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Immunology Exam 3
for next semester when you retake
| Question | Answer |
|---|---|
| T or F: TCR is always membrane bound | True |
| What are effector cells? | What are effector cells? macrophages, neutrophils, NK cells (anything that induces phagocytosis) |
| What is part of V-domain on TCR? | β sheet on framework region, 3 loops of CDR (additional HV loop not part of Ag binding) |
| What is part of C-domain on TCR? | Cβ similar to IgC, Cα has one βsheet and one short αhelix. Cα and Cβ is enforced by hydrogen bonds formed by carbohydrates |
| What is TCR somatic recombination? | cause of TCR diversity. DNA recomb b/w segs on Ig genes and TCR genes to generate a complete exon |
| Where does TCR somatic recomb occur? | in the thymus |
| T or F: α chain has V-J rearrangement | True |
| T or F: β chain has V-D-J rearrangement | True |
| What does it mean when VDJ has two chances for rearrangment? | bc there are 2 C regions of β chain proceeded with its D and J segments |
| What does CDR stand for? | Complementarity-determining-region |
| Where are each of the 3 CDRs found on V-domain of TCR? | CDR1 and CDR2 are in the V-segment, while CDR3 is formed at the VDJ or VJ junctions. |
| How is TCR diversity caused? | Somatic recomination |
| What is TCR somatic recombination mediated by? | RAG1 and RAG2, RSS, p and n nucleotides, and more extensive junctional diversity |
| What is a TREC (T cell excision circle)? | the looped out DNA during TCR recombination, a marker for new T cells |
| T or F: TCRs have more diversity than BCRs | True |
| What is the other TCR? (hint: not α/β) | γ/δ TCR |
| Where are the entire δ-chain genes located? | within α-chain locus between V and J segments. Rearrangement of α-chain will delete all δ chain genes |
| What chromosome is the α-chain located? | Chromosome 14 |
| What chromosome is the γ chain located? | Chromosome 7 |
| T or F: γ/δ V regions have limited VDJ segments (limited combinatorial diversity) | True |
| What is the TCR complex? | It is the TCR associated with the CD3 complex on both sides |
| What is the CD3 complex made of? | 6 invariant membrane proteins: γ, δ, ε, ε, ζ, ζ. Where γ/ε, δ/ε, and ζ/ζ are dimers. |
| What are ITAMs on CD3 responsible for? | Signal transduction after TCR activation by an Ag |
| What are the 2 subpopulations of αβ T cells? | those with CD4 co-receptors or CD8 co-receptors |
| What MHC class does the CD4 co-receptor interact with? | MHC class 2, where the T cells are helper or regulatory cells |
| What MHC class does CD8 interact with? | MHC class 1, where the T cells cytotoxic T cells (kill viruses or tumor cells) |
| What is the difference between class 1 and 2 MHC proteins? | Class 1 MHC proteins are found on the surface of all nucleated cells CLass 2 MHC proteins are found on the surface of APC cells (B, Dendritic, and macrophages) |
| what is the main STRUCTURAL difference between MHC class 1 and MHC class 2? | MHC class 1 have only 2 alpha chains forming antigen-binding site. MHC class 2 have 2 alpha AND 2 beta chains forming antigen-binding site. |
| structure of CD4 co receptor | straight line made of 4 complexes D4,D3,D2,D1 |
| Structure of CD8 co-receptor? | Dimer of αβ chains, binds to α3 domain of MHC class 1. Cytoplasmic domain = signal transduction after TCR Ag binding, enhances activation signals. |
| What does MHC stand for? | Major Histocompatibility Complex |
| What are MHCs? | membrane glycoproteins that are highly polymorphic. Critical in development of adaptive immune response. |
| MHC class 1 structure | GET THE PICTURE. Heavy α chain (made of α1,α2,α3 where 1 and 2 form a peptide Ag binding groove) and an invariable β2-microgloblin. |
| MHC Class 2 structure | GET THE PICTURE. An α chain (α1,α2) and β chain (β1,β2). The α1 and β1 form the peptide Ag binding groove. |
| Where are MHC class 2 cells expressed? | on APCs (Ag presenting cells) like DC, MΦΦ, and B cells. Recognized by CD4 T cells. On all nucleated cells. |
| How is the MHC class 1 Ag binding groove formed? | by α1 and α2 domains |
| How is the MHC class 2 binding groove formed? | by α1 and β1 domains |
| How is the MHC binding groove formed in general? | by 2 α-helices at either side and a β sheet at floor |
| How does TCR interact with MHC? | CDR1 and CDR2 interact with helix sides of Ag binding groove. CDR3 interacts with peptide in Ag binding groove |
| How does the peptide Ag bind to MHC? | MHC has promiscuous binding specificity. Peptides share specific anchor residues for particular MHC's = peptide-binding motif |
| Describe peptide bonding to MHC class 1 | 8-10 aa long Residues at end of MHC Ag binding groove interact with N-orC-terminus of aa peptide to STABILIZE binding Most peptides have hydrophobic/basic AA residue at carboxyl terminus |
| Describe peptide bonding on MHC class 2 | 13 aa or longer Can extend out of the binding groove Ag binding depends on side chains that fit into pockets of MHC binding groove. Anchor residues of peptide Ag for MHC class 2 molecules are more variable and harder to predict |
| T or F: there are multiple MHC class 1 or class 2 molecules (polygenic) | True |
| T or F: there are 3 MHC class 1 α chains | True. HLA-A, HLA-B, HLA-C |
| T or F: there are 3 MHC class 2 α/β chains | True. HLA-DP, HLA-DQ, HLA-DR |
| What chromosome is gene for β2-microglobulin located? | Chromosome 15 |
| Where do most of the genetic variations occur on MHCs? | at sites of peptide binding or T cell receptor interaction areas |
| What is that unique feature of the HLA-DR on the β-chain? | there is one HLA-DRA gene on one chromosome. Some ppl have an additional HLA-DR β chain gene (DRB3,4, or 5). DRA is oligomorphic. HLA-DRA pairs with HLA-DRB1 and sometimes can pair with additional β-chain (DRB3,4, or 5). A maximum of 8 combinations from |
| T or F: different forms of a gene are "alleles" and their products are "allotypes or isoforms" | True |
| T or F: a gene with many different alleles is "polymorphic" | True |
| T or F: a gene with few different alleles is "oligomorphic" | True |
| T or F: a gene with only one allele is "monomorphic" | True |
| T or F: different alleles on two chromosomes is "heterozygous" | True |
| T or F: same alleles on two chromosomes is "homozygous" | True |
| T or F: MHC alleles on a single chromosome is an "MHC haplotype" | True |
| What are 3 reasons MHC molecules can bind to genetically diverse peptide Ag? | 1) Polygeny - Class 1 (A, B, C) and Class 2 (DP, DQ, DR) 2) Polymorphism and co-dominance - each gene has multiple alleles and alleles on both chromosomes can be expressed 3) Promiscuous - each MHC molecule can bind to several different peptides, peptid |
| T or F: MHC diversity is NOT caused by somatic recombination or somatic hypermutation | True |
| T or F: MHC class 2 expressed only on Ag presenting cells and thymic epithelium cells | True |
| T or F: any viral infected or transformed cell can stimulate CD8 T cell and be targets for CD8 T cell cytotoxicity | True |
| T or F: Ag presenting cells like DC or MΦ can present Ag to BOTH CD4 and CD8 T cells | True. B cells present Ag to primed CD4 T cells |
| Expression of MHC can be enhanced during infection by... | IFN-γ |
| What are the 2 distinct pathways that pathogens or pathogen Ags enter cells? | 1) Produced in cytosol - by virus, cytosolic bacteria, or tumor 2) Endosomal vesiscles - phagocytosis, receptor mediated endocytosis, macropinocytosis. From extracellular bacteria or virus, phagocytosed intracellular bacteria, or toxins |
| Does the source of the pathogen affect Ag presentation by MHC? | Yes. Cytosolic Ag is presented by MHC class 1 to CD8 T cells, and Endocytic vesicle Ag is presented by MHC class 2 to CD4 T cells. |
| T or F: presenting cytosolic Ag on MHC class 1 is important for activating CD8 T cells to kill infected cells | True, bc cytosolic pathogens can replicate in any cell |
| T or F: Ag activated CD4 T cells can enhance MΦ killing of pathogens | True |
| T or F: B cells endocytose Ag using surface Ig and present Ag on MHC class 2 to elicit CD4 T cell help | True |
| T or F: DC's are most important APC | True, bc it presents Ag on MHC class 1/2 and activate naive CD8 and CD4 T cells |
| Steps of cytosolic Ag presentation by MHC class 1 | 1) Proteins in cytoplasm are degraded by proteasome into peptides 2) Peptides transported to ER 3) Peptides loaded onto MHC class 1 molecules 4) Ag loaded MHC class 1 are translocated on cell surface |
| What are Cytosolic Ag's? | they are... Pathogen-Ag = intracellular like a virus Tumor-Ag = tumor specific protein Self-Ag = cellular proteins (old, damaged, misfolded) |
| What is the proteasome? | it has 2 19s regulatory caps and 1 cylindrical 20s catalytic core. 19s caps bind to Ubiquitin tagged protein and bring protein to catalytic core to be degraded IFN-γ induces its modification making IMMUNOPROTEASOME |
| What does Immunoproteasome do? | 1) increase protein degration efficiency 2) Increase protein cleavage after hydrophobic residues, decrease protein cleavage after acidic residues... making more peptides with hydrophobic or basic carboxyl terminus which fit well in class 1 MHC molecules |
| Cleaved peptides are transported by... | TAP (transporter associated with Ag process) |
| What is TAP? | Heterodimer made of TAP1 and TAP2. An ATP-binding cassette (ABC) that transports peptides to ER |
| What enhances TAP transport? | IFN-γ |
| What is needed to load Ag to MHC class 1? | MHC class 1 loading complex. It contains calreticulin, ERp57, tapasin and TAP |
| What trims excess AA to fit the peptide into the binding groove? | ERAP (endoplasmic reticulum aminopeptidase) |
| What are the steps of endosomal Ag presentation by MHC class 2? | 1) entry via phagoytosis, receptor mediated endocytosis, or macropinocytosis 2) Lysosome in cell fuses with phagosome = phagolysosome 3) Acidic proteases degrade protein Ags to peptides 4) Processed peptides are loaded to MHC class 2 in phagolysosome |
| How is peptide Ag loaded to MHC class 2 molecule? | 1) newly synth MHC class 2 in ER is associated with INVARIANT CHAIN (Ii) to prevent binding of peptides in ER and facilitate entry to phagolysosome 2) Entry to phagolysosome = MIIC (MHC class 2 compartment) 3) Ii is cleaved by acid protease and remainin |
| How does TRIMERIC invariant chain bind to MHC class 2? | 1)Trimer binds to 3 newly synthesized MHC class 2 at Ag binding groove in ER to prevent binding of peptides in ER. 2) Ii is cleaved to be CLIP that remains on Ag binding groove of MHC class 2 3) MHC class 2 dissociates with Ii in MIIC and loads with pe |
| What is Ag cross presentation? | when extracellular Ags are presented on MHC class 1 without infecting the APC (viral infection). Ag in endosome exits the cytosol and is processed by proteasome and transported to ER by TAP to be loaded to class 1 MHC by MHC loading complex. |
| How is cytosolic Ag presented to MHC class 2? | Autophage mediated Ag processing and presentation. Autophage is a process to remove cellular proteins and damaged organelles. Then enters autophagosome to be processed by protease and loaded to MHC class 2 |
| What 2 ways to naive T cells enter LN? | 1) From blood circulation through HEV 2) From other LN through lymphatic system |
| T or F: Naive T cell activation is dependent on Ag presentation by APC especially DC | True. DCs carry Ag from tissues to peripheral LN |
| What is involved in lymphocyte entry into LN? | Interactions between: Adhesion molecules between lymphocytes and HEV, and chemokines (from tissue) and chemokine receptors (on lymphocyte) |
| Name the three pairs of lymphocytes/HEV (in order)... | -L-selectin (lectin) with CD34/GlyCAM-1 (vascular addressin) -LFA-1 (integrin) with ICAM-1 (Ig superfamily) -CCR7 (chemokine receptor) with CCL21/CCL19 (chemokine) |
| How do naive lymphocytes (T cells) home to the lymph node? | *Rolling = weak interact b/w L-selectin and vascular addressin *tight bonding = chemokine activates integrin on T cells and allows tight binding to ICAM-1 on HEV *T cell with CCR7 migrates to LN T cell area following Chemokine (CCL21,19) gradient produc |
| What is the role of Immature DCs? | They distribute most tissues in the body |
| What are the 4 ways that Immature DCs intake Ag? | 1)Phagocytosis 2)Receptor (complement, Fc etc.) mediated endocytosis 3)Macropinocytosis (non-specific) 4)Infected by virus |
| After PAMPs activate DC through PRR, what do the activated DCs do? | Increase Ag processing. Express CCR7 (to enter LN), co-stimulatory molecules CD80 and CD86, and MHC to become mature DCs |
| What do Mature DCs do? | No longer phagocytic and express more adhesion molecules (DC-SIGN, ICAM-1, ICAM-2, LFA-1) to enhance interactions with naive T cells and become strong T cell activator |
| What are the 3 types of professional APCs? | 1) Dendritic Cell = activate naive T cells 2) Macrophage = phagocytose, but CAN activate effector cells and memory cells 3) B cell = obtain T cell help for B cell proliferation and differentiation (see chart) |
| How are naive T cells activated in secondary LN tissues (spleen)? | Naive T cells interact with Ag presenting DCs to be activated, which DOWN-REGULATE S1P receptor. Then it is proliferated, differentiated to become EFFECTOR T cells, which consequently UP-REGULATES S1P receptor. They exit LN and migrate to the site of inf |
| What is S1P receptor? | Sphingosine-1-phosphate receptor |
| T or F: T cell activation needs receptor/co-receptor and co-stimulatory signals | True. T cell activation requires 1) signal from T cell receptor complex and co-receptor and 2) Co-stimulatory signals |
| What are the co-stimulatory signals? | CD28 (on the T cell) and B7 (on the APC). B7 consists of B7.1 (CD80) and B7.2 (CD86). Co-stim requirment ensures T cell activation only occurs during infection |
| How is the signal pathway initiated and cause gene expression and T cell activation? | TCR-AgMHC and CD4/8-MHC brings TCR close to co-receptor. ITAMs on CD3 of TCR complex are Phosphorylated by Lck or Fyn. Those ITAMs then recruit ZAP-70 which initiates the signal pathway. |
| What are the 2 zones of T cell synapse? | 1) c-SMAC containing interaction for activation signaling 2) p-SMAC forming the tight connection between T cell and APC |
| What does c-SMAC contain? | T cell-APC TCR-Ag+MHC --> signal 1 CD4/8 - MHC CD28 - B7s (CD80/86) --> signal 2 CD2 - LFA-3 (Ig family adhesion molecules) |
| What does the p-SMAC contain? | LFA-1 -- ICAM1 |
| T or F: Activated T cells express high affinity IL-2 receptor and Il-2 to induce proliferation | True |
| What is IL-2? | a strong lymphocyte growth factor and acts as autocrine to promote T cell proliferation. It is the third signal resulting in T cell activation and proliferation |
| T or F: T cell activation is regulated by inhibitory CTLA-4 | True. It induces an inhibitory signal, while it interact with B7 to activate T cell |
| How does CTLA-4 limit T cell activation? (2 ways) | 1) outcompetes CD28 - no secondary signal for T cell activation 2) binding to B7 elicits an intracellular inhibitory signal that tells the B cell not to proliferate |
| T or F: CD4 T cells differentiate into functionally distinct helper T cells | True |
| What types of helper T cels are there? | Th17, Th1, Th2, Follicular Helper (Tfh), and regulatory (Treg) cells |
| T or F: Differentiation of CD4 T cells is determined by APC cytokines | True. APCs are in turn influenced by the types of infection and microenvironments |
| How exactly is CD4 T cell differentiation done? | Different pathogens influence APCs to produce different polarizing CYTOKINES (signal 3). Each Th population expresses different Master Transcription Factor and produces distinct signature cytokines that relate to its specific functions |
| How are Th17 cells made? | APC produces TGF-β and IL-6 that promote its differentiation and inflammation |
| What is the function of Th17 cells? | 1) produce IL-17A, IL-17F that activates fibroblasts and epithelial cells to produce CYTOKINES THAT RECRUIT NEUTROPHILS 2) Immunity against extracellular bacterial and fungal infections in mucosal sites |
| What is the funciton of Th1 cells? | 1) produce IFN-γ to activate MΦ which activates phagolysosome which kill phagocytosed INTRACELLULAR bacteria 2) activate CD8 T cells that kill virus infected cells 3) promote antibody isotype switch to strong opsonin Ab classes such as IgG1 |
| How are Th2 cells made? | During parasitic infection, mast cells, basophils, and NKT cells produce IL-4 that promote Th2 cell differentiation |
| What is the function of Th2 cells? | 1) produce IL-4 and IL-5 enhancing recruitment/function of mast cells and eosinophils to promote IgE SWITCH during parasite infection 2) Promote Ab isotype switch to IgG2 (neutralization), IgG4 (allergenic response), IgA (mucosal immunity) |
| T or F: Th1 differentiation suppresses Th2 differentiation and vice versa | True. In acute infection, Lepromatous leprosy turns Th2 on and supresses Th1 that help cure it. (what about tuberculoid leprosy?) |
| How are Tfh cells made? | IL-6 from DC induces differentiation of Tfh cells |
| What is the function of Tfh cells? | B cell proliferation, express ICOS and IL-21 which promote B cell activation/survival/Ig production. Also express Th1 or Th2 type cytokines that promote specific Ig class-switch. |
| what is ICOS | Inducible T-cell co-stimulator |
| How are Treg cells made? | In absence of infection and presence of TGF-β without IL-6, Treg cells differentiate. |
| What is the function of Treg cells? | express IL-10 and TGF-β 1)suppress T cell activation 2)inhibit APC function 3)prevent immunopathology |
| T or F: effector T cells change their surface molecules that alter their functions | True. Naive T cells express L-selectin, are activated/diff, DOWN-REGULATE L-selectin but UP-REGULATE LFA-1 and VLA-4. Both bind to ICAM-1 and VCAM-1. Naive T cells also express CD45RA (isoform of CD45) while Effector T cells express isoform CD45RO = |
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Hamncheese52
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