Lecture 14 Flashcards
(42 cards)
Humoral immune responses are initiated by the recognition of Ags by what specific receptor on what specific cell?
BCR’s on B lymphocytes
then a single B cell gives rise to thousands of plasma cells that secrete tons of Abs ; 10 to the 12th at it’s maximum
Ag activates naive B cells by binding to which 2 Ab types?
membrane IgM and IgD
After an Ag and other stimuli, including helper T cells, stimulates the proliferation and differentiation of a specific B cell clone, state the 3 types of progeny that the B cell clones may become (3 of them)
- Plasma cells that produce IgM (has lots of Ag binding sites, which make up for their low affinity)
- B cells that express other Ig isotypes after undergoing class switching (these usually undergo affinity maturation to make up for the fewer Ag binding sites compared to IgM)
- They may persist as memory cells
About how many days does it take for a primary antibody response to an antigen to reach it’s peak levels of antibodies?
about 7 days (then contraction occurs)
Compare the type of Ags that can be found in a primary and secondary immune response (Include the Ig types that belong in both of these types of responses as well)
Primary immune responses feature mainly “nonprotein Ags” and feature mostly IgM antibodies
(bc they are produced prior to helper cell interactions with B cells)
Secondary immune responses feature mainly “Protein Ags” and feature mostly IgG antibodies
(bc they are produced from memory cells)
True or False:
Primary and secondary Ab responses to PROTEIN Ags differ qualitatively but are very similar quantitatively. explain.
FALSE
Primary and secondary Ab responses to PROTEIN Ags differ qualitatively AND quantitatively.
State the 4 characteristics that differentiate a secondary response from a primary response to an antigen.
More rapid production of Abs
larger amounts of Abs produced
Isotype switching of the heavy chain
Affinity maturation Ag-Ab binding
B cell responses are divided into 2 categories, T Cell-dependent (TD) and T Cell-Independent (TI) responses. Compare the types of Ags that fit into these categories and what each response is facilitated by.
TD responses occur with “Protein Ags and REQUIRE CD4+ T helper cells”
Follicular T helper cells form germinal centers where activated B cells proliferate
TI responses occur with “Multivalent non-protein Ags” with repeating epitopes (polysaccharides, lipids, and nucleic acids)
These responses are elicited by BCR engagement and may be potentiated by other signals
Describe the following subsets of B cells in terms of the types of Ags they respond to and whether they are TD or TI.
Follicular B-2 cells:
Marginal Zone B cells:
B-1 cells: (where are these found?)
Follicular B-2 cells: respond to protein Ags and initiate TD Ab responses
(these make up the majority of B cells in circulation)
Marginal Zone B cells: respond to multivalent (non-protein) Ags and are TI
(in the marginal zone in the spleen)
B-1 cells: are found in mucosal sites only, respond to multivalent Ags and are TI
True or False:
Both B-1 and B-2 cells express IgM and IgD on their surface. explain.
True
While B-1 cells tend to express IgM > IgD and B-2 cells tend to express IgD > IgM, they both express both types of membrane Abs
Compare B-1 and B-2 cells in terms of the following characteristics.
When they arise:
Location:
Diversity level:
Memory ability:
Usual target:
Isotype switching ability:
TD or TI:
How they are replaced:
B-1 When they arise: Fetal (liver) Location: mucosal areas (resp and GI tract) Diversity level: low Memory ability: little/none Usual target: Carbohydrates Isotype switching ability: limited TD or TI: usually TI How they are replaced: self-renewing in the periphery
B-2 When they arise: perinatal/postnatal Location: Widespread Diversity level: high Memory ability: yes Usual target: proteins Isotype switching ability: yes TD or TI: usually TD How they are replaced: continuously replaced from the bone marrow
Which type, B-1 or B-2, creates Abs that are often directed against conserved microbial Ags and bridges between the innate and adaptive immune systems?
B-1
Describe which area of the lymph node is the T cell zone and which is the B cell zone? what is another name for the B cell zone of a LN?
T cell zone: central part of LN
B cell zone: peripheral part of LN
“Follicles” are another name for the B cell zone of a LN
What chemokine is secreted by FDCs (follicular DCs, which are NOT the DCs coming from the tissues) in order to guide the movement of naive B cells into follicles? is this an attractant or repulsive chemokine?
CXCL13 is and attractant chemokine that is secreted by FDCs into the follicle of LNs to guide naive B cells to the periphery
Describe the function of the macrophages in the subscapular sinus of the LN and how this can be important for secondary infections from an Ag.
They pick up antigens that are too large to enter the follicle via the “conduit”, glue them to their surface without breaking them down, and bring them to the follicle to be presented
This presents the Ag in it’s intact, native conformation (which will allow the Abs to respond to the native conformation of the Ag incase of a secondary infection. Does not need to take the time to respond to the digested version of the Ag if it recognizes its native conformation)
For the following Ag types, explain how they are handled in the LN.
Most Ags: (how to they enter and where do they go
Soluble Ags:
Large Ags:
Microbes and Ag-Ab complexes:
Most Ags: transported to the LN via afferent lymphatic vessels and drain into the Subcapsular sinus
Soluble Ags: reach the B cell zone and interact DIRECTLY with B cells
Large Ags: captured by FDCs and transported to the follicle intact so they may interact with B cells
Microbes and Ag-Ab complexes: captured by subcapsular sinus resident macrophages and are delivered to the follicles (intact, not processed)
True or False:
FDCs are not professional APC’s, despite regular DC’s being professional APC’s. explain.
True.
FDCs do not express MHC class II molecules, they do not phagocytose, and they do not process exogenous Ags.
Since FDCs only “glue” Ag’s to their surface, they are not considered professional APC’s like regular DCs are.
When an FDC binds an Ag to it’s surface, it forms what is called an Ag-Ab immune complex. State the 3 possible receptors that retain this complex on the surface of FDC’s and state how long they can retain this complex on their surface.
Ags retention on the surface of FDCs is mediated by:
FcgammaRIIb (Fc receptors
CR1 or CR2 (CD21) complement receptors
these complexes can be retained for long periods of time (weeks to months)
Immune complexes on FDCs play a key role in germinal center reactions by providing an antigenic substrate that drives ____ _____ ______.
antibody affinity maturation.
Follicular B cell survival depends on signals from the BCR as well as signals from which cytokine? what signals does this cytokine provide for the follicular B cell, and what cells secrete it (also where does this secretion happen?)?
BAFF (B cell Activating Factor of the TNF family)
BAFF provides “maturation and survival signals” through the BAFF receptor on follicular B cells
BAFF is produced by Myeloid cells in lymphoid follicles and in the bone marrow
What initiates the process of B cell activation? what occurs directly after this?
BCR signaling initiates B cell activation
At the same time, the BCR internalizes the bound Ag into endosomal vesicles If the Ag is a protein, it is processed and presented (via MHC class II molecules) on the B cell surface to be recognized by T helper cells
State and describe the 2 complementary receptors on the surface of a B cell (these occur simultaneously alongside BCR recognition of the Ag) that can potentiate B cell activation.
CR2(CD21) coreceptors that recognize complement-coated Ags via the C3d bound to the Ag surface
TLR’s that recognize PAMPs
(Both of these occur simultaneously alongside BCR signaling from the Ag)
Explain how a B cell presents an antigen to T cells and be sure to address how the Ag receptors on the B cell and T cell are usually different yet they can both respond to the same Ag.
Membrane Ig on the B cell recognizes a conformational epitome of an antigen, bind to the Ag, endocytose it, and present a “linear peptide” from the Ag on the surface of the B cell via a “class II MHC-peptide complex”
Helper T cells then recognize the linear peptide from the Ag in the Class II MHC-peptide complex and stimulate B cells responses
(the B cell finds the Ag, prepares it in a linear peptide form that the T cell can recognize, and then is stimulated by the T cell after it is activated)
After a B cell has presented a linear peptide version of the Ag to the T cell, explain how a T cell then activates the B cell (2 mechanisms)
After being activated by recognizing an Ag, the T cell expresses CD40L which then interacts with the CD40 molecules on the B cell to stimulate proliferation and differentiation
The T cell also produces cytokines to help activate the B cell
