POSTGRADUATE
SCHOOL OF MEDICINE
EFFECTOR MECHANISMS OF GRAFT INJURY
David Lowe
MDSC175: Transplantation Science for Transplant Clinicians
(Online)
A MEMBER OF THE RUSSELL GROUP
CONTINUING PROFESSIONAL DEVELOPMENT
Effector Mechanisms
Effector Mechanisms of Graft Injury
Lymphocytemedicated
cytotoxicity
Antibodies and
complement
Delayed Type
Hypersensitivity
2
Effector Mechanisms
Lymphocyte mediated Cytotoxicity
3
Effector Mechanisms
CTL Induced Graft Damage
Source: Rocha et al, 2003:Effector mechanisms in transplant rejection
4
Effector Mechanisms
Delayed Type Hypersensitivity
(B) Effector Phase
MNG
Cl II
TNF
receptor
IFN-ϒ
TH1
cells
TNF-β
Resting Macrophage
TH1 products:
IFN-ϒ, TNF-β, IL-2, IL3, IL-8, MCAF, MIF
Activated Macrophage
Macrophage activation
MHC cl II, TNF
receptor, oxygen
radicals, nitric oxide
5
Effector Mechanisms
Antibodies and Complement
6
Effector Mechanisms
Classical
Pathway
C1qrs
Alternative
Pathway
MBL
Pathwa
MASP-1/2 y
___
___
__
C1qrs
C3bBb
MASP-1/2
C4
Factor D
C4b
C3
C2
C3bB
___
C4b2a
C3a
&C3b
______
C4b2a3b
C5
C5a & C5b
C6, C7, C8,
C9
C5b-C9
Factor B
______
C3bBb3
b
7
Effector Mechanisms
Complement Protein
C3a
C3b
C3d
C4a
C4b
C5a
C5-C9
Immunological Effect
Mast cell degranulation
Opsonisation
Immune complex clearance
Mast cell degranulation
B-cell activation
Mast cell degranulation
Opsonisation
Mast cell degranulation
Cell lysis
8
Main Target
Mast cell
Pathogen surface
Red blood cell
Mast cell
B-cell
Mast cell
Pathogen surface
Mast cell
Infected cell
FACULTY OF HEALTH & LIFE SCIENCES – CPD
Institute for Learning & Teaching
Faculty of Health & Life Sciences
Room 2.16A, 4th Floor
Thompson Yates Building
Brownlow Hill
Liverpool
L69 3GB
www.liv.ac.uk/learning-and-teaching/cpd
A MEMBER OF THE RUSSELL GROUP