Term
| Where are blood-borne and lymph-borne antigens presented the adaptive immune system? |
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Definition
These are the places where innate and adaptive responses meet!
1) Blood-borne= Spleen
2) Lymph-borne= Lymph nodes |
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Term
| Where does affinity maturation/somatic hypermutation occur? |
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Definition
| In germinal centers of the lymph nodes and spleen, where intense B-cell proliferation to T-dependent antigens occurs. |
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Term
| Distinguish between "Affinity" and "Avidity" in terms of BCR-antigen interactions. |
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Definition
1) Affinity- strength with which one molecule binds to another when using a single epitope
2) Avidity- stability of interaction of the sum of reactions in an immune complex (i.e. the more receptors, the more avidity!).
Remember, if you don't have affinity, get a BUNCH of receptors! |
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Term
How can the body mount an immune response to Haptens, despite the fact that they are not immunogenic?
How does this process relate to the development of a Penicillin allergy? |
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Definition
1) haptens such as Uroshiol (toxin in poison ivy) couple to large protein "carriers", which form a new epitope that IS immunogenic.
2) The hapten, Penicillin, attaches to a large self protein or cell and elicits an immune response to the hapten as well as the self carrier molecule. |
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Term
| Discuss 4 ways B-cell activation can occur in the lymph node? |
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Definition
SHORT-
1) Toll-LPS
2) B1 (T-cell independent) cell Ab with low affinity cross-link to increase avidity
3) B2 (T-cell dependent) cell BCR:Ab affinity increases with T-cell interaction (AFFINITY MATURATION)
4) B-cell interacts with CR2 danger signal.
1) TLR4 interacts with LPS, resulting in polyclonal activation.
2) Antigen-specific interaction with cognate antibody by crosslinking many antibodies with low affinity but high avidity, usually in B1 cells
3) Antigen-specific cross-linking with specific BCR and CR2 complement receptor, which is a danger signal.
4) Antigen specific BCR engagement including set of interactions with T-cells (primarily with B2 cells), that increase B-cell affinity for antigens. |
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Term
| What are the primary distinguishing features between T-cell-dependent and T-independent antigens? |
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Definition
1) T-cell-independent (high AVIDITY and mostly B1 C5+)
carbs, sugars, lipids that are CD5+ in peritoneum and CD5- in marginal zones of lymph nodes.
NO class switching, affinity maturation or memory
CAN divide, increase cytokine receptors and secrete IgM
2) T-dependent (follicular, C5-, B2 cells)
Protein antigens
Associated with Ig class switching, affinity maturation and memory. |
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Term
| Explain how T-cell cytokines influence Ig isotype of B-cells (providing examples). |
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Definition
These cytokines work by activating transcription of the isotype C-region and opening up the chromatin, facilitating SWITCH RECOMBINATION, followed by affinity maturation.
1) IL-4 drives IgE production (eosinophil allergic response)
2) IFN-gamma drives IgG1 and IgG3
3) TGF-b drives IGA |
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Term
True or False:
Heavy chain class switching (i.e. SWITCH RECOMBINATION)
requires T-cell help |
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Definition
True!
Remember, specific cytokines activate transcription of different heavy chain loci and subsequent DNA rearangments. |
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Term
| Explain the meaning of "signal 1" and "signal 2" in T-independent antigen recognition by B-cells. |
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Definition
1) Antigens cross-link (i.e. accumulate) multiple Ig molecules (signal 1) and PRRs (signal 2), creating a hi- avidity response primarily in B1, CD5+ cells
2) This BCR engagement is followed by "clonal selection," when B cells enter the cell cycle and the "J chain clasp" of the IgM molecule is synthesized
** No IgG is made** |
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Term
| Explain how T-dependent antigens are recognized by B-cells. |
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Definition
Cannot cross-link Ig molecules, and requires CD4+ T-cells to produce secreted antibody in follicular (CD5 -) B2 cells.
SHORT-
1)B7 and MHC-II are up-regulated in response to antigen
2) MHC-II binds up DIGESTED antigen and presents it on surface
3) B-cells migrate from follicle to parafollicular zone, where MHC-II interacts with CD 4+ T-cells and upregulate CD40 on B-cell
4) B7 interacts with CD28 on T-cell and CD40 interacts with the CD40 ligand from T-cells, leading to T-cell release of cytokines
5) B-cells go to germinal centers and mature into Ig-releasing plasma cells
LONG
1) BCR binds and internalizes antigen
2) MHC Class II and B7 expression upregulated
3) Antigen is digested and binds to MHC-II, which is transported to cell surface
4) MHC II is presents linear AA stretches from antigen and B-cells leave follicle to enter T-cell area (parafollicular cortex)
5) MHC-11:antigen interacts with CD4+, TCR bearing T cell (Th), causing CD40 on B ell to increase.
6) B7 on B interacts with CD28 on T-cell and T cell sends cytokine signal to B cell to help.
7) B cell enters geminal center light zone where proliferation, class switching, improved affinity, memory and selection occur.
8) Plasma cells are formed with Ig secretion (alternate RNA processing). |
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Term
| Explain the basic molecular mechanism that is thought to underlie Affinity Maturation in B-cells exposed to T-cell-dependent antigens. |
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Definition
MORE COMPLEX THAN T-INDEPENDENT
Net effect- Generate BCR diversity with AID and then follicular DCs select B-cells with BCRs that bind to antigens with highest affinity
You need to fix you pants.
AID is the taylor and follicular DCs are the friends who judge how they look.
1) T-cell-dependent activation of Activation-induced cytidine deaminase (AID) in B cells results in DNA point mutations in V-region, that appear to cluster in CDRs (antigen contact sites)
2) B-cells with high affinity Igs bind antigen in follicular dendritic cells where they are positively selected for by follicular DCs |
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Term
| True or False: B1 plasma cells undergo further recombination with downstream H-loci |
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Definition
False!
B1 cells are involved in T-independent antigen recognition and DO NOT undergo further recombination after the antigen-activated B-cell stage.
B1 cells make IgM and are short lived (may return to the bone).
B2 plasma cells are involved in the T-dependent antigen response and DO undergo further recombination events during affinity maturation (mediated by AID action in V-region). They may IgM, IgG, IgA or IgE, and may acquire CD138 (Syndecan-1 proteoglycan) and lose CD20/CD19 |
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Term
| How does Ig behavior differ in B2 Plasma cells and Memory B2 cells? |
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Definition
B2 plasma cells secrete IgM, IgG, IgA or IgE and are usually short-lived
Memory B2 cells express the membrane-bound form of Ig isotype and may be long-lived. |
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Term
| How can you tell that a T-dependent secondary memory response is occurring in terms of the kind of IgG? |
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Definition
More IgG isotype switching with short lag, high affinity immune response.
Remember, T-independent antigens cannot create a memory response |
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Term
| How is the humoral immune response regulated by the antigen-Ab complex? |
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Definition
| When antigen is coated with soluble IgG, that antigen:antibody complex binds to B-cell surface and blocks further proliferation. |
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Term
| Why can polysaccharides aggregate in such a large number in a single spot on BCRs during T-independent antigen recognition? What is this called? |
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Definition
This is called "cross-linking" and it has to do with proximity, NOT covalent interactions.
They share repeating identical epitopes. |
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Term
| What are "germinal centers" and why are they important? |
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Definition
They are sites in the lymph nodes where antigens meet B cells and T-cell-mediated B-cell proliferation is occurring (B2 cells).
Recall- B2 cells bind antigens and present them to T-cells/T-cells release cytokines that stimulate B-cell maturation and Ab production. |
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Term
| Why are there so many epitope possibilities, despite there being a limited number of possible 5AA stretches? |
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Definition
| Conformational diversity adds to the pot! |
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Term
| What is the most important feature of Haptens? |
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Definition
| They combine with large proteins to MAKE NEW EPITOPES |
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Term
| Why are hapten molecules sometimes associated with Hemolytic anemia? |
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Definition
| If haptens combine with self-proteins that induce an immune response, autoimmune conditions like "hemolytic anemia" can occur. |
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Term
| Explain the concept of "Affinity Maturation" |
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Definition
| Antigens can interact with B2 cells, which activate Th cells and induce them to release cytokines which increase B2-BCR affinity. |
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Term
| What is "class switching" and under what conditions can it occur? |
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Definition
Switching Fc regions of BCRs (i.e. IgA to IgM to IgD)
It occurs in T-cell-dependent antigen interactions with B2 cells.
Remember, these interactions are also where you see Affinity Maturation and Memory |
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Term
| What is "Switch Recombination" and when/how does it differ from "Receptor Editing" |
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Definition
Switch Recombination (also called "Heavy chain class switching") is a T-cell dependent process that occurs late in a primary infection or early in a secondary response and involves cytokines which lead to AID-mediated "switching" of the "mu-HC."
Receptor Editing is a RAG-dependent process that takes place in immature B-cells, where LC rearachngement occurs prior to maturation and export to lymphoid organs. |
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Term
Which T-cell cytokine influences each of the following Ig isotype of B-cell and how do these "isotype switches" take place?
1) IgG1 and IgG3
2) IgA
3) IgE |
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Definition
This is "Switch Recombination" where transcription of isotype C-regions and opening up of the chromatin occurs and AID switches C-mu region. It occurs late in a primary infection or early in a secondary infection.
1) INF-y
2) TGF-b
3) IL-4 |
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Term
What effect does primary, secondary and tertiary CDR rearrangements taking place through "Switch Recombination" have on the Kd of antigen-BCR interactions?
What is another term of this process? |
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Definition
Each progressive rearrangement progressively decreases Kd (thus, increasing affinity by 100x ultimately!).
This is AFFINITY MATURATION (AID-mediated in V-region) |
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Term
| How may rearrangements are required for the formation of IgG-releasing plasma cells? What about IgM? |
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Definition
1) IgG= 4 (D:J and V:DJ in HC, V:J in LC and Switch Recombination in H-mu
2) IgM= 3 (same as above, but without Switch Recombination) |
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Term
| How can one distinguish between the primary and secondary antibody response? |
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Definition
1) Primary involves IgM>IgG release- Secondary involves relative increase in IgG
2) Primary has a smaller "peak response"
3) Secondary has 1-3d lag time, while Primary has 5-10d
4) Affinity |
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