Download - Prof. Marsetyawan RespirImunSyst
-
7/29/2019 Prof. Marsetyawan RespirImunSyst
1/18
The Mucosal Immune System :Studies on Respiratory Defense Mechanism
-
7/29/2019 Prof. Marsetyawan RespirImunSyst
2/18
Mucosal Surfaces of the Body
Comprises approx. 400 m2 (adulthood)
Continuously exposed to environmental
antigens, including dietary proteins
Mucosal infections, e.g. respiratory and
gastrointestinal, are still prevalent
Equipped with an unique mucosal defence
system
-
7/29/2019 Prof. Marsetyawan RespirImunSyst
3/18
Concept of Common Mucosal Immune
System (CMIS)
Mucosa Associated Lymphoid Tissues (MALT)
Mucosal surfaces / secretions
BALT
NALT
GALT OALT
Inductive sites
Effector sites Migration of sensitized B - and T- cells
A framework for the development of clinically
useful vaccin
-
7/29/2019 Prof. Marsetyawan RespirImunSyst
4/18
Common Mucosal Immune System (CMIS)
-
7/29/2019 Prof. Marsetyawan RespirImunSyst
5/18
Bronchus-Associated Lymphoid Tissue (BALT)
Animal models
(RAT, RABBIT, MICE)
Human
Organized lymphoreticular
structure
Less organized (mostly),
with exceptional
-
7/29/2019 Prof. Marsetyawan RespirImunSyst
6/18
-
7/29/2019 Prof. Marsetyawan RespirImunSyst
7/18
-
7/29/2019 Prof. Marsetyawan RespirImunSyst
8/18
Respiratory infections
Viral
Bacterial
H. influenzae (NTHI)
H. parainfluenzae
Mycobacteria
others
infants : RSV (Respiratory Syncitial Virus)
adults : Influenza Virus
-
7/29/2019 Prof. Marsetyawan RespirImunSyst
9/18
Immune Responses
Local
Systemic
Natural response
Adaptive response
Ab - mediated : SIgA, IgE T cell - mediated : CD4+ Th, CD8+ CTL
Natural response Adaptive response
Ab - mediated : IgM, IgG
T cell - mediated : CD4+Th, CD8+CTL
-
7/29/2019 Prof. Marsetyawan RespirImunSyst
10/18
Mucosal IgA responses
-
7/29/2019 Prof. Marsetyawan RespirImunSyst
11/18
Respiratory Immunity after Mucosal
Immunization
Human
Rat model
Vaccin candidate : killed nontypable
Haemophilus influenzae (NTHI)
Different routes of immunization :
PO, IT, IPP, SC
-
7/29/2019 Prof. Marsetyawan RespirImunSyst
12/18
Table 1. The influence of ingested H. influenzae on
acquisition of Haemophylus species in
throat 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)
-
7/29/2019 Prof. Marsetyawan RespirImunSyst
13/18
Animal model : Rats
-
7/29/2019 Prof. Marsetyawan RespirImunSyst
14/18
T cell response
Evidence
Adaptive transfer of T cells protection T cell response without detectable Ab
Antigen - specific CD4+ T cells
The presence of CD8+ T cells lytic action
-
7/29/2019 Prof. Marsetyawan RespirImunSyst
15/18
Action in Concert : T cells - M - neutrophilsThree stages
1. Activation of alveolar M and Tissue cellsLPS Mo
MTNF-IL-1
IL-1 CD4+Tcells IL-2
CD4+TH1
CD8+
NK cellsIFN-
M TNF-
-
7/29/2019 Prof. Marsetyawan RespirImunSyst
16/18
2. Recruitment of neutrophil leukocytes
Expression of adhesion molecules
(leukocytes endothelium)e.g. LPS L - selectin
TNF- ICAM-1, E-selectin,
CR3/Mac-1/CD11b/CD18, CR4
TNF- activates neutrophils
INF- activates M : ROI secretionTNF- (TH1-cytokine) activates neutrophil
3. Activation of recruited neutrophil
Respiratory burst degranulation
-
7/29/2019 Prof. Marsetyawan RespirImunSyst
17/18
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
-
7/29/2019 Prof. Marsetyawan RespirImunSyst
18/18
Conclusion
Specific immunity of the respiratory system comprises
Ab-responses and Tcell-mediated reactions
The functional property of Ab seems to inhibit the
attachment and colonization of pathogens onto
mucosal surfaces
No correlation could be observed between the
presence of raised levels of spesific Abs and their
ability to clear pathogens
T cell responses, besides their function in regulating
Ab production, interact directly to some pathogens by
working in concert with M and neutrophils aseffector cells