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The Mucosal Immune System :Studies on Respiratory efense Mechanism
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Mucosal Surfaces of the Body
Comprises approx. 400 m 2 (adulthood)
Continuously exposed to environmentalantigens, including dietary proteinsMucosal infections, e.g. respiratory andgastrointestinal, are still prevalent
Equipped with an unique mucosal defencesystem
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Immune responses (Immunity) Natural/innate/nonspecific
Humoral: type I IFN (IFN- a/b), lysozyme,Complement proteins (C)
Cellular: phagocytes (neutrophils, macrophages), NK cells
Adaptive/acquired/specific
Humoral: Antibodies: IgM, IgG, IgA, IgE, IgD Cellular: T cells:
CD4 + Th, CD8 +CTL (cytolytic T lymphocytes )
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Concept of Common Mucosal ImmuneSystem (CMIS)
Mucosa Associated Lymphoid Tissues (MALT)
Mucosal surfaces / secretions
BALTNALT
GALTOALT
Inductive sites
Effector sitesMigration of sensitized B - and T- cells
A framework for the development of clinicallyuseful vaccin
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Common Mucosal Immune System (CMIS)
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Respiratory infections
Viral
Bacterial
H. influenzae (NTHI)
H. parainfluenzae
Mycobacteria
others
infants : RSV (Respiratory Syncitial Virus)
adults : Influenza Virus
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Immune Responses
Local
Systemic
Natural response Adaptive response
Ab - mediated : SIgA, IgE T cell - mediated : CD 4+ Th, CD 8+ CTL
Natural response Adaptive response
Ab - mediated : IgM, IgG T cell - mediated : CD 4+Th, CD 8+CTL
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Mucosal IgA responses
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Respiratory Immunity after MucosalImmunization
Human
Rat model
Vaccin candidate : killed nontypable
Haemophilus influenzae (NTHI)
Different routes of immunization :
PO, IT, IPP, SC
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Table 1. The influence of ingested H. influenzae onacquisition of Haemophylus species inthroat swabs
No of subjects withH species
H. influenzae (% of total growing)
H. parainfluenzae (% of total growing)
6
17
83
7
0
57
8
25
100
9
11
100
7
100
100
9
11
100
Placebo HI* Placebo HI* Placebo HI *
Month I Month IV Month VII
* being immunized with 10 11
killed NTHI orally(Clancy et.al ., 1990)
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Animal model : Rats
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T cell response
Evidence
Adaptive transfer of T cells protectionT cell response without detectable Ab
Antigen - specific CD 4+ T cells
The presence of CD 8+ T cells lytic action
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2. Recruitment of neutrophil leukocytes
Expression of adhesion molecules
(leukocytes endothelium)e.g. LPS L - selectin
TNF- a ICAM-1, E-selectin,
CR3/Mac-1/CD 11 b/CD 18 , CR4
TNF- a activates neutrophils
INF- activates M : ROI secretionTNF- b (TH1-cytokine) activates neutrophil
3. Activation of recruited neutrophil
Respiratory burst degranulation
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Down-regulatory Role for TH2 - typecytokines
IL - 4
IL - 10
IL - 5
IL - 6
Inhibits TH1 - type cytokines (IFN- ),
inhibits cell-mediated immunity
Ab production
Terminal diff. of B cells Plasma cells
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Conclusion
Specific immunity of the respiratory systemcomprises Ab-responses and Tcell-mediatedreactions
The functional property of IgA antibodiesseems to inhibit the attachment andcolonization of pathogens onto mucosalsurfacesT cell-mediated responses act directly tosome pathogens or by inducing M aseffector cells