Page 48 - Clinical Immunology_ Principles and Practice ( PDFDrive )

34 Part one Principles of Immune Response

immediately beneath the epithelium. It contains large numbers tonsil into lobules. Blood vessels and nerves enter through the
of B lymphocytes and plasma cells. A key effector function of capsule and extend within trabeculae (Fig. 2.10). The surface of
the lamina propria is the secretion of antibodies, primarily IgA. the tonsil is covered by pits, which are the openings of crypts.
IgM represents only 10–18% and IgG 3–5% of all Ig produced The crypts extend down into the tissue of the tonsil with branch-
from the lamina propria. Two IgA subclasses, IgA1 and IgA2, ing, increasing surface area. Abundant lymphoid follicles in each
occur. IgA1 represents greater than 90% of IgA in the respira- lobule contain germinal centers that are predominantly B cells.
tory tract and greater than 60% in the lamina propria of the The lymphoid tissue surrounding the follicles contains T cells,
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small intestine. IgA2 increases in the lower ileum and becomes macrophages, DCs, and some B cells. The lingual tonsils consist
predominant in the colon and the rectum. IgA is transported of 35–100 separate crypts surrounded by lymphoid tissue and
from the lamina propria into epithelial cells through polymeric are located at the root of the tongue. The pharyngeal tonsils, or
immunoglobulin receptor-mediated uptake and subsequently adenoids, are accumulations of lymphoid tissue, 2.5–4.0 cm long,
secreted into the lumen. Normally, very few IgG B cells are located on the median dorsal wall of the nasopharynx. They
present in the lamina propria. However, under certain inflam- contain a series of longitudinal folds, but not crypts. The lingual
matory conditions, such as inflammatory bowel disease, the and pharyngeal tonsils also contain lymphoid nodules with
number of IgG-producing B cells and plasma cells increases germinal centers. The palatine tonsils and adenoids (nasopha-
dramatically. ryngeal tonsils) comprise the nasopharyngeal–associated lym-
The lamina propria also contains large numbers of both CD4 phoreticular tissues.
and CD8 T cells in a 2 : 1 ratio. Almost all lamina propria T cells Inductive immune responses to inhaled antigens within the
(>95%) express αβ TCR. respiratory tract occur mainly in the bronchus-associated
Several specialized T cell subsets are present within the GI lymphoid tissue (BALT). BALT consists of lymphoid aggregates
tract. IELs are found at the basal surface of the epithelium as located within the bronchial wall near bifurcations of the major
well as interdigitated with epithelial cells. The vast majority of bronchial branches (Fig. 2.11). These structures are analogous
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IEL (>90%) are T cells, which are either CD8 or CD4 CD8 . to the GALT present in the GI tract and function to provide
Although the majority of IEL T cells express TCRαβ, a substantial T- and B-cell protection against inhaled microbes. BALT is present
number express TCRγδ. The function of IELs remains incom- at birth and rapidly expands when exposed to antigenic stimula-
pletely understood, but they can be cytotoxic and also maintain tion. The specialized epithelium overlying the lymphoid aggregates
oral tolerance. As part of their effector function, they produce consists of M cells heavily infiltrated with lymphocytes and with
several cytokines, including IL-5 and IFN-γ. Two other T-cell DCs below the epithelium. The main result of BALT immune
subsets play antagonizing roles in controlling inflammation within induction is secretory IgA production. 54
the intestinal lamina propria: Tregs and Th17 cells. Tregs are The diffuse mucosal tissue of the respiratory tract is minimal.
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FOXP3 and function to repress inflammation, whereas Th17 Pools of lymphocytes are present within the lung interstitium,
cells mount inflammatory and autoimmune responses through which is 10–20% T cells. Macrophages are present on both the
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production of IL-17. Another T-cell subset, which comprises air and the mucosal sides of the lungs and airways. Minimal
NKT cells, expresses the characteristics of both T cells and NK inflammation occurs in the bronchial mucosa as a result of Tregs
cells. NKT cells express perforin and granzymes but recognize that inhibit T-cell activation and expansion. Instead, antigen is
antigens through non-MHC–mediated pathways. 53 carried by local macrophages to the regional lymph nodes, where
Other cells, including macrophages, DCs, eosinophils, mast most respiratory effector immune responses originate. Com-
cells, and a few neutrophils, are also found in the lamina propria munication occurs between the GI and respiratory mucosae
and mediate effector functions. There is an elaborate network through cell trafficking. Antigen-reactive T and B cells from
of APCs, including DCs and macrophages distributed within Peyer patches can populate the bronchial mucosa. This sharing
the lamina propria and GALT. Two major DC subsets, character- feature has been exploited in the development of oral vaccines
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ized by CD103 CD11b and CD103 CD11b , develop into distinct against respiratory microbes. 55
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lineages on the basis of secreted factor requirement. CD103 CD11b
are predominately localized to the lamina propria and migrate Genital Tract
to the mesenteric lymph nodes upon activation. In contrast, The male and female reproductive tracts are components of the
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CD103 CD11b populations are localized to the Peyer patches. common mucosal system. The genital tract immune system must
The GI tract contains the largest number of resident macrophages maintain a delicate balance between tolerance of germinal center
in the body. These macrophages are similar to macrophages in cells, spermatozoa, and the fetus and the recognition of microbes.
other tissues and express CD68, lysozyme, ferritin, MHC II, The female reproductive tract has been studied the most. Its
CD11b, CX3CR1, and CD74 but do not migrate to the mesenteric mucosal immune system is influenced by hormones that regulate
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lymph nodes. all aspects of innate and adaptive immunity. “Professional”
APCs, including macrophages and DCs, are present in the stroma
Respiratory Tract of both the uterus and the vaginal tract, where they have unique
Surrounding the entrance to the throat are three tonsillar groups: phenotypes. Reproductive tract NK cells play a role in host defense,
palatine tonsils, lingual tonsils, and pharyngeal tonsils or adenoids. implantation of the embryo, and pregnancy and also express a
Together, these are known as Waldeyer ring. Tonsils reach full distinct phenotype. CD8 T cells predominate and, along with B
development in childhood and involute by puberty. The palatine cells and macrophages, form unique lymphoid aggregates. Forma-
tonsils, one located on each side of the pharynx, each measures tion of these nodules depends heavily on hormone regulation.
approximately 2.5 × 1.25 cm. Except at the pharyngeal surface, Both secretory IgA and IgG are expressed in genital secretions,
they are surrounded by a poorly organized capsule that is covered and levels vary with the stage of the menstrual cycle. The produc-
with stratified squamous epithelium. Trabeculae subdivide the tion and transport of antibody produced in the genital tract