Download Immunology 06

Immunology
IMMUNOLOGY
Sherko A Omer
MB ChB, MSc., PhD
1
Immunology
THE MUCOSAL IMMUNE SYSYEM
An immune system characterised by:
 Lymphoid tissues associated with mucosal surfaces
(MALT).
 Mucosa-related immunoglobulin (IgA).
 Mucosal-oriented cell traffic system (cells initially
induced in mucosal follicles to migrate to diffuse
mucosal lymphoid tissues under epithelium.
 T regulatory cells.
2
Immunology
THE MUCOSAL IMMUNE SYSYEM
MALT, the lymphoid tissues of the intestinal tract
(GALT), genitourinary tract, tracheobronchial tree
(BALT) , and mammary glands.
Unencapsulated lymphoid tissues.
Contain predominating B lymphocytes.
3
Immunology
THE MUCOSAL IMMUNE SYSYEM
MALT
4
Immunology
THE MUCOSAL IMMUNE SYSYEM
The outer mucosal epithelial layer contains so-called
intraepithelial lymphocytes (IELs) mainly T cells with 
TCRs.
Lamina propria contains large numbers of B cells, plasma
cells, activated TH cells, and macrophages in loose
clusters.
The submucosal layer contains Peyer’s patches, nodules
of 30–40 lymphoid follicles that develop into secondary
follicles with germinal centres.
5
Immunology
THE MUCOSAL IMMUNE SYSYEM
Antigen transport from mucosal surfaces is carried out by
specialized cells (M cells).
 M cells are located in so-called inductive sites—small
regions of a mucous membrane that lie over organized
lymphoid follicles.
 M cells are flattened epithelial cells lacking the
microvilli as the rest of the mucous epithelium.
 M cells have a deep invagination, or pocket, in the
basolateral plasma membrane; this pocket is filled with a
cluster of B cells, T cells, and macrophages.
6
Immunology
THE MUCOSAL IMMUNE SYSYEM
Luminal antigens are endocytosed
into vesicles that are transported
from the luminal membrane to the
underlying pocket membrane. The
vesicles then fuse with the pocket
membrane, delivering the potentially
response-activating antigens to the
clusters of lymphocytes contained
within the pocket..
7
Immunology
THE MUCOSAL IMMUNE SYSYEM
Antigens transported across the mucous membrane by
M cells can activate B cells within these lymphoid
follicles.
Activated B cells differentiate into plasma cells, which
leave the follicles and secrete the IgA class of antibodies.
These antibodies then are transported across the
epithelial cells and released as secretory IgA in to the
lumen, where they can interact with antigens.
8
Immunology
THE MUCOSAL IMMUNE SYSYEM
9
Immunology
THE MUCOSAL IMMUNE SYSYEM
Immunoglobulins rather than
IgA are produced in mucosal
tissues, but usually not
passed into the lumen
10
Immunology
THE MUCOSAL IMMUNE SYSYEM
Secretory IgA serves an important effector function at
mucous membrane surfaces. Secretory IgA has may
features:
 Because it is polymeric, secretory IgA can cross-link
large antigens with multiple epitopes.
 Secretory component makes IgA less* susceptible to
proteolysis and more mucophilic .
 Binding of secretory IgA to bacterial and viral surface
antigens prevents attachment of the pathogens to the
mucosal cells, thus inhibiting viral infection and bacterial
colonization.
11
Immunology
THE MUCOSAL IMMUNE SYSYEM
 Complexes of secretory IgA and antigen are easily
entrapped in mucus and then eliminated by the ciliated
epithelial cells of the respiratory tract or by peristalsis of
the gut.
 Secretory IgA has been shown to provide an important
line of defense against bacteria such as Salmonella,
Vibrio cholerae, and Neisseria gonorrhoeae and viruses
such as polio, influenza, and reovirus.
 Breast milk contains secretory IgA and many other
molecules that help protect the newborn against infection
during the first month of life.
12
Immunology
THE MUCOSAL IMMUNE SYSYEM
 Clearance of mucosal antigens via hepatic clearance
system, circulating IgA will bind to antigens and
transported by blood to liver where it is joined to SC and
secreted with bile.
13
Immunology
THE MUCOSAL IMMUNE SYSYEM
Antigen-sensitized cells from the gut-associated lymphoid
tissue (GALT), or from the peribronchial lymphoid tissues,
enter the general circulation via the draining lymphatic
vessels.
Their systemic recirculation results in their migration
towards the remaining secretory-associated lymphoid
tissues including the gastro-intestinal tract, the airways,
the urinary tract, and the mammary glands, the salivary
glands, and the cervical glands of the uterus.
14
Immunology
THE MUCOSAL IMMUNE SYSYEM
15
Immunology
THE MUCOSAL IMMUNE SYSYEM
Mucosal Tolerance, a process by which mucosal
immune system normally prevent immune response to
food and intestinal bacteria while responding to potential
pathogens
A proposed framework for this type of suppression is as
follows:
The ingested antigen ( usually a protein) is transported to
submucosal accessory cells in the Peyer’s patches where
it is processed and presented to T regs (both of CD4+
and CD8+) phenotypes, including special subpopulations
of  CD4+ and  CD8+ T cells).
16
Immunology
THE MUCOSAL IMMUNE SYSYEM
After proliferation and differentiation these cells become
functionally suppressor cells.
The suppressor effect is mediated by secretion of IL-10,
and IL-4 after re exposure to the tolerizing antigen.
The activated T regs enter the circulation and are
attracted to areas of ongoing reactivity.
In the peripheral lymphoid tissues they may downregulate
immune responses to the tolerizing antigen.
17
Immunology
THE MUCOSAL IMMUNE SYSYEM
Breast Feeding
The lactating breast is an important component of mucosal
traffic loop and ensures that mucosal Immunoglobulins
and cells are available to protect the neonate during a
critical period of immunological incompetence.
The colostrum contain large amount of IgA and this level
will be reduced in the next days. IgA is synthesized from
IgA B cells in breast tissue, these cells have been migrated
to breast from gastrointestinal tract or from respiratory tract
lymphoid cells.
18
Immunology
THE MUCOSAL IMMUNE SYSYEM
The colostrum and breast milk contain a variety of
antibodies which protect the newborn.
Colostrum is important in establishment of normal flora
and preventing uptake of certain macromolecules which
may play role in prevention of allergic diseases.
Beast milk contains significant numbers of cells and when
ingested it result in the transfer of as many as 108 cells
daily, cell such as macrophages, granulocytes, B and T
cells.
19
Immunology
THE MUCOSAL IMMUNE SYSYEM
Macrophages delivered via lactation contain ingested IgA
so act as a vehicle for delivery of IgA.
Small amount of T cells can transfer immune reactivity as
they may enter the circulation of the new born?.
20