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33 Cards in this Set
- Front
- Back
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What are the 3 phases of Bcell development?
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1. Maturation
2. Activation 3. Differentiation |
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Where does it occur:
-Maturation -Activation -Proliferation |
Maturation - in the bone marrow
Activ/Prolif - in peripheral lymphoid organs. |
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Which phases are dependent or independent of antigen?
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Maturation - Ag independent
Acitvation/Proliferation - Ag dependent |
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What takes place during Bcell maturation?
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-Immunoglobulin genes rearrange.
-Stromal cells assist Bcell progenitors into differentiating and proliferating into Mature B cells. -Negative selection |
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What is Negative Bcell Selection?
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Clonal deletion of Bcells that have antibody to self-proteins IN THE BONE MARROW.
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How can self-reactive Bcells sneak out of being deleted?
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-Editing their light chains. There are two - lambda/kappa; replacing the self-reactive one can allow the B cell to survive.
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What type of a Bcell is prduced from maturation in the bone marrow?
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A mature naive Bcell that expresses only IgM on membrane; so far has never seen an antigen.
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What tells you if a Bcell is fully mature and ready to encounter Ag (without going into anergy)?
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if it has IgM and IgD both on membrane.
This shows that differential RNA processing and class switching has occurred. |
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What occurs after mature Bcell exports from bone marrow?
-Where does it go -What is it dependent on? |
Bcell activation/prolif/differentiation.
In the periphery Antigen-dependent. |
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What are the 2 routes Bcell activation can proceed by?
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-THYMUS dependent
-Thymus INDEPENDENT |
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What's the difference between Thymus Dependent and Independent Ag activation?
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Thymus Dependent requires direct contact with Thelper cells secreting cytokines
thymus independent doesn't |
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2 types of Thymus-Independent Ag
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TI vs. T2
TI is LPS T2 is repetitious polysaccaharide or flagella. |
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What can LPS at high concentrations do?
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Activate polyclonal Bcells.
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What molecule similar to CD3 helps mIg become a Bcell receptor for activation?
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Iga/IgB
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What is the purpose of the Iga/IgB molecule?
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Has intracellular ITAM motifs that can be phosphorylated to mediate signal transduction and Bcell activation
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how many signals are necessary for Bcell activation/proliferation?
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3
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What are signals 1 and 2?
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1. Cross-linking of the Bcell receptor by Antigen.
2. CD40 binds CD40-Ligand 3. Cytokines bind receptors |
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What is the response to signal 1 -> cross-linking?
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ITAM of Iga/Igb is phosphorylated.
-Upregulates Class2 MHC and B7 -Allows Ag to present to Th cells, and Th cells can bind cuz B7 is there. -Thelper cells then secrete CD40-L and cytokines. |
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What is signal 2 for?
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CD40 binds CD40-L on Thelper cells.
This upregulates cytokine RECEPTORS on the B cell, so it can hear signal 3 |
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What is signal 3, and what is it for?
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Binding of cytokines to the receptors produced by signal 2.
Tells the Bcell to differentiate into memory cells, and which classes of Ig to switch to. |
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Which signal starts Bcell proliferation?
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Signal 1.
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How are the signal requirements different between Thymus-dependent and Thymus-independent antigens?
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Thymus Independent crosslinks Bcells nonspecifically.
As a result, no requirement for -CD40-CD40L signal #2 AND -cytokine signal #3 Where all 3 are required for T-depnt Ag |
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What 3 things are lacking in the Bcell response to Thymus-independent ag?
As a result, what type of population is activated? |
-No somatic hypermutation
-No affinity maturation -No class switching. Bcell population: POLYCLONAL, nonspecific. |
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What are the differences between a primary and secondary humoral response?
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-Memory Bcells respond in a 2ndary
-Virgin naive cells do in a primary -Mem Bcells take less time to proliferate/produce Abs; produce more Ab at peak, occurs sooner than for naive. The Ab affinities in 2ary are higher than in primary. -IgG predominates in 2' -IgM predominates in primary. |
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What is required of both Bcells and Th cells for a humoral response?
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both have to recognize epitopes on the same antigenic molecule.
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In peripheral lymphoid organs:
Where are naive b cells? Where are naive T cells? |
Naive B cells are in cortex
Naive T cells are in paracortex. |
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Where do B cells first encounter Ag?
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In primary follicles in secondary lymphoid tissue.
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What cells present Ag to B cells in primary follicles?
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Macrophages, B cells, and Dendritic cells.
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Where are primary lymphoid follicles located within 2ndary lymphoid tissue?
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in the paracortex.
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After initial Ag encounter by Bcells near the Tcell-rich paracortex, what happens?
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Some activated Bcells and Th cells migrate to Primary Follicles in center of spleen or wahtever 2ndary organ it is.
Allows maturation/selection with Follicular Dendritic cells. |
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3 important things that happen in Germinal Centers:
When is this? |
-Affinity maturation
-Class switching -Generation of plasma/memory B cells. about 7 days after initial activation. |
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2 ways you can regulate the immune response:
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-Antigenic competition (inject sheep RBC, then horse RBC will not cause as high of response cuz Sheep Ag takes up ab)
-Ab suppression (don't give infants some vaccines, because Maternal Ab to the Ag suppresses the humoral response generated). |
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There are 2 Cytokines for which you must know how they affect class switching:
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1.IL-4 causes IgE class switching (will result in allergies, type 1 hypersens)
2. IFN-y causes swithcing to Ig-G. |
