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Allan W Cripps AOMucosal Immunology Research Group
menzies.griffith.edu.au
Mucosal Immunisation(Lung and Middle Ear)
Small Intestinal Lumen
T B
Antigen
Peyer’sPatch
Cells migrate
via the
afferent lymph
Mesenteric
Lymph NodesEfferent
lymphatics
Thoracic Duct
Blood
circulation
Mucosal Tissues
Salivary
glands
Lacrimal
glands
Mammary
glands
Lungs GIT
UGT
Oral
cavity
Eye Milk
Middle
ear URT
The lungs as part of the CMIS
Small Intestinal Lumen
T B
Antigen
Peyer’sPatch
Cells migrate
via the
afferent lymph
Mesenteric
Lymph NodesEfferent
lymphatics
Thoracic Duct
Blood
circulation
Mucosal Tissues
Salivary
glands
Lacrimal
glands
Mammary
glands
Lungs GIT
UGT
Oral
cavity
Eye Milk
Middle
ear URT
The lungs as part of the CMIS
Experimental BackgroundIn an animal model of acute NTHi and Pa infection in the lungs we have demonstrated:
Mucosal immunisation results in enhanced clearance of bacteria
Mucosal immunisation modifies the inflammatory response observed as a result of infection
Primary interest in application to COPD and cystic fibrosis exacerbations and middle ear infections
Clearance of an acute NTHi infection from the lung
# p<0.05
TNFα response in BAL during acute NTHi infection
PMN and macrophage response in BAL during acute NTHi infection
Oral Immunisation against NTHi exacerbations in
patients with COPD
•HI-H005 – RCT in 320 patients with COPD (FEV1 < 60%)
•Oral immunisation with HI-164OV followed for 9 months over winter + spring
•Post-hoc analysis in those aged <64yrs (n=35) or placebo (n=56)
Multi-centre Australian trial
Clancy 2013
Significantly reduced moderate-severe exacerbations (54%), corticosteroid use (63%) hospitalisations (57%), hospitals days (59%), Antibiotic courses (29%) and SGRQ scores
HI-164OV
Time to first moderate-severe exacerbation
Conclusions
• Mucosal immunisation modulates inflammatory processes in the lung (and middle ear).
• Mucosal immunisation strategies are available against acute (and chronic) NTHi infections of the lung and middle ear.
Clearance of acute Pa infection from the lung
Immune Mechanisms in the Lung
Upper and lower respiratory epithelium Ciliated Mucocillary clearance: ~1010 particles per day
Alveolar Macrophages Poor APC but excellent “cleaners” without initiating inflammation
Neutrophils Excellent “cleaners” but cause significant collateral damage
Dendritic Cells Predominant APC in the lung
Lymphatic tissue Immune induction sites (BALT, NALT) Part of common mucosal immune network
Antigen specific responses (T cells, B cells, secretory IgA, IgG)