B cells Flashcards
List the effector functions of B cell antibodies
Neutralization of microbes and toxins, opsonization and phagocytosis of microbes, antibody-dependent cellular cytotoxicity, complement activation, inflammation, and lysis of microbes
What are the functions of the Fc receptor?
Deliver antibody to inaccessible anatomical sites and link bound antigen to molecules/cells that effect destruction
What region of the antibody does complement And Fc receptors bind to?
Fc
T/F: Antigen-bound antibodies can bind to Fc receptors in order to act as opsonins or to activate cells
True
Describe the affinity for Ig, cell distribution, and function of the Fc receptor Fc-gamma-RI (CD64)
High affinity and can bind IgG1, IgG3, and monomeric IgG; found on macrophages, neutrophils, and eosinophils; function is phagocytosis and activation of phagocytes
Describe the affinity for Ig, cell distribution, and function of the Fc receptor Fc-gamma-RIIA (CD32)
Low affinity for Ig; found on macrophages, neutrophils, eosinophils, and platelets; functions in phagocytosis and cell activation (inefficient)
Describe the affinity for Ig, cell distribution, and function of the Fc receptor Fc-gamma-RIIB (CD32)
Low affinity for Ig; found on lymphocytes, DCs, mast cells, neutrophils, and macrophages; function is feedback inhibition of B cells and attenuation of inflammation
Describe the affinity for Ig, cell distribution, and function of the Fc receptor Fc-gamma-RIIIA (CD16)
Low affinity for Ig; found on NK cells; function is antibody-dependent cellular cytotoxicity (ADCC)
Describe the affinity for Ig, cell distribution, and function of the Fc receptor Fc-epsilon-RI
High affinity for monomeric IgE; found on mast cells, basophils, and eosinophils; function is activation (degranulation) of mast cells and basophils
What are some effects of antibody binding to antigens or toxins as it relates to neutralization?
Blocks penetration of microbes through epithelial barriers, blocks binding of microbe and infection of cells, and blocks binding of toxins to cellular receptors and thus, the associated pathological effects
Explain the process of opsonization and phagocytosis
Microbe is floating around and gets opsonized (bound) by antibodies; the opsonized microbe (immune complex) binds to its Fc receptor; the Fc receptor sends signals that activate the phagocyte; this results in phagocytosis of the immune complex and subsequent killing of the ingested microbe
What is the function of CR1 on erythrocytes?
Binds circulating immune complexes with attached C3b and C4b and transports the complexes to the liver and spleen; organ resident phagocytes remove the immune complexes from the erythrocyte surface and the erythrocytes continue to circulate
Describe the process of NK killing of a cell infected with a virus
Virus infects a cell and surface antigens are placed on the surface of the infected cell; antibodies bind to the antigens on the cell surface, tagging it as “infected”; NKs with Fc receptors for that antibody bind to the Fc region of the antibody and kill the antibody-coated cell
What is the function of intravenous Ig (IVIG)?
For rapid protection after exposure to a disease; also used in autoimmune or inflammatory diseases by engaging the inhibitory FcR on B cells and (maybe DCs?) and suppresses the immune response
What are the natural antibodies and who produces them? What is their function?
IgM mainly, but some IgG; produced by B-1 and marginal zone B cells; specific for bacteria in the area and cross react with blood alloantigens
What do IgA and IgM have in common?
Both have J chains
Explain the exchange of IgG between a mother and a fetus
IgG can leave the circulation and enter extracellular spaces within tissues via transcytosis via FcRn (natal FcR); this transports IgG from the maternal circulation across the placental barrier as well as the transfer of maternal IgG across the intestine; FcRn takes bound IgG and recycles it to the cell surface and releases it at neutral pH, returning the IgG to the circulation
Where is the FcRn found?
Surface of endothelial cells, macrophages, and other cell types
What antibodies are produced at the time of birth and what antibodies are produced 6-12 months post-birth?
IgM and then IgG and IgA come later
Define immunization
Antigenic stimulus that elicits a specific adaptive immune response(s) that can be recalled during subsequent infections
What is a passive immunization? Give examples
Introduction of antibody or antiserum into a naive recipient; immediate immunity but transient; uses preformed antibodies
Ex: snake bite venom, passive transfer of Ig from mother to child
What is an active immunization? Give examples
Introduction of an antigen that provokes an adaptive immune response; delayed immunity but more permanent; produces memory
Ex: natural exposure to pathogens and vaccines
Define vaccination
Intentional delivery of an antigenic stimulus
Explain how immunizations work
A normal immune response is invoked to destroy and clear the components of the vaccine; the primary immune response results in immunological memory (priming); each subsequent immunization results in increased intensity and magnitude of response
What is hyper-immunization?
Occurs when repetitive challenge with antigen achieves a heightened state of immunity
What is the function of a combined passive-active immunization? Give examples
Designed to give both immediate, transient protection as well as slowly developing durable protection
Ex: tetanus and rabies
What are the criteria for an effective vaccine?
Needs to be safe, protective, give sustained protection, induce neutralizing antibodies, induce protective T cells, and it needs to be practical (inexpensive and easily distributable)
What are some potential problems with vaccines?
Clinically important epitomes may not be intact in vaccine; individual genetics may effect efficacy; some individuals may be genetically predisposed to adverse events (allergies); often work poorly in very young infants or the elderly; many do NOT induce CMI and antibody may not be sufficient
What do mature naive B cells express?
BCR expresses IgM, IgG, IgA and IgB CoBCR elements: CD19, CD81, CR2 (CD21) HLA class II CD40 CD20
What are the two categories of B-2 cells?
Follicular: recirculating B cells, make up the majority of the B cells
Marginal: in the spleen; blood borne polysaccharide
What are B1 cells?
mucosa; specific Ag specificity
Describe the migration of naive B cells
The B cells enter the lymph nodes through the lymphatics and the spleen through the blood
Enter through the HEV. If there is no antigen present, then they migrate into the primary follicle and express CXCR5 which helps them to respond to the chemokine that are being made in the B cell zone
FDCs give them signals to survive, if there are too many B cells, then some will die if there is no antigen present
What are the two signals that are involved in B cell activation?
- Ag recognition by the membrane bound Igs
(must crosslink with at least 2 BCRs) - costimulation via the connection to the T cell
Given that the steps of the B cell signaling is basically identical to that of the T cell signaling, describe the subtle differences that are present in B cell signaling
B cell signaling utilizes Syk for phosphorylation of the ITAMS (with the help of Fyn, Lyn, Blk) and also stimulates a response in PLCgamma and ras/rac
Myc is an additional transcription factor that is at the end
Describe the mechanism and the results of the first signal
- process of Ag binding
- what happens
Ag binds via C3d and is recognized by miss and CR2 (CD21) and signaling commences through the ITAMS that are present on IgA and IgB, CD21, and CD19 tails
TLR signaling can also be used
Both result in proliferation and differentiation of the B cell
What are the various changes that can occur following the Ag binding to the B cell and what do these changes result in?
- B cells can express proteins that will promote survival and cell cycling which leads to increased survival and proliferation
- B cells can express the Ag with an increased B7 expression which will lead to the interaction with T cells
- B cells can have increased cytokine receptors which will lead to increased responsiveness to the cytokines
- B cells can have increased expression of CCR7 which will allow for migration in to the T cell areas from the follicle
- B cells can secrete IgM
Describe how B cells change their signals in order to migrate to the T cell zone
They increase the expression of CCR7 and decrease the expression of CXCR5 so that they are able to go into the T cell region at the edge of the follicle and interact with the T cells
Describe the two ways in which the second signal can be received by the B cell
Through a TI-1 antigen (T cell independent)
or through a TD antigen (T cell dependent) and an interaction with CD40/CD40L which leads to proliferation of B cells
Describe what kind of effect the T cell has on the B cell during binding
Whatever cytokines the T cell is giving off the cytokines that will lead to class switching on the B cell
increases the expression of the AID enzyme
affinity maturation of the secreted Abs from the B cell (class switching and affinity maturation can happen at the same time)
Where does class switching occur and briefly describe that process
After the B cell receives T cell help, it migrates back to the follicle where it creates germinal centers, which is where class switching occurs. The T cells continue to provide help from an extracellular focus
What is the function of the cytokines that are released by the Th cells?
- induce H chain class switching
2. augment B cell differentiation and proliferation
how is the CD40:CD40L able to trigger isotope switching and the affinity maturation?
- modulation of switch regions
- increasing the accessibility of DNA at the C regions
- expression of AID (activation induced deaminase)
Describe the mechanisms behind class recombination
The VDJ region that is in the DNA of the B cells is combined with a c region that is stimulated by the cytokines that is released by the T cells, that allows for class switching to occur
Describe the process of affinity maturation
Point mutations are introduced in the switch regions of the variable regions in the Igs that will expand the antibody repertoire.
Done with the help of AID, which allows Ape endonuclease to create double stranded breaks in the DNA
Describe the number of point mutations that are seen in the antibodies in primary, secondary, and tertiary reactions
INCREASE LIKE CRAZY
Describe how T follicular helper cells (Tfh) are able to help the B cells with class switching and affinity maturation
- CD4+ low levels of CD25
- ICOS/ICOSL is essential for germinal center reactions co-stimulator with B7
- secrete IL21 which facilitates differentiation to plasmablases
- provide cytokines for class switching
Describe the selection checkpoint
The B cells with the highest affinity Abs are selected to survive and receive the interactions with the FDCs and Tfh which help them to survive
Describe the role of plasma cells and what they are made of
plasma cells are terminally differentiated effector B cells; they have a decrease in CD19, CD20, and HLA class 2 but and INCREASE in CD27, are Ig independent
plasma cells can secrete a crap ton of Abs per second and help out with the humoral immunity
Describe T cell independent B cell activation
B1 cells respond to the Ags that are in the mucosa and B2 cells respond to the blood bourne pathogens
Describe memory B cells
can survive for a long time without additional Ag stimulation
High levels of anti-apoptotic Bcl-2
Ig class independent
can create a rapid response with subsequent exposures
Define humoral immunity
Branch of adaptive immunity that consists of B cells and Abs that is key in defending against extracellular pathogens
Where are the effector functions of the Abs mediated?
The Fc region but ALL FUNCTIONS ARE TRIGGERED BY THE BINDING OF AG TO THE Fab (V) REGION
