Study sets, textbooks, questions
Upgrade to remove ads
Immunology Exam II, lectures 13+14
Terms in this set (76)
individuals w/ deficiencies in B cells/antibody production are more susceptible to
combinatorial diversity enzyme
junctional diversity enzyme
Pro-B heavy chain and Pre-B heavy chain
Pro= D and J to form DJ
pre= V and DJ= VDJ
D and J bind first
Pre-BCR complex formation
u heavy chain rearranges along with a surrogate (temp) light chain Igα/Igß
light chain has 2 k and 2 λ therefore has 4 chances to combine into a successful light chain
k always first
Igα and Igß are analagous to
CD3 + zetta chain of TCR
B cells that do not successfully rearrange light chain will undergo
Immature B cells express H and L chains as
mIgM (membrane bound)
Immature B cells that express mIgM that bind w/ high avidity to self antigen under go ___________ to avoid apoptosis
What is negative selection
light chain editing (rearranging different light chain allele to create a non-self reactive BCR)
2 k chains tried first, then 2 λ chains
What occurs after negative selection in B cells?
immature B cell splice heavy-chain primary RNA transcripts to secrete IgM and IgD on surface
Expression of IgM and IgD and B cell surface=
B cell cell is mature
What is expressed first IgM or IgD?
IgM as umRNA is transcribed first then delta
Progenitor B cell
initial expression of CD19 and CD20
Initiation of somatic recombination of the u heavy chain
Precursor B cell (pre-B cell)
immunoglobulin heavy chain successfully rearranged and is expressed on surface w/ surrogate light chain
surrogate light chain starts recombining
Immature B cell
Heavy and light chain successfully rearranged
expression of membrane bound IgM (mIgM)
naive mature B cell
expression of membrane bound IgM and IgD (mIgM/mIgD)
exported from bone marrow to peripheral lymphoid organs to be activated
Where does activation of Mature, Naive B cells occur
peripheral secondary lymphoid organs and require antigen
spleen (blood-born antigen)
Lymph nodes (tissue antigen)
MALT and tonsils (tissue antigen)
What happens if naive B cells don't have an antigen bound in secondary lymph?
undergo apoptosis w/in months
antigen-driven activation and clonal selection of naive B cells leads to
plasma cell (effector B cell) and memory B cells
what are the 2 signals needed for B cell activation
first signal: binding of antigen by the BCR complex
second signal: specific second signal varies and depends on nature of the antigen
types of second signals
spleen/lymph-->follicular B cells-->IgD, IgM expressed-->protein antigen+Th-->T-dependent, isotpe-switched, high-affinity antibodies; long-lived plasma cells
marginal zone B cell (spleen)-->IgM-->polysaccharides, lipids-->T independent; IgM short-lived plasma cells
B-1 cells (mucosal tissues)-->IgM, CD5-->polysaccharides, lipids-->T independent; mainly IgM produced; short-lived plasma cels
what is most effective receptor to B cell activation
follicular B cells
First and second signal of B cell activation for T-dependent antigen
1st- B cell receptor binding to peptide antigen
2nd-direct contact with T helper cells (CD40-CD40L)
T-cell dependent (TD) antigens are associated with?
proteins and follicular B cells
What 3 things are caused by TD activation of B cells?
extensive class switching
memory cell generation
First and second signal for T-independent (TI) antigen
2nd- signal provided by toll-like receptor or cytokines produced by Th cells
what is associated with TI (T-cell independent antigen)
nonproteins: polysaccharide, lipid, nucleic acid
What are the two types of TI antigens
TI-1: non-protein binding to a toll like receptor; leads to complement (CR2-->C3d)
TI-2: non-protein, multi-valent antigen-->extensive BCR cross-linking
What is BCR cross linking?
cluster of B cell receptors cross link allowing for very tight binding of antigens
cross-linking of BCR w/ CR2/CD21 coreceptors of TI antigen or PRR
TI activation leads to efficient B cell proliferation but
limited class switching
limited memory cell generation
What are the 3 distinct subset of B cells specialized in recognizing TD or TI antigens that differentiate from immature B cells
Follicular B cells
Marginal Zone (MZ) B cells
B-1 B cells
Follicular B cells
in follicles of lymph
respond primarily to T-dependent antigens (proteins/peptides)
Marginal Zone (MZ) B cells
in marginal zone of spleen (white pulp)
respond to T-independent antigens (polysaccharide, encapsulated bacteria)
first line in blood-born pathogens
in MALTS/mucosal area
respond to T-independent antigens (polysaccharide, encapuslated bacteria)
first line of defense against pathogens in these locations
How do MZ and B-1 B cells get activated?
receiving first and second signals by TI antigen.
second signal usually heavy cross linking.
What does activation of MZ and B-1 B cells lead to?
survival and proliferation via transduction pathways to get NFAT, NF-kB, AP-1 transcription factors.
the B cells differentiate into short-lived plasma cells secreted IgM antibodies w/ low affinity
Why are short-lived plasma cells that arise from MZ and B-1B cell activation important?
allow for rapid, initial antibody response to bacterial polysaccharides
Do MZ and B1-B cell acivation have T cell input?
No; hence why they are short-lived plasma cells
Follicular B cell activation
follicular B cell recognizs its antigen (TD/protein) it activates and proliferates
differentiates into Effector B cells (plasma cells) and memory B cells
What is unique about follicular B cell activation?
they are able to isotype class switch due to T cell involvement
IgM, IgG, IgA, etc.
What percentage of IgG are circulating?
What isotype predominately class switches?
What is the B-cell specific chemokine that attractes Follicular B cells to lymph follicles?
What produces CXCL13?
follicular dendritic cells (FDC)
If mature, naive follicular B cell circulates through follicles w/in secondary lymphoid tissues and does not become activated it: stays in the lymph or exits following the S1P conc. gradient
exits following S1P conc. gradient (like mature, naive T cells)
are follicular B Cells able to recognize T-independent antigens?
yes, but not common. primarily recognize T-dependent
What are the 3 ways to initiate signal transduction pathways in B cell proliferation?
antigen binding and cross-linking BCRs
antigen cross linking a BCR w/ CR2/CD21 coreceptor
Antigen cross-linking a BCR w/ a PRR
what molecules are involved with CR2/CD21 cross-linking?
CD19 and TAPA-1 (CD81), complement (C3d) coated antigen crosslinks the BCR and the CR2/CD21 coreceptor
how do antigen cross-linking a BCR w/ PRR occur?
epitopes on antgen bind and signal the B cell through teh BCR and PRR such as toll-like receptor
After signal transduction, what do the transcription factors (NFAT, NF-kB, AP-1) result in?
expression of CD69 to retain B cell in lymph to proliferate
snthesis of proteins to promote survival and proliferation
expression of B7 and chemokine receptors to bind to Th cell CD28 receptor
B cells can activate naive Th cells first (B cells can act as APC)
Effector Th cell provides second signal via CD40-CD40L binding and B7-CD28
some activated B cell migrate back into the follicle (germinal center) to?
stimulate differentiation of activated helper T cells to become follicular helper T cells (Tfh)
How do follicular B cells proliferate/mature in germanal center (follicle)?
interact with FDC (follicular dendritic cell) and Tfh (follicular T helper cells)
B cells undergo affinity maturation producing antibodies with same specificity but higher affinity for antigen
B cell can undergo isotype class switching from IgM to others (mostly IgG)
some develop into memory
What is affinity maturation?
increased affinity/binding of antibody to antigen via point mutation on heavy and light chain (mostly heavy)
do point mutations occur at low or high rate?
How are point mutations initiated?
AID (activation-induced deaminase)
expressed by follicular B cell upon second activation
vaccines are inactivated, fractional or recombinant vaccines that are good for
stimulating B cells triggering development of antibodies and memory B cells. Able to stop infection in humoral fluid before virus gets into cell upon exposure
Why are titers a good test for Ab?
B cells secrete antibodies that circulate in the humoral (blood/fluid); upon exposure to virus, able to detect, bind and trigger immune response
Why are vaccines mostly composed of proteins?
initial exposure is from Tcells which only recognize peptides/proteins
are follicular dendritic cells APCs?
no; they just present antigens for follicular B cells
ONly B cells with _____________ are able to competitibely bind to antigen and are selected to survive
high-affinity antigen receptor (via somatic hypermutation)
after somatic hypermutation, high affinity B cells bind again with Tfh to
undergo class switching then differentiation into plasma (effecotor) and memory B cells
W/o class switching, B cells secrete IgM; however interaction with T cells provides variation.
What are the B cells new isotype interacting with Th1, Th2, Th17 cells?
B cell=IgM=complement activation
Th1=IFN-γ=IgG=opsonization, complement activation
Th2=IL-4=IgE=IL4,IL-5,IL-13=IgE=parasite/mast cell degranulation
Th17=TGFß=IL-17, IL-21, IL-22=IgA=extracellular bacteria and fungi
Why is IgM produced first in primary immune response?
The C (constant) region is closest to the VDJ region on the heavy chain
other isotypes recquire recombining via interaction with Th cells
How do people get hyper IgM syndrome?
mutation in CD40L gene;
B cells secrete IgM on their own w/o T cell interaction; however, CD40 (b cell) interacting with CD40L (T cell) results in production of AID to trigger somatic hypermutation to get class switching;
w/o CD40L, no class switching therefore, overproduction of IgM
Where do long-lived plasma cells reside?
inside bone marrow secreting antibodies for months to years for same antigen
where do memory B cells reside
all Ig isotypes (IgG is best)
mass cell degranulation
What inactivates signal pathways to prevent B cell activation?
FcR (follicle constant region) binding with BCR
What is XLA (x-linked agammaglobulinemai)
mutations in Bruton's tyrosine kinase (Btk)
Btk helps B cells synthesisze and express BCR during differentation of pre-B cells into immature B cells w/in bone marrow
Pre-B cells undergo apoptosis
x-linked gene therefore men more susceptible
who is most at risk for XLA?
men due to it being x-linked disease
what are the 5 antimicrobial substances
What is the secreted form of IgE?
how long can chronic inflammation last
What are the 3 types of adaptive immunity ?
Sets with similar terms
B cell development and activation
BLD 434 Exam 2 Practice Questions
immunology exam 2
Other sets by this creator
Oncology 1: 1
ID 2: part 4
Why is chemiluminescence also called “cold light”?
What are some ways that scientists communicate with each other?
How does the principle of biogenesis pose a scientific question regarding the origin of life on Earth?
Competition for resources in an area is usually more intense within a single species than between two different species. Suggest an explanation for this observation.