Immuno Exam 2

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T cell chapter, part of Ab chapter....a few typos....sorry...but i think all the info is correct...tried to take it all straight out of the book without copying exact word for word....
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Marjorie P
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CD4 binds to which domain of which class of MHC on which cell(s)? This TCR coreceptor binds to MHCII's beta 2 domain on pro APCs
CD8 binds to which domain of which class of MHC on which cell(s)? This TCR coreceptor binds to the alpha 3 domain on MHC1 on target cells
Put the following 6 into the correct 3 pairs: CD11aCD18, CD28, CD58, CD2, B7, CD54, ICAM-1, CD80, LFA-2, LFA-3 CD11aCD18 and CD54(ICAM-1) CD28 and B7 (CD80) CD2 (LFA-2) and CD58 (LFA-3)
What are the components of the TCR complex? TCR, CD3 complex, and zeta proteins
What makes up signal 2 and why? CD28 and B7 make up signal 2 for co-stimulatory signals to activate naive T cells.
Which region is the most diverse on the TCR? CDR3 (complementarity-determining region or hypervariable region)
Describe CDRs interaction with the peptide and MHC CDR1: peptide and MHC CDR2: MHC only CDR3: Antigenic peptide only
T/F the TCRs on one cell are clonotypic True, all the TCRs on the same cell will recognize the same epitope
The CDRs are located on the: alpha chain, beta chain, both, neither the CDRs are located on both the alpha and the beta chains
rearrangement of the TCR and BCR gene segments are regulated by which enzyme(s)? RAG-1, RAG-2, DNA repair enzymes
What is SCID? (ex: in Arabian foals) SCID is a lack of DNA repair enzymes resulting in no functional T or B lymphocytes
On the TCR which chain rearranges first? Alpha or Beta? The beta chain rearranges first on this cell receptor
Describe the beta chain gene rearrangement 1. Dn region binds to Jn 2. Vn binds to Dn Result: V-D-J
Describe the alpha chain rearrangement Vn to Jn (No Dn region!)
What 3 things contribute to junctional diversity? Base Deletions N-region nucleotide addition P-nucleotides
What is the most common way to create diversity to the TCR alpha and beta chains? N-region nucleotide addition is the most common way to create ...............
What is N-region nucleotide addition? This is when up to 10 nucleotides can be added to DNA at the coding regions for the alpha or beta chains (adds diversity)
What is TdT? This enzyme assists in adding nucleotides to DNA at the alpha and beta chain coding regions
What are P-nucleotides? If the V/J and V/D/J coding chains on the DNA are asymmetrical these nucleotides will add in to fill the gaps
T/F: TCRs have the ability to edit False: Only B cells can edit their BCR, and they only have one chance
What two things does the TCR require for signal transduction? CD3 Complex (2x) Zeta proteins (2x)
Name the 2 functions of the CD3 complex 1. Signal Transduction (with Zeta proteins) 2. TCR stabilization on the surface
What is the result of a mutation in the CD3 complex? The TCR cannot be expressed
T cells are selected for in the Red Pulp Medulla Bone Marrow Cortex These cells undergo selection in the cortex
What is the approximate ratio of T Helper to T Killer cells? Helper: Killer 2:1
Do T helper cells help out adaptive immunity, innate immunity, or both? Both
Which cells are responsible for thymocyte selection? thymic stromal cells (ex: cortical epithelial cells, M0s, and dendritic cells)
Do thymic stromal cells possess MCHI, MCHII, both, or none? Thymic stromal cells have both MCH I and MCH II
What cell is the most potent activator of Naive T cells and why? Dendritic cells because they always express B7 and MHC molecules
What causes enhanced expression of B7? APC stimulated by endotoxin [LPS] interferon-gamma CD40-CD40L binding
What does a signal by CD28 cause? IL-2 production Differentiation of Naive T cell into Effector and Memory
In regards to T cells, what is the function of IL-6? IL-6 promotes IL-2 and IL-2 receptor production and T cell proliferation
Which cytokine is the major co-stimulator of Th2 cells? IL-1 is the major co-stimulator for this kind of cell
What are the first 2 steps after and antigen is recognized by a helper T cell? Antigen recognition induces expression of CD40L on the T cell so it can bind to CD40 on the APC. This CD40-CD40L binding stimulates expression of B7 on the APC.
T/F: When T cells proliferate and differentiate, they mostly become antigen-specific memory cells False: most T cell differentiate into effector cells (small numbers are memory)
Where can one find Effector T Helper cells? Peripheral tissues
T/F: Effector T helper cells only need signal 1 for activation TRUE! they are more sensitive to TCR/CD4 recognition
What happens to the effector T cells after an antigen has been eliminated and why is this significant? There will be a major decline in the effector T cell population which will allow the immune system to return to homeostasis
For the most part, where will you find Naive T cells? Peripheral lymphoid organs
Do Naive T Cells have effector functions? No, they only become activate and differentiate. The Effector T cells actually have effects like cytokine secretion, CD40L presentation, etc
Which cells are responsible for the accelerated secondary responses on subsequent exposure to the same antigen? Memory T helper cells
Memory T helper cells differentiate into which types of cells? More memory and more effector T helper cells
How do effector T cells leave the vascular system to enter the infected peripheral tissue? Since effector T cells down regulate L-selectin and CCR7, while up-regulating CCR10, LFA-1 and VLA-4, this allows LFA-1 to bind to ICAM-1 and VLA-4 to bind to VCAM-1. ICAM-1 and VCAM-1 are found on the peripheral vascular endothelium at the sight of inflammation
Where do the Th1 and Th2 subsets develop? peripheral lymphoid organs
What is the function of IL-12 in relation to the T helper subsets? promotes T-Bet production T-Bet is the Th1 promoting transcription factor
What is the function of IL-4 in relation to the T helper subsets? promotes GATA-3 production GATA-3 is the transcription factor for Th2
What is unique about the IL-12/IL-4 relation? IL-12 and IL-4 promote their respective transcription factor, while cross regulating the other They keep each other in check basically "Neither can live while the other survives"? Harry Potter anyone? :P
What cells can produce IL-12 and why might they do so? M0s and NKs can produce IL-12 or IFN-gamma in response to pathogens, specifically intracellular bacteria and viruses (Remember IL-12 promotes T-Bet, the Th1 transcription factor)
Which IL is produced in response to helminths? What does this cause CD4 cells to do? IL-4 is produced in response to helminths and causes CD4 cells to differentiate into Th2.
Which cytokines does Th1 enhance and suppress? Enhances: IL-2, IL-12, IFN-gamma Suppresses: IL-4, IL-10
What cytokines does Th2 enhance and suppress? Enhances: IL-4, IL-5, IL-6, IL-10 Suppresses: IFN-gamma, IL-12
Draw a typical Antibody structure (Seriously, grab a piece of paper and do it labeling all possible parts that you can remember)
Which antibodies do not have a hinge region and why? Due to an extra constant region, IgM and IgE do not possess this region on the antibody structure
Antibodies act in 2 different phases. Which phases? Recognition phase (BCRs) Effector phase (secreted Abs in humoral immunity)
What percentage of plasma proteins is made up by secreted antibodies? ~20%
Alpha, beta, and gamma type globulins have been ID'd due to electrophoretic migration rate. What type of globulin are antibodies? Antibodies are gamma globulins
Which Ig has the shortest percentage of carbohydrate content? IgG at 3-4% (I know it is a stupidly specific question...but as anything is fair game, had to throw it in...Pg 106, 3rd bullet)
If papain is mixed with IgG, what will happen? Papain cleaves IgG above the hinge region resulting in 2 Fab regions and one Fc region
What will happen if IgG is mixed with pepsin? Pepsin will cut the Ab below the hinge region keeping it intact. The Fc portion will be degraded but the 2 Fab regions are still connected and will be called F(ab')2
What did papain/pepsin experiment tell us about the Fab regions? If the Ab is cut below or above the hinge region, the Fab can still bind to antigens but will not activate Fc-dependent effector functions
What did the papain/pepsin experiment tell us about the Fc region? If the Fc is still intact (papain) then it can bind to Fc receptors, activate complement, etc
T/F: the light chain on an antibody determines the type False: the heavy chain determines the type of antibody
T/F: An Ab has 2 light chains, 2 lambda, 2 kappa, or 1 of each False: An Ab has either 2 of one, or 2 of the other. It cannot have a mix of both kappa and lambda light chains
In humans, which type of light chain is more common? Kappa -60% Lambda -40%
What forms the antigen binding site on the antibody? the 3 hypervariable regions of the heavy and light chains TOGETHER form the antigen binding site
T/F: Each hypervariable region is up to 10 amino acids long False: Each hypervariable region is only 5-10 amino acids long (I know also a crappy question, but I had to throw it in there)
What is another name for the hypervariable regions? Complimentarity-determining regions (CDRs) because they are complementary to the epitopes on the antigen
T/F: Antigen-Ab interaction is irreversible False: Ag-Ab interaction is non-covalent and reversible
Name some noncovalent forces that contribute to Ag-Ab binding Ionic bonds, van der Waals forces, hydrogen bonds, hydrophobic interactions
With regards to Abs, define affinity This refers to the binding strength between 1 Fab and the epitope
With regards to Abs, define avidity. The total of all the Fab and antigen bindings
T/F: IgM has a higher avidity than IgG True because IgM has more Fab regions that can bind to epitopes
When can Abs act as antigens? Abs can act as antigens if introduced into a foreign host. The host would then begin to make anti-antibodies.
Define isotype The 'class' of Ig which is determined by the variations in the constant regions of the heavy and light chains
Define allotype This refers to the differences in Ig between individuals of the same species *Differences can be used to establish paternity
Define idiotypes This is most specific and refers to the aa combo in the variable regions of each chain. Each idiotype is specific for a particular antigen
What is the primary function of an antibody and the possible result(s)? ***First: bind to the Ag Next it can have a direct effect like neutralization of microbial toxins or...more likely, it will engage other effector molecules like complement proteins or N0s
T/F: most effector functions of an Ab are mediated by the Fab region False: most effector functions of an Ab are mediated by the Fc region of the heavy chain
What are Fc receptors? They are signaling cell surface receptors that bind the Fc portion of an Ab.
Which antibodies do not have Fc receptors? IgM, IgD
What is the major Ig in serum? IgG
Where is IgG found? blood, tissue spaces, extravascular spaces
Name the FcgammaR receptors FcgammaRI FcgammaRII FcgammaRIII (AKA CD64, CD32, CD16)
Which Fc gamma receptor is found on B cells? What is it's significance? Fc gamma RIIB is found on this cell When crosslinked to BCR it inhibits the cell and blocks activation
Which Fcgamma receptor has the highest affinity? FcgammaRI AKA CD64
Which cells have all 3 of the Fcgamma receptors? Macrophages and Eosinophils
Fcgamma receptors on phagocytes interact more or less efficiently with IgG bound to an antigen? Why? More efficiently because the IgGs basically form a multivalent array and bind with a much higher avidity than free circulating IgG...the IgG surrounding the antigen will trigger engulfment and microbicidal activities
Which antibody is most likely to cross the placenta in most species? IgG
How does IgG function as an opsonin? IgG can assist in agglutination of particulate antigens
Neutralizatoin of viruses and microbial toxins form IgG can result in what? complement activation
Which Ig is most efficient in agglutination? IgM due to its pentamer
Which Ig has the highest avidity? IgM because it has 10 Fab regions
Which Ig is the predominant Ig produced by the fetus? IgM
An elevated IgM level in the blood of a newborn is indicative of what? transplacental infection
Where does synthesis of IgA mostly occur? mucosal lymphoid tissue, especially respiratory and GI tracts
Which is the most abundant Ig in the body? IgA
T/F: Secretory IgA is a dimer and serum IgA is generally a monomer True! Don't forget that the secreted form has a joining chain and secretory component
What composes the secretory component of IgA to help transport IgA to the mucosal surface? What other function does the secretory component have? It is synthesized by epithelial cells and helps protect IgA from proteolytic degradation
Which Ig is predominant in various secretions? IgA
How does IgA protect mucosal surfaces? it prevents attachment of microorganisms and microbial toxins
Which Ig(s) participate in agglutination? IgA, IgG, IgM
Which Ig(s) are heat liable at 56 degrees? IgE, IgD
Which Ig is referred to as an reaginic antibody and why? IgE because it causes histamine release (Hypersensitivity 1)
Which three cells has Fcepsilon receptors? Mast cells, basophils, eosinophils
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