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<div>What are T cells activated by?</div><div>t cells are activated by pAPCs</div><ul><li><div>they present antigens on MHC molecules</div></li><li><div>provide other signals for activation</div></li></ul>
<div>What are the two main T cell subsets?</div><ul><li><div><strong>CD4+: helper T cells</strong></div><ul><li><div>binds to MHC Class II</div></li><li><div>secrete cytokines to help other immune cells</div></li><li><div>most important effector functions = help activation of B cells</div></li></ul></li><li><div><strong>CD8+: cytotoxic T cells (CTLs)</strong></div><ul><li><div>binds to MHC Class I</div></li><li><div>killers</div></li></ul></li></ul>
<div>How does the TCR facilitate T cell activation?</div><div>by binding antigen presented on MHC molecules</div>
<div>What are developing T cells called?</div><div>Thymocytes</div><ul><li><div>T cells = Thymus cells</div></li></ul>
<div>What does the T cell precursor do in the thymus?</div><div>It rearranges its T cell receptors</div>
<div>Immature T cells that recognize self MHC...</div><div>receive signal for survival</div>
<div>Immature T cells that interact strongly with self antigen...</div><div>are removed from repertoire</div>
<div>Where do T cells begin their maturation? What do they mature as?</div>"<ul data-pm-slice=""3 5 []""><li><p>maturation happens in the thymus</p></li><li><p>they mature as double-negative Pro-T cells</p><ul><li><p>which DOES NOT express CD4, CD8, or TCR</p></li></ul></li></ul>"
<div>What do Double-negative Pro-T cells undergo?</div><div>they undergo VDJ recombination of their B-chain first</div>
<div>What is an invariant placeholder? When is it expressed?</div><ul><li><div>Pre-T⍺ is an invariant placeholder</div></li><li><div>it is expressed until ⍺-chain rearrangement occurs</div></li></ul>
<div>What induces further development of T cells?</div><div>expression of pre-T⍺ as part of pre-TCR</div>
<div>What is Pre-TCR?</div><div>rearranged B-chain + pre-T⍺</div>
<div>What are T cells expressing Pre-TCR called?</div><div>Pre-T cells</div>
<div>What is the expression of the Pre-TCR signal?</div><div>Signals the T cell to:</div><ul><li><div>proliferate</div></li><li><div>start <strong>expressing</strong> CD4 and CD8</div></li><li><div>begin rearrangement of ⍺-chain</div></li></ul>
<div>What do Pre-T cells start expressing? What do they rearrange?</div><div>start expressing CD4 and CD8 and rearrange their ⍺-chain</div>
<div>What are immature T cells?</div><div>T cells with a functioning (but untested) TCR</div>
<div>What random rearrangement of TCR genes generates useless receptors?</div><div>some TCRs that may not recognize self-MHC at all</div>
<div>What random rearrangement of TCR genes can cause an autoimmune disease?</div><ul><li><div>TCRs that recognize self-MHC VERY STRONGLY and/or bind self-antigens VERY STRONGLY</div></li><li><div>may have a weak affinity for self-MHC and bind VERY STRONGLY to self-antigens</div></li></ul>
<div>What random rearrangement of TCR genes are considered perfect?</div><div>TCRs that may have a weak affinity for self-MHC and NO affinity for self-antigens</div>
"<div>How do you get rid of T cells expressing ""bad"" receptors?</div>""<div>test each TCR on each T cell to make sure the T cells expressing ""bad"" receptors are removed</div>"
<div>Why do T cells undergo positive selection?</div><div>to ensure recognition of self-MHC</div>
<div>What must T cells recognize? What happens if they don't?</div><ul><li><div>T cells must be able to recognize self-MHC</div></li><li><div>If they don't they wouldn't be able to be activated by APCs</div></li></ul>
<div>What is positive selection? It underlies the concept of what?</div><ul><li><div>Positive selection = selecting FOR TCRs that can bind self-MHC</div></li><li><div>this process underlies the concept of MHC restriction</div></li></ul>
<div>Why do T cells undergo negative selection?</div><div>to remove self-reactive clones</div>
<div>What happens if a TCR reacts strongly to self-MHC or recognizes self-antigens presented on MHC?</div><div>Those TCRs are selected against for cell death</div>
<div>What happens to T cells with non-functioning TCRs?</div><div>they are deleted (failure of positive selection)</div>
<div>Weak recognition of self-MHC + peptide =</div><div>allowed to live</div>
<div>Strong recognition of self-MHC + peptide =</div><div>death</div>
<div>T cell selection occurs where?</div><div>thymic cortex &amp; medulla</div>
<div>What cells mediate positive and negative selection by providing self-MHC + antigen?</div><div>cortical and medullary cells</div>
<div>(True/False): Positive and Negative selection occurs in the same part of the thymus during T cell selection.</div><div>TRUE</div>
<div>What is AIRE and what does it do?</div><ul><li><div>AIRE (autoimmune regulator) = transcription factor</div></li><li><div>allows medullary thymic epithelial cells to express proteins normally found in other tissues</div></li></ul>
<div>What kind of selection do T cells undergo in the thymic cortex?</div><div>both positive and negative selection</div>
<div>After leaving the thymic cortex, where do T cells migrate to? What happens there?</div><div>they migrate to the medulla where they undergo another round of NEGATIVE selection only</div>
<div>What does AIRE induce? What can T cells do with this?</div><ul><li><div>it induces the expression of peripheral antigens in medullary thymic epithelial cells</div></li><li><div>T cells can test their TCRs against peripheral antigens to ensure no self-reactiveness</div></li></ul>
<div>What happens if AIRE is <strong>ABSENT</strong> in the thymus? What results from this outcome?</div><ul><li><div>the thymus can only express thymic antigens</div></li><li><div>The results of this is:</div><ul><li><div>T cells self-reactive to thymic antigens = deleted</div></li><li><div>T cells self-reactive to self-antigens expressed in periphery = ALLOWED to leave (this is bad)</div></li></ul></li></ul>
<div>Where does positive selection occur?</div><div>thymic cortex</div>
<div>Where does negative selection occur?</div><div>BOTH thymic cortex &amp; medulla</div>
<div>Where does the expression of AIRE occur?</div><div>ONLY in medullary epithelial cells</div>
<div>Where does T cell activation occur?</div><div>in the peripheral lymphoid organs</div>
<div>Where do T cells go after activation?</div><div>they migrate to the site of infection</div>
<div>List the 3 signals T cells require for initial activation</div><ol><li><div>Appropriate self-MHC molecule presenting specific antigen</div></li><li><div>Co-stimulation with other receptors</div><ul><li><div>Lacking co-stimulation = anergy (inactivation)</div></li></ul></li><li><div>Release of cytokines from pAPC (aka differentiation)</div></li></ol>
<div>How do activated pAPCs strengthen binding?</div><div>they express additional adhesion and costimulatory molecules</div>
<div>The stimulation of the TCR complex does what? What results from this?</div><ul><li><div>initiates a cascade of intracellular signaling pathways</div></li><li><div>the result of the signaling pathways is the stimulation of transcription via transcription factors, cytokine production, cytokine receptors, cell signal inducers, and effector molecules</div></li></ul>
<div>What are the 3 important transcription factors that result from the signaling pathways?</div><ol><li><div>NFAT</div></li><li><div>NF-kB</div></li><li><div>AP-1</div></li></ol>
<div>Why would APC not be expressing co-stimulatory molecules?</div>"<div>Non-activated APC is presenting self-peptide on its MHC and the Naive T cell is specific for that peptide</div><ul><li><div>the interaction occurs but there is NO CO-STIMULATION</div></li><li><div>w/o a co-stimulatory molecule, it only gets an Activation signal (signal #1), and none of the others</div></li><li><div>Result: nothing happens</div></li></ul>"
<div>(True/False) Co-stimulation alone is sufficient to induce T-cell activation</div><div>FALSE</div><ul><li><div>Correct Statement: Co-stimulation alone is NOT sufficient to induce T cell activation</div></li></ul>
<ol><li><div>Where are B7-1 and B7-2 expressed?</div></li><li><div>What happens if they bind to CD28?</div></li><li><div>What happens if they bind to CTLA-4?</div></li></ol><ol><li><div>they are expressed on APCs</div></li><li><div>bind to CD28 = Activation</div></li><li><div>bind to CTLA-4 = Inhibition</div></li></ol>
<div>What happens when PD-L1/PD-L2 binds to PD-1?</div><div>leads to inhibition of T cell</div>
<div>What happens when ICOS-L binds to ICOS?</div><div>leads to the activation of follicular responses (T_FH cells)</div>
<div>What happens when CD40L (on T cells) interacts with CD40 (on APCs)?</div><ul><li><div>it activates APCs to express more B7 costimulatory molecules</div></li><li><div>secrete cytokines to enhance T-cell differentiation</div></li></ul>
<div>What is inhibitory signaling crucial for?</div><div>It is crucial for limiting and ending immune reactions:</div><ul><li><div>Prevents responses to self-peptides</div></li><li><div>Terminate immune response through T-regulatory cells and other mechanisms</div></li></ul>
<div>(True/False): Expression of CD28 is upregulated on activated T cells</div>"<p data-pm-slice=""1 3 []"">FALSE</p><ul><li><p>Correct Statement: Expression of <strong>CTLA-4 </strong>is upregulated on activated T cells</p></li></ul>"
<div>What binds to B7 to regulate the proliferation of T cells?</div><div>CTLA-4</div>
<div>Which has a higher affinity for B7, CD28 or CTLA-4?</div><div>CTLA-4 has a higher affinity for B7</div>
<div>What stabilizes the binding of T cells to APCs?</div><div>Adhesion molecules</div>
<div>(True/False): Binding of TCR:MHC antigen is with strong affinity</div><div>FALSE</div><ul><li><div>Correct Statement: Binding of TCR:MHC antigen is with <strong>WEAK</strong> affinity</div></li></ul>
<div>(True/False): T cells first bind to APCs using low-affinity cell-surface adhesion molecules</div><div>TRUE</div>
<div>TCR to MHC:antigen binding causes what kind of change in adhesion molecules? What happens to affinity?</div><ul><li><div>it causes conformational change</div></li><li><div>affinity increases as a result</div></li></ul>
<div>Two things cause a stable interaction between T cells and APCs, what are they?</div><ol><li><div>increased affinity of adhesion molecules</div></li><li><div>binding of TCR to MHC:antigen</div></li></ol>
"<div>Pick the answer that fits the definition.</div><div>""controls cell migration and retention in lymph nodes""</div><ul><li><div>CTLA-4</div></li><li><div>IL-2R</div></li><li><div>CD40L</div></li><li><div>CD69</div></li></ul>"<div>CD69</div>
"<div>Pick the answer that fits the definition.</div><div>""strong co-stimulation for interactions with B cells and other APCs""</div><ul><li><div>CTLA-4</div></li><li><div>IL-2R</div></li><li><div>CD40L</div></li><li><div>CD69</div></li></ul>"<div>CD40L</div>
"<div>Pick the answer that fits the definition.</div><div>""inhibitory signal for termination of immune response""</div><ul><li><div>CTLA-4</div></li><li><div>IL-2R</div></li><li><div>CD40L</div></li><li><div>CD69</div></li></ul>"<div>CTLA-4</div>
"<div>Pick the answer that fits the definition.</div><div>""receptor for IL-2, strong stimulus for T cell proliferation""</div><ul><li><div>CTLA-4</div></li><li><div>IL-2R</div></li><li><div>CD40L</div></li><li><div>CD69</div></li></ul>"<div>IL-2R</div>
<div>(True/False): IL-2 is not essential for the survival and proliferation of T cells</div><div>FALSE</div><div><u>Correct Statement</u>: IL-2 is a <strong>CRITICAL</strong> cytokine for the survival and proliferation of T cells</div>
<div>(True/False): Activation of T cells induces transient expression of a high-affinity 3-chain receptor that allows strong signaling</div><div>TRUE</div>
<div>Choose the right answer in the parentheses:</div><div>A (strong/weak) signaling stimulates survival and proliferation of T cells ⎯ which (increase/decrease) the number of clones specific for inciting antigen</div><ul><li><div>strong</div></li><li><div>increase</div></li></ul>
<div>What leads to clonal expansion of antigen-specific T cells?</div><div>proliferation signals</div>
<div>What is clonal expansion of T lymphocytes needed for?</div><div>combat infection</div>
<div>Which T cell is needed in large quantities? Why?</div><ul><li><div>CD8+ T cells</div></li><li><div>because they directly target and kill infected cells</div></li></ul>
<div>How does CD4+ T cells assist other cells?</div><div>by secreting cytokines</div>
<div>After your body is done fighting an infection what happens to some of the T cells?</div><div>some T cells will persist as memory T cells</div>
<div>Once activated what happens to T cells? What does signal 3 do?</div><ul><li><div>once activated T cells undergo clonal expansion and further differentiation</div></li><li><div>signal 3 dictates this</div></li></ul>
<div>(True/False): Activated T cells no longer require multiple signals to engage their effector functions</div><div>TRUE</div>
<div>What controls the differentiation of CD4+ T cells into specific effector pathways?</div><div>cytokines</div>
<div>The STAT family of transcription factors is induced by what?</div><div>cytokine signals</div>
<div>What is the STAT family of transcription factors responsible for?</div><div>turning on other transcription factors associated with specific helper T cell lineages</div>
<div>What are the two locations where memory T cells are found?</div><div>lymphoid organs &amp; peripheral tissues</div>
<div>What do central memory cells do? Where are they found?</div><ul><li><div>they are cells that can rapidly proliferate upon re-exposure to antigen</div></li><li><div>they are found in lymphoid organs</div></li></ul>
<div>What does effector memory &amp; tissue-resident cells do? Where are they found?</div><ul><li><div>they can rapidly engage effector functions when they see their antigen again</div></li><li><div>they are found in peripheral tissue</div></li></ul>
<div>Why do naive T cells migrate between blood and lymphoid organs?</div><div>to find a dendritic cell that is carrying its specific antigen</div>
<div>(True/False): After activation, T cells don't migrate back to the site of infection to engage their effector functions</div><div>FALSE</div><div><u>Correct Statement</u>: After activation, <strong>SOME</strong> T cells <strong>MUST</strong> migrate back to the site of infection to engage their effector functions</div>
<div>What are the key adhesion molecule families for T cells?</div><ul><li><div>selectins</div></li><li><div>integrins</div></li><li><div>chemokines</div></li></ul>
<div>Activated T cells recognize adhesion molecules expressed on what? What do they use them for?</div><ul><li><div>expressed on activated vascular endothelium</div></li><li><div>use the adhesion molecules to migrate OUT of circulation and INTO sites of infection</div></li></ul>
Naive T cells preferentially express certain adhesion molecules and chemokine receptors. What are they?L selectin (CD6L) &amp; CCR7
The T cell homing receptor, LFA-1, binds to what ligand? What is the fuction?<ul><li>ICAM-1</li><li>stable arrest on HEV</li></ul>
What are high endothelial venules?specialized vasculature in T cell zone of secondary lymphoid organ
How do T cells exit the blood and go into lymphoid oragan?via high endothelial venules
The expression of ____ controls naive T cells retention in or trafficking out of secondary lymphoid organs.S1P
S1P levels are high in ____ &amp; low in ____"<ul><li><span style=""color: rgb(85, 170, 0);"">High in blood/lymph</span></li><li><span style=""color: rgb(255, 0, 0);"">Low in lymph nodes</span></li></ul>"
What happens when S1P binds to it's receptor?receptor becomes internalized &amp; no longer expressed on cell membrane<br><br>*does get put back eventually*
If there are fewer S1P receptors on the surface of T cell, what results?<ul><li>T cells become less sensitive to S1P</li><li>this causes them to move to the lymphoid organs</li></ul>
(True/False): Naive T cells inside lymph nodes are exposed to higher concentrations of S1P, so S1P receptors are downregulatedFALSE<br><ul><li><u>Correct Statement:</u>&nbsp;Naive T cells inside lymph nodes are exposed to <b>LOWER</b> concentrations of S1P, so S1P receptors are <b>UPREGULATED</b></li></ul>
If a naieve T cell does not recognize the antigen in the lymph node, what happens to it?It follows S1P concentration gradient OUT of the lymph node and back INTO the blood/lymph
If a naive T cell recognizes its antigen in the lymph node, what happens?it loses expression of S1P receptor which allows it to be retained in the lymph node for proliferation and differentiation
For effector T cells to not have the ability to go back into the lymph node it must lose the expression of what?Lose the expression of L-selectin and CCR7
The increased expression of E- and P-selectin, LFA-1, and VLA-4 are indicative of what T cell?Activated/Effector T cells
What does that immunological synpase facilitate?the interation between effector T cells and their targets
What are the two types of immunological synapses? What are their roles?<ul><li>cSMAC = central</li><ul><li>contains signaling proteins for T cell activation</li></ul><li>pSMAC = peripheral</li><ul><li>contains adhestion molecules for T cells binding to target cells</li></ul></ul>
"Match the definition with the correct answer choice:<br><br>""stimulate production of macrophages &amp; granulocytes""<br><ul><li>IFN-y</li><li>GM-CSF</li><li>IL-17A/F</li></ul>"GM-CSF
"Match the definition with the correct answer choice:<br><br>""stimulate production of G-CSF from stromal cells, which increases production of neutrophils in the bone marrow""<br><ul><li>IFN-y</li><li>GM-CSF</li><li>IL-17A/F</li></ul>"IL-17A/F
"Match the definition with the correct answer choice:<br><br>""macrophage activation""<br><ul><li>IFN-y</li><li>GM-CSF</li><li>IL-17A/F</li></ul>"IFN-y
T_H1 cells are inhibited by ____ which are expressed by ____.<ul><li>IL-4</li><li>T_H2</li></ul>
T_H2&nbsp;cells are inhibited by ____ which are expressed by ____.<ul><li>IFN-y</li><li>T_H1</li></ul>
What two cytokins can inhibit development of T_H17?<ul><li>IFN-y &amp; IL-4</li><li>expressed from T_H1 &amp; T_H2 respectively</li></ul>
"<span style=""color: rgb(255, 85, 0);"">IFN-y</span> and <span style=""color: rgb(255, 85, 0);"">IL-12</span> make what helper T cell? What's the transcription factor used?""<ul><li>Helper T cell:&nbsp;<span style=""color: rgb(255, 85, 0);"">T_H1</span></li><li>Transcription factor: <span style=""color: rgb(255, 85, 0);"">T-bet</span></li></ul>"
"<span style=""color: rgb(0, 170, 255);"">IL-4 </span>makes what helper T cell? What's the transcription factor used?""<ul><li>Helper T cell: <span style=""color: rgb(0, 170, 255);"">T_H2</span></li><li>Transcription factor: <span style=""color: rgb(0, 170, 255);"">GATA-3</span></li></ul>"
"<span style=""color: rgb(170, 85, 255);"">IL-6</span> and <span style=""color: rgb(170, 85, 255);"">IL-23</span> make what helper T cell? What's the transcription factor used?""<ul><li>Helper T cell: <span style=""color: rgb(170, 85, 255);"">T_H17</span></li><li>Transcription factor: <span style=""color: rgb(170, 85, 255);"">RORyT</span></li></ul>"
"<span style=""color: rgb(255, 56, 56);"">IL-6 </span>makes what helper T cell? What's the transcription factor used?""<ul><li>Helper T cell: <span style=""color: rgb(255, 56, 56);"">T_FH</span></li><li>Transcription factor: <span style=""color: rgb(255, 56, 56);"">Bcl-6</span><br></li></ul>"
"<span style=""color: rgb(0, 170, 0);"">IL-2</span> makes what helper T cell? What's the transcription factor used?""<ul><li>Helper T cell: <span style=""color: rgb(0, 170, 0);"">T_reg</span></li><li>Transcription factor: <span style=""color: rgb(0, 170, 0);"">FoxP3</span></li></ul>"
What is considered the “classical pathway” for macrophage activation?Th1 stimulation of macrophages<div><br></div><div>These macrophages are also known as M1</div>
What are 2 things that B-cells persist as?<ul><li>antibody-secreting plasma cells</li><li>memory B cells</li></ul>
What are B cells?powerhouse of the immune system responsible for the creation and production of antibodies
What are the 2 forms that BCRs exist as?<ul><li>membrane-bound</li><li>secreted</li></ul>
"What are the types of <span style=""color: rgb(255, 170, 255);"">light</span> chains?""<span style=""color: rgb(255, 170, 255);"">λ </span>and <span style=""color: rgb(255, 170, 255);"">κ&nbsp;</span>"
"What are the types of <span style=""color: rgb(85, 255, 255);"">heavy</span> chains?""<ul><li><span style=""color: rgb(255, 255, 255);"">μ = IgM</span></li><li><span style=""color: rgb(255, 255, 255);"">δ = IgD</span></li><li><span style=""color: rgb(255, 255, 255);"">γ = IgG</span></li><li><span style=""color: rgb(255, 255, 255);"">α = IgA</span></li><li><span style=""color: rgb(255, 255, 255);"">ε = IgE</span></li></ul>"
What part of the heavy and light chains are responsible for receptor specificity?Variable regions
B cells begin maturation in the bone marrow as ____ and proceed with ____<ul><li>pro-B cells</li><li>VDJ recombination</li></ul>
In early pro-B cells, what are the heavy chain genes?D-J rearranging
What goes first for VDJ recombination in B cell receptor?Heavy chain
What is the smilarities between the α-chain in T cells and the light chain in B cells?both have V and J recombination
What is the smilarities between the β-chain in T cells and the heavy chain in B cells?both undergo VDJ recombination
What are the 4 proteins needed to open the hairpin structure during VDJ recombination? What do they Do?<ul><li>Ku70</li><li>Ku80</li><li>DNA-PK</li><li>Artemis</li></ul><div>This complex of proteins OPEN the hairpin from one side</div>
What do the RAG-1/2 enzyme complex do?makes a cut in the DNA and separates into two regions:<br><ul><li>(BOTTOM aka Coding) one with the V and J</li><li>(TOP aka Signaling) other with the intervening DNA&nbsp;</li></ul>
What is the function of the enzyme TdT? What does DNA ligase IV and XRCC4 do?<ul><li><b>TdT</b>: sits on the open hairpins (which happened bc of the 4 proteins) and starts adding nucleotides</li><li><b>DNA Ligase IV:XRCC4</b>: joins the lose strands of DNA that are floating around the V and J</li></ul><div>This is the completion of VDJ recombination (in this case VJ)</div>
What is recombinatorial diversity?random joining of any number of V, D, and J segments
What is junctional diversity?random addition of nucleotides between V, D and J segments during recombination by&nbsp;<u><b>TdT</b></u><br><br>(nucleotides can also be deleted)
What is pairing diversity?"<ul><li>random pairing of heavy and light chains </li></ul><div style=""text-align: left;"">OR</div><ul><li>use of alternate γ and δ TCR chains</li></ul>"
What happens during Late pro-B cell at the heavy chain?DJ recombination is joined with a V gene
What ends heavy chain rearrangement?the expression of pre-B cell receptor signals
Where is the VDJ finally rearranged in the heavy chain?<br><ul><li>Late pro-B cell</li><li>Small pre-B cell</li><li>Large pre-B cell</li><li>Early pro-B cell</li></ul>Large pre-B cell
What does the surrogate light chain do?tells the B cell to turn off rearrangement of heavy chain genes and start the rearrangement of light chain genes
(True/False): Both the light and heavy chain can have repeated rearrangements during VDJ recombinationFALSE<br><ul><li><u>Correct Statement</u>: <b>ONLY</b> the <b>LIGHT</b> chain can have repeated rearrangements during VDJ recombination</li></ul><div>**remember: this is also true for T cell VDJ recombination except it's the α-chain that is allowed this**</div>
Light chain starts V-J rearranging during which of the following:<br><ul><li>Large pre-B cell</li><li>Late pro-B cell</li><li>Small pre-B cell</li><li>Early pro-B cell</li></ul>Small pre-B cell
In B cells, when the heavy chain has VDJ rearranged and the light chain has VJ rearranged, what is the B cell called? What is expressed on this cells surface?<ul><li>Immature B cell</li><li>IgM is expressed on the cell surface</li></ul>
Which of the following is expressed first on the cell surface? Why?<br><ul><li>IgA</li><li>IgG</li><li>IgM</li><li>IgD</li></ul><ul><li>IgM</li><li>because the first constant region that is there following all the V, D, and J genes, is the μ region</li></ul>
Where does B cell selection occur, and what is this process?<ul><li>happens in bone marrow</li><li>basically, the B cell is presented with self antigents in the bone marrow:</li><ul><li>if it doesn't react with them then...well...its gucci</li><li>once these guys are cleared they can they go to the periphery and do whatever tf they gotta do</li></ul></ul><div>**this has&nbsp;<b><u>NOTHING</u></b>&nbsp;to do with&nbsp;<b>AIRE</b>!!** remember this shit</div>
(True/False): The B cell can undergo receptor editing in only the bone marrow and not the spleen.TRUE
Once the immature B cells leaves the bone marrow what gets turned off? What is the signifiance of this?<ul><li>RAG1:2 gets turned <b>OFF</b></li><li>this is important because this means the the B cell can <b><u>no longer</u></b> participate in receptor editing</li></ul>
If a B cell reacts to no self-antigens in the spleen, what happens to it?<ul><li>It becomes a mature B cell that continues the expression of IgM and upregulate the expression of IgD</li></ul>
What is used as a marker to tell if a B cell is mature or not?If the B cell <u><b>expresses</b> <b>IgD</b></u> that it is looked at as <u><b>mature</b></u>
What is central tolerance?the removal of self-reactive B cells in the bone marrow
What is peripheral tolerance?where a majority of the immature B cells that leave the bone marrow don't survive to become mature
"<span style=""color: rgb(0, 85, 255);"">T_H2</span> Summary:""<ul><li>Produces <span style=""color: rgb(0, 85, 255);"">IL-13 </span>→ help w/ tissue repair and parasite expulsion</li><li>Recruits and activates → M2 macrophages w/ <span style=""color: rgb(0, 85, 255);"">IL-4</span> &amp; IL-13</li><li>Recruits and activates → eosinophils (<span style=""color: rgb(0, 85, 255);"">IL-5</span>)</li><li>Releases → IL-4 (to induce production of IgE)</li></ul>"
"<span style=""color: rgb(255, 85, 0);"">T_H1 </span>Summary:""<ul><li>activate M1 macrophages and enhance intracellular killing</li><li>produce <span style=""color: rgb(255, 85, 0);"">IL-2</span> to activate other T cells</li><li>differentiate in response to <span style=""color: rgb(255, 85, 0);"">IFN-γ</span> and <span style=""color: rgb(255, 85, 0);"">IL-12&nbsp;</span><span style=""color: rgb(255, 255, 255);"">signaling</span></li><li><span style=""color: rgb(255, 255, 255);"">cause apoptosis of infected cells, releasing their antigens ofr further immune activation</span></li><li><span style=""color: rgb(255, 255, 255);"">enhance inflammation</span></li></ul>"
Which Fc receptor pairs with the following: <br><ul><li>Antibody-dependent cellular cytotoxicity (ADCC)</li></ul>FCγRIIIA (low affinity for Ig)
Which Fc receptor pairs with the following:<br><ul><li>Feedback inhibition of B cells, attenuation of inflammation</li></ul>FcγRIIB (low affinity for Ig)
Which Fc receptor pairs with the following:<br><ul><li>Phagocytosis; activation of phagocytes</li></ul>FcγRI (high affinity for Ig; IgG)
Which Fc receptor pairs with the following:<br><ul><li>Activation (degranulation) of mast cells and basophils</li></ul>FcεRI (high affinity for Ig; binds IgE)
"<span style=""color: rgb(170, 85, 255);"">T_H17 </span>Summary:""<ul><li>respond to extracellular infections (recruits neutrophils)</li><li><span style=""color: rgb(170, 85, 255);"">TGF-β, IL-1/6/23</span> signaling → activates <span style=""color: rgb(170, 85, 255);"">RORγT</span></li><li>produce <span style=""color: rgb(170, 85, 255);"">IL-17</span> (stimulate production of <span style=""color: rgb(170, 85, 255);"">neutrophils</span>) &amp; <span style=""color: rgb(170, 85, 255);"">IL-22 </span>(promote <span style=""color: rgb(170, 85, 255);"">turnover of epithelial cells</span> = harder for bacteria to colonize)</li></ul>"
Steps in VDJ recombination:"<ul><li>V and J gene chosen (light chain) / D and J chain chosen (heavy chain) → this is random choosing</li><li><span style=""color: rgb(255, 255, 127);"">RAG1:2 </span>binds to the genes</li><li>It then cuts them and forms the CLOSED hairpins</li><li><span style=""color: rgb(255, 255, 127);"">Ku70:80</span> bind to the coding joints</li><li><span style=""color: rgb(255, 255, 127);"">DNA-PK:Artemis</span> bind and OPENS the hairpin</li><li><span style=""color: rgb(255, 255, 127);"">TdT</span> bind and adds nucleotides</li><li><span style=""color: rgb(255, 255, 127);"">DNA ligase IV:XRCC4</span> → ligates (repairs) DNA</li><li>V-J are joined (imprecisely)</li></ul>"
How do activated T cells migrate away from T cell zone and go towards B cells zones?REDUCE expression of CCR7 and INCREASE expression of CXCR5
B cells that have recognized antigen move away from B cell zone and towards T cell zone. How do they do this?INCREASE expression of CCR7 and REDUCE expression of CXCR5
The CD40:CD40L interaction tells B cells to do what?proliferate and begin making antibodies
Which of the following loses majority of expression of BCR?<br><ul><li>Plasmablasts</li><li>Plasma cells</li></ul>Plasma cells
What cells assist germinal center reaction?"<span style=""color: rgb(255, 0, 0);"">T_FH</span>"
"The generation of <span style=""color: rgb(255, 0, 0);"">T</span>_{<span style=""color: rgb(255, 0, 0);"">FH</span>&nbsp;}requires what?""<span style=""color: rgb(255, 0, 0);"">ICOS-L </span>binding to <span style=""color: rgb(255, 0, 0);"">ICOS</span> receptors"
You have no expression of CXCR4 and you express CXCL13, what zone are you in?Light Zone
You have expression of CXCR4 and you express CXCL12, what zone are you in?Dark Zone
What are hallmarks of the germinal center reaction?<ul><li>Class Switch Recombination (CSR) → changes effector function</li><li>Somatic Hypermutation/Affinity Maturation → changes specificity</li></ul>
What relies on beneficial mutations of the V-region that increase BCR specificity?Somatic Hypermutation
What results from the creation of double-stranded DNA breaks after AID-induced damage?Class Switch Recombination
What is encoded for in DNA and preceded by a unique promotor &amp; switch region?each isotype constant region
(True/False): Transcription through the switch region is initiated via activation of the downstream promoter.FALSE<br><ul><li><u>Correct Statement:</u> Transcription through the switch region is initiated via activation of the <b>UPSTREAM</b> promoter.</li></ul>
Chronic Granulomatous Disease<ul><li>Genetic Defects → problem w/ NADPH oxidase</li><li>Pathophysiology → phagocytes UNABLE to kill phagocytosed microbes</li><li>Typical Infections → sensitive to bacteria that make catalase (degrades hydrogen perioxide)</li><li>Other key features → immune system is retarded and doens't know it's not working properly</li></ul>
Leukocyte Adhesion Deficiency"<ul><li><b>Genetic Defects</b> → problems with integrins and selectins (<span style=""background-color: rgb(170, 0, 0);"">LFA-1, ICAM-1</span>)</li><li><b>Pathophysiology</b> → phagocytes are <span style=""background-color: rgb(170, 0, 0);"">unable to migrate</span> properly to extravascular sites of infections</li><li><b>Typical Infections </b>→ infections early in life w/ impaired wound healing &amp; <span style=""color: rgb(255, 255, 255); background-color: rgb(170, 0, 0);"">absence of pus</span></li></ul>"
Chediak-Higashi Syndrome"<ul><li>Genetic Defects → mutations in <span style=""background-color: rgb(170, 0, 0);"">LYST</span> (lysosomal trafficking regulator)</li><li>Pathophysiology → disruption in fuctioning, size transport of vesicles; <span style=""background-color: rgb(170, 0, 0);"">defective phago-lysosomal fusion and killing of intracellular and extracellular pathogens</span></li><li>Typical Infections → early severe recurrent infections</li><li>Other key features → problems in processes involving <span style=""background-color: rgb(170, 0, 0);"">secretory vesicles and skin pigmentation</span></li></ul>"
Toll-like receptor signaling defects"<ul><li>Genetic Defects → defects in <span style=""background-color: rgb(170, 0, 0);"">SIGNALING</span> components of TLRs</li><li>Pathophysiology → disruption of innate recognition of <span style=""background-color: rgb(170, 0, 0);"">PAMPs</span> = <span style=""background-color: rgb(170, 0, 0);"">small/ineffective inflammatory response</span></li><li>Typical Infections → severe, recurrent, and invasive infections</li><li>Other key features → not due to TLRs themselves, rather strictly because of signaling; <span style=""background-color: rgb(170, 0, 0);"">TLR-3 → herpes &amp; encephalitis</span></li></ul>"
X-Linked SCID"<ul><li>Genetic Defects → mutations in <span style=""background-color: rgb(170, 0, 0);"">common γ-chain of IL-2</span> (needed for almost all receptors)</li><li>Pathophysiology → <span style=""background-color: rgb(170, 0, 0);"">pro-T cells cannot proliferate in response to IL-7</span> = reduced survival and maturation</li><li>Other key features → seen in only <span style=""background-color: rgb(170, 0, 0);"">Males</span> (duh x-linked); <span style=""background-color: rgb(170, 0, 0);"">deficiency in IL-5 so NK cells don't develop</span>; <span style=""background-color: rgb(170, 0, 0);"">normal B cell numbers</span> but can't do T-dependent responses<br></li></ul>"
Autosomal Recessive SCID - Purine Slavage Pathway"<ul><li><b>Genetic Defects </b>→ mutations in (adenosine deaminase) <span style=""background-color: rgb(170, 0, 0);"">ADA</span> or (purine nucleotide phosphorylase) <span style=""background-color: rgb(170, 0, 0);"">PNP</span></li><li><b>Pathophysiology</b> → <span style=""background-color: rgb(170, 0, 0);"">T</span> and <span style=""background-color: rgb(170, 0, 0);"">B</span> <span style=""background-color: rgb(170, 0, 0);"">variable</span> <span style=""background-color: rgb(170, 0, 0);"">toxicity</span> due to <span style=""background-color: rgb(170, 0, 0);"">accumulation of deoxyadenosine</span></li><li><b>Other key features </b>→ ADA and PNP expressed throughout the body so <span style=""background-color: rgb(170, 0, 0);"">many systems can be affected</span></li></ul>"
Autosomal Recessive SCID - Receptor Gene Rearrangement Defects"<ul><li><b>Genetic Defects </b>→ <span style=""background-color: rgb(170, 0, 0);"">RAG1</span>, <span style=""background-color: rgb(170, 0, 0);"">RAG2</span>, and <span style=""background-color: rgb(170, 0, 0);"">ARTEMIS</span> defect</li><li><b>Pathophysiology</b> → <span style=""background-color: rgb(170, 0, 0);"">NO DNA rearrangement</span> because VDJ recombination is compromised = <span style=""background-color: rgb(170, 0, 0);"">T and B cell development arrested</span></li><li><b>Other key features </b>→ <span style=""background-color: rgb(170, 0, 0);"">Omenn Syndrome</span> (variant of RAG1:2 deficiency where only a small amount are made), some symptoms can resemble graft-vs-host disease</li></ul>"
DiGeorge Syndrome (22q11 Syndrome)"<ul><li>Genetic Defects → deletion of <span style=""background-color: rgb(170, 0, 0);"">chromosome 22</span> = deletion of <span style=""background-color: rgb(170, 0, 0);"">TBX1</span></li><li>Pathophysiology → <span style=""background-color: rgb(170, 0, 0);"">thymic epithelium doesn't develop</span> = <span style=""background-color: rgb(170, 0, 0);"">T</span> cells <span style=""background-color: rgb(170, 0, 0);"">can't</span> <span style=""background-color: rgb(170, 0, 0);"">mature</span></li><li>Other key features → no cellular-mediated or humoral immunity b/c of LACK of T cell maturation; patients are <span style=""background-color: rgb(170, 0, 0);"">haploinsufficient for TBX1</span></li></ul>"
Complete B cell deficiency ‒ X-Linked agammaglobulinemia"<ul><li><b>Genetic Defects </b>→ mutation in <span style=""background-color: rgb(170, 0, 0);"">BTK</span> gene</li><li><b>Pathophysiology</b> → arrest of B cell maturation in <span style=""background-color: rgb(170, 0, 0);"">pre-B cell stage</span>&nbsp;= B cells DON'T develop</li><li><b>Typical Infections</b> → pyogenic &amp; <span style=""background-color: rgb(170, 0, 0);"">enteroviruses</span></li><li><b>Other key features</b> →</li><ul><li>identified <span style=""background-color: rgb(170, 0, 0);"">several months after birth</span> when <span style=""background-color: rgb(170, 0, 0);"">maternal IgG</span> levels decrease</li><li>Males</li><li>can be <span style=""background-color: rgb(170, 0, 0);"">treated w/ antibiotics and immunoglobulin therapy</span></li></ul></ul>"
Hyper-IgM Syndrome"<ul><li><b>Genetic Defects</b> → mutations in <span style=""background-color: rgb(170, 0, 0);"">CD40L (x-linked)</span> or <span style=""background-color: rgb(170, 0, 0);"">CD40 (autosomal recessive)</span></li><li><b>Pathophysiology</b> → CD40:CD40L interaction required for T cells to activation of macrophages, and dendritic cells; <span style=""background-color: rgb(170, 0, 0);"">NO T-dependent B cell responses</span>; no germinal center reaction</li><li><b>Typical Infections </b>→ extracellular, intracellular, and opportunistic pathogens</li><li><b>Other key features</b> →</li><ul><li>Extracellular pathogens = cleared by antibodies</li><li>Intracellular and opportunistic infections = cleared by macrophages (<span style=""background-color: rgb(170, 0, 0);"">Pneumocystis jiroveci</span>)</li><li>IgM levels normal just no expression of the others</li></ul></ul>"
Selective IgA Deficiency"<ul><li><b>Genetic Defects </b>→ unknown</li><li><b>Pathophysiology</b> → <span style=""background-color: rgb(170, 0, 0);"">inability to produce IgA</span></li><li><b>Typical Infections</b> → <span style=""background-color: rgb(170, 0, 0);"">asymptomatic</span></li><li><b>Other key features</b> →</li><ul><li><span style=""background-color: rgb(170, 0, 0);"">most common primary immunodeficiency</span></li><li><span style=""background-color: rgb(170, 0, 0);"">IgM</span> can <span style=""background-color: rgb(170, 0, 0);"">compensate</span> for IgA deficiency</li><li>high risk for <span style=""background-color: rgb(170, 0, 0);"">anaphylaxis</span> during blood transfusions due to <span style=""background-color: rgb(170, 0, 0);"">anti-IgA antibodies</span>&nbsp;(transfusion must be washed)</li></ul></ul>"
Common Variable Immune Deficiency"<ul><li><b>Genetic Defects</b> → mutations in genes involved in <span style=""background-color: rgb(170, 0, 0);"">B cell maturation/activation</span> or <span style=""background-color: rgb(170, 0, 0);"">T-B interactions</span></li><li><b>Pathophysiology</b> → <span style=""background-color: rgb(170, 0, 0);"">poor antibody response</span> to infections</li><li><b>Typical Infections </b>→ <span style=""background-color: rgb(170, 0, 0);"">heterogeneous</span> disorder</li><li><b>Other key features</b> →</li><ul><li>used to put a <span style=""background-color: rgb(170, 0, 0);"">label</span> on patients who <span style=""background-color: rgb(170, 0, 0);"">mutations cannot be identified</span>, this disease lable is remove once we find out wtf is wrong with the person</li></ul></ul>"
MHC Class II Deficiency"<ul><li>Genetic Defects → mutations in transcription factors or genes for MHC Class II molecules (CD4+ stuff)</li><li>Pathophysiology → <span style=""background-color: rgb(170, 0, 0);"">NO positive selection of CD4+ cells in thymus</span></li><li>Typical Infections → lack of cell mediated and hurmoral immunity</li><li>Other key features → MHC Class I not affected &amp; <span style=""background-color: rgb(170, 0, 0);"">CD8+ cells develop normally</span></li></ul>"
Selective T cell deficiencies"<ul><li>Genetic Defects → mutations in genes coding for TCR signaling complex components to genes needed for helper T cell differentiation</li><li>Other key features →</li><ul><li><span style=""color: rgb(255, 85, 0);"">Th1 Deficiency</span></li><ul><li>mutations in <span style=""background-color: rgb(170, 0, 0);"">IL-12 and IFN-γ</span></li><li>recurrent infections with intracellular pathogens that survive with macrophages</li></ul><li><span style=""color: rgb(170, 85, 255);"">Th17 Deficiency</span>: (Hyper-IgE or Job's Syndrome)</li><ul><li><span style=""background-color: rgb(170, 0, 0);"">impaired neutrophil response</span> to staph infections &amp; abcesses, skin reactions, <span style=""background-color: rgb(170, 0, 0);"">elevated IgE</span></li></ul></ul></ul>"
X-linked lymphoproliferative syndrome"<ul><li>Genetic Defects → mutation in gene encoding for <span style=""background-color: rgb(170, 0, 0);"">SAP</span> or in the gene <span style=""background-color: rgb(170, 0, 0);"">XIAP</span></li><li>Pathophysiology → dificiency of key signaling molecules for T and NK cell activation</li><li>Typical Infections → <span style=""background-color: rgb(170, 0, 0);"">Epstein-Barr virus</span> (<span style=""background-color: rgb(170, 0, 0);"">mononucleosis</span>)</li><li>Other key features →</li><ul><li>proliferation of EBV-infected B cells and cytotoxic T cells, hypogammaglobulinemia, and <span style=""background-color: rgb(170, 0, 0);"">non-hodgkin's lymphoma</span></li></ul></ul>"
What type of virus is HIV?enveloped RNA retrovirus
What does a retrovirus do?reverse transcribe RNA into DNA
What cells do HIV attack? How?CD4+ using gp120<br><ul><li>less than 200 CD4+ = AIDS (aka NYCPM)</li></ul>
What is HAART?<ul><li>high effective antirestroviral therapy → cocktail of viral protease inhibitors and nucleoside analogs</li><li>it does not elimitate HIV infection from body HOWEVER if you stop this treatment then HIV viral load come back</li><li>this therapy treatment can also reduce the transmission of HIV</li></ul>
What is the goal of CSR?bring the DNA for the recombined VDJ next to the desired constant region (IgM)
What directs the choice of isotype during CSR?"<span style=""color: rgb(255, 0, 0);"">T_FH</span>"
IL-4 allows the switch to what isotype during CSR?IgE
TGF-β allows the switch to what isotype during CSR?IgA
(True/False): T-independent B cell activation leads to low affinity antibody productionTRUE
(True/False): Affinity maturation is present in T-independent antigenFALSE<br><ul><li><b>LITTLE or NO</b> afffinity maturation is present</li></ul>
What are most B cells?Follicular B cells → they reside in B cell follicles and respond to T-dependent antigens
What are marginal zone B cells?<ul><li>reside in periphery of splenic white pulp and outer rim of lymph node follicles</li><li>respond to blood-borne polysaccharide and lipid antigens</li></ul>
What are B-1 cells?they respond to multivalent antigens at mucosal sites
What two types of B cells respond primarily to T-independent antigens?MZ and B-1 cells
What contributes to neonatal antibody protection and to IgG half-life?FcRn
What is ADCC mediated by?IgG binding to FcγRIII