B cells Flashcards
What do mature naieve B cells express?
BCR: IgM, IgD, (Iga and IgB): signaling complex Co BCR: CD19, CD81 and CR2 HLA class 1/2 CD20 CD 40
B 2 Cells
Follicular B cells (re circulating B cells) the majority
marginal B cells: reside in the spleen and attack blood borne poly saccharides
B-1 Cells
found in mucosa, limited Ag specificity
Where do naieve B cells go?
- travel to secondary lymphoid tissue if it is coming from lymphatics. Will enter through the HEV and pass through the secondary lymphoid organs.
- if it coming from blood it will go through the spleen
B cell activation: first singal
- must cross link 2 BCR -SIGNALING will then occur through the Ig alpha and beta cytoplasmic tails by ITAM (phosporylated by SYK)
- many steps occur which will make transcripton factors like Myc and NF-kB
mlg
membrane bound immunoglobulin
is crosslinking enough?
No, you need to have another signal that enances it -a bound C3d on the pathogen will bind to CR2/CD21 which will increase signaling via that receptor and CD 19 which will enahance BCR singaling: will cause proliferation and differntation.
How can you also activate b cells first singal
via TLR signaling as it recognizes pamp.
If C3d is attached to protein Ag, Ag is what?
1000x more immunogenic
what are the outcomes of the first signal
- express proteins that promote prolferation (inc prolif and survial)
- B7 is expressed which helps with T cell interaction
- increased cytokine receptors on cell
- increase expression of CCR7 (can migrate out of the follilce to T cells)
- secretion of IgM
After first activation signal what does a B cell do?
- change chemokine receptor expression and migrate to the edge of the follicular zone
- activated B cells secrete a low level of IgM and increase expression of co stimulatory molecuels and cytokine receptors to prepare for T helper cell reaction
what is the second activation singal?
-T dependent antigen: protein antigen is shown to the b cell -t independent antigen: long erpititve epitops that cross link many surface bound Igs and cause signaling
Steps of T dependent antigen activation
- recognition by membrane bound Ig of the epitope
- will endocytose the antigen and process it and express it via class 2 MHC (first step activation)
- B7 is upregulated because of the first signal and will bind to CD28 on the Th cell that is always expressed
- This will cause CD40 L to be expressed on the T cell and bind to cd40 on the B cell which is consitituvley expressed
- this will cause cytokines to be released from the T cell and activate the B cell which will cause prolieferation and expantion
ALL HAPPENS IN THE MEDULARY REGION OF THE SECONDARY LYMPHOID ORGANS
After B cells are activated by t cells what do they do. What happens in the germinal centers?
- they change their chemokine recptors and expression to mgirate to follicular areas and establish in the germinal centers in the follicules
- Class switching occurs in the germinal centers by Th cells OR they can STAY OUTISDE and become plasma cells (short lived)
What do Th cells do when they release their cytokines in the germinal cells?
- induce H chain class switching and somatic hypremuation (by AID) (occurs at the same time)
- cause cell diff and proliferation
IL4 causes what
released by t helper cells: class switching IgM to IgE and IgG 4 these protect against helminths and cause mast cell degranulation (immediate hyerseitivity)
TGF-B and April cause what
Which cause IgA formation: important in mucosal immunity
Describe switch recombilation
CD 40:CD40L ligation and cytokines trigger isotype switching by modulation of the switch region (this region is increasing the accebility of the DNA at the specific C region)
What happens after switch recomination
VDJ gene segment is attached with a new downstream c region and the rest is deleted of the DNA sequence. Thus you are not going back to your original sequence.
What does AID do?
Helps with affinity maturation: there are somatic hyper mutations that covert C to U which allows APE 1 endonuclease to make Ds breaks in the DNA of THE variable areas in the IG genes: this may be helpful but may be not.
T folicular helper cells do what?
- Will bind to activated B cells via I cos and I cos ligand (on b cell) which are essential for geminal center reactions and taken to the genminal center
- will bind CD40 and CD40L and secrete IL21 which facilates the differentiation of the B cell to a palsmablast
- then secretes ifn gamma and IL4 for cytokine switching
Steps for the selection check point
- A naieve mature b cell will be activated in the SLT
- then a Th cell will bind to it and migrate into the gernminal center and cause the indcution of AID
- the b cells are somatically mutated at V spots (hypermutation) and also constant spots (switch recombination)
- the B cell then with the high affinity antigen receptor are best able to regognize antigens of both folicular dendritic cells and antigen on TFH cell which will allow it to survive and cause it to move on and prolieferate into either plasma cells or memory cells
some will become plasma cells
Plasma cells
- Decrease of CD19,20 AND HLA class 2 markers but increase CD 27 their surface.
- They are either long or short lived and are terminally differentiated effector B cells.
- They secrete Ab at rates ranging from 100 - 1k and have an expantion of their er.
- they are effector molecules of humoral immunity
Plasma cells make what
antibodies, the effector molecule of humoral immunity.
B - 1 cells and marginal zone B cells respond to what?
- T independent responses in antigens. NON PROTIEN SINGALS -B1 cells respond to Ag in muscoaal tissue.
- MARGINAL zone B2 in spleen recognize blood borne poly saccharides.
Characteristics of T independent activation
- mainly make IgM, low affinity ab, short lived plasma cells.
- DO NOT DO SOMATIC HYPERMUTATION or switch recominaiton.
What are memory B cells
- survive for a long period w/o antigen sitmulation
- express high levels of antiapoptotic protein bcl2
- have surface markers cd27 and cd45r
- they are surface ig class dependent
- can produce a secondary immune response when exposed to an antigen
How are antibodies regulated
- excess/ secreted IgG ab will bind to the Fc(gama)RIIB on its Fc region which will block B cell signaling.
- it will cross link with the antigen and the membrane bound B receptor and bind to the receptor
You use ITIMs for singaling (activity shuts down response). Note: both the IG receptor and soluble IG must bind. for this to occur.
Ab are produced by _____ in the ______.
- plasma cells
- lymphoid tissues and organs
Abs will preform their functions at _____.
Sites distant from production
The effector functions of Abs are mediated by _____.
Fc region -diff isotypes serve as different effector functions
all functions are triggered by the binding of ag to the
Fab’(variable) region
primary response
- usually 5-10 days
- smaller response
- ab Igm>IgG
- lower average affinity and more variable
Secondary response
- usually 1-3 days
- larger
- inc of igG and ige/a under -heavy chain isotype switching
- higher avg affinity
effector functions of ab
- neutralize toxins
- phagocytosis of microbes
- ab dependent cellular cytotocity via Nk cells bdining to fc regions
- complement
- inflamation
- lysis
Fc regions serve two distinct functions
- deliver ab to inaccessible anatomical sites
- link bound antigens to molecules and cells that affect distruction
Neutrilization
only requires binding to Ag: any ab works but the higher the affnity the better.
Opsinization
- Igg serves as the opsin
- binding of opsonized microbes to phagocyte receptor Fcgama RI -Fc receptor singlas activate the phagocyte
- killed and ingested
Waste mamagement
- Cr1 on rbc bind to cirulating immune complexes with attached c3b and c4b and then transports the complexes to liver and spleen
- organ resident phagocytes will remove the complexes from rbcs and let them to continue to move
NK will do what
bind to ab coated fc receptors and destroy the infected cell (fcgamaRIII) and kill it
What is IVIG
-used for exposure or autoimmune/ inlamatory dz -engages the inhibotory fcR on be cells and dendtiric cell to supress immune reponse
natrual ab
IgM but some IgG
- produced by B-1 and marginal zone B cells
- specific for bacteria in the area
- cross react with blood alloantigens
IgE mediation rxn
bind to FCe receptors on mast cells to activate eosinophils and cause helminth death via degranulation
How does a kid get ab from her mom?
gets igg by leaving cirulation and entering extracellular space within the tissues via trancytosis of FcRn -this then transports the igg across the placental barier and then is returned -FcRN is found on endothelial cells, macrophages and other cell types
baby immuno
- kid gets passivley transfred igG right before she is born
- synth of IgM rises slowly before birth and Igg and IGA RISE after birth
Child is not immunocompetent till when?
due to lag of 6-12 months (of igG and IgA) , baby isnt immuno competent
immunization
mimics a natrual infection, a normal immune response is invoked to destroy and clear the components of the vaccine.
This primary immune response is called primiing.
Each subsequent immunization results in increaseda intensitity and magintude of the response.
Hyper immunization
when repetitive challange with antigen achives a heightened state of immunity.
Passive immunity
- used to prevent diseases after known exposure
- amelioriate Sx of an ongoing issue
- protect immunosuppresed pts -block baterial toxins and prevent dz they cause
avctive immuno
- natrual exposure to pathogens
- vaccines
Ex of combined passive/active immuno?
tetanus and rabies vaccines
Evasion of humoral immunity
change surface Ag or outer capsule or coat to prevent compement activation. The campsule prevents binding of Ab and pagocytosis.
