| What are the antigen recognition roles of T cells and the co receptors? | T lymphocytes = T cells
express membrane attached T-cell receptors
TCR – recognize only peptides presented by MHC molecules |
| What are the antigen recognition roles of B cells and the co receptors? | B lymphocytes= B cells
may express membrane attached or soluble antibodies
B-cells – membrane bond antibodies or B-cell receptors (BCR)
BCR and soluble antibodies recognize wide range of antigens
With CD40 coreceptor |
| What are the steps in differentiation of B cells? | N |
| What are the types of B cells that contribute to immune responses? | Plasma cells - antibody secretion
Memory cells-
IgG expressing B cells - isotope switching
High affinity ig-expressing B cells- affinity maturation
B-1 cells -localized in mucosal tissues and peritoneum.
Express receptors of limited diversity and secrete IgM that can be produced without stimulation with antigen (natural antibodies).
IgM+IgD+ lymphocytes are mature B cells that can respond to antigens. Why both classes of Ig are needed is unknown. |
| Explain the mechanisms that induce activation of B cells to proliferate and secrete antibodies? | Only cells that express Igm heavy chain are selected to survive to become pre-B cells.
Igm heavy chain and surrogate light chains are expressed on cell surface and associate with Iga and Igb to form pre-BCR complex. Pre-BCR complex is a first checkpoint for cells that express functional Igm heavy chain. It sends survival signals.
If Igm heavy chain is failed to be made – pre-B cells will die by apoptosis= first checkpoint.
Allelic exclusion
Pre-BCR complex also send signal to inhibit recombination on the homologous chromosome, so only one allele will express BCR of single specificity.
If k light chain fail to produce functional receptor or k light chain encodes a self-reacting BCR, then BCR will trigger recombination of k with l light chain.
If functional IgM receptor is produced it will send survival signal, otherwise – apoptosis. Signals from IgM will also shut off light chain recombination, so either k or l light chains are made by given B cells.
Signaling by functional IgM is a second checkpoint. B lymphocyte expressing IgM is the immature B cell. Further maturation occurs in bone marrow or in spleen. Heavy chain is splices into Cm or Cd. As a result, IgM and IgD are expressed by the same cells. |
| Explain the mechanisms of inhibition of B cell function by excess antibodies through Fc receptors? | receptor FcgRIIB shuts down antibody production by B cells and decrease inflammation when activated on macrophages and dendritic cells.
Injecting IgG has anti-inflammatory effect (IVIG=intravenous immune globulin). |
| What tare the roles of Tcells CD4+ in the immune response? | activate phagocytes in tissues
activate B cells in lymphatic follicles CD4+ T cells activate B lymphocytes to produce high affinity isotype switched antibodies
Effects are mediated by cytokines including CD40L that binds CD40 on macrophages, dendritic cells and B cells.
CD40L and CD40 form positive self-amplification loop for activation of T cells by APCs and antibodies production by plasma B cells |
| What tare the roles of Tcells CD8+ in the immune response? | kill infected cells at the cite of infection
Require cross-presentation of cytosolic antigen by dendritic cells.
Differentiation of CD8+ into CTL (cytotoxic T lymphocytes )or memory cell require co-stimulation with helper CD4+ T lymphocyte. |
| What are the role of specific cytokines in attracting immune cells to the site of inflammation? | N |
| What is the purpose and mechanisms of antigen cross-presentation? | to present pathogens infecting cells that cannot travel to lymph nodes |
| What are the roles of MHC-I and MHC-II? | MHC proteins determine “self” from non-self.
Membrane proteins on antigen presenting cells that display peptide antigens for recognition by T lymphocytes.
•MHC proteins control immune responses to all peptide antigens recognized by T lymphocytes.
•Class I expressed on all nucleated cells; class II on dendritic cells, macrophages, B – lymphocytes. |
| Explain the process of antigen presentation by MHC-I and MHC-II (type of antigen, sources of antigens, which cells will recognize antigens presented on MHC-I and MHC-II)? | Class I MHC:
●Expressed on all nucleated cells
●Consists of a single α chain tethered to the cell membrane non-covalently associated with a β-microglobulin molecule.
●Polymorphic regions lie in α1 and α2 domains which form a cleft big enough to accommodate peptides 8-11 amino acids long.
●α3 domain is invariant and contains the binding site for the CD8 co-receptor
Recognized by CD8+ T Cells.
Class II MHC: Expressed on dendritic cells, B cells, macrophages, thymic epithelial cells, some endothelial cells. Consists of α and β chains. Polymorphic residues lie in α1 and β1 domains which form a cleft which can accommodate peptides 10-30 amino acids long. ●β2 domain is CD4 co-receptor binding site.Recognized be CD4+ cells |
| What are the signals that trigger antibody class switching? | N |
| What are TH1 cells? And what cytokines they produce? | Th1 cells induced by microbes ingested by phagocytes
M1 macrophages secrete cytokines that amplify T-cell response.
Th1 cell activate macrophages by cytokines.
IFN-g triggers production of IgG that promote phagocytosis because Fc receptors on phagocytes bind to IgG that cover bacteria – opsonisation |
| What are TH2 cells? And what cytokines they produce? | Th2 and Tfh stimulate production of IgE by B cells. IgE coat helminths, then eosinophils bind via Fc receptors and release toxic granule content.
Similar mechanism involved in allergic reactions.
That is why exposure to helminths in childhood may prevent allergies.
IL-4 creates an autocrine loop that facilitates Th2 development |
| What are the different types of secreted antibodies, where they present antibodies present in mucus, saliva, tears.? | N |
| Where is the igA antibodies present? | Lining of the respiratory tract, digestive system, saliva, tears, and breast milk (mucous membranes) |
| Explain characteristics of passive immunity? | occurs when antibodies are obtained from someone else
Naturally Acquired
from a mother to fetus through placenta
from a mother to newborn through breast-feeding
Artificially Acquired
from immune serum or gamma globulin
Immunological memory does not occur
Protection provided by “borrowed antibodies” |
| Explain characteristics of active immunity? | Occurs when B cells encounter antigens and produce antibodies
●Active immunity can be
–Naturally acquired infections
–Artificially acquired from vaccines |
| which cytokines play role in repair of damaged tissues? | IL-1b , TGF-b , TNF-a IL-4, IL-13 |
| What is the Antibodies type expressed on plasma membrane of mature B cells? | IgM , IgD |
| Explain the selection of B cells that produce high affinity antibodies? | N |
| Know how B cells respond to antigen stimulation? | N |
| How are B cells Activated by antigen? | Antigen binding triggers clustering of 2 or more Ig receptors that leads to the formation of B cell receptor (BCR) complex that initiates downstream signaling cascade. End result - activation of transcription factors that control proliferation and differentiation. |
| How are Enhanced B cell activated by innate signals? | Simultaneous recognition of antigen and:
• binding of C3d complement product
by compliment receptor type 2 (CR2) • or binding of microbial PAMP by TLR
(Toll-like receptor).
greatly enhance antigen-dependent activation of B cells. |
| How are B cells activated? | Initiates proliferation and differentiation to prepare for interaction with helper T cells
Maximal B cell activation is accomplished by multivalent antigen that crosslinks many receptors + engagement of CR2 and TLR.
Protein antigens do not have these features, but they induce interactions with helper Th cells by presenting antigen on MHCII receptors. |
| What are the mechanisms that drive selection of B cell? | Only cells that express Igm heavy chain are selected to survive to become pre-B cells.
Igm heavy chain and surrogate light chains are expressed on cell surface and associate with Iga and Igb to form pre-BCR complex. Pre-BCR complex is a first checkpoint for cells that express functional Igm heavy chain. It sends survival signals.
If Igm heavy chain is failed to be made – pre-B cells will die by apoptosis= first checkpoint. |
| What is Allelic exclusion relation the b-cell selection? | Pre-BCR complex also send signal to inhibit recombination on the homologous chromosome, so only one allele will express BCR of single specificity.
-If k light chain fail to produce functional receptor or k light chain encodes a self-reacting BCR, then BCR will trigger recombination of k with ⋋ light chain.
If functional IgM receptor is produced it will send survival signal, otherwise – apoptosis. Signals from IgM will also shut off light chain recombination, so either k or ⋋ light chains are made by given B cells. |
| What are the two types of B-lymphocytes selection ? | • Positive selection→intact receptors (IgM)
• Negative selection→recognition of self antigen:
B cell deletion: Alternatively, immature B cells that recognize antigens in bone marrow will die.
Mature B cells: follicular B cells in lymph nodes and spleen. B-1 lymphocytes in lymphoid organs and in peritoneal cavity develop earlier. |
| what is immunologic synapse? | is the interface between an antigen-presenting cell or target cell that has a large amout of ligant molecules and receptors. |
| what is the difference between primary and secondary adaptive immune response ? | N |
| What's the function of plasma cells ? | They synthesyse and excrete of large amounts of antigen-specific antibody which targets microbes for destruction by other immune cells. |
| Roles of C3a and C3b in complement response.
What the role of C3a?
What's the role of C3b? | C3b binds Factor B, which is cleaved by Factor D to make Bb. C3bBb complexes act as C5 convertase to generate C5b and C5a |
| Signaling molecules secreted by regulatory T cells (Tregs). | Production of cytokines that inhibit activation of lymphocytes, dendritic cells, macrophages (IL- 10, TGF-b). Interleukin 35 |
| Purpose of bone marrow transplantation. | Replace diseased or damaged marrow with new stem cells. Provide new stem cells, which can help kill cancer cells directly. |
| Targets of pro-inflammatory cytokines (IFN-y) | Activation of macrophages
Stimulation of antibody response |
| Role of CD40-CD40L interaction | CD40 – CD40L interaction is critical for isotype switching. Without CD40 – all are IgM |
| Role of Th cells in heavy chain isotype switching by activated B cells. | Cytokines produced by Tfh cells determine what type of antibodies will be produced.
Secreted cytokines depend on Th cell type (Th1, Th2 etc).
Activated helper T cells that express CXCR5 that direct migration to adjacent follicles They become follicular T cells (Tfh) ,Some B cells are coming back and rapidly dividing (6h doubling time) in response to Tfh to form germinal center where mutations and isotype switching takes place |
| What does epitope mean ? | the part of an antigen molecule to which an antibody attaches itself. |
| What does memory of a cell mean ? | A cell being able to remember a specific antigen to know how to respond |
| What's IgE? | If you have an allergy, your immune system overreacts to an allergen by producing antibodies called Immunoglobulin E (IgE). These antibodies travel to cells that release chemicals, causing an allergic reaction. |
| what is isotype switching? | is a biological mechanism that changes a B cell's production of immunoglobulin from one type to another |
| What are antigens? | They are foreign substance which induces an immune response in the body. |
