HRR: humoral immune response Flashcards
__ receptors can bind to free floating antigens, while ___ receptors require antigens to be presented
B cell; T cell
What are the steps involved in B cell maturation
1.Proliferation of immature cells
2.VDJ recombination of antigen receptor genes
3.Selection of lymphocytes with useful receptors
Name the phases of the humoral immune response
1.Naïve IgM, IgD B cell waits for an antigen
2.The B cell becomes activated upon antigen recognition
3.The B cell proliferates
4.Without T cell activation, the B cell will make IgM. With T cell activation, there are other options. They can create memory B cells, do isotype switching, and affinity maturation
Describe how B cells change with repeat exposure to antigen
They change quantitatively and qualitatively. Their infinity for antigen increases and their response is larger. This is why we do boosters in vaccines!
If A B cell receives a T signal to switch to an isotype other than IgM, what happens?
The B cell will produce memory cells with the new isotype as the B cell receptors.
What can an IgM to IgG ratio tell us?
If IgM is higher, it likely means it’s their first time being infected. If IgG is higher, it likely means it is a repeat or chronic infection
Describe activation of B cells
Cross-linking of two or more B cell receptors is required for activation. This means a multivalent antigen is needed; this requires either two copies of the same epitope, or a clump of different epitopes
What is the purpose/significance of costimulatory signals
It is the required second signal from the innate immune system that indicates danger, keeping B cells from responding to autoantigens
List the two types of costimulatory molecules for B cell receptors
Iga and Igb; they have ITAMs that can be phosphorylated
What are the kinases seen in B cell receptors for phosphorylating ITAMS?
Lyn, Fyn, and Blk
What adaptors are used in signal transduction pathways for B cells?
Syk that binds to phosphorylated ITAMS, which then activates btk
What transcription factors are relevant in B cells?
Myc, NFAT, NF-kb, and AP-1
List the two costimulatory molecules and signals for B cells
CR2 stimulates C3d
stimulation of toll-like receptors expressed by B cells
List 3 clinically relevant ways that secondary humoral responses differ from primary immune responses.
-High IgM in first-time infection allows to distinguish between a primary or secondary immune response
-Immunizing with T dependent antigens can protect from disease due to a faster and more robust secondary response
-Boosters (secondary) strengthen the memory immune response
What changes are seen in antigen-activated B cells?
Antigen presentation of MHC II and increased expression of B-7, increased IL-2R and IL-4R and BAFF-R, increased CCR7, and generation of plasma cells
What are plasma cells?
Terminally differentiated B cells that no longer have receptors and just make low levels of IgM for the rest of their life.
Explain how and where T and B cells for the same antigen find each other and interact.
they migrate towards each other by changing their chemokine secretion. T cells increase CXCR5 and decrease CCR7, while B cells decrease CXCR5 and increase CCR7. This allows helper T cells and B cells to meet.
Describe the molecular nature of T-cell “help.”
-A cell-cell contact via CD40 on B cell and CD40L on T cell occurs. The T cell will also make cytokines for B cell cytokine receptors.
-These signals can lead a B cell to switch isotype, undergo affinity maturation, or become memory B cells
Describe the molecular basis of isotype switching
-A cytokine secreted from a helper T cell activates a switch region on the chromosome
-Activation induced deaminase causes two switch regions to come together, cutting ut the DNA in-between the two
-The VDJ region is closer to a C gene that codes for the isotype
-This occurs only in heavy chains!
Is isotype switching permanent?
yes
What are follicular dendritic cells?
Follicular dendritic cells: hold full antigen molecules on their surface
What are T follicular helper cells
T follicular helper cells: stays in the follicle and waits for signal from the B cell and provides help to the B cell
List the steps in affinity maturation and explain the role of follicular dendritic
cells and activation-induced deaminase (AID).
-Naïve B cells are activated by antigen and helper T cells in the follicle of a lymoh node
-B cells migrate to the germinal center
-B cells with high affinity membrane Ig bind antigen on the follicular dendritic cells and present it to T follicular helper cells. These will be able to survive and be mature.
-B cells that do not have high affinity for the antigen on follicular dendritic cells die
List the steps of antigen-induced B cell maturation
-Activation and migration of T and B cells
-T and B cells interact
-B cell differentiation: isotype switching and Ig secretion
-Germinal center reaction: affinity maturation, plasma cells, isotype switching, memory B cells
Explain the difference between T-dependent and T-independent antigens and provide examples.
T-dependent antigens have proteins, and T-independent antigens do not.
What are haptens?
Small molecules that cannot induce immune response on their own, but can when they are conjugated to a protein
Diagram the T-cell:B cell interaction during a response to a hapten-protein conjugate.
-A carrier protein containing a linear peptide binds to B cell receptors
-The B cell internalizes the carrier protein
-The carrier peptide binds to MHC II
-The MHC II with the carrier peptide can be expressed on the B cell membrane and be presented to a T cell!
In what context are hapten-protein conjugated useful?
Conjugate vaccines!
Explain how excess circulating antibody to an antigen downregulates the humoral immune response to that antigen
Secreted antibodies will form complexes with antigens. When this antigen encounters BCR, the cell will come in contact with both the antigen and Fc portion of antibodies. This interaction blocks B cell receptors signaling by shutting down the tyrosine kinase pathway in the B cell.
