3 The lymphoid cells are densely packed in rounded nodules/follicles
in parts of the spleen and nodes. Aggregates of nodules occur in the
tonsils, appendix and ileal Peyer's patches of the GI tract;
whereas solitary nodules may exist anywhere in the mucosae of all
Wherever nodules may be found, close by are lymphoid cells dispersed more diffusely.
4 Most nodules have paler central regions - germinal centres, but these are not essential for cell proliferation. Germinal centres recruit virgin B cells, and follicular dendritic cells then present them with antigen. The B cells progressively refine their response to the antigen, in terms of Ig class, affinity, cell numbers, and whether to be plasma cells or memory cells.
5 The primary lymphoid organs - thymus and fetal bone marrow - store, release and confer competence on the lymphocytes that populate the secondary organs and CTs, but do not participate directly in defence. Primary-secondary Powerpoint.
6 Lymphocytes migrate in the blood and lymphatic flows for:
.. (a) the initial colonization of spleen, etc;
.. (b) a constant vigilant patrol by recirculation around the body, as memory or naïve cells;
.. (c) the propagation of an active immune response, as activated cells.
7 The secondary lymphoid organs provide:
2 Lymph-node structure
l A CT capsule, with some smooth muscle cells, sends in thin CT trabeculae, supporting a network of reticular fibres, and reticular cells of fibroblastic and the accessory dendritic kinds.
2 A denser outer cortex and a looser, inner medulla are present.
3 Efferent lymphatics leave at a hilus: the point of entry for blood vessels, serving a mostly cortical microvasculature.
4 Afferent lymphatics open through the capsule at several places to feed a system of 'sinus' channels running so:
subcapsular/marginal sinus --> cortical/intermediate sinuses --> medullary sinuses --> efferent lymphatics.
Sinuses are lined by reticular cells, accompanied by macrophages.
5 Denser masses of lymphoid tissue, extensive and follicular/nodular in the cortex, and continuing into the medulla as widely spaced medullary cords, have packed cells: lymphocytes, lymphoblasts and antigen-trapping dendritic reticular cells with processes. Lymphoblasts/centroblasts occur in the paler germinal centres of the cortical follicles.
The follicular zone contains B lymphocytes separated by follicular dendritic cells (FDCs).
6 The deeper lying paracortical region has mostly T lymphocytes, and dendritic APCs wrapping so intimately around lymphocytes that they received the name interdigitating reticular cells (IPCs).
3 Lymph-node functions
2 Splenic structure
l Thick fibro-elastic CT capsule has some myofibroblasts and a covering mesothelium.
2 Internally, thick CT trabeculae bear branches of the splenic artery and veins, entering and leaving at the hilum.
3 To the naked eye, most of the freshly cut organ is red pulp with white spots - white pulp.
4 Red pulp consists of a loose reticular tissue infiltrated with blood cells, and arranged in the so-called cords of Billroth around sinusoidal channels/sinuses - a Swiss-cheese situation of red-pulp cheese and sinusoidal holes.
The outermost white pulp, abutting the red pulp, is a boundary zone - the marginal zone, not to be confused with the mantle zone of densely packed mature lymphocytes around germinal centres.
(A mantle zone is not usually symmetrical; it is concentrated to one side of its germinal centre.)
5 Cord tissue has dendritic and fibroblastic reticular cells, and collagen fibrils supporting macrophages, and white and red blood cells.
6 Sinusoids/sinuses are lined by non-phagocytic endothelial/littoral cells, separated by slits and oriented longitudinally on a fenestrated BL. Blood cells thus can pass from sinusoid to cord and back, and cordal macrophages can extend pseudopodia into the sinusoidal lumen.
7 White pulp is a dense lymphoid tissue ensheathing branches of the arteries, once these have left the trabeculae. The sheath (PALS) dilates into follicles/nodules, some with germinal centres.
8 Lymphocytes are predominantly B in the nodules, and T in the periarterial lymphoid sheath (PALS). To match, reticular antigen-presenting cells are follicular/dendritic in the B-zone, interdigitating (IDCs) in the T-zone.
However, PALS and nodules/follicles work together, in that, the outer PALS is where B lymphocytes are initially selected for population-expansion in the nodules.
3 Splenic blood flow
4 Splenic functions
l Until birth, the spleen takes part in myelopoiesis, as do lymph nodes.
2 White pulp serves for:
.. (a) recirculation of lymphocytes;
.. (b) formation of new lymphocytes and plasma cells for immune responses to blood-borne antigens, met first at the marginal zone.
3 Red pulp provides:
.. (a) blood cleansing by the sequestration and phagocytic destruction by macrophages of unfit blood cells and platelets, and bacteria;
.. (b) metabolic breakdown of RBCs so that their iron can be reused;
.. (c) a place to accumulate platelets;
.. (d) sites by the marginal zone for plasma cells after antigenic stimulation, analogous to the cords and medulla of the active lymph node.
2 Thymic finer structure
l Cells are:
3 Thymic function
l Neonatal removal of the thymus causes the secondary lymphoid organs - nodes, spleen, tonsils, etc - to develop only partially and be unable to respond to many antigens.
2 Before birth, the thymus - a primary lymphoid organ - receives stem cells from the marrow that proliferate and undergo selection and maturation (by interacting with epithelial-reticular cells and APC reticular cells), before seeding out via the blood to populate the secondary organs with T or thymus-dependent immunologically competent lymphocytes.
Self-reactive lymphocytes are selected against, die, and are phagocytosed, while the surviving T lymphocytes migrate from subcapsular cortex towards the medulla.
3 At puberty the thymus starts a slow involution and replacement by adipose tissue, accelerated by severe stresses.
4 Despite the involution, the adult thymus maintains a low level of T-cell development from immature precursors that have not yet rearranged their TCR genes.
5 The thymus was assigned the status of an endocrine organ because the epithelio-reticular cells produce thymosin. It turns out that members of this family are not made solely by the thymus; and they act intracellularly as actin-binders and locally as cytokines.
4 More details of T-lymphocyte development based on the mouse
1 T progenitor cells arrive in the subcapsular region, where they multiply and express each its own pre-T cell receptor type.
2 This expression is used to select thymocytes to become cells that are double positive (CD4+8+) and expressing low levels of TCR-alpha/beta.
3 From encounters with peptide-MHC on the membranes of cortical thymic epithelial cells, some double-positive thymocytes - those with the appropriate TCR - are positively selected to become active and to downregulate either CD4 or CD8 expression to become mature CD8+ or CD4+ thymocytes.
4 Meanwhile, in both inner cortex and medulla, dendritic antigen-presenting cells negatively select, by the MHC-complexed presentation of self peptides, those thymocytes with TCRs for self antigens. Autoreactive thymocytes undergo apoptosis and removal by macrophages.
5 Thus, the thymocytes leaving the medulla as T lymphocytes have experienced positive selection and survived negative selection, and now await any further peripheral instruction on tolerance - how not to react with one's own tissues.
6 The story is similar, but more complicated for lymphocytes with gamma/delta TCRs.