Target Organ Trafficking
Lindsay Nicholson
University of Bristol
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Biothechnology, Lecture Notes - Engineering - 7, Study notes of Biotechnology
Target Organ Trafficking, Immunosurvillance Cell, trafficking, Lymphocyte, Phenotype, Limphonite Retension, Cellular Localisation, EAN analysis protocol, TNFR1
Typology: Study notes
2010/2011
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Target Organ Trafficking^ Lindsay Nicholson^ University of Bristol
Useful References
^ Butcher & Picker Science
^272 ,60-66 (1996)
^ von Andrian & Mackay
^343 , 1020-1034 (2000)
^ McLachlan & Jenkins
^4 , 439-442 (2007)
The mechanisms of cell trafficking
von Andrian & Mackay NEJM^^343 :1020 (2000) A multi-step process: Both commonmechanisms andselective expressionof specific ligandsplays a role
The challenges of immunosurveillance^ ^ To bring antigen in contact with the rarecells that can respond to it^ ^ To expand antigen specific cellsefficiently and distribute these cells to alltissues^ ^ To do this as fast as possible
Gowans et al. Nature 196:651 (1962) 5 days:^9 2x10small lymphocytes
5 days:^9 2x10small lymphocytes First dose^
Second dose
Subdividing the immune system Small lymphocytesinitiate immuneresponses^
B cells (humoral)T cells (DTH)
Cytotoxiccells (CD8)^ Helpercells(CD4)
Natural^ Treg Induced Th3 Th17^ Effector andMemory^ cells
1960-^
1975-
1986-present^ Th2^ Th1^ Naive cells
Mackay et al J. Exp. Med.
171:^ 801-817 (1990) Data from canulation of the popliteal lymph nodeof sheep
Lymphocytes from blood Naive cells Lymphocytes from tissue Memory cells
Tissue dependent lymphocyte
phenotype
FTY720 antagonises S1P receptors It’s an effective immunosuppressant Administration leads to the retentionof lymphocytes in 2
o^ lymphoid tissue Lymphocytes express S1P
and S1P 1
4
Controlling recirculation helps optimise
immune responses
CD69 contributes to lymphocyteretention in 2
o^ lymphoid tissue^ Shiow et al Nature
^440 :540 (2006)
control Type I interferon signal
Local concentration of antigen specificand antigen presenting cells
Activation ofimmune response
Upregulation ofCD69:S1P^1 signalling inhibited Activatedlymphocytes trappedin lymph node withAPCs Several rounds ofdivision before releaseto the circulation
Experimental autoimmuneencephalomyelitis (EAE)
Antigen presentingcell MOG35-55 typical EAE MOG79-90 typical EAE MOG97-114 atypical EAE
Clinical disease correlates with patternof target organ localisation
Stromnes et al. Nature Med.
^14 :337 (2008)
Pathology reflects T cell phenotype
Antigen influencesT cell phenotype
T cell phenotypeinfluences targetorgan infiltration Target organinflammationinfluences pathology Different pattern ofautoimmune disease