Cumulative Learning Objectives – Flashcards
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Somatic recombination occurs in what cells?
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B and T cells
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Junctional diversity occurs in what cells?
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B and T cells
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Somatic hypermutation occurs in what cells?
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B cells
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Isotype switching occurs in what cells?
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B cells
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Affinity maturation occurs in what cells?
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B cells
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What does somatic recombination accomplish?
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-Creates combinatorial diversity -Uses RAG-1/RAG-2 for recombination in BCR and TCR
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What does somatic hypermutation accomplish?
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increase points of mutation that are initiated bu the AID enzyme through the heavy and light chain variable regions; 1 point mutation/V region/ Cell devision
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Is somatic hypermutation more common in B-1 or B-2 lymphocytes?
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High in B-2, low in B-1
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How does somatic hypermutation play a role in germinal centers?
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Germinal center: where activated B cells undergo somatic hypermutation to become centroblasts
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How does somatic hypermutation and isotype switching play a role in centroblasts?
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become small non-proliferating centroblasts after being isotype switched and undergoing somatic hypermutation
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What cell interaction triggers isotype switching and somatic hypermutation?
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Triggered by T cell interaction/ linked recognition
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What controls isotype switching?
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what are where the pathogen is
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Describe the process of isotype switching
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-B cell receptor binds -Gene is turned on -AID introduces cytokine to uracil -the base from uracil nucleotide is removed by UNG -APE1 leaves a hole where there is missing DNA -Looping occurs and DNA strand recombination is promote -rearranged V region is matched with a new C region
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What is the IL that is an isotype switch factor?
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IL-5 from Th2
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What are that cognate pairs?
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B cell and Tfh form a cognate pair and trigger isotype switching and somatic hypermutation
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Explain the relevance of isotype switching in somatic hypermutation in T-dependant and T-independant B cell interactions
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T-Dependant Isotype: occurs Hypermutation: occurs T-Independant Isotype: minimum, mostly IgM Hypermutation: NONE
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What are the 4 cytokines that cause plasma cells located in the cut to isotype switch to IgA production
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TGF-beta --> BAFF, IL-10 --> IL-10, APRIL
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What is negative selection? What is positive selection?
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Neg: removal of lymphocytes that recognizes self-antigen, makes sure T cell doesn't attack self-antigen Pos: guarantees that a T cell is capable of binding/ recognizing an MHC class
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What is receptor editing? What chain does it occur in? What does it prevent?
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Editing the light chain is edited; self-reactive B cells in bone marrow edit their antigen binding site; prevents negative selection
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Do the following cells go through positive or negative selection? -B cells -Alpha-Beta T cells -Gamma-Delta T cells
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-B cells: negative -Alpha-Beta T cells: both -Gamma-Delta T cells: neither
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Does negative or positive selection occur first?
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Positive
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What cells mediate negative selection of T cells? What about positive ?
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Neg: cortical epithelial cells Pos: DC, macrophages, thymocytes
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What is central tolerance?
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deletion of self reactive T lymphocytes in the thymus through negative selection
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What is the two-signal hypothesis?
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states that a T cell must receive a minimum of two signals to respond to an antigen
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What are the two signals that T cells must receive according to the two-signal hypothesis?
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1) primary through MHC 2) Co-stimulatory signal through molecules on APC; need B7 for APCs to express co-stimulatory molecule)
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What would happen if the two-signal hypothesis was not satisfied?
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The T cell is not activated
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What is linked recognition?
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T cell interaction; T and B cells specific for different epitopes of the same antigen can cooperate
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What cells participate in linked recognition?
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T cells and B cells
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How is linked recognition responsible for epitope spreading?
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the sloppiness of T cell's held to B cells
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What are the cytokines required for a naive (CD4+) T cell to activate?
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IL-2
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What cytokines are released by Th1?
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IL-2, IFN-gamma, GM-CSF
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What cytokines are released by Th2?
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IL-4, IL-5, and IL-13
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What cytokines create the Th1 subset?
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IL-12 and IFN-gamma
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What cytokines create the Th2 subset?
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IL-4
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What cytokines create the Th17 subset?
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IL-6 and IL-21
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What cytokines create the Treg subset?
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TGF-beta
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What cytokines create the Tfh subset?
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IL-16, TGF-beta, IL-23
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What cytokines are released by Treg?
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TGF-beta and IL-10
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What cytokines are released by Th17?
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IL-6 and IL-17
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What cytokines are released by Tfh?
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IL-21
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What cells function as professional APCs?
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dentritic, macrophages, and B cells
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What cells function as phagocytes?
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neutrophils and macrophages (aslo basophils and eosinophils)
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What are the common CD markers for T cells?
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CD3, CD4, CD8
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What are the common CD markers for B cells?
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CD19, CD21, CD84
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What are the common CD markers for NK cells?
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CD16, CD56
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What CD markers are on Cytotoxic T Cells?
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CD8, CD3
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What CD markers are on Helper T cells?
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CD4, CD3
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What CD markers are on gamma-delta T cells?
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CD3 ONLY
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True or False: NK cells lack CD3
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True (only have Cd16 and CD56)
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What is innate Immunity?
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-rapid response -fixed -limited specificities -constant during a response -no memory
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What is adaptive immunity?
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-slow response -variable -numerous specificities -improves during a response -memory formed
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What cells are active in innate immunity?
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alpha-2-macroglobulins, pentraxins, defensins
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What cells are active in adaptive immunity?
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B cells and T cells
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What are the advantages of adaptive immunity?
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improves over time, can remember how to fight reoccurring pathogens
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What is the role of TLR in innate immune responses
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activate inflammatory cytokine production, recognize an array of microbial components, activates cytokine gene expression in infected cell
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What are features of B-1 B lymphocytes?
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-produced in a fetus -self renewing -high levels of spontaneous Ig production -secretes more IgM -no somatic hypermutation -Responds to carb antigens
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What are features of B-2 B lymphocytes?
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-Produced after birth -Produced in bone marrow throughout lifetime -Low levels of spontaneous Ig production -Secretes more IgG -High levels of somatic hypermutation -Responds to protein antigens
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What two CD markers can identify a B-1 cell from B and T cells?
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CD5 and CD19/CD20
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What are features of T-dependant B lymphocyte antibody responses?
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-B cell reaction antigens require T cell help for proper response -isotype switching occurs -somatic hypermutation occurs -affinity maturation occurs -Memory
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What are features of T-independant B lymphocyte antibody responses?
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-No T cells -Low affinity -Minimal isotype switching -No somatic hypermutation -No memory
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What are characteristics of alpha-beta T cells?
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-express both CD4 and CD8 -recognize peptide antigens -presented by MHC I and II -TCR diversity -Abundant in blood -Adaptive immunity
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What are characteristics of gamma-delta T cells?
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-express CD3 only -recognize non-peptide antigens -presented by MHC I -Plentiful in tissues -Function in tissue homeostasis, protection, and repair
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What are the signaling molecules for BCR and TCR?
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BCR: Ig-alpha and Ig-beta TCR: CD3, CD4, and CD8
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What is the structure of BCR and TCR?
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BCR: two heavy chains, two light chains TCR: single alpha and single beta chain
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What proteins compose a complete BCR?
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Vh, Vl, Ch, Cl (variable light and heavy, constant light and heavy) Ig-alpha and Ig-beta
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What cell receptor variable domains contain junctional diversity?
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both BCR and TCR
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What are the 5 main antibody isotypes?
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IgA IgD IgE IgG IgM
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What antibody isotype has the highest concentration in mucus?
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IgA
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Which antibody isotype is transported across blood vessel endothelial cells and delivered to tissues?
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IgG
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Which antibody isotype appears as a dimer?
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IgA The J-Chain
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What antibodies are expressed on the surface of naive B lymphocytes?
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IgM and IgD
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What antibody is transported through breast milk?
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IgA
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Which antibody is transported through the placenta from mother to baby?
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IgG
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What antibody must be a pentamer to be affective and why?
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IgM b/c of low affinity
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What antibody is the largest/ has the highest molecular weight?
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IgM
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What antibody is the most abundant in serum and body fluids?
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IgG
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What three antibodies together that compose 99% of all blood/body fluids?
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IgG, IgM, IgA
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What two antibodies can bind/fix complement?
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IgG, IgM
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What antibody is primarily found in the respiratory tract?
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IgG
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What antibody is best at neutralization?
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IgG and IgA
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What antibody is best at opsonization?
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IgG
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What antibody is best at sensitizing for NK killing?
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IgG
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What antibody is best at sensitizing mast cells?
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IgE
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What antibody is best at activating complement?
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IgG and IgM
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What FcR does IgG bind to?
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FcRn/FcRB OR Fc-gamma-R1
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what FcR does IgE bind to?
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Fc-epsilon-R1
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What FcR does IgA bind to?
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Fc-alpha-R1
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What initiates the activation of the alternative pathway?
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triggered by spontaneous hydrolysis of C3
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What initiates the activation of the lectin pathway?
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triggered by mannose-binding lectin being bound to pathogen surface
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What initiates the activation of the classical pathway?
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C-reactive protein or antibody binds to antigen on pathogen's surface
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What are components of the membrane attack complexes (MAC) of complement?
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C5-C9
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When do the three complement pathways converge?
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when C3b is present
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What type of bond does complement form? What about antibody?
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Complement is covalent Antibody is non-covalent
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What are the two primary lymphoid cites?
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Bone Marrow (B cells) Thymus (T Cells)
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What are the secondary lymphoid tissues?
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lymph nodes, Peyer's patch, spleen, adenoids, tonsils
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What occurs in primary lymph tissues?
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cells of the adaptive immune system are made
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What occurs in secondary lymph tissues?
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B and T cells become activated by an antigen
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A lymph follicle containing a germinal center is called a:
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secondary lymphoid follicle
