Lecture # 20 B Cell Activation and Effector Function Flashcards
Why do CD8 cells require more co-stimulation?
Because they are destructive
LFA-1
Receptor on the surface of T cells, binds to ICAM-1 on an infected cell or APC
Immunological synapse
The point of contact between a CD8+ cell and its APC; outer ring adhesion molecules; inner ring: signaling molecules. granules behind the synapse align with cytoskeleton once binding occurs
What are the two compounds that CD8 cell produce to induce apoptosis?
Perforin and Granzymes
Perforin
Pore forming protein-aids in delivering contents of granules into the target cells
Granzymes
serine proteases-activate apoptosis once inside the target cell; activate caspases–GrB cleaves and activates caspase 3; acts on mitochondrial proteins and eventually activates CAD that fragments DNA and leads to cell death.
Serglycin
a part of the perforin/granzyme complex; may play an important role in protecting the CD8 cell from damage.
What dictates follicular B Cell location in the LN?
The expression of CXCL13 and CXCR5.
How many signals do B cells require for full activation?
Two signals: Signal #1 T microbial antigen binding to BCR; #2 PRR engagement or complement by R (PRR engagement is T independent) T dependent require interaction with CD40L
Thymus Independent Responses type 1
TI-1; some TI-1 antigens are called B cell mitogens; LPS can induce polyclonal activation, non specific antibodies at high concentrations-activates TLR4
Thymus Independent Responses type 2
TI-2; Ags are characterized by having multiple identical epitopes: polysaccharides; B1 cells and marginal zone B cells important for TI-2 responses;Usually IgM produced but some cases switching to IgG
What is signal # 2 for T-dependent Antigens?
Signal 2 is provided by CD40:CD40L and cytokines
CXCR5
Present on lymphocytes. Is up-regulated after CCR7 is down-regulated;purpose is to aid in migration to the follicle; is a receptor for CXCL13 (chemokine)
Ki67
proliferating cell marker (centroblasts); present on actively proliferating B cells
FDC (anti-CD3)
Help to retain Ag in the GC secretes CXC13;
What happens as B-Cells move through GCs?
they undergo somatic hypermutation, affinity maturation and isotype switching
IgM function
Complement activation
IgG function
opsonization, phagocytosis, complement activation, neonatal immunity
IgE, IgG4 function
Immunity against helminths, mast cell degranulation (immediate hypersensitivity); Th2 cell induced
IgA function
mucosal immunity (transport of IgA through epithelia)
Receptors on B cell (for T cell interaction)
(B7-1 and B7-2); CD40; MHC II or I
Receptors on T cell (for B cell interaction)
(CD28 reacts with B7-1/2) CD40L
Class switching
Activated by cytokines inducing transcription of switch region upstream of C region; lies in intron b/w J region and C u and upstream of all other C genes; Th1-> IgG1, IgG3, while Th2 -> IgG4 and IgE
Process of class switching
Occurs after B cells encounter Ag; RNA-DNA hybrids for in the switch region; AID (activation induced cytidine deaminase) converts cytidine to uracil; UNG removes the uracil leaving abasic sites APE1 cleaves abasic sites leaving a nick in the DNA, ds breaks are repaired by normal ds break repair mechanisms.
Somatic Hypermutation
mechanism to induce point mutation in the V regions of existing BCR; mutations occur 1000x; AID also plays a huge role; result is a multitude of B cells with different affinity receptors. Those BCRs that bind with high affinity receive survival signals. (selection occurs by follicular DCs)
Where do the point mutations in somatic hypermutation accumulate?
Point mutations accumulate in the BCRs of the VH and VL chains.
Which Co-receptor is necessary for the Th activation?
CD28 not CTLA-4 binds to B7-1/B7-2 for activation. CTLA-4 binds to B7-1/2 with higher affinity and tells the cell to stop proliferating and limits the binding of CD28 and B7-1/2
CTL binding and destruction of target cells depends on:
antigen presentation on the surface of the target cells.
Antigen binds to T cells first and divide in response to IL-2 and then differentiate into effector helper or cytotoxic cells (T/F)
T (CD8 and CD4 proliferate in repsonse to IL-2) and then other cytokines cause differentiation
Only viral or bacterial infected cells are susceptible to CTL-mediated apoptosis (T/F)
T (CTL-mediated apoptosis only occurs on virally infected cells; non-infected cells are spared)
Conventional DCs secrete high levels of IFN-b in response to viral infection (T/F)
F CDCs secrete IL-12; uptake antigen; migrate from sites from infection to lymph nodes; involved in presentation
