Lecture 15 - Differentiation and Functions of CD8+ T cells Flashcards
The activation of B cells is initiated by what?
Specific recognition of Ags by the surface BCRs
What stimulates the proliferation and differentiation of specific B cell clone?
Ags and other stimuli, including T helper cells
Progeny of the B cell clone may differentiate into what?
- Plasma cells that produce IgM or
- Other Ig isotypes e.g IgG
- May undergo affinity maturation
- May persist as memory cells
Mature Ag-responsive B cells develop from what?
Bone marrow precursors in the absence of Ag
Humoral immune responses are initiated by what?
The recognition of Ags by specific BCR on B lymphocytes
On naive B cells, Ag binds to what?
IgM and IgD and activates these cells
The activation of B cells results in what?
Their proliferation, leading to clonal expansion, followed by differentiation, culminating in the generation of Ab-secreting plasma cells and memory B cells
A single B cells may give rise to how may cells per week?
5000 Ab-secreting cells
At the peak of humoral immune response, about how many Abs molecules are produced every day?
10^12
Some activated B cells begin to produce Abs other than IgM and IgD. This process is called what?
Heavy chain isotype (class) switching
As humoral immune response develops, activated B cells that produce Abs that bind to Ags with increasing affinity progressively do what?
Dominate the response, a process called affinity maturation
What determines the humoral immune response?
The type and amount of Abs
Humoral immune response can be what?
Either primary or secondary
Responses are divided on what?
T-dependent and T-independent
Ab responses to protein Ags require participation of what?
Of CD4+ Helper T lymphocytes
Therefore, proteins are classified as T-Dependent Ags
A specialized type of helper T cell facilitates the formation of germinal centers. What type of T cell is it?
Follicular helper T cells
What are germinal centers?
Structures generated in secondary lymphoid organs where several steps of T-dependent humoral immune responses occur
In T-dependent responses, activated B cells differentiate into what?
Ab-secreting plasma cells
Plasma cells migrate from GCs in the peripheral lymphoid organs to where?
The bone marrow where they may live for many years
The long-lived plasma B cells do what?
Continuously secrete Abs that provide immediate protection
Ab responses to multivalent non-protein Ags with repeating epitopes, such as polysaccharides, some lipids, and nucleic acids, do not require what?
Ag-specific helper T cells
Multivalent Ags are called what?
T-independent Ags
T-independent responses are elicited by what?
Engagement of BCR and may be potentiated by the signals froom other receptors on the B cells
B cells activated by protein Ags may differentiate into what?
memory cells
Memory B cells survive in a resting state without secreting Abs for many years, but they mount rapid responses on what?
Subsequent encounters with the Ags
Isotype switching and affinity maturation are typically seen in what?
Humoral immune responses to protein Ags
T cell-dependent signals drive what?
Isotype switching and affinity maturation
Primary and secondary Ab responses to protein Ags differ in what?
Qualitatively and quantitatively
In primary immune responses, What happens to naive B cells?
Stimulated by Ag, become activated, and differentiate into Ab-secreting cells that produce Abs specific for the eliciting Ag
In secondary immune responses, what occurs with B cells?
The same Ag stimulates memory B cells, leading to the production of greater quantities of specific Abs than are produced in the primary response
What response develops more rapidly?
The secondary-larger amounts of Abs are produced
Heavy chain isotype switching and affinity maturation are increased in what response?
Secondary responses (multiple) to protein Ags
Follicular B cells respond to what?
Protein Ags and thus initiate T-dependent Ab responses
T-independent responses to multivalent Ags are mediated mainly by what?
Marginal zone B cells in the spleen and B-1 cells in mucosal sites
True or False
The functional distinctions between B cells subsets are not absolute?
True
Follicular B cells respond to protein Ags and thus initiate what response?
T-dependent Ab responses
Follicular B cells, protein antigen, isotype-switched, high-affinity; long-lived plasma cells
T-independent or T-dependent?
T-dependent
Marginal zone B cells, polysaccharides, lipids, etc. mainly IgM, short-lived plasma cells.
T-independent or T-dependent?
T-Independent
B-1 Cells, multivalent, mainly IgM, short-lived plasma cells
T-independent or T-dependent?
T-independent
Antibody isotype is usually IgM>IgG
Primary or secondary response?
Primary
Relative increases in IgG, and under certain situation, in IgA or IgE?
Primary or secondary response?
Secondary
Response induced by all immunogens
Primary or secondary response?
Primary
Response induced by mainly protein antigens
Primary or secondary response?
Secondary
To initiate Ab responses, Ags have to be captured and transported where?
To the B cell areas of lymphoid organs
Most mature naive B lymphocytes are what type of cells?
Follicular B cells which are also called recirculating B cells
Follicular B cells constantly recirculate between what areas?
Recirculate in the blood and migrate from one secondary lympoid organ (spleen, lymph nodes, mucosal lymphoid tissues)
In secondary lymphoid tissues, follicular B cells migrate into what zone?
The B cell zones called follicles
What is the movement of follicular B cells guided by?
Chemokine CXCL13 secreted by follicular DCs
What is the major stromal cell type in the follicle?
Follicular DCs
Proteins are classified as what?
T-dependent Ags
True or false?
Ag may be delivered to naive B cells in lymphoid organs in different forms and by multiple routes
True
Most Ags from tissue sites are transported to lymph nodes by what vessels?
Afferent lymphatic vessels that drain into the subscapsular sinus of the LNs
What Ags may reach the B cell zone of the follicle and interact DIRECTLY with specific B cells?
Soluble Ags (generally smaller than 70 kD)
What are captured by subscapsular sinus macrophages which deliver Ags to follicles?
Microbes and Ag-Ab complexes
What may be captured by resident DCs and transported into follicles, where they can activate B cells?
Many large Ags
Follicular DCs can present Ags in what complexes to follicular B cells?
They express CR2 complement receptors and create complexes with the receptor
In the spleen, Ags in immune complexes may bind to what on marginal zone B cells?
CR2 complement receptors
What is the state of maturation of T lymphocytes in the bone?
pre-T cell
What is the state of maturation of T lymphocytes in the thymus?
Selection of T cells with appropriately rearranged receptors for antigen
That is the state of maturation of T lymphocytes in the LN?
- naive T cell
- Encounter with antigen-bearing DC leads to activation and functional polarisation to effector or memory T cell
- Memory T cell
What is the state of maturation of T lymphocytes in the peripheral tissue?
T cells that carry out effector functions
What can transfer the immune complex-containing Ags to follicular B cells?
Marginal zone B cells
Blood-born pathogens may be captures by what cells in the blood and transported to the spleen where they may be delivered to marginal zone B cells?
Plasmacytoid dendritic cells
What antigens can be captured by Mo in the marginal zone of the splenic lymphoid follicles and displayed or transferred to B cells in this area?
Polysaccharide
The antigen that is presented to B cells is generally in what form?
Intact, native conformation and is not processed APCs
How are small Ags delivered to B cells in follicles?
Through afferent lymphatics and via conduits
How are larger Ags delivered to follicular B cells?
By subcapsular sinus Mo or by DCs in the medulla
Follicular B cell survival depends on signals from the BCR as well as inputs received from what?
Cytokine called BAFF
What is BAFF mainly produced by in lymphoid follicles and in the bone marrow?
Myeloid cells
BAFF provides maturation and survival signals through what?
baff RECEPTOR
What makes up the Ag receptor complex of mature B cells?
Membrane Ig molecules, Igα and Igβ proteins
The initiates the process of B cell activation?
BCR initiates
When the BCR initiates the process of B cell activation, what happens at the same time to the bound Ag?
The BCR internalizes the bound Ag into endosomal vesicles
If the Ag is a protein, how is it processed in a B cell?
It is presented on Class II MHC on the B cell surface for recognition by T helper cells
B cell activation is facilitated by what coreceptor on B cells?
CR2/CD21
Activation of B cells through the BCR may be enhanced by complement-coated Ags that can ligate what?
Both the BCR and the CR2
Simultaneous PAMPs recognition and TLRs signaling may contribute to what?
B cell activation
Ag-induced cross-linking of the BCRs induces several cellular responses including what?
- production of proteins that promote survival and proliferation
- expression costimulators and cytokine receptors that promot interactions with and responsiveness to helper T cells
- migration of the cells towards T cells as a result of the expression of CCR7
The activated T cells and B cells migrate towards one another and interact causing what?
B cell proliferation and differentiation
B-T interaction in extrafollicular sites leads to what?
Isotype switching and short-lived plasma cell generation
Activation of T cells by B cells results in the induction of what cells?
follicular helper T cells
The late events of the immune defense that occur in the germinal centers include:
- somatic mutation and affinity maturation
- isotype switching
- generation of memory B cells and long-lived plasma cells
what happens in responses to hapten-carrier conjugates?
The hapten (the B cell epitope) is recognized by a specific B cell The conjugate is endocytosed, the carrier protein is processed int he B cell Peptides from the carrier (the T cell epitopes) are presented to the helper T cell
The germinal center is within the follicle and includes a dark and light zones. What do the zones contain?
Dark zone contains proliferating B cells stained with an anti-Ki67 Ab - red which detects cycling cells
The light zone contains follicular DCs stained with an anti-CD23 Ab (green)
Activated B cells migrate into the follicle and proliferate, forming the dark zone of the germinal center. What do these B cells undero?
Extensive isotype switching and somatic hypermutation of Ig V genes
B cells migrate into the light zone, where they encounter what?
follicular DCs displaying Ag and Tfh cells
B cells with the highest affinity Ig receptors are selected to do what?
Survive, and they differentiate into Ab-secreting cells and memory B cells
Ab-secreting cells leave and reside in what?
In the bone marrow as long-lived plasma cells
What do memory B cells enter?
The recirculating lymphocyte pool?
Within 4 to 7 days after Ag exposure, activated Ag-specific B cells induce what?
Some previously activated T cells to differentiate into Tfh cells
Tfh cells are drawn into lymphoid follicles by what?
CXCL13
Tfh cells play critical roles in ___ formation and function
GC
Tfh cells express what 4 things?
ICOS, PD-1, IL-21, and Bcl-6
Tfh cells have a unique phenotype that makes them distinct from what ?
Th1, Th2, Treg, and IL-17 subsets of effector T cells
Tfh cells play several important roles in the activation and differentiation of B cells in the GC reaction that involves what on B cells
ICOSL, CD40L, IL-21R on B cells
The generation of Tfh cells requires sequential activation of T cells first by what?
First B DCs and then by activated B cells.
The Tfh cells migrate to GCs, where they activate B cells
What is secreted by Tfh cells and it is required for GC development and generation of plasma cells?
IL-21
Tfh cells secrete what that controls isotype switching?
IFN-γ or IL-4
