effector mechanisms

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

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Effector Mechanisms

Lymphocyte mediated Cytotoxicity

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Effector Mechanisms

CTL Induced Graft Damage

Source: Rocha et al, 2003:Effector mechanisms in transplant rejection

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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

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Effector Mechanisms

Antibodies and Complement

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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

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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

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Main Target Mast cell Pathogen surface Red blood cell Mast cell B-cell Mast cell Pathogen surface Mast cell Infected cell

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www.liv.ac.uk/learning-and-teaching/cpd

A MEMBER OF THE RUSSELL GROUP