Binding to Complement : Humoral Immune Answer - Lysis of Opsonized Cells

Binding to Complement: Humoral Immune Answer- Lysis of Opsonized Cells

Binding to Fc Receptors: Cellular Immune Response- Endocytosis- Secretion of Inflammatory Mediators

Antibodies are Central Mediatorsof the Immune Response

Huber, R., Deisenhofer, J., Colman, P.M., Matsushima, M., and Palm, W. (1976) Nature 264, 415-420

FcR/Fc-Wechselwirkung

Sondermann, Huber, Oosthuizen, Jacob (2000) Nature 406,267-273

P6522, a=b=115 Å, c=140 Å, ==90°, =120°

• Suppremol• Fc-receptors as therapeutic proteins

• in autoimmune diseases

• located in Martinsried, Germany

• founded in 2003

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FcR

Fc fragment

sFcR as Fc-Receptor Antagonists

Fc-Receptor

Specific antibody

Antigen

Immune complex

Unspecific antibody

Soluble Fc-Receptor

Activation

Fc-Receptor inhibitor

Inhibition

Soluble-FcR: Proof of Principle inanimal models

• Systemic Lupus Erythematodes (NZ B/W)

• Rheumatoide Arthritis (Collagen Induced)

• Multiple Sclerosis (EAE)

• Farmers Lung (Alveolitis)

sFcR bei Autoimmunerkrankungen

MS

PBSTryptophan-SynthaseFc-Rezeptor

Tage

Kan

khei

tsin

dex

SLEWochen

Übe

rleb

ensr

ate

Fc-Rezeptor

Kontolle

RA

Fc-Rezeptor

Kontolle

Tage

Kan

khei

tsin

dex

Alveolitis

PM

N x

108

RB

C x

108

Sondermann, Burkhardt, Schmidt, Linington, Jacob, unveröffentlicht

AK

AK

+O

VA

AK

+O

VA

+s

Fc

R

AK

AK

+O

VA

AK

+O

VA

+s

Fc

R

Sondermann, P., Huber, R., Oosthuizen, V. and Jacob, U. (2000).   Nature 406, 267-273.Huber, R., Deisenhofer, J., Colman, P. M., Matsushima, M. and Palm, W. (1976). Nature 264, 415-420.

Structure of the complex of the soluble Fc-receptor and theFc-fragment of an IgG antibody