prof. marsetyawan respirimunsyst

7/29/2019 Prof. Marsetyawan RespirImunSyst

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The Mucosal Immune System :Studies on Respiratory Defense Mechanism


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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


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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


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Common Mucosal Immune System (CMIS)


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Bronchus-Associated Lymphoid Tissue (BALT)

Animal models

(RAT, RABBIT, MICE)

Human

Organized lymphoreticular

structure

Less organized (mostly),

with exceptional


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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 : CD4+ Th, CD8+ CTL

Natural response Adaptive response

Ab - mediated : IgM, IgG

T cell - mediated : CD4+Th, CD8+CTL


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Mucosal IgA responses


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Respiratory Immunity after Mucosal

Immunization

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 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)


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Animal model : Rats


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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


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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-


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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


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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 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

prof. marsetyawan respirimunsyst

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