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43 Cards in this Set
- Front
- Back
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CD 19
CD81 |
Reinforce Iga and Igb signal transduction
Does not initiate message CD19 has ITAM |
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T Cell Independent
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Uses non-protein antigen
Frequently MZB and B-1 Quickly diff into IgM secreting plasma cells |
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T Cell Dependent
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uses protein antigen
Can create memory cells, via CD4+ help CD40:CD40L interaction important |
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Chemokine receptor attract B Cell entrance into lymph node
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CXCR5
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Cytokines produced for survival and proliferation in node
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(TNF):
BAFF, APRIL, BLys |
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Antigen entrance into node
Antigen Action |
via DC
Free soluble antigen 1. stim B cell activation 2. endocytosed for T cell presentation |
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Inital signal transducers
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Iga and Igb:
disulfide bonded no ligand initiates signal transduction w/ ITAM after antigen is cross-linked by Ab receptors |
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Src family kinases
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After Iga and Igb:
anchored Lyn, Fyn, Blk Forms lipid raft |
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After Src phosphorylates ITAM on Iga and Igb
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Recruits Syk (equiv of ZAP-70 in T)
activated by interacting w/ phosphor of ITAM recruits adapter protein |
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Adapter protein
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SLP-65
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2 signal transduction pathway
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Ras-MAP: mitogen activated protein
PLC: phospholipase C |
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Ras-MAP pathway
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Using Sos, as GTP/GDP exchanger
Sos recruited to SLP-65 Enzyme production: ERK, JNK |
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PLC Pathway
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PLC bind to SLP-65 --> phos by Syk
Breaks down mem PIP2 --> DAG IP3 DAG remain at surface, waiting for Ca2+ released by IP3 IP3 enter ER and release CA2+ from stores Enzyme production: PKC-B and Ca2+- dep enzyme |
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NFAT, enzyme
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Ca2+ dep enzyme
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NF-KB, enzyme
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PKC-B
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AP-1, enzyme
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ERK, JNK
(made of Fos + Jun) |
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Role of complement
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to enhance B cell activation; links innate and adaptive
strengthens activating signal by amplification For reaction, must be simult stim. w/ antigen-Ab receptor opsonize stim neutrophils MAC |
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C3 parts
Receptor? |
C3b: attaches to antigen
C3d: broken down from C3b, remain at antigen surface CR2: C3d receptor |
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Receptor changes once B cell is activated
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first more CD86, then CD80
cytokine receptor increased (ie. IL-2, BAFF) changed chemokine (CXCR5 --> CCR7) |
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Locations of:
early phase activation late phase activation |
Early: border of primary follicle
Late: germinal centers in secondary follicle |
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Sequence of T dependent B cells
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T cell activation
B cell activation Interaction and Activation |
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T cell activation
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antigen presented by DC
Induced expression of CD40L Change chemokine receptor (CCR7 --> CXCR5) |
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B cell activation
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Antigen recognition (can be soluble); display antigen w/ MHC II
Change chemokine receptor (CXCR5-->CCR7) |
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Interaction and Activation
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B and T meet at primary follicle border
Isotype switching at primary (some small amounts of affinity mat) Affinity mat and selection in germinal center of secondary follicle Some diff into memory or long-lived plasma cell: migrate to bone marrow Short lived plasma: remain in medullary cord |
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TLR can affect B cell activation
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TLR induces which cytokine CD4+ secretes, which determines the isotype switching of B
B cells can sense pathogen --> quick dif into IgM plasma |
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T and B interface
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Immunological synapse: Cytokine production
CD40:CD40L |
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Importance of CD40:CD40L
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General Mech of CD4+ targeting (DC, MQ..)
Promotes prolif and diff via txt factors for AID Promotes isotype switching via cytokine secretion of T cell Promote germinal center formation (immune complex) |
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CD40
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On APC- of TNF receptor family
constitutive on B TRAF assoc to CD40 and initiate enzyme cascade |
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CD40L
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On T cell- sim to Fas
Must be induced by APC |
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CD40:CD40L Sequencing
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Antigen on DC presented to CD4+
CD40L expression induced on CD4+ activated B and T bind B prolif and diff |
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TRAF
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TNF- recept assoc factors;
initiate enzyme cascade crucial for germinal center formation increase expression of AID TXT: Ca2+ dep --> NFAT PKC-B --> NF-KB ERK, JNK --> AP-1 |
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CD40:CD40L Knockout
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Leads to X-linked Hyper-IgM syndrome b/c can't isotype switch
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Epstein-Barr
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Mono
Simulates the CD40:CD40L bond and promotes proliferation of virus infected cells |
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Germinal Center: Dark Zone
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High amounts of proliferation
centroblasts Isotype switching moves upward into light |
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Germinal Center: light zone
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stops proliferation and undergoes somatic mutation and selection
selection by FDC |
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FDC
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origination unknown;not from bone marrow
initiates germinal center formation via chemokine secretion and cytoplasmic projections; recruits one or two B cell to initiate important for selection; want HIGH affinity (b/c went through affinity maturation) |
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Isotype switching
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Permanent change in germline. No changes in VDJ, only Constant Heavy Chain
Uses AID (induced by CD40:CD40L) as the mechanism Identity conferred by CD4+ cytokine secretion Ab formation can be localized Ultimately, CD4+ is the controller of immune response |
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IgA ?
IgG ? cytokine and CD4+ IgE ? |
IgA --> TGF-B (T-indep; protein antigen)
IgG --> IFN-g (TH1) IgE --> IL-4 (TH2) |
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roles in isotype switching
Cytokine CD40:CD40L |
cytokines determine Ig identity by opening DNA in front of the switch region of Ig constant regions
CD40:CD40L initiates AID to txt through Exon I |
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Linear sequence of coding region
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Sense strand has the switches
Exon I Promoter...Exon I...Switch...Constant Regions |
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where are the nicks?
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first nick: At S miu
Second nick: at S region before identifying constant region |
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Enzymes involved in isotype switching
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AID: activating induced deaminase; converts C-->U
UNG: Uracil N-Glycosylate; removes U Ape1 Endonuclease: nicks DNA |
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AID initiation
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initiated by CD:40CD40L
DNA txt bubble w/ RNA pol txt top (sense strand) Bottom: (antisense strand) is in open R loop, where AID can convert C-->U |
