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-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)
 Concept of Common Mucosal Immune
System (CMIS)

Mucosa Associated Lymphoid Tissues (MALT)

BALT
NALT
Inductive sites
GALT
OALT
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 Organized lymphoreticular

(RAT, RABBIT, MICE) structure

Human 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 Month VII

Placebo HI* Placebo HI* Placebo HI *

No of subjects with
H species 6 7 8 9 7 9

H. influenzae
(% of total growing) 17 0 25 11 100 11

H. parainfluenzae
(% of total growing)
83 57 100 100 100 100
* being immunized with 10 11 killed NTHI orally
(Clancy et.al., 1990)
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 TNF-a
M IL-1
IL-1 CD4+Tcells IL-2

M TNF-a
CD4+TH1
CD8+ IFN-
NK cells
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/CD11b/CD18, CR4

3. Activation of recruited neutrophil

TNF-a activates neutrophils
INF- activates M : ROI secretion
TNF-b (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