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32 Cards in this Set
- Front
- Back
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B cell activation differentiation: |
Antigen recognition. Signal transduction for B cell activation. B cell proliferation and differentiation into plasma cells. Antibody production. |
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Ab-mediated effector function: |
Fab-dependent neutralization. Fc-mediation effect: + complement-mediated cytotoxicity. + opsonization. + antibody-dependent cellular cytoxicity. |
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BCR: specific target binding B cell interaction with Ags: |
- a large and wide range of targets, small molecules to viruses, bacteria, and cells. - both linear and conformational epitopes. - only binding to targets that are accessible (extracellular bacteria). |
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B cell interaction site for finding the Ag: LNs: |
- Ag brought to LNs through lymph. - antigen enrichment by: + special types of transport and retain Ag -- subcapsular sinus macrophage (low protease). -- follicular dendritic cells (low phagocytic activity to retain intact Ag structures) + interaction between complement receptor 2 (CR2) and Ag coated by C3d (innate component). |
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B cells recirculate through _____. |
LNs. |
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Naive B cells migrate from _____ to _____. |
Blood. LNs. |
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Naive B cells search for specific antigen displayed by FDC in the B-cell area; naive T cells search for specific antigen presented by dendritic cells in the T-cell area. |
2. Antigen-activated T cells proliferate and differentiate; antigen-activated B cells move to the boundary region. 3. Antigen-activated B cells present antigen to effector TFH cells, forming cognate interactions and cognate pairs. |
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BCR-signaling: |
cross-linking by pathogens or proteins (minimal requirement for B cell activation) - surface IgM. - Ig-alpha/Ig-alpha. |
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Co-receptor signaling: |
to assist BCR for amplification of the activation signal. - CD19. - CD81. - CD21 (CR2). |
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Type of Ags: |
T cell independent Ag (TI-Ag). T cell dependent Ag (TD-Ag). |
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T cell independent Ag (TI-Ag): |
repetitive binding epitopes to engage BCR and co-receptors. - polymers (eg. polysaccharide, glyco-lipids, and nucleic acids) - patients with DiGeorge syndrome (no thymus) are responsive to TI-Ag. - primary and IgM response. |
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T cell dependent Ag (TD-Ag): |
- Ag alone (eg, protein) is insufficient to activate B cells. - T cells help induce potent and effective antibody response. - Secondary responses with different isotypes and high affinity. |
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T cell dependent B cell primary responses: |
linked recognition for T-B cell interaction. cognate interactions with TFH (effector Th) for B cell activation. |
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Linked recognition for T-B cell interaction: |
epitopes recognized by T and B cells are linked. - T cell epitopes: peptides. - B cell epitopes: many different chemical structures. - both of epitopes on the same antigen complex. Process: - Ig-specific B cell captures Ag by its surface Ig. - internalization of Ag-Ab complex. - presentation of degraded peptides to T cells through MHC-II. |
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Cognate interactions with TFH (effector Th) for B cell activation: |
MHC-II/peptide of B cells with TCR of T cells. CD40 on B cells with CD40L on T cells. |
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Helper T cell adheres to the B cell and begins to synthesize IL-4 and CD40 ligand. |
2. The helper T cell reorients its cytoskeleton and secretory apparatus towards the B cell. 3. IL-4 is released and is confined to the space between the B cell and the T cell. |
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Local environment for B cell interactions with Ags and TFH cells: |
- naive B cells recycle through LN and spleen and reside in primary follicles. - antigens brought to the follicles for B cells to sample Ags: macrophages & follicular dendritic cells. - B cells move to T-B cell boundary for seeking TFH cell help. |
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T cell dependent B cell primary response: Activation/differentiation: |
cognate interactions between TFH and B cells required for B cell activation. - first phase in primary focus to generate plasmablast and subsequent plasma cells to produce IgM for immediate protection (medullary cords). - second phase in germinal center for sustained B cell activation and differentiation. + B cells that undergo switch recombination and hypersomatic mutations. + memory B cell production. |
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LNs: |
1. The primary focus for expansion of antigen-activated B cells in the medullary cords. 2. The secondary focus for expansion of antigen-activated B cells in the primary follicle. 3. Expansion of antigen-activated B cells in the primary follicle creates the germinal center. |
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Spleen: |
1. Antigen-binding B cells are trapped in the T-cell zone of the spleen. 2. Antigen-binding B cells interact with armed helper T cells and begin to divide. 3. Antigen-binding B and T cells migrate to the T zone-red pulp border, where they proliferate to form a primary focus and form plasmablasts. |
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Structure of germinal center: |
- Dark zone: proliferating B cells (centroblasts). - Light zone: centrocytes & follicular dendritic cells. - Cycles of proliferation and differentiation (between dark zone and light zone). |
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B cell differentiation: |
- affinity maturation and isotype switching. - plasma cells vs memory cells: + plasma cells: Ab production: -- plasmablasts: intermediated between B and plasma cells. -- long lived plasma cells in bone marrow. + generation of memory B cells for secondary response. |
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Affinity maturation: two step event: |
1. somatic hypermutation during B cell proliferation (centroblasts in dark zone of GC). 2. selection of Ag in the progeny of centroblasts (centrocytes in light zone of GC). |
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1. somatic hypermutation during B cell proliferation (centroblasts in dark zone of GC). |
- interaction between TFH and B cells is essential for B cell proliferation. - mutations introduced in the variable region of Ig (both CDR and FR) during proliferation at a rate of 1/10^13 nt per cell division. |
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2. selection of Ag in the progeny of centroblasts (centrocytes in light zone of GC). |
Interactions with FCD and TFH to up-regulate Bclx. - B cell capture Ag via interacting with FDC. + Ag-C3d. + Ag-Ab complexes present in FDC. - Interaction between Ag-binding B cells and TFH. + TCR/MHC-II-peptides. + CD40L/CD40. Lack of interactions: apoptosis and removal by macrophages. |
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Lack of Ag-binding: |
no specific antigen. BCR changes due to SM. |
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Presence of Ag-binding: |
persistent Ag presented by FDR. B cells with high-affinity BCR. Presence of Ag-specific TFH. |
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Isotype switching: |
- TFH cell-dependent process: + TCR/MHC-II-peptides. + CD40L/CD40 interaction. + Cytokine production. - recombination between switch-regions (S) flanking each constant region. - cytokines influence the selection of switch-region for recombination by activating transcription at S-regions. |
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Plasma cells influenced by cytokines: |
dedicated for Ab production. short life span. |
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Memory cells influenced by cytokines: |
long lived. rapid activation by the same Ag: + high affinity receptor renders more robust reactivation than naive B cells. + proliferation and differentiation allows another round of SH and SW. + plasma cells: produce antibodies with higher affinity and Igs other than IgM. |
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Antigen-selected centrocytes mature under the influence of an IL-10-secreting helper TFH cell. |
2. Centrocytes differentiate into plasma cells. 3. Make antibodies that fight and terminate the current infection. |
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Antigen-selected centrocytes mature under the influence of an IL-4-secreting helper TFH cell. |
2. Centrocytes differentiation into memory B cells. 3. The investment that prevents future infections from causing disease. |
