presentation
TRANSCRIPT
![Page 2: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/2.jpg)
Ig isotypes: structural features
4:89, 2004
![Page 3: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/3.jpg)
![Page 4: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/4.jpg)
Role of Fc receptors Link Ig to cells of the innate immune
system - macrophages, neutrophils, mast cells, NK cells.
Provides innate immune system with high degree of specificity (Fab portion)
Separate Fc receptors for each isotype (6 for IgG)
![Page 5: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/5.jpg)
![Page 6: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/6.jpg)
4:89, 2004
![Page 7: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/7.jpg)
4:89, 2004
![Page 8: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/8.jpg)
![Page 9: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/9.jpg)
![Page 10: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/10.jpg)
![Page 11: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/11.jpg)
![Page 12: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/12.jpg)
![Page 13: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/13.jpg)
FcR1 gamma chain is required for
expression of several FcR Mice lacking FcR1 chain do not
express FcR1, FcRI (CD64), FcRIII (CD16)
Defect in IgE-triggered anaphylaxis No ADCC by NK cells
![Page 14: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/14.jpg)
![Page 15: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/15.jpg)
![Page 16: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/16.jpg)
FcRIV = FcRIIIA (h) Expressed on neutrophils, Monocytes,
macrophages, DCs Associates with FcR1 chain Induced by IFN-, downregulated by IL-
4, IL-10 and TGF- Binds IgG2a and IgG2b - not IgG1 or
IgG3
![Page 17: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/17.jpg)
FcR isotype binding specificity
FcRIIb
FcRIII
FcRIV
![Page 18: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/18.jpg)
IgG2a is most effective in ADCC
Science 310:1510, 2005
![Page 19: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/19.jpg)
![Page 20: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/20.jpg)
The Journal of Immunology, 2008, 181: 8745-8752
IgG2a also important for Ab-induced glomerular damage
![Page 21: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/21.jpg)
Inhibition via FcR
ITIM motif: (L/V/I/S)xYxx(L/V)
CD32FcRIIB1 B, mast cells Inhibition
No uptakeFcRIIB2 Macs, eos, PMN Inhibition
uptake Two isoforms are generated by alternative splicing
![Page 22: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/22.jpg)
![Page 23: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/23.jpg)
Inhibits IgE mediated degranulation of mast cells
2:773, 2002
![Page 24: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/24.jpg)
FcRIIB on B cells
![Page 25: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/25.jpg)
FcγRIIB as a checkpoint of humoral tolerance. Autoreactive B cells (shown in red) that arise during the random rearrangement of antibody gene segments in developing B cells in the bone marrow or during the process of somatic hypermutation and affinity maturation in the spleen are controlled by several pathways, including receptor editing, clonal deletion or anergy induction. The inhibitory low-affinity Fc receptor for IgG (FcγRIIB) operates at several stages during later peripheral B-cell development. This receptor has been shown to be important for the follicular exclusion of low-affinity autoreactive B cells, for preventing B cells with a higher-affinity self-reactive receptor from becoming IgG positive plasma cells, and for triggering apoptosis of plasma cells upon immune complex binding, which is potentially important for regulating plasma-cell homeostasis during an immune response and deleting autoreactive plasma cells. BCR, B-cell receptor.
![Page 26: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/26.jpg)
FcRIIB -/-
Spontaneously develop autoantibodies More susceptible to autoimmune
disease models - collagen induced arthritis
Enhanced antibody response to antigen
![Page 27: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/27.jpg)
FcRIIB -/- mice developanti-DNA antibodies
![Page 28: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/28.jpg)
Role of FcR in collagen induced
arthritis
FcR1 -/- protected FcRIIB -/- more susceptibleJ. Exp. Med. 191:1611, 2000
![Page 29: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/29.jpg)
Role of FcRIV in KBRN arthritis model
The Journal of Immunology, 2008, 180: 5083-5091.
![Page 30: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/30.jpg)
![Page 31: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/31.jpg)
Activation/inhibition
![Page 32: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/32.jpg)
Cytokines influence FcR expression
![Page 33: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/33.jpg)
Antibody mediated inflammation Type I (immediate hypersensitivity):
requires FcR1 Type 2 (cytotoxic IgG): requires FcRIII
and FcRIV Type 3 (immune complex-induced
damage): requires FcRIII FcRIIB modulates all of these
responses
![Page 34: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/34.jpg)
Other Fc Receptors
![Page 35: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/35.jpg)
FcRII/CD23 Low affinity IgE receptor B cells, T cells, monocytes FDC, eos
etc May act to enhance Ab response to
antigen in presence of IgE:Ag complex Could act by capturing Ab for APC
presentation C-type lectin
![Page 36: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/36.jpg)
FcR1 (CD89) Binds IgA1 and IgA2 Low affinity Macs, PMN and eosinophils Induces Ag uptake and pathogen killing Associates with FcR1 chain
![Page 37: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/37.jpg)
Transport receptors Poly Ig receptor on epithelial cells for
IgA transport FcRn: MHC class I-like, contains 2m,
transports IgG to extracellular spaces, and across placenta
![Page 38: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/38.jpg)
![Page 39: Presentation](https://reader033.vdocuments.net/reader033/viewer/2022060112/556e09b0d8b42aba5d8b4cb6/html5/thumbnails/39.jpg)