The Mucosal Immune System :

Studies on Respiratory
Defense Mechanism

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

Immune responses (Immunity)

Natural/innate/nonspecific
Humoral: type I IFN (IFN-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)

Concept of Common Mucosal Immune

System (CMIS)

Mucosa Associated Lymphoid Tissues (MALT)

BALT
NALT
GALT
OALT

Inductive sites

Mucosal surfaces / secretions

Effector sites

Migration of sensitized B - and T- cells

A framework for the development of clinically

useful vaccin

Common Mucosal Immune System (CMIS)

Bronchus-Associated Lymphoid Tissue (BALT)

Animal models
(RAT, RABBIT, MICE)

Human

Organized lymphoreticular
structure

Less organized (mostly),

with exceptional

Respiratory infections

Viral

infants : RSV (Respiratory Syncitial Virus)

adults : Influenza Virus

Bacterial

H. influenzae (NTHI)

H. parainfluenzae

Mycobacteria

others

Immune Responses

Local

Natural response
Adaptive response
Ab - mediated
: SIgA, IgE
T cell - mediated : CD4+ Th, CD8+ CTL

Systemic

Natural response
Adaptive response
Ab - mediated
: IgM, IgG
T cell - mediated : CD4+Th, CD8+CTL

Mucosal IgA responses

Respiratory Immunity after Mucosal

Immunization

Human

Rat model

Vaccin candidate : killed nontypable

Haemophilus influenzae (NTHI)

Different routes of immunization :

PO, IT, IPP, SC

Table 1. The influence of ingested H. influenzae on

acquisition of Haemophylus species in
throat swabs
Month I

Month IV

Placebo HI*

Placebo

Month VII
HI* Placebo

HI *

No of subjects with
H species

H. influenzae
(% of total growing)

17

25

11

100

11

83
57
100
* being immunized with 10 killed NTHI orally
(Clancy et.al., 1990)

100

100

100

H. parainfluenzae
(% of total growing)
11

Animal model : Rats

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

Action in Concert : T cells - M - neutrophils

Three stages
1. Activation of alveolar M and Tissue cells
LPS

Mo
M

IL-1

CD4+Tcells

TNF-
IL-1
IL-2
M

CD4+TH1
CD8+
NK cells

IFN-

TNF-

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
3. Activation of recruited neutrophil
TNF-

activates

neutrophils

INF-
activates M : ROI secretion
TNF- (TH1-cytokine) activates neutrophil

Respiratory burst

degranulation

Down-regulatory Role for TH2 - type

cytokines
IL - 4

Inhibits TH1 - type cytokines (IFN-),

IL - 10

inhibits cell-mediated immunity

IL - 5

Ab production

IL - 6

Terminal diff. of B cells Plasma cells

Conclusion

Specific immunity of the respiratory system

comprises Ab-responses and Tcell-mediated
reactions

The functional property of IgA antibodies

seems to inhibit the attachment and
colonization of pathogens onto mucosal
surfaces

T cell-mediated responses act directly to

some pathogens or by inducing M as
effector cells