Exam 3 Flashcards
What are the 3 populations of B cells?
- B-1
- B-2
- Marginal Zone B cells
Where do B-1 B cells usually reside?
body cavities
What is the primary job of B-1 B cells?
protect gut and lung tissue
Where are B-1 B cells generated?
fetal liver (self-renewing)
Does B-1 B cells have diversity?
Not much; no VDJ recombination or class switching
Do B-1 B cells require T helper cells for activation?
No (T cell independent)
B-1 B cell primary produce the _____ isotype
IgM
Do B-1 B cells produce memory B cells?
No
Where do B-2 B cells reside?
most parts of the body
What population of B cells makes up most of the B cell population?
B-2
Where are B-2 B cells generated?
bone marrow
Do B-2 B cells require Helper T cells for activation?
yes (T dependent)
Do B-2 B cells produce memory B cells?
yes
Do B-2 B cells have diversity?
yes; undergo class switching and recombination
What isotypes can B-2 B cells produce?
All the Igs
Where do marginal-zone B cells reside?
marginal zone of spleen
What is the purpose of marginal-zone B cells?
bloodborne pathogens
What isotypes can marginal zone B cells produce?
mainly IgM
sometimes IgG
Where do B cells start and complete thier development?
start: Bone marrow
end: spleen
What is the commitment signal for B cells in the bone marrow?
IL-7
___________ expresses IL-7 while _________ expresses IL-7R
bone marrow
lymphoid precursor
What are the 8 Stages of B-2 cell development
- Early Pro-B
- Late Pro-B
- Large Pre-B
- Small Pre-B
- Immature B
- Transitional 1
- Transitional 2
- Mature B cell
What happens during Early Pro-B stage?
Heavy chain D+J rearrangement
What happens during Late Pro-B stage?
Heavy chain V+DJ rearrangement
What is used to check the heavy chain rearrngment?
surrogate light chain
What is the surrogate light chain made of?
VpreB
gamma5
When and what are the checkpoints for B-2 recombination?
1st: test for heavy chain function (after late pro B)
2nd: test for functional B cell receptor (after small pre B)
What does the VpreB part of the surrogate light chain mimic?
variable region of light chain
What does the gamma5 part of the surrogate light chain mimic?
constant region of light chain
After the surrogate light chain is used to check if the heavy chain is working, the heavy chain forms a complex with Ig alpha and Ig beta to test for ….
ability to form Pre-B cell receptor
What happens during Large Pre-B cell stage?
allelic exclusion of the heavy chain
What happens during the Small Pre-B cell stage?
light chain V+J recombination
What are the 2 possible light chain loci on B cells?
kappa
lambda
What happens during the immature B cell stage?
negative selection in bone marrow
Immature B cells in the bone marrow that recognize self-antigen have one of three fates….
- clonal deletion (apoptosis)
- receptor editing (another chance)
- anergy (nonresponsive)
Why is negative selection in B cells not as stringent compared to T cells?
B-2 don’t have AIRE so activation is dependent on helper T cells that themselves have already gone through very strict selection
When do B cells traffic out of the bone marrow to the spleen?
immature to transitional 1
What happens during the Transitional 1 B cell stage?
negative selection
During the second round of negative selection during T1; the B cells begin expressing low levels of ________
BAFF-R (survival factor)
What happens during transitional 2 B cell stage?
positive selection (post receptor editing)
During the T2 stage; B cells begin expressing higher levels of ________
BAFF-R (survival factor)
Where do mature B-2 cells go after development in the spleen?
circulatory system then enter secondary lymph tissue for activation
Do B-1 or B-2 B cells need BAFF signaling for survival?
B-2
Because the heavy chain of BCR are so short they require ______ and _______ to mediate signaling
Ig beta
Ig alpha
What is the first signal of naive B cell activation?
crosslinking of the BCR
What is cross linking in B cell activation?
binding of antigen induces BCRs to cluster on the B cell surface
BCR crosslinking induces the activation of _________ on the Ig alpha and Ig beta
ITAMS
What is the B cell coreceptor made of?
CR2
CD19
CD81
What does CR2 do in the B cell coreceptor?
binds with C3b on the pathogen causing signaling
What does CD19 do in the B cell coreceptor?
cytoplasmic domain that signals
What does CD81 do in the B cell coreceptor?
stabilizes the complex
What is the signal transduction steps of B cell activation?
- Lyn/Fyn/Blk
- ITAMs
- Syk
What does Syk induce in the signal transduction of B cells?
the three signaling pathways
What are the three signaling pathways for B cells?
NFAT
NFkB
AP-1
Some B-2 B cells generate a ____________ and differentiate into plasma cells that produce soluble IgM
primary focus
Some B-2 B cells generate a ______________ and will become a memory B cell or plasma cell encoding high affinity antibodies of isotypes other than IgM and IgD
germinal centers
T-independent 1 antigens do crosslinking with BCR and co-receptor and express ______
PRR
T-independent 2 antigens do excessive ____________ of BCR and co-receptors
crosslinking
What T-independent B antigen uses PRR (TLR) as well as BCR to drive B cell activation?
TI-1 antigen
Which T independent antigen doesn’t require a secondary signal?
TI-2 (uses excessive crosslinking of BCR and co-receptor)
What 2 signals does T-dependent B cells require for activation?
- BCR and co-receptor signaling
- CD40 signaling (CD40L expressed on helper T cell)
How does T-dependent B cell activation work?
T helper cells position themselves on the boarder of the B cell follicles and interact with B cells to activate them
What is it called when T-dependent B cell’s peptide/MHC II complex is recognized by a helper T cell?
conjugate pair
When T-dependent B cell’s peptide/MHC II complex is recognized by a helper T cell, CD40-CD40L signaling induces the expression of __________ on B cells and ______ on T cells tightening the binding of the conjugate pair?
ICAM-1
LFA-1
What does the creation of a conjugate pair induce?
cytokine signaling for activation
What are the 2 fates of the conjugate pair?
- pair can migrate to medulla to become a primary focus
- pair can migrate back to primary lymph follicle to form a germinal center
What do B cells in a primary focus do?
differentiate into plasmablast that expresses IgM
What do B cells in germinal centers do?
AID is up regulated = somatic hypermutation in the CDR
(change the affinity of the BCR)
Centroblast migrate to the light zone to become ___________ where positive selection occurs
centrocytes
Do you want centrocytes to express high or low affinity of BCR?
high
Does negative and positive selection occur in the germinal center?
yes
Where does class switching occur for TD B cells?
germinal centers
________ on TFH binds with _______ on centrocytes during the selection process which induces AID and class switching in germinal centers
CD40L
CD40
What do centrocytes differentiate into?
plasma cells or memory B cells
What does the Fc fragment of antibodies do?
attaches to other immune cells
What does the Fab fragment of antibodies do?
antigen binding region
What are the loci of the light chain of an antibody?
lambda
kappa
What are the heavy chain isotypes of antibodies?
all the Igs
Do surface bound of secreted BCR initiate signaling pathways?
surface bound
The heavy chain of each isotype of antibodies differ how?
- varying number of constant regions
- level of glycosylation
- length of hinge region
What does the level of glycosyaltion of an antibodies Fc constant region determine?
which Fc receptors it can bind
Where is the hinge region on an antibody?
where the Y arms come together
What does the hinge region of an antibody allow?
Fab flexability
What is the first 2 isotypes expressed by mature naive B cells?
IgM
IgD
Soluble IgM form pentamers connected by a ___________
J chain
What is the purpose of IgM?
- neutralize
- activate classical pathway
What is the purpose of IgD?
- induce mast cells and basophils (degranulation)
What is the purpose of IgA?
- protect mucosal surfaces
- neutralize
Ig___ can come as a dimer or momer
IgA
What Ig protects breast milk?
IgA
What is the most abundant isotype?
IgG
What Ig protects the fetus?
IgG
Why are there some any different types of IgG?
differing hinge regions of diversity
What is the purpose of IgG?
- neutralize
- opsonization
- classical complement
EVERYTHING
How is IgG “bispecific”?
is can mix one heavy chain and light chain dimer with another heavy and light chain dimer
What is the purpose of IgE?
- combat inhaled and ingested pathogens
- activate granulocytes
What Ig isotype is involved with allergies?
IgE
What isotypes neutralize?
G
A
M
What isotypes opsonize (phagocytosis)?
G (especially IgG1 and 2)
A
What isotypes activate complement?
G
A
M
What isotypes activate innate immune cells (granulocytes) ?
D
E
G
What isotypes protect internal tissues?
G
A
M
What isotype activates NK cells?
IgG
How do IgG antibodies kill pathogens?
recruit NK cells and induce antibody-dependent cell-mediated cytotoxicity
IgA, M, and G protect interal tissues using _________
transcytosis
IgA, M, and G protect against __________ pathogens
bloodborne
Epithelial cells lining mucosal surfaces express __________ that covalently binds to dimeric IgA via its J chain; engulfing the antibody
poly-Ig
The classical pathway can be activated by _______ instead of CRP
antibodies (IgM and G)
IgM or IgG binding to a soluble multivalent antigen allowing C1 binding forms a ___________ complex
immune complex
Immune complex bind with _____ and are recognized by RBC and travel through the liver and spleen where macrophages clear the complex (part of the activation of complement)
C3b
What are the 2 severe combined immunodeficiencies (SCID)?
- Omenn syndrome
- ADA deficiency
What are the 3 B cell specific immunodeficiencies?
- X-linked agammaglobulinemia
- Hyper-IgM syndrome
- selective IgA deficiency
What is Omenn syndrome?
mutation in Rag1/2 = no recombination
What is ADA deficiency?
deficient in ADA = inhibits cell proliferation = increased dATP
What is X-linked agammaglobulinemia?
mutation in Btk = no survival signal sent
What is Hyper-IgM syndrome and why is the defect in?
defect in CD40
defect in IKK
defect in AID
= blocks class switching
What is Selective IgA deficiency?
lack of IgA making mucosal surfaces vulnerable
What are 2 acquired B cell immunodeficiencies?
- B cel leukemia (pushes out healthy cells)
- Alcohol (lowers number of B cell)
What are the 3 type II hypersensitivities?
- Goodpasture Syndrome
- Hashimoto Syndrome
- Myasthenia gravis
What are the 2 type III hypersensitivities?
- Systemic Lupus Erythematosus (SLEE)
- Rheumatoid arthritis (RA)
What is Goodpasture Syndrome?
destruction of basement membranes of kidney and lungs
What is Hashimoto Disease?
destruction of thyroid epithelial cells via antibody-dependent cell-mediated cytotoxicity
What is Myasthenia gravis?
acetylcholine receptor is blocked
What is Systemic Lupus Erythematosus (SLE)?
targeted destruction communication cells causing tissue damage
What is Rheumatoid Arthritis (RA)?
formation immune complexes in joints
What is Multiple Sclerosis (MS)?
EBV infection and mimics GlyCAM affecting the CNS
cant tell the difference between self and virus
What is Type II hypersensitivity?
autoantibodies of IgM or IgG binding cell surface molecules
What is Type III hypersensitivity?
prouction of small immune complexes made of IgM or IgG that cannot be cleared
How does the adaptive immune response differ when exposed a second time?
the response is stronger and fast
The goal of vaccination is to form a _________ immunity (lessens disease) not a ___________ immunity (prevent infection)
protective
sterilizing
Upon primary exposure to a pathogen, it can take up to _____ days to clear an infection
14 days
Why is the primary response slow?
needs to coordinate the different arms of the immune system
Are naive or memory cells long lived?
memory
Are naive or memory cells easier to activate?
memory
What are the 4 memory T cells?
- T SCM (stem memory)
- T CM (central memory)
- T EM (effector memory)
- T RM (resident memory(
What is the first memory T cell produced during clonal expansion?
T SCM (T memory stem cells)
Where do T SCM exist?
circulatory and lymph tissue
What memory T cell is pluripotent?
T SCM
What 2 types of memory T cells comes from T SCM?
T CM
T EM
What T memory cell is self renewing?
T SCM
Where do T CM exist?
circulatory and lymph tissue
What is the job of T CM memory cells?
scan for antigen presenting DC in secondary lymph tissue
T CM memory cells express high levels of ______ allow for activation of effector T cells
IL-2
Where can T EM memory T cells exist?
anywhere in body
T EM memory T cells can quickly activate and differentiate into effector T cells because they secrete ____ and _____
INF-g
TNF-a
______ memory T cells can migrate close to site of infection preventing tissue from future infection
T EM
Where do T RM memory cells reside?
tissue of origin
What can T EM memory cells differentiate into?
T RM
T RM have the same function as ______ memory T cells
T EM
What are the 2 main sources of memory B cells?
- germinal center dependent
- germinal center independent
Do germinal center dependent or independent memory B cells undergo somatic hypermutation and class switching?
germinal center dependent
Are germinal center dependent or independent memory B cells more specialized and diverse?
germinal center dependent (undergo class switching)
During the secondary immune response the activation of _________ is limited
naive B cells (too general need more specialized response; high affinity class switching antibodies)
How is naive B cells inhibited during secondary immune response?
IgG bound to pathogen interacts with Fc-gamma-RIIB1 on naive B cells
Why are vaccine challenging to design?
most pathogens do not have a closely related nonpathogenic counterparts (like small pocks)
What are inactivated vaccines?
pathogen that is killed or inactivated
What are live attenuated vaccines?
weakened pathogen
What is an advantage of live attenuated vaccines?
most pathogen antigens are capable or producing a primary immune response
What is a disadvantage of live attenuated vaccines?
cannot be given to immunocompromised people
What are toxoid vaccines?
generate a primary immune response to toxins produced by pathogens
What are subunit vaccines?
neutralizing antibodies bind to intracellular pathogens’ adhesion molecules blocking virus from binding to host cells
What are conjugate vaccinees?
weak antigen with a stronger antigen (requires a non-protein antigen to stimulate IgG) like polysaccharides
What is a advantage to conjugate vaccines?
young children and the elderly (they have a reduced amount of T-cell independent response to polysaccharides)
What are adjuvants?
retain antigen and slowly release it allowing for a maintained innate response that isn’t cleared as quickly which can build a better immune response
What are recombinant vector vaccines (viral vector vaccines)?
attenuated (weakened) virus infects host and uses it transcription/translation machinery to express pathogenic proteins
What are DNA vaccines?
virus is used as a carrier for pathogen genes carried in an expression plasmid
What is messenger RNA vaccines?
mRNA molecules that encodes a pathogenic protein packed in lipid nanoparticles and delivered to the cytoplasm of cell where mRNA is translated into protein and induces immune response
monovalent antigens result in __________ while multivalent results in ___________ or __________
anergy
clonal deletion or receptor editing
Where does peripheral and center tolerance happen for B-2 B cells?
central:bone marrow
peripheral: spleen
TI-1 antigens require BCR signaling and _________
PRR
What is the B cell receptor complex made of?
heavy chain
light chain
Ig alpha
Ig beta
What must T-dependent B cells present on MHC II to helper T cells?
proteins
What is the fate of plasmablasts?
primary focus (no class switching)
BLIMP-1 is required for ….
B cells to become plasma cells
centroblasts migrate to light zone and turn into __________ where they are tested for high affinity
centrocytes
Once centrocytes are tested for high affinity, what happens to them?
cytokines are released to promote class switching
Ig___ can form a pentamer connected by a J chain
IgM
Why are IgM pentamers useful?
increases affinity since there are more binding sites
What Ig is the most diverse?
IgG
Ig___ and Ig___ activate the classical pathway once they go through a conformational change
IgM and IgG
Where will most B cells be removed with Omenn Syndrome?
first checkpoint
Where will most B cells be removed with X-linked agammaglobulinemia?
2nd checkpoint
high affinity antibodies inhibit _______ B cells
naive
Is the polio (salk) or polio (saban) more dangerous and why?
Saban (live attenuated) is more effective but its more dangerous
What is an example of an adjuvant?
ISCOMS
lipid carriers encapsulate viral protein and deliver to cytoplasm allowing presentation on MHC I (which is difficult to do)
