prof.marstyawan RespirImunSyst.ppt

8/14/2019 prof.marstyawan RespirImunSyst.ppt

1/19

The Mucosal Immune System :Studies on Respiratory efense Mechanism


2/19

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


3/19

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 )


4/19

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


5/19

Common Mucosal Immune System (CMIS)


6/19


7/19


8/19


9/19

Respiratory infections

Viral

Bacterial

H. influenzae (NTHI)

H. parainfluenzae

Mycobacteria

others

infants : RSV (Respiratory Syncitial Virus)

adults : Influenza Virus


10/19

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


11/19

Mucosal IgA responses


12/19

Respiratory Immunity after MucosalImmunization

Human

Rat model

Vaccin candidate : killed nontypable

Haemophilus influenzae (NTHI)

Different routes of immunization :

PO, IT, IPP, SC


13/19

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)


14/19

Animal model : Rats


15/19

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


16/19


17/19

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


18/19

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


19/19

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

prof.marstyawan RespirImunSyst.ppt

Documents

Transcript of prof.marstyawan RespirImunSyst.ppt