Download
Skip this Video
1 / 26
The Complement System and Kinin System - PowerPoint PPT Presentation
- 1160 Views
- Uploaded on
The Complement System and Kinin System. Manfred Maitz www.manfred.maitz-online.de. Outline. Complement System Background Reactions of the complement cascade Regulation and activation of the complement cascade Effects of Complement activation Evaluation methods
Download Presentation 
An Image/Link below is provided (as is) to download presentation
PowerPoint Slideshow about 'The Complement System and Kinin System' - Albert_Lan
An Image/Link below is provided (as is) to download presentation
Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.
While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.
- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
Outline
Complement System
- Background
- Reactions of the complement cascade
- Regulation and activation of the complement cascade
- Effects of Complement activation
- Evaluation methods
- Consequences for biomaterials
Kinin System
- Reactions and interactions with other systems
Summary and Conclusions
Background
- Evolutionary old system
- Non specific defence system
- Constitutive
- Very fast
- Selectivity and self-tolerance
- Activation by antibodies possible
- Interaction with the specific immune system
- Functions
- Lysis of cells/ bacteria and viruses
- Opsonization for phagocytes
- Immune Clearance
- Similarities and crosstalks with the clotting cascade
- Cascade of serine proteases, which activate each other
- Two (three) pathways of activation
- Factor XIIa (Hageman-Factor) activates both the clotting cascade and the complement cascade
Outline
Complement System
- Background
- Reactions of the complement cascade
- Regulation and activation of the complement cascade
- Effects of Complement activation
- Evaluation methods
- Consequences for biomaterials
Kinin System
- Reactions and interactions with other systems
Summary and Conclusions
C3
P
C3a
Properidin
Ba
B
C3b
C3bB
C3bBb
C3bBbP
C3bBb3b
D
B
C3a
C3iBb
C3iB
C3i
C3
Ba
The Tick-over Activation
C3
The Classical Pathway
C5b
Antibody + C1qrs
C4
C4b
C4b2a
C4b2a3b
C2
C3
C2b
C3a
C4a
The Complement CascadeC5a
C5
Outline
Complement System
- Background
- Reactions of the complement cascade
- Regulation and activation of the complement cascade
- Effects of Complement activation
- Evaluation methods
- Consequences for biomaterials
Kinin System
- Reactions and interactions with other systems
Summary and Conclusions
Regulation of the Complement Cascade
- Short half-time of
- C3b
- C3bBb
- C5b
- C1 inhibitor
- Inhibits the C1s activity
- Protein S in Serum
- Binds to C5b67
- Inhibits Formation of the Membrane Attack Complex
- HRF or CD59
- Bind to C8
- Inhibits C9 binding
- Factor H
- Binds to C3b
- Facilitates binding of Factor I
- cleaves C3b to inactive iC3b
- cleaves C4b to inactive fragments
- Decay Accelerating Factor
- Increased dissociation of C3 convertase (both pathways)
Complement Activation
General
- Hydrophobic surfaces
- Oxides
- Strong binding of C3(b) to nucleophilic groups (-NH2, -OH)
- Higher absorption of C3 to crystalline TiO2 than to amorphous
- Kallikrein directly activates C5
- Plasmin directly activates C5
Classical Pathway
- Antibodies IgM, IgG1, IgG2, IgG3
- Lectin via the mannan binding protein (MBP) “Lectin Pathway”
- Hageman Factor (F XIIa)
- Rough surfaces
- C-reactive protein (CRP)
- (Zirkonium, transiently)
Alternative Pathway
- PE debries
- Acetylated chitosan
Outline
Complement System
- Background
- Reactions of the complement cascade
- Regulation and activation of the complement cascade
- Effects of Complement activation
- Evaluation methods
- Consequences for biomaterials
Kinin System
- Reactions and interactions with other systems
Summary and Conclusions
Anaphylatoxins
Fragments C5a, C3a, C4a
- Degranulation of Phagocytes
- Reactive oxygen species
- Prostaglandins
- Monocytes IL-1, IL-6
- Mast cells Histamine
- Chemotaxis
- Only C5a
Consequences in vitro
- Lysis of “innocent” neighbour cells
- Red blood cells
- Activation of phagocytic cells
- Release of reactive oxygen species
- Release of mediators
Consequences in vivo
- Factors of complement activation at revised hip implants
- One single study(Tang L. et al.J Biomed Mater Res41: 333-340 (1998))
Au-Mercaptoglycerol induces strong inflammatory response in control animals.
No reaction in Complement-depleted animals.
Outline
Complement System
- Background
- Reactions of the complement cascade
- Regulation and activation of the complement cascade
- Effects of Complement activation
- Evaluation methods
- Consequences for biomaterials
Kinin System
- Reactions and interactions with other systems
Summary and Conclusions
C3
P
C3a
Properidin
Ba
B
C3b
C3bB
C3bBb
C3bBbP
C3bBb3b
D
B
C3a
C3iBb
C3iB
C3i
C3
Ba
The Tick-over Activation
C3
The Classical Pathway
C5b
Antibody + C1qrs
C4
C4b
C4b2a
C4b2a3b
C2
C3
C2b
C3a
C4a
The Complement CascadeC5a
C5
Methods for Investigation
General/Common pathway
- Lysis of sheep red blood cells
- Solid phase methods (ELISA, RIA)
- Products: C3a, C5a, sC5b-9
- Consumption of C3
- Ellipsometry
Classical Pathway
- Measurement of C1qrs
- Measurement of C2b or C4b2a
Alternative Pathway
- Measurement of Ba or C3bBb
- Measurement of Properidin
Outline
Complement System
- Background
- Reactions of the complement cascade
- Regulation and activation of the complement cascade
- Effects of Complement activation
- Evaluation methods
- Consequences for biomaterials
Kinin System
- Reactions and interactions with other systems
Summary and Conclusions
Biomaterials Consequences
- Testing for complement activation included in standard test programs
- Covalent binding of Factor H to the surface of a blood contacting implant
- Reduced C3a, sC5b-9
- Inhibition of FXII activation by Heparin-ATIII
Outline
Complement System
- Background
- Reactions of the complement cascade
- Regulation and activation of the complement cascade
- Effects of Complement activation
- Evaluation methods
- Consequences for biomaterials
Kinin System
- Reactions and interactions with other systems
Summary and Conclusions
F V
The Clotting CascadeIntrinsic Pathway
Extrinsic Pathway
Surface Contact
Collagen
FXII activator
Tissue/Cell Defect
F XII
F XIIa
F VIIa
F VII
Ca2+
F XI
F XIa
Ca2+
F IX
F IXa
F III (Tissue Thromboplastin)
Ca2+
F VIII
F VIIIa
Platelet Factor 3
Factor F X
Factor F Xa
Factor F X
Ca2+
Ca2+
Prothrombin I
Thrombin
Ca2+
F XIIIa
F XIII
Fibrinpolymers
Fibrinmonomers
Fibrinogen
CrosslinkedFibrin Meshwork
Fibrinolytic Pathway
Clotting Cascade (intrinsic pathway)
F XII
F XIIa
Plasmin
Complement Activation
Kallikrein
Pre-Kallikrein
Plasminogen
KininogenHMWK, LMWK
Kinine.g. Bradykinin
The Kinin System- Effects
- vascular smooth muscle relaxation
- Increased permeability of blood vessels Oedema
- Pain
- Interaction with clotting cascade
- Interaction with fibrinolytic cascade
- Interaction with complement cascade
Outline
Complement System
- Background
- Reactions of the complement cascade
- Regulation and activation of the complement cascade
- Effects of Complement activation
- Evaluation methods
- Consequences for biomaterials
Kinin System
- Reactions and interactions with other systems
Summary and Conclusions
Conclusions
- The blood plasma has four cascade systems
- Clotting cascade
- Fibrinolytic cascade
- Complement system
- Kinin system
- All four systems are proteolytic cascades
- Besides the main streams there are many cross connections with minor importance
- Common activators and cross activation
- Common inhibitors/ regulators
- C1 Esterase Inhibitor
- Hageman Factor (F XII)
- Effective in all systems
- Directly activated by surfaces (esp. negatively charged)
- 1-3% people have deficiencies without clinical syndromes
- Plasmin
- Directly effective in three systems
- Indirectly also effective on the clotting cascade
General Conclusions
Biomaterials research is an interdisciplinary field
- Physics/Materials science
- Modification and check of physical surface properties
- Roughness
- Surface free energy
- Hardness, tribological properties
- Surface charges, electrical and electronic properties
- Bulk properties
- Chemistry
- Corrosion
- Polymers
- Chemical surface modification
- Chemical reactions of the biomolecules with the biomaterial
- Life science
- Knowledge about the normal biochemical situation
- Knowledge about changes at certain diseases
- Check of influences due to the biomaterial
- Support of the physiological situation
