Host Tissue Defence

Host tissue defence concerns the biological response of tissues to environmental or infective agents that are encountered throughout life. It is essential to understand the biological mechanisms employed by host cells in responding to attack by exogenous or deleterious stimuli, but also to compare diseased tissues where the host response is weaker, disrupted, exacerbated or triggered by exogenous factors. Many chronic diseases appear to involve intrinsic misregulation of host tissue responses or autoimmunity to host tissues, where the trigger may be known or unknown.

Research within Medicine on host tissue defence is underpinned by the close proximity of the clinical research base and facilitates access to samples from normal and diseased tissues, which is vital in the quest to resolve many of the chronic health problems in our society. In addition, ethically approved clinical research studies, involving direct interaction with patients or volunteers, are carried out in the Biomedical Research Facility embedded between the University and University Hospital Southampton Foundation Trust.

Tissues display highly-ordered defence mechanisms that interface externally with the environment in organs such as skin, eye, lung, kidney and gut and internally with the adaptive immune response. These can be viewed essentially as layers:

Chemical barrier with forms of protection such as mucus, tears, antimicrobial peptides, surfactants and gastric acid.

Physical cellular barrier with tight junctions TJ to selectively regulate tissue permeability.

Innate immune response with rapid, maximal and low specificity characteristics against many pathogens and toxins.

Adaptive immunity with pathogen and antigen specific responses facilitating the development of an immunological memory.

Schematic example (left) showing components of host tissue defence in the human airway with electron micrograph (right) with goblet cell (g), columnar cell (c), basal cell (b), lamina reticularis (lr), and mast cell (m). J.E.Collins and D.E.Davies

Research areas encompassing studies of host tissue defence include :

Respiratory medicine with studies into airways disease

Asthma
( Stephen Holgate , Donna Davies , Ratko Djukanovic , Peter Howarth , Hasan Arshad , Graham Roberts , John Holloway , Judith Holloway , Andrew Walls , Tony Sampson , Jane Collins , Tilman Sanchez-Elsner , Tony Postle , Pandurangan Vijayanand, Hans Michael Haitchi , Emily Swindle , Karl Staples . Chris Grainge , Tim Hinks , Christopher Woelk ) .

COPD
( Ratko Djukanovic , Peter Howarth , Donna Davies , Tom Wilkinson , Jane Warner , Howard Clark , Simon Bourne , Karl Staples )

Interstitial lung disease
( Luca Richeldi , Donna Davies , Jane Collins , Paul Elkington , Marc Tebruegge )

Cystic fibrosis
( Mary Carroll NHS, Julian Legg NHS, Jane Lucas , Gary Connett NHS, Luanne Hall-Stoodley )

Rhinosinusitis and paediatric ENT infection
( Peter Howarth , Rami Salib , Saul Faust , Luanne Hall-Stoodley , Howard Clark )

Primary Ciliary Dyskinesis
( Jane Lucas , Peter Lackie )

Lung and airway infection including Influena and Biofilms
( Rob Read , Donna Davies , Emily Swindle , Jane Collins , Saul Faust , Howard Clark , Janet Carroll , Julian Legg , Rami Salib , Jane Lucas , Gary Connett NHS , Luanne Hall-Stoodley , Marc Tebruegge , Jens Madsen , Howard Clark , Myron Christodoulides , Tom Wilkinson , Tristan Clark )

Tuberculosis Research
( Paul Elkington , Mark Tebruegge , Tim Hinks , Luca Richeldi , Salah Mansour )

Neonatal lung injury
( Howard Clark , Tony Postle , Jens Madsen , Alan Hunt )

Acute lung injury and adult critical care
( Michael Grocott , Martin Feelisch , Tony Postle )

Pulmonary sarcoidosis
( Luca Richeldi , Ben Marshall NHS )

Exacerbations of COPD and cognitive function
( Clive Holmes , Hugh Perry , Jessica Teeling , Ratko Djukanovic )

Inflammation research

Epithelial barrier in controlling inflammatory processes

Asthmatic lung ( Donna Davies , Jane Collins ), eye ( Parwez Hossain ), gut and kidney ( Jane Collins ) and skin ( Mike Ardern-Jones ).

Mast cells in lung disease
( Emily Swindle , Andrew Walls )

MMPs, Proteases

Mast cell proteases Andrew Walls - mast cell proteases, Hans Michael Haitchi , Donna Davies and Stephen Holgate - ADAM proteases; Sylvia Pender , Jane Warner , MMPs Paul Elkington , Parwez Hossain

Inflammatory bowel disease ( Sylvia Pender , Jane Collins , Tilman Sanchez-Elsner )

Hepatology – viral hepatitis ( Salim Khakoo , Chris McCormick )

Population Hepatology - alcohol and adverse life style ( Nick Sheron )

Corneal inflammatory disease ( Parwez Hossain )

Age related macsular degeneration ( Andrew Lotery )

• Skin research with studies in psoriasis and allergic skin disease

Skin remodelling in eczema ( Michael Ardern-Jones )

• Infection research with studies of viruses, including Norovirus, Meningococcus, Chlamydia and and Hepatitis Virus C

Noroviruses ( Ian Clarke )

Neisseria Research ( Rob Read , Myron Christodoulides and John Heckels )

Chlamydiae ( Ian Clarke )

Bacterial carriage and molecular epidemiology ( Stuart Clarke , Jo Jefferies )

Developing vaccines to infectious diseases ( Rob Read , Tom Wilkinson , Tristan Clark , Stuart Clarke , Christopher Woelk )

Hepatitis Virus C ( Salim Khakoo , Chris McCormick )

Biofilms ( Saul Faust , Luanne Hall-Stoodley, Rami Salib , Stuart Clarke , Parwez Hossain )

Molecular and Cellular Immunology with studies of T cell regulation, autoimmunity and anti-tumour immunity

Role of mucosal associated invariant T cells in human lung ( Tim Hinks , Salim Khakoo , Karl Staples )

Antigen presentation via MHC molecules ( Salim Khakoo , Tim Elliott , Tony Williams )

T-cell regulation at the T-cell/ dendritic cell interface ( Aymen Al-Shamkhani )

Antibody therapeutics ( Professors Martin Glennie , Peter Johnson , Aymen Al-Shamkhani and Mark Cragg , Drs Juliet Gray , Stephen Beers , Ann White and Andrew Davies )

DNA vaccines (Professors Freda Stevenson and Christian Ottensmeier , Drs Surinder Sahota , Stephen Thirdborough and Natalia Savelyeva )

Immune monitoring of responses after vaccination ( Dr Gianfranco Di Genova )

Immunotherapy using allogeneic dendritic cells ( Prof Christian Ottensmeier and Dr Simon Crabb )

Immunotherapy for neurodegenerative diseases ( Delphine Boche , Clive Holmes and James Nicoll )