Lymphoid Tissues Lymphoid Architecture: Primary (Generative) Lymphoid Organs
咸鸡怎么烧好吃There are two discrete organs that involved mainly or solely with development of the immune system: the bone marrow and the thymus.
From an immunologic perspective, the various tissues of the body can be functionally divided into primary, condary, and tertiary lymphoid organs. Such tissues include the thymus and bone marrow (primary lymphoid tissues), lymph nodes, Peyer’s patches, and spleen (condary lymphoid tissues), and skin and mucosal lamina propria (tertiary lymphoid tissues).
Primary lymphoid tissues reprent tho sites that contain microenvironments capable of supporting the production of functionally mature (albeit naive) T and B cells from nonfunctional progenitors. Key events that occur in the sites include the concomitant development of (a) antigen-recognition capabili
ty, as determined by rearrangement of antigen-receptor genes [immunoglobulin (Ig) and T-cell receptors (TCRs)], expression of the receptors, and lection of cells with functionally
―appropriate‖ receptors; (b) the necessary cellular apparatus (cell surface molecules and associated signal transduction pathways) required (in addition to antigen receptors) to interact with accessory populations and allow differentiation into functionally disparate memory–effector cell populations; and (c) homing capability—the ability to recirculate and localize in the proper microenvironment in the periphery.
Secondary lymphoid tissues reprent tho sites in which naive lymphocytes and exogenous antigen are brought together for the first time. The tissues are designed and situated so as to funnel antigen derived from esntially any site of entry into highly organized lymphoid microenvironments capable of driving the antigen-dependent activation and differentiation of naive (also known as virgin) T and B cells into expanded effector and memory populations. Antigen-receptor repertoire lection also occurs in the sites, deleting or ina ctivating autoreactive cells that ―escaped‖ the lection process during primary lymphogenesis.
The tertiary lymphoid tissues compri the immune effector sites of the body, sites in which memory
–effector lymphocytes manifest immunologic respons such as immunoglobulin cretion, cytotoxicity, delayed-type hypernsitivity, or immunoregulation. The sites, the ―battlefield‖ on which the immune system defends the tissues from microbial invasion, can be interpreted to include esntially all tissues of the body; however, the quantitatively most important of the sites are tho tissues with
direct contact with the ―external‖ environment, primarily the skin and mucosal lining of the gastrointestinal, pulmonary, and genitourinary tracts.
I. Primary Lymphoid Tissues
A. Bone Marrow--
∙Virtually all cells of the immune system originate in the bone marrow from pluripotent stem cells. This is especially true in adults
∙In fetal life, a major source of hematopoiesis is the liver and spleen
∙Hematopoiesis reverts to bone marrow in adult life, and specifically the flat bones until, at puberty, most hematopoiesis is found in the sternum.
∙Hematopoiesis is driven by cytokines: stem cell factor; IL-3; GM-CSF; G-CSF; M-CSF; IL-7 and probably IL-9 and IL-11
∙The stem cells progressively differentiate into different lineages with the cells becoming more differentiated. Lineages include:
Erythrocyte-stimulated by erythropoitin(EPO) (Amgen)
Megakaryocyte/Platelets-stimulated by IL-11 creted by fibroblasts.
Granulocyte/Monocyte-stimulated by GM-CSF, G-CSF, and M-CSF creted by
T-cells and monocytes.
Lymphocyte -stimulated by IL-7 creted by bone marrow.
Stem cell factor (SCF) is synthesized by stromal cells of the bone marrow
including adipocytes, fibroblasts, and endothelial cells.
B. Thymus--
∙The thymus is an organ strictly dedicated to the development and production of T lymphocytes. The T cell precursor cells originate in the bone marrow and then go through a ries of developmental steps resulting in the production of a population of mature, antigen-nsitive T cells.
∙The T cells are considered naive (in a previous era "virgin") T cells that are either CD4+ and have been lected to express an MHC class II specific T cell receptor (TCR), or CD8+ and lected to express an MHC class I specific TCR. The
development and lection of T-cells in the thymus will be extensively discusd later.
∙The thymus is made up of a cortex and a medulla. The cortex consists of denly packed immature thymocytes, macrophages, and dendritic cells supported by a
thymus stroma largely made up of epithelial cells. The medulla contains mainly
mature thymocytes and macrophages (and a stroma), and the cells are much less den.
明景帝基准面∙The thymus is not the site of immune respons. There are no afferent lymphatic connections. It is thought of as strictly involved in T cell maturation and lection.
∙The thymus reaches its maximum size at six months in humans and then begins to atrophy. It shrinks in size and accumulates fat cells in the subcortical region.
However, it never completely stops functioning.
踔绝之能Morphology of the thymus
The thymus is situated in the upper parts of the thorax, behind the sternum and the upper four costal cartilages, in the anterior and superior mediastina. The size of the thymus changes in the cour of life. It weighs about 10-15 g at birth and reaches its top weight (about 30-40 g) at puberty. After puberty a progressive involution (e below) occurs, which leaves a middle-aged person with a thymus weighing about 10 g. The thymus consists of a right and left lobe which are joined by connective tissue.
厦门周边旅游The thymus is enclod
by a thin connective
tissue capsule from
which numerous ptae
extend into the thymus
subdividing the two lobes
into numerous lobules
(about 0.5 -2 mm in
diameter). Blood vesls
enter and leave the
thymus via the
connective tissue ptae.
Each lobulus is divided
into a darker peripheral zone, the cortex, and a lighter, central zone, the medulla. Medullary tissue is continuous from lobule to lobule throughout each lobe.
CLONAL SELECTION BY THE THYMUS
Lymphocytes are activated by antigen to give ri to clones of antigen-specific cells that mediate adaptive immunity.
The defen systems of innate immunity are effective in combating many bacterial pathogens. Inste
ad of bearing veral receptors each specifically recognizing a conrved surface molecule of a pathogen, each naive lymphocyte entering the bloodstream bears receptors of only a single specificity. However, the specificity of the receptors is determined by a unique genetic mechanism that operates during the development of lymphocytes in the bone marrow and thymus to generate hundreds of different variants of the genes encoding the receptor molecules. Thus, although the individual lymphocyte carries receptors of only one specificity, the specificity of each lymphocyte is different, and thus the millions of lymphocytes in the body give ri to millions of different antigen specificity’s. The lymphocytes then undergo a process akin to natural lection during the lifetime of an individual.
This lective mechanism was first propod in the 1950s by F. McFarlane
Burnet to explain why antibodies, which can be induced in respon to virtually any
antigen, are produced in each individual only to tho antigens to which he or she is
非法吸收公众存款expod. On binding antigen, the cell is activated to proliferate and produce many identical progeny, known as a clone, which now crete antibodies with a specificity
identical to that of the surface receptor. McFarlane Burnet called this the clonal lection
theory.
烈火中永生电影
Clonal lection of lymphocytes is the central principle of adaptive immunity. Remarkably, at the time that McFarlane Burnet formulated his theory, nothing was known of the antigen receptors of lymphocytes and indeed the function of lymphocytes themlves was still obscure. Lymphocytes did not take center stage until the early 1960s, when James Gow ans discovered that removal of the small lymphocytes from rats resulted in the loss of all known immune respons. The immune respons were restored when the lymphocytes were replaced. This led to the realization that lymphocytes must be the units of clonal lection and their biology became the focus of the new field
of cellular immunology.速生法桐
Clonal lection of lymphocytes with diver receptors elegantly explained
adaptive immunity, but it raid one significant intellectual problem. If the antigen receptors of lymphocytes are randomly generated during the lifetime of an individual, how are lymphocytes prevented from recognizing antigens on the tissues of the body and attacking them? Peter Medaw ar had shown in 1953 that if expod to foreign tissues during embryonic development, animals will become immunologically tolerant to the tissues and will not subquently make immune respons to them
Clonal lection of lymphocytes is the single most important principle in adaptive
II. Secondary Lymphoid Tissues
A. Lymph Nodes
Lymph nodes are small, flattened, Array oval or bean shaped organs, which
are situated in the cour of the
collecting lymph vesls. Their size
is variable (from a few mm to more
than 2 cm). The capsule and
trabeculae of lymph nodes are
formed by connective tissue.
Afferent lymph vesls penetrate the
capsule and empty into the
subcapsular space. The lymph
continues thereafter through cortical
and medullary sinus towards the
efferent lymph vesls, which
emerge from the hilus of the lymph
node. The walls of the sinus can be traverd freely by all components of the lymph, which allows lymphocytes to enter/leave the lymphoid tissue (as part of their constant circulation) or to get in contact with antigens/antigen-prenting cells that may arrive with the lymph.
In lymph nodes we find B- and T-lymphocytes, macrophages and reticular cells.
Reticular cells
(and reticular fibres) form a delicate network between the capsule and trabeculae.
Lymphocytes and macrophages are houd in the network of reticular cells and
the reticular fibres formed by them. The process of reticular cells and reticular
fibres extend into and criss-cross within the sinus.
Lymphocytes
which are located in the outer cortex of the lymph node are likely to reprent B-
lymphocytes. They are organid into spherical mass - lymphoid nodules or
follicles. Sites within the cortex at which B-lymphocytes have been stimulated to
proliferate (by contact with an antigen) appear lighter than the surrounding tissue and allow you to identify the centers of lymphoid nodules. The lighter stained
parts of the nodules are called germinal centers. Mature B-lymphocytes
(plasma cells) are located in cord-like extensions of the lymphoid tissue into the
medulla, the medullary cords. T-lymphocytes are located in the more diffu
tissue between the nodules and in the paracortex, i.e. the deep part of the
cortex.
The production of T-cell immune effector respons requires the cooperative function of both condary and tertiary lympoid sites. The above illustration patterns the T-cell mediated delayed type hypernsitivity respon to an epidermally applied antigen. Epidermal dendritic cells take up the an
tigen and transport it to draining lymph nodes where it is prented to antigen-specific (naïve) T-cells that are located in the lymph node in the high endothelial venules. The moble dendritic cells have been given different names depending on their location – in the skin Langerhan’s cells, in the lymph, veiled cells, in the T-zone of the lymph node, interdigitating cells. Under the
