Term
| Difference between immunogen and Hapten? |
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Definition
Immunogen always cause one, foreign and complex
Haptens ony generate one when bound to larger macromolecules |
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Term
| What are the types of epitopes |
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Definition
Discontinuous - unchanged and can be bound to B cells.
Linear - Processes and the epitopic part of the antigen are right next to each other. T cell need this type |
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Term
| Describe the antibody structure |
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Definition
| Two heavy, two light chains linked by disulfide bridge |
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Term
| What is the variability in light chains made of? |
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Definition
| Two types, kappa or lambda. Has V and D regions |
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Term
What is Fab and Fc?
Function of Fc? |
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Definition
Fab - Area for antigen binding (consists of heavy and light areas) and Fc- constant area (also heavy and light)
Fc activates complement cascade when bound to antigen (binds C1) |
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Term
| How many domains do light chains and heavy chains have? |
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Definition
Light - 1 variable and 1 constant
Heavy - 1 variable, 3 constant |
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Term
| What are the role of antibodies? |
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Definition
| To bind pathogen. Could destroy pathogen by agglutination, could also opsonize and enhance phagocytosis |
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Term
| Describe IgM structure and role |
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Definition
First antibody responder, best opsonizer, pentamer.
best at agglutination |
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Term
| Role and structure of IgD |
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Definition
| Non soluble, surface receptor. Monomer |
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Term
| Role and structure of IgA |
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Definition
Dimer, biggest role in mucosal immunity. Th2 responses
Forms a dimer by joining the J chain and has a secretory component which function to protect it from proteolytic attack |
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Term
| Role of IgG and structure? |
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Definition
Monomer, most prevalent antibody
Longest half life, Th1 - cell mediated cytotoxicity
Primary responded to LPS |
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Term
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Definition
Th2 responder, monomer, response to parasitic infection
bind to mast cell and activation leads to degranulation |
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Term
| What are the different types of T cell chains? |
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Definition
| A/B chains (95%), gamma/delta (5%) |
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Term
| What is weird about G/D T cells? |
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Definition
| don't recognize MHC associated cells, but can recognize non peptide antigens |
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Term
| What are the similarities between light chains and alpha chains? Heavy and beta? |
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Definition
both only use V and J segments
use V,D and J segments |
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Term
| how is T cell diversity created? |
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Definition
No somatic hypermuation, class switiching etc...
Existence of multiple V region, junctional diversity, combination of chains. Greater potential for junctional diversity because of randomness of TdT enzyme |
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Term
| how is B cell receptor diversity created? (5) |
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Definition
1) Germline diversity - multiple (V,D, and J segmentS)
2) Combinatorial diversity (different ways to match V,D and J)
3)Junctional diversity - different sequences at the joints between V, D and J (need DNA rearrangements to Join)
4) Light and heavy chain diversity
5) Somatic hypermuation |
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Term
| What has more diversity: T cell receptor or B cell receptor? |
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Definition
| TCR because of junctional diversity, could be 10^18 |
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Term
| What are superantigens and how do they work? |
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Definition
| They activate all T cells bearing a Vbeta region, therefore can initiate an immune response that includes 20% of all T cells |
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Term
| What are necessary accessory molecules for T cell stimulation? |
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Definition
| CD3 and CD4/CD8. CD4/CD8 stabilize the TCR peptide MHC complex as they bind to MHC molecules, biding tyrosine kinases near CD3 to activate signal transduciton |
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Term
| How is the MHC system inherited? |
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Definition
| In haplotypes, or block of alleles that are identical within families. However, within a family, none of the member shave identical combination, there is no recombination in th eMHC |
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Term
| What is allelic exclusion? |
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Definition
There is only one form expressed on each cell (like how Ig and TCR only express one type per cell)
But MHC is codominantly expressed, and only certain types are selected. |
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Term
| What causes polymorphism in MHC molecules? |
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Definition
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Term
| What is T cell restriction? |
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Definition
| T cells need to be specific to both antigen and MHC molecule, in that sense, MHC function to be a ligand and a binding site |
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Term
| How are antigen processes? which type leads to MHC types? |
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Definition
| Peptide generated intracellularly leads to CD8+ cells (MHC I viral) and peptides generated extracellulary lead to CD4+ cell activation (MHC II) |
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Term
| How are extracellular antigens processed? |
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Definition
| Internalized by receptor mediated endocytosis, degraded by proteases, lysosomes and eventually amino acids. APC synthesizes MHC II in the ER, bud with endosomes and expressed on the surface. However, while the MHC is in the ER, it is protected by an invariant chain to prevent activation - the acidic environment cleaves the invariant chains and allows the MHC to bind antigen |
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Term
| What molecules are important for intracellular antigens? |
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Definition
Proteasome complex (degrade cytosolic antigens)
TAP to transport them to ER
Antigens- needed for MHC I folding, otherwise they wilt and die |
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Term
| How does Tuberculosis evade pathogen processing? |
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Definition
| It doesn't prevent uptake, but rather fusing of endosome and lysosome, so the macrophage can do no better than conain it. Leads to granulomas |
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Term
| What happens when a CD4 cells binds to an APC that has internalized an antigen? |
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Definition
| If it binds to a killing capable cell, like a macrophage, binding will activate phagocytosis and killing of antigen. B cells can function as APCs as well |
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Term
| Describe in detail B cell activation |
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Definition
| Igalpha/beta contain ITAM motifs required for signal transduction. Once bound to antigen, Syk phosphorylates ITAMs in IGA/beta. This bindings leads to changing in transcription, phospholipase C etc... |
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Term
| Describe in detail T cell activation with kinases? |
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Definition
| The TCR is made up of CD3, CD4 and the alpha/beta chains. Clustering leads to LCk phosphorylates CD3 (contains ITAMs) once activated, leads to intracellular signaling pathways |
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Term
| What is the end result of B/T cell activation via phosphorylation? |
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Definition
| Proliferation of cell, activation of Th cells leads to release of proliferatory cytokines like IL-2 |
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Term
| When does B cell development first occur? |
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Definition
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Term
| What are the stages of B cell development? |
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Definition
| Stem - Pro B - early pre-b - late pre-b |
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Term
| How do differentiate between the various stages of B cell development? |
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Definition
| By rearrangement of IG heavy and light chain genes, |
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Term
| What rearranges first, heavy or light chain? What is allelic exclusion? |
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Definition
| Heavy chain rearranges first in the pro-B stage. Allelic exclusion is where only one gene for rearrangemen (either heavy or light) is activated at once. Prevents wasteful secretion of unfinished or damaged antibodies |
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Term
| What defines the pro-b, early pre-b, late pre-b stages? |
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Definition
| Early pro-b is heavy chain rearrangement, early pre-b is light chain formation, late pre-b is light chain rearrangment |
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Term
| When are immature cells considered mature? |
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Definition
| when they express surface IgM/IgD |
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Term
| What is B cell tolerance? What is supposed to occur? |
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Definition
| Those cells that display self reactivity are destroyed or made anergic. The B cell is not supposed to recognize any antigens in the bone marrow. Antigen binding leads to tolerance and maturational arrest. |
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Term
| What is receptor editing? |
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Definition
| If they become tolerant to self antigen, VDJ machinery is upregulated so to alter specificity from autoreactivity |
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Term
| As B cells are dependant on costimulatory molecules, how does this prevent autoreactivity |
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Definition
| If a mature B cell engages an antigen, but no T cell specific for antigen responds, conscious realization that it is an auto antigen. B cell is not fully activated and becomes anergic |
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Term
| What is the role of FDCs and B cell activation? |
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Definition
| Create environment where antigen are concerntraed and displayed to naive b cells. Only found in lymphoid follicles, not MHC II, but retain antigen/antibody complexes. |
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Term
| Once a B cell has seen antigen, thanks possibly to FDC, what happens? |
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Definition
| Moves to 2ndy lymphoid organ, finds target antigen and internalizes it via the BCR complex. Antigen is degraded and processed into MHC II receptors. Here the B cell may undergo somatic hypermuation to get a bette fit to the antigen |
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Term
| What are thymus dependant antigens? |
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Definition
| Those that require B and T cell collaboration, as though B cells can internalize antigen, they require costimulatory molecules from CD4 cells to activate to effector (plasma cells) that secrete antibodies |
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Term
| How does somatic hypermutation benefit antigen binding? |
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Definition
| Creates BCR with best fit, those that bind receives survival signals from FDCs (positive selection) and then differentiate. With each round of somatic mutation, B cells has increasing affinity towards antigen = affinity maturation |
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Term
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Definition
| Fetus and neonatal lymphocytes, but don't replenish via bone marrow, rather through division in peripheral tissues. Low divesity, and produce cross reactive antibodies |
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Term
| What % of thymocytes die in maturation process? |
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Definition
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Term
| What are the stages of selection T cells undergo in the Thymus? |
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Definition
| Start as double negative cells (no cd8 or cd4) - commit to alpha/beta or gamma/delta lineage, then become double positive cells (CD4 and CD8), then are selected as either CD4 or CD8 based on ability to associate with MHC, release of single positive cells |
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Term
| When do TCR rearrangements occur during thymus development? |
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Definition
During the double negative (neither CD4/CD8) stage
Beta TCR chain and alpha TCR chain complex with CD3 to form pre-TCR complex |
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Term
| What leads to transition from double negative cells to double positive cells? |
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Definition
| The formation of the pre-TCR complex (alpha/beta/cd3) allows for signal transduction. This leads to proliferation of double positive cells |
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Term
| What determines if a double positive T cell with become a SP cell? |
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Definition
| Ability to interact with MHC self peptide antigen complex - transduce a signal that lead to differentiation |
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Term
| What form of negative selection happens in T cell development? |
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Definition
| clones that are strongly reactive with self peptides are eliminated. however, asmany soluble self antigens are recognized in the thymus, it isn't a perfect system. AIRE mutations prevent expression of endocrine organs - leads to autoreactivity |
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Term
| When and how is a naive T cell activated? |
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Definition
| Move from blood to lymphoid organs, in 2ndry lympoid organs encounters APC with antigen. If recognizes MHC, antigen and gets costimulatory signal - activation. become effector cells and move to peripheral tissues to handle pathogen directly or help activate B cells |
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Term
| What could CD4 cells become? |
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Definition
Either TH1 or TH2 cells depending of type of immune response taking place and cytokines present.
IL-2, IFN-G --> CD4.stimulates IgG and CD8+. IL-4 - TH2 - switch to either IgA or IgE |
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Term
| How are CD8 cells activated? |
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Definition
| Either by interacting with professional APC (DC's can have MHC I also) and receiving costimulatory molecules, or by interacting with nonprofessional APC and receiving second signal from CD4 cells like cytokines |
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Term
| What is the role of the gamma/delta T cell subset? |
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Definition
| Recognizes antigen without processing in absence of MHC class I or II. First line of defense. More like PRMS |
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Term
| Describe the steps of apoptosis |
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Definition
| Triggered through fas-fas ligan interaction. Leads to cascade to activate caspase, leads to DNAse cleaves into fragments, cell death |
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Term
| What are the steps of BCR formation (Recombinase and such) |
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Definition
| First Combine D and J regions (for heavy chains) V and J for light, then rearrange, add other regions, remove leader sequences |
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Term
| What is the role of RAG enzymes |
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Definition
| Initiate immunoglobulin gene rearrangements in B cells and T cells. Deficienceis leads to immunodeficency diseases |
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Term
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Definition
| enzymes responsible for all of TCR junctional diversity |
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