytokine production (IL-12 and IFN gamma from macrophages, which determines Th1 vs. Th2 responses).
what does the bound C3b protein attach to when opsonizing RBCs?
the CR1 on RBC surfaces.
what is the most important level of control in all three pathways?
C3 step.
how is the C3 step controlled?
via factors which bind C3 convertase.
what is the action of Factor I
it cleaves C3 into inactive components iC3b and C3d. these remain attached to cell surface. *on HOST cells only, so microbes are still vulnerable.
what does Factor H do?
it inhibits the alternative pathway by binding C3b and preventing association with Factor B
What is the function of the S protein?
it binds C5b67 if released by target cell. it helps prevent bystander cell lysis. it is supposed to only react with the host cell.
which pathway does factor I affect?
classical, alternative, lectin.
what is the immunological fxn of factor I?
it's a serine protease which cleaves C4b or C3b.
what protein affects the alternative pathway by blocking formation of C3 convertase by binding C3b and is a cofactor for cleavage of C3b by factor I?
factor H
what prevents insertion of MAC?
g- bacteria with long-chain polysaccharides to LPS (e.coli and salmonella)
how do certain gram negative outer membrane proteins fxn in evasion?
the MAC interacts with the pr- instead of cell membrane (n.gonorrhea)
what inactivates anaphylotoxins?
elastase (pseudomonas aeruginosa)
how do gram + bacteria evade c'proteins?
their thick peptidoglycan layer and capsule.
how does a capsule help evade complement?
it's a barrier between C3b deposited on the cell membrane and CR1 on phagocytic cell. this decreases opsonization.
what is needed to lyse encapsulated bacteria?
C3b and Abs
what are vaccinia virus, HSV, EBV, trypanosoma cruzi and candida albicans all examples of?
microbes which produce mimics of c' proteins. they are usually inhibitory of complement activation.
why are MHC molecules considered 'promiscuous'?
b/c they can bind a variety of peptides. they are not Ag specific.
is polymorphism of MHC molecules of individual benefit?
no, it is a population benefit.
how are T-cells selected for negative selection?
if they bind self-antigens or if they bind self-MHC too strongly.
how does positive selection protect T-cells from destruction?
once T-cells demonstrate that they can interact safely with self-MHC, a protective signal is sent into the T-cell for it's survival. this also stops alpha chain rearrangement (allelic exclusion).
how long does it take for a T-cell to go from bone marrow to thymus to periphery?
about 3 weeks
what type of cells are important in positive and negative selection? why?
thymic stromal cells b/c they have high levels of class I and class II MHC.
which cells specifically regulate positive selection? negative?
cortical epithelial cells mediate positive selection. dendritic cells mediate negative selection.
what are the two steps of the two signal T-cell activation hypothesis?
1.TCR + Ag-MHC
what is the function of B7? where is it found? how many B7s are there?
B7 first binds CD28 on T-cells to activate it. later, B7 binds CTLA-4 on activated T-cells sending a suppression signal. they are found on APCs and some target cells. there are two B7s (1 & 2) for ensured activation.
which molecule does B7 have a higher affinity for?
without two signals, what happens to a T-cell?
anergy or apoptosis
how do superantigens conform to the two signal hypothesis?
they activate a large population of T-cells, generally. cytokines are released (inflammation, shock). ultimately the 2nd signal is NOT present and there is death of the stimulated T-cells.
why do some people have a more severe rxn to superantigens than others?
b/c superantigens are v.specific for the V-beta family of T-cells to which they'll bind. V-beta T-cells are individual. more binding = sicker
superantigens binding to V-beta are associated with which MHC class?
MHC class II
what are two subsets of T cells? which are more present in early fetal life? what else is unusual about them?
gamma delta and alpha beta. gamma delta are present in early fetal life and they do NOT respond to MHC. they don't recirculate, have limited diversity and are present on skin/intestines.
which subset of T-cells has similar function to natural killer cells? what is unique about them? how do they function?
NK1-T cells. they have rearranged TCRs (alpha/beta)and bind to CD1 molecules and Ag lipids.
how do NK1-T cells attract Th cells?
they secrete cytokines which may function as a rapid response to an invader (no Ag processing needed).
what are the three subsets of Th cells? which alpha beta subset are Th cells?
Th0 = precursor helper cell
Th1 & Th2
they are subsets of CD4
what cytokines does Th1 secrete?
how does the T-cell arrive at the thymus? does it secrete cytokines?
it arrives as Th0 and it secretes IL-2 and IL-4, but they are not specified for Th1 or Th2.
which Th cell stimulates inflammation?
delayed type hypersensitive T cells (Tdth)
what are the two forms of CD8 cells?
Tc and Ts
what are the three ways in which cytokines can work?
paracrine, autocrine and some endocrine.
give an example of two endocrine cytokines and where they work.
IL-6 works on the bone marrow
IL-1 works on the hypothalamus to cause fever.
define cytokine
proteins secreted by cells of host defense that regulate the immune response.
which cytokines are produced by lymphocytes? by monocytes/macrophages? give examples of these.

monokines (IL-1, TNFalpha, IL-6)
which cytokines are produced by WBCs? where do they act? give specific examples.
interleukins, they act on WBCs. IL-1 through IL-25
which cytokines are important in the inflammatory response? IL-8 and RANTES are examples.
chemokines, low weight molecular molecules.
what does pleiotrophic mean? give an example of a cytokine like this.
different biological effects on different target cells.

IL-4 has many different fxns for different cells.
which cytokines are redundant? how?
IL-2, 4 and 5 all cause proliferation of B-cells.
which cytokines act synergistically to induce a class switch to IgE?
IL-4 and IL-5
which cytokine can block the class switch to IgE induced by IL-4?
TNF gamma
which interleukin produced by a macrophage goes on to produce Th1 cells?
how does a Th cell decide to be Th1 or Th2?
once a subset is activated, there is repression of the other.
which interleukin promotes Th1 production? which inhibits Th2?
IL-12 from macrophages promotes Th1.
IFN gamma inhibits Th2
which interleukin promotes Th2? what is the role if IL-10 and how is it related to Th subsets?
IL-4 promotes Th2.

IL-10 inhibits macrophages, which produce IL-12 which promote Th1.
which interleukins promote Th2 production?
IL-4 and 5.
what is the importance of Th subsets? which dz illustrates this?
certain dz respond better to a particular type of immune response. tuberculoid leprosy causes a CMI response, generating Th1. survival rate is much higher than for lepromatous leprosy which generates a Th2 Ab response. both are caused by m.leprae, an intracellular pathogen.
what are the signs of tuberculoid leprosy?
CMI and granuloma
Th1 response
damage of skin and nervous tissue.
patient survives.
what are the symptoms of lepromatous leprosy?
Ab and Th2 response
disseminated dz
fatal outcome
a pt. presents with high mRNA values of IL-2, IFN gamma and TNF beta. what can you tell them about their chances of survival?
these cytokine levels indicate tuberculoid leprosy. their prognosis is good.
which cytokines are elevated in lepromatous leprosy? what are these cytokines often associated with?
IL-4, IL-5 and IL-10. they are associated with Th2 immune response.
how are Th subsets associated with HIV infection? why?
a shift from Th1 to Th2 has been associated with a progression to AIDS. it indicates that all Th1 cells have been killed off.
how are cytokines activated?
via two chains (a binding and an activating unit), the cytokine binds a specific receptor which initiates a signalling cascade within the cell to exert a biological activity (changes in gene expression).
what are the two chains of cytokines called?
the cytokine specific unit and the signal transducing unit.
how long do cytokines last? where do they act?
they have a short in vivo half life. they act locally.
are cytokine signaling chains very specific? what do multiple chains cause?
no, families of receptors often share the same chain. two or three chains cause higher affinity.
how does increased cytokine receptor expression come about?
after cell activation via receptor binding, signals sent into the cell can cause the exposure/production of more cytokine receptors. this allows for stronger binding and greater activation.
which chains of the IL-2 family are increased upon cell activation? which is constitutive?
alpha and beta are increased. gamma is constitutive.
what are cytokine antagonists? give two examples and their effects.
molecules that bind cytokine receptors but don't send signals.
EBV - IL-10 (inhibit Th1)
HHV8 - IL-6 (inflammation)
how do microbes evade host response?
cytokine antagonists
microbes that BIND cytokines
microbes that MIMIC " "
what are poxviruses and CMVs (chemokine receptor homologues)? what form are they in?
they are cytokine mimic-ers. they are secreted (soluble).
what are some cytokine related dz?
bacterial septic shock
toxic shock dz
lymphoid and myeloid cancers
what can cause bacterial septic shock? which cytokines are involved?
LPS causes high levels of cytokine release, especially IL-1 and TNF alpha from macrophages. also, systemic inflammation.
what causes toxic shock dz?
what cytokine is overproduced in adult T-cell leukemia?
how is graft rejection related to cytokines?
graft rejection is an immune response. blockage of antibodies to IL-2 or IL-2R can allow for graft survival.
what is an example of lymphokine activated killer cells?
IL-2 activated NK cells
what is the therapeutic use of tumor infiltrating lymphocytes?
T-cells in tumors have often been suppressed. if removed and activated in vitro they could potentially be replaced in the tumor and activate an immune response.
how does direct administration of cytokines work for some viral infections?
the cytokines are activated outside the body and then re-introduced. this can be lethal.