Neurobiology 104 Read G&H Chap 12

October 20, 2003

Lymphatic Tissues

Lymphatic (= lymphoid) tissue is connective tissue specialized

for 3 functions:

1. Removal of foreign or undesirable materials.

2. Production of lymphocytes.

3. Immune functions, especially making antibodies.

Lymphatic tissues is characterized by large numbers of lymphoid cells:

lymphocytes, plasma cells, macrophages, antigen presenting

cells (APC's), and reticular cells.

Any ordinary connective tissue can be stimulated to become lymphatic.

Lymphatic tissue can be "diffuse", or "nodular".

Reticular cells support lymphatic tissues in place of fibroblasts.

They are the stromal cells of reticular tissue.

They originate from mesenchyme and are not phagocytic.

They synthesize reticular fibers and spread their arms of

cytoplasm along them to form a meshwork to house other cells.

Proteins on their cell surface attract and activate other cells.

The degree of diversity among reticular cells is unknown.

Reticular cells look different in different tissues.

They specifically attract different wandering cells into

the meshworks of different tissues.

Reticular cells may be substantially diverse and responsible

for the individuality of reticular tissues.

Lymphatic nodules (= Lymphatic follicles):

Nodules: - are balls of lymphoid cells, about 1-2 mm across.

- are temporary structures, lasting several months

- occur in tissues containing B lymphocytes.

- indicate that the immune system has been activated.

Activated B cells can enter a lymphatic nodule.

Here they divide and mutate their expressed antibody gene.

The nodule develops an inner ball of paler staining cells,

the germinal center, surrounded by a darkly staining

mantle (= corona) of small lymphocytes

An activated nodule is called a secondary nodule

As an example, see G&H Fig 12-8

The cells of germinal centers mostly have large, pale nuclei and

more cytoplasm than small lymphocytes. They include:

Centroblast (lymphoblasts/immunoblasts/plasmablasts)

Macrophages

Reticular cells

Follicular dendritic cells (which present antigens to B cells)

_________________________

Key term are in bold font

The physiology of germinal centers is complex and incompletely known:

An activated B cell enters a primary nodule.

Antigens presented by dendritic cells stimulate the B cell to revert to a lymphoblast form (“centroblast”).

The blast cell divides and mutates its antibody gene.

The resulting cells compete for antigen on the dendritic cells.

Mutants with an antibody that binds the antigen more tightly displace the other B cells from the APC’s.

They continue to be stimulated and to divide whereas

the displaced cells give up and are phagocytized.

Consequently, the antibodies become better and better with time.

Some centroblasts differentiate into B memory cells, move to the

mantle as dividing prolymphocytes and gradually wander away.

Others differentiate into proplasmacytes, move out and become

plasma cells.

Dendritic cells constitute a heterogeneous collection of APC’s.

Many organs contain dendritic cells, derived from monocytes

eg Langerhans cells in the epidermis.

These dendritic cells collect and process antigens.

Inflammation causes them to migrate through the blood or lymph to the T cell regions of lymph nodes or spleen.

There they “present” their collected antigens to T cells.

Follicular dendritic cells of germinal centers are different.

They arise from mesenchyme, hold unprocessed antigens on their cell surface with antibody molecules (instead of with MHC proteins) and display it for B cells to compete over.

Gut associated Lymphatic Tissue (GALT)

Most lymphatic tissue and lymphocytes of the body are in the GI tract.

They protect the gut from pathogens and toxins.

Much of their antibody is IgA that can be secreted cross epithelia.

The GALT includes three forms.

1. Intra-epithelial lymphocytes invade the gut epithelium.

You have seen their prominent dark round nuclei in

the simple columnar epithelium of the duodenum.

In tonsils so many invade that the epithelium cannot

even be recognized in some places.

Intra-epithelial lymphocytes are distinct from those

which circulate elsewhere, eg through the lymph nodes.

2. Lymphocytes can accumulate in any lamina propria due to

local antigenic stimulation.

They can be diffuse or form primary or secondary nodules.

3. Lymphocytes are programmed always to be present in some tissues:

Tonsils in the throat region

Peyer's patches in the ileum

Appendix of the large intestine.

Specialized venules cause lymphocytes to accumulate at these regions. They are called high endothelial venules ( = HEV) because their endothelium is cuboidal. Proteins on the endothelial surface (selectins) grab passing lymphocytes in the blood and activate them to push through the endothelium by amoeboid movement, a process called diapedesis.

Tonsils

Palatine tonsils are structures ~3/4 inches across on the

sides of the pharynx (see diagram next page)

Their stratified squamous (unkeratinized) epithelium infolds

deeply into the underlying lamina propria to form crypts.

These crevices accumulate antigenic debris which diffuses

into the mucosa to titillate the B cells and APC's.

Nodules form in the lamina propria, especially in children.

Lymphocytes invade into, and even through, the epithelium.

(Look at the tonsils in your pedo patients. You may see

lymphocytes oozing from their crypts as a white pus.

Plasma cells usually are abundant throughout the tonsils.

Pharyngeal tonsils (= "adenoids") lie above the soft palate.

They are similar to the palatine tonsils except covered by

pseudostratified columnar instead of stratified squamous epithelium.

Lingual tonsils occur on the posterior tongue.

Their epithelium is stratified squamous.

Glands often empty into the bottoms of the crypts, keeping

them cleaner and less subject to infection than other tonsils.

Peyer's patches

Clusters of nodules regularly form in the mucosa of the ileum.

The lymphocytes induce the epithelial cells to become flattened M cells. M cells transport antigens from the gut to APC's below.

Appendix

The appendix is a small tubular outgrowth of the colon (large

intestine) at its junction with the small intestine.

It has the same fundamental organization of the colon except that

its lamina propria and submucosa are lymphatic tissue.

Nodules are especially abundant in the appendixes of children.

MALT

Lymphoid accumulations can occur under any wet epithelium,

hence the acronym for all "mucosa associated lymphatic tissue".

All lymphatic tissues and organs become less active with age.

The number of nodules and plasma cells decrease markedly.

Lymph

Lymph comes from fluid in connective tissue. Hydrostatic pressure forces water and salts out of the blood and into the C.T. at the arterial ends of capillaries. The plasma proteins remain in the vessels. The extra osmotic pressure which they generate causes water to be reabsorbed at the venous end of the capillaries. The

resorption is incomplete and the residual fluid drain into lymphatic vessels as lymph. Interference with this process can cause edema, that is accumulation of water in the connective tissue.

Lymph vessels resemble enlarged, thin walled sinusoidal venules with incomplete endothelial lining. They eventually conduct the lymph back into the blood stream at the vena cava.

Lymph nodes

Lymph vessels are potential passageways for pathogens in C.T. to get into the blood stream.

Lymph nodes are distributed along the lymph vessels as filters.

All lymph goes through at least one lymph node before

returning to the blood. Much of it goes through two or more.

Lymph nodes have several parts with different organization to carry out the three functions of lymphatic tissue listed earlier.

Reticular cells map out these regions and cause particular

types of cells to each of them.

You should understand the structures labeled on: G&H Fig 12-7

Cortex

The cortex is densely jammed with small lymphocytes.

The outer cortex, just under the capsule, has nodules.

Nodules indicate a region populated with B lymphocytes.

The deep cortex = paracortex = thymus-dependent region

contains mostly T cells and lacks nodules.

Suppresser T cells predominate in the outer part of the

paracortex, helper T cells in the inner portion.

Medulla

The medulla forms the inner part of the lymph node.

It has medullary cords densely packed with cells interposed between medullary sinuses, with relatively fewer cells, (but not empty).

Reticular cells and macrophages straddle the medullary sinuses.

Plasmablasts from the germinal centers of the cortex move to the

medullary cords and differentiate into plasma cells. There they release their antibodies into the lymph.

Pathway for lymph through a node

Many afferent lymph vessels drain lymph from surrounding

C.T. through the capsule and into the subcapsular sinus.

The lymph percolates through the less clogged parts of the node to the hilus where it leaves through efferent lymphatic vessels.

Most follows the route:

subcapsular sinus à peritrabecular sinus à medullary sinus.

Lymph brings both APC's and antigens into the lymph node.

Blood vasculature of the lymph node.

Blood enter at the hilus, travels through small arterioles

in the trabeculae of the medulla, supplies capillaries in the

cortex and returns to the hilus in venules.

The venules in the paracortex are specialized as high endothelium

Venules (sometimes called tall post capillary venules, TPCV).

Lymphocyte circulation

Lymphocytes circulate between the blood and lymph as follows:

Arterial blood --> lymph node --> HEV --> paracortex

--> sinuses --> efferent lymph vessel --> thoracic duct

--> vena cava --> --> arterial blood

Frequently Lymph from one lymph node drains through a second node.

In this case lymphocytes will also enter the secondary node through its afferent lymphatic vessels

Hint for the lab

To observe the various cell types on your slides look for:

Macrophages, dendritic cells, lymphoblasts: in germinal centers.

Reticular cells: between nodules and in the medulla of nodes.

Plasma cells: in the tonsil, especially near the capsule.

"That's

And as the lady said: all

is to

there that".