Histology of Lymphoid system

Abbas A. A. Shawka

Immune system• he immune system provides defense or immunity against

infectious agents ranging from viruses to multicellular parasites.

• Parts of this system include Leukocytes Lymphoid organs Blood vessels Lymphoid vessels ( lymphoid circulatory )

Types of immunity Innate immunity• involves immediate, nonspecific

actions• including physical barriers• Bacteria,• fungi, and parasites that manage

to penetrate these barriers are quickly removed by neutrophils and other leukocytes in the adjacent connective tissue

Adaptive immunity• acquired gradually by

exposure to microorganisms, is more specific, slower to respond, and an evolutionarily more recent development than innate immunity

• Involves B and T lymphocytes

Innate immune system also include :

• Hydrochloric acid (HCl) and organic Defensins. • neutrophils and various epithelial cells. • Lysozyme enzyme.• Complement.• Interferons.

Cytokines

Immune cells communicate with one another and regulate oneanother’s activities via polypeptide hormones called cytokines .

Antigens• Antigens are the regions of macromolecules, usually proteins,

that are recognized by lymphocytes to elicit a specific immune response against them.

Antibodies • Antibodies are immunoglobulins

produced by plasma cells after a progenitor B cell is activated by a specific antigen and rearranges its immunoglobulin genes so the antibody matches the antigen.

• Different types of Antibodies and there characteristics in the next slide.

Simple structure of antibody

Antibodies‘ Functions

• Surfaces of all nucleated cells bear fragments of their constituent proteins on major histocompatibility complex (MHC) class I molecules.

• Only antigen-presenting cells (APCs) mostly derived from monocytes, also present fragments of endocytosed foreign (usually from microorganisms) proteins on surface MHC class II molecules.

Lymphoid organs 1. Lymphocytes 2. Thymus 3. Mucosa associated lymphoid tissue ( MALT ) 4. Lymph nodes5. Spleen

Antigen presenting cells ( APCs ) are part of mononuclear phagocytic system, usually they are dendritic cells, associated with adaptive immune system.

Lymphocytes• Lymphocytes originate in the primary lymphoid organs : bone marrow for B lymphocytes and the thymus for T lymphocytes• B cells produce antibodies for humoral immunity ; T cells

function in cell-mediated immunity .

Receptors on lymphocytes

T-Lymphocytes Activation

B-Lymphocyte Activation

AIDS• The retrovirus that produces acquired immunodeficiency

syndrome (AIDS) infects and rapidly kills helper T cells. Reduction of this key lymphocyte group cripples the patient’s immune system rendering them susceptible to opportunistic bacterial, fungal, protozoan, and other infections that usually dealt with easily in immunocompetent individuals.

Lymphoid nodule• When B cells become activated and

become larger, they aggregate in a group called “ primary lymphoid nodule “ and with adjacent cells, they form “ secondary lymphoid nodule “.

• secondary lymphoid nodule characterized by

1. Germinal center : - cells undergo gene recombine. - proliferate & grow -push nonproliferate cells ( GC ) peripherally 2. Peripheral mantel : slightly darker region contain naive,nonproliferative

B cells ( M )

Thymus• the primary or central lymphoid organ in which T cells are produced is

the thymus, a bilobed structure in the mediastinum• A main function of the thymus is induction of central tolerance, which

along with regulatory T cells prevents autoimmunity.• The organ originates from the embryo’s endoderm precursor

lymphoblasts circulating from the bone marrow to invade and proliferate in this unique thymic epithelium during its development.

• Fully formed and functional at birth, the thymus remains large and very active in T-cell production until puberty.

• During puberty, which it undergoes involution, decreasing greatly in size and activity and becoming largely filled with adipose tissue.

Layers of Thymus• 1- vascularized connective tissue

capsule. - extends septa into paranchyme - dividing this organ into many incompletely lobules.• 2- Cortex • 3- Medulla

Cortex of thymus• Cortex is composed of

1. Newly arrived lymphoblast 2. Macrophages.3. Thymic epithelial cells ( TECs ) - cells have both characteristics of epithelial and reticular cells. - this TECs morphologically and functionally diverse - divided into three groups ( layers )

TECs “ Thymic epithelial cells “1. Squamous TECs• joined by desmosomes and occluding junctions, • line the connective tissue of the capsule and septa and

surround the microvasculature.• This creates an isolated cortical compartment.• Together with the vascular endothelial cells and pericytes,

forms a blood-thymus barrier preventing unregulated exposure of thymocytes to antigens.

2. Stellate TECs• Cells contain keratin and forming

cytoreticulin in wich lymphocytes and microphage attache to instead of reticulin fiber.

3. Squamous corticle TECs ( corticomedullary barrier )

between two regions of lobules.

Medulla of thymus• contains fewer and larger,mature lymphocytes.• Three related types of medullary TECs form the following:• 1- A second layer of the boundary between cortex and medulla.• 2- A cytoreticulum that • (1) supports less densely packed T lymphocytes, dendritic cells, and

macrophages • (2) expresses many specialized proteins specific to cells of other organs.• 3- Large aggregates of TECs, sometimes concentrically arranged, called

Hassall corpuscles .• thymic corpuscles are unique to the medulla.

Medulla of the thymus with Hassall corpuscles

MUCOSA-ASSOCIATED LYMPHOID TISSUE

• Secondary lymphoid structure.• The mucosa or inner lining of the digestive, respiratory, and

genitourinary tracts is a common site of invasion by pathogens because their lumens open to the external environment.

• Most of the immune cells in MALT are dispersed diffusely in the connective tissue; others are found in aggregates that form large, conspicuous structures such as the tonsils, the Peyer patches in the ileum, and the appendix.

• Collectively the MALT is one of the largest lymphoid organs, containing up to 70% of all the body’s immune cells. Most of the lymphocytes here are B cells; among T cells, CD4+ helper T cells predominate.

Tonsils1. Palatine tonsils• located posteriorly on the soft palate,• covered by stratified squamous epithelium.• The surface area of each is enlarged with 10-20 deep invaginations or tonsillar

crypts in which the epithelial lining is densely infiltrated with lymphocytes and other leukocytes

• The lymphoid tissue is filled diffusely with lymphocytes, with many secondary lymphoid nodules around the crypts.

• This tissue is underlain by dense connective tissue that acts as a partial capsule.

2. Lingual tonsils 3. Pharyngeal tonsils

Tonsillar CryptA section showing several lymphoid nodules (LN), collectively covered by stratified squamous epithelium (E) on one side and a connective tissue capsule (CT) on the other. Some nodules show lighter staining germinal centers (GC). Infoldings of the mucosa in some tonsils form crypts (C), along which nodules are especially numerous. Lumens of crypts contain desquamated epithelial cells, live anddead lymphocytes, and bacteria.

Peyer patches • Diffuse MALT extends from the pharynx

along the entire gastrointestinal tract but becomes very well-developed again in the mucosa and submucosa of the ileum. Here large aggregates of lymphoid nodules comprise the Peyer patches, each containing dozens of nodules with no underlying connective tissue capsule.

• A section through a Peyer patch shows a few lymphoid nodules (N), some with germinal centers (arrow). The mucosa of the small intestine is folded into many projecting villi (V).

• The simple columnar epithelium that covers the lymphoid nodules of Peyer patches includes large epithelial M cells with apical microfolds rather than the brush border typical of the neighboring enterocytes. On the basal side M cells have large intracellular pockets that contain transient populations of lymphocytes and dendritic cells and open to the underlying lymphoid tissue through a highly porous basement membrane.

The TEM shows that the epithelium directly over a Peyer patch lymphoid nodule has unique cells called M (microfold) cells with short apical folds but no brush border. The basal surface of M cells forms a large intracellular pocket that harbors a transient population of T and B lymphocytes (L) and dendritic cells (D) which move through the openings in the basement membrane (BM). Darker cytoplasm of adjacent enterocytes (E) with brush borders (B) is also seen.

Appendix• Another significant collection of MALT occurs in the mucosa of

the appendix.a short, small-diameter projection from the cecum.

• Typically the mucosa of the appendix is almost completely filled with lymphoid tissue, effacing the glands otherwise found in the large intestine wall .

• The lumen contains the normal bacterial flora of the large intestine and may serve to retain some of these beneficial bacteria there during diarrheal illnesses.

A blind evagination off the cecum, the appendix is a significant part of the MALT with its lamina propria and submucosa filled with lymphocytes and lymphoid follicles (L). The small lumen contains a sample of the microbial flora of the intestine, along with undigested material

Lymph nodes • Lymph nodes are bean-shaped, encapsulated structures.• most abundantly in the axillae (armpits) and groin, along the

major vessels of the neck, and in the thorax and abdomen, especially in mesenteries.

• Embedded in loose connective tissue, a lymph node has a convex surface where afferent lymphatics enter and a concave depression, the hilum, where an efferent lymphatic leaves and where an artery, vein, and nerve penetrate the organ.

• A dense connective tissue capsule surrounds the lymph node, extending trabeculae internally through which the blood vessels branch.

3 regions , Cortex• The most abundant cells of lymph nodes are lymphocytes of all

types, plasma cells, dendritic cells, macrophages, and other APCs. FDCs are present within lymphoid nodules.

• All of these cells are arranged in a stroma of reticulin fibers and reticular cells to form three major regions: an outer cortex, a central medulla, and a smaller area between these two called the paracortex

• The cortex includes the following components:1- subcapsular sinus.2- Lymphoid nodule.

Paracortex• The region between the cortex

and medulla, the paracortex does not have precise boundaries but can be distinguishe from the outer cortex by its lack of B-cell lymphoid nodules Unlike the superficial cortex, the paracortex contains lymphoid tissue rich T cells that can be seen by immunohistochemistry

Medulla• The medulla of a lymph node has two major components :• Medullary cords are branched cordlike masses of lymphoid tissue extending from the paracortex. They contain T and B lymphocytes and many plasma cells.• Medullary sinuses are dilated spaces lined by discontinuous endothelium that separate the medullary cords. As shown in Figure 14–20, the lumens of medullary sinuses include a meshwork of processes from reticular cells, which represent a final lymph filter. These sinuses contain many macrophages and sometimes neutrophils if the lymph node is draining an infected region. They are continuous with the cortical sinuses and converge at the hilum as the efferent lymphatic vessel

Medical correlates• Neoplastic proliferation of lymphocytes, producing a

malignant lymphoma, may occur diffusely but is often located in one or more lymph nodes. Such growth can completely obliterate the normal architecture of the node and convert it to an enlarged, encapsulated structure filled wit lymphocytes, a condition called lymphadenopathy.

Spleen • The spleen contains the largest single accumulation of

lymphoid tissue in the body • it is the only lymphoid organ involved in filtration of blood,

making it an important organ in defense against blood-borne antigens.

• It is also the main site of old erythrocyte destruction. • As is true of other secondary lymphoid organs, the spleen is a

production site of antibodies and activated lymphocytes, which here are delivered directly into the blood.

• The spleen is filled with reticular tissue containing reticular cells and fibers, many lymphocytes and other blood cells, macrophages, and APCs.

• This splenic pulp has two components:

the white pulp (20% of the spleen)

and the red pulp

PulpsWhit pulp

• white pulp consist of

lymphoid nodules and the periarteriolar

lymphoid sheaths PALS

Red pulp

• the red pulp consists of

blood-filled sinusoidsand splenic cords.

White pulp

• The splenic white pulp consists of lymphoid tissue surrounding the central arterioles as the PALS and the nodules of proliferating B cells in this sheath. (a) Longitudinal section of white pulp (W) in a PALS surrounding a central arteriole (arrowhead). Surrounding the PALS is much red pulp (R). (b) A large nodule with a germinal center forms in the PALS and the central arteriole (arrowhead) is displaced to the nodule’s periphery. Small vascular sinuses can be seen at the margin between white (W) and red (R) pulp.

Red pulp

• (a) The splenic red pulp is composed entirely of sinusoids (S) and splenic cords (C), both of which contain blood cells of all types. The cords, often called cords of Billroth, are reticular tissue rich in macrophages and lymphocytes.

• (b) Higher magnification shows that the sinusoids (S) are lined by endothelial cells (arrows) with large nuclei bulging into the sinusoidal lumens. The unusual endothelial cells are called stave cells and have special properties that allow separation of healthy from effete red blood cells in the splenic cords (C).

Schematic view of the blood circulation and the structure of the spleen, from the trabecular artery to the trabecular vein. Small branches of these arteries are called central arterioles and become enclosed within a sheath of lymphoid cells, the periarteriolar lymphoid sheath (PALS) in white pulp. B cells in these sheaths can form nodules as the largest masses of white pulp, and around these nodules are located the marginal zone sinuses. Emerging from the white pulp, the central arteriole branches as the penicillar arterioles, which lead to sheathed capillaries. From these, blood flows into either a closed circulation passing directly into splenic sinuses (S) or an open circulation, being dumped from the vasculature into the lymphoid tissue of the red pulp’s splenic cords. From there viable blood cells reenter the vasculature through the walls of the sinuses.

Review “ important notes “