Lecture 13 Flashcards
(44 cards)
How do dendritic cells produce different signals to dictate naive CD4 T cell fates?
sense the type of pathogen through PRRs, respond by secreting specific cytokines
How is Th1 differentiation driven?
intracellular pathogens sensed by TLR3/TLR7/TLR9 (viral RNA/DNA), secretes IL-12 –> Th1 differentiation
How is Th2 differentiation driven?
helminths or allergen components recognized by TLR2/TLR6, C-type lectin receptors to detect helminth glycans, produces IL-4 –> Th2 differentiation
How is Th17 differentiation driven?
extracellular pathogens sensed by TLR4, Dectin-1 for fungal β-glucans, secretes TGF-β + IL-6 –> Th17 differentiation
Does CD8 need signal 3 to become cytotoxic?
primarily activated in response to intracellular such as virus and some intracellular bacteria –> IL-12 (and IFN-α/β) key Signal 3 cytokine that drives CD8+ T cell differentiation into cytotoxic T lymphocytes (CTLs)
Why is the humoral immune response critical?
many pathogens multiply/spread in extracellular fluid, antibodies produced by B cells act to destroy extracellular pathogens/products and prevent spread of infection
How do B cells get activated by antigen without T cell’s help?
Signal 1: non-protein antigens (highly repetitive epitopes like bacterial polysaccharides or LPS)
Signal 2: activate via TLRs, recognizing LPS via TLR4 or bacterial DNA via TLR9
results in: rapid IgM production, early protection against extracellular bacteria
How do B cells get activated by antigen with T cell’s help?
Signal 1 (BCR binding): B cell recognizes a protein antigen, internalizes it, degraded and presented on MHC II
Signal 2 (helper T cell): TFH (follicular helper) can enter B cell follicular, TCR binds to peptide-MHCII presented by B cells, T cells provide help by CD40-CD40L binding, cytokine IL-21 enhances proliferation/differentiation
–> activate NF-kb pathways, AP-1, NFAT. B cell proliferation to generate plasmablasts
How does linked epitope recognition work?
B cell recognizes antigen through BCR, binds to specific part of antigen –> internalizes/processes whole antigen, presents to MHC II –> Tfh helps B if TCR recognizes processed peptide on MHCII
How do we increase probability of B cell and TFH recognizing different epitopes from the same antigen?
spatial organization of lymph nodes helps T/B cells meet
DCs act as common source of antigen
antigen persistence & repeated encounters
clonal expansion of both T/B
What do subcapsular sinus macrophages do?
poorly endocytic, opsonized antigen binds to CR1 and CR2 on surface, antigen is retained where it can be presented to follicular B cells –> follicular DCs –> repeated B engagement –> long-term reservoir of antigen
What are the chemokines that drive migration of B cells and activated T cells?
CCR7
CXCR5
What do SLAM family receptors do? What are they?
SLAM, Ly108, CD84
found on both T/B, enable homotypic adhesions
strengthen TCR signaling, enhancing cytokine production (and therefore B cell activation)
What is SAP?
SLAM-associated protein, signaling adaptor required for stable SLAM-SLAM interactions
How does SAP expression change over time in T cells?
initially low to prevent prolonged T-B adhesion, as Tfh fully differentiate, Bcl-6 upregulated –> increases SAP, allowing sustained interactions, effective delivery of CD40L and cytokine signals to B
What are fates of proliferating B cells?
2-3 days: downregulate CCR7 while maintaining EBl2 –> directs away from boundary, back to interfollicular region
differentiate into antibody-secreting plasmablasts in primary focus
What is the primary focus?
site in medullary cords where early antibody production occurs before germinal center reaction and plasma cell differentiation
What is the phenotype of plasmablasts?
secrete antibody, retain substantial surface Ig and MHCII, can continue to take up/present antigen to T
What is the phenotype of plasma cells?
low levels of surface Ig, can express MHCII and may suppress Tfh in negative feedback pathway while differentiating
may survive for days/weeks (or longer - persistence)
What is the germinal center?
sites of intense B cell proliferation and differentiation in lymphoid follicle during adaptive immune response to increase antibody affinity and function
What does somatic hypermutation do?
introduces mutations that change one or a few amino acids in V region, producing a B-cell clone that improves the affinity for antigen
What is class switching?
heavy chain region of another isotype is replaced, modifying effector activity of antibody but not its antigen specificity
Where does somatic hypermutation occur?
dark zone of the germinal center (GC)
What is the negative fate of somatic hypermutation?
prevent correct Ig folding, loss of functional BCR, B cells have low/no affinity and die
