The bone marrow gives rise to all of the cells engaged in the defense mechanisms of the body (with minor exceptions). In babies it is found in all the bones, but moving through puberty it is replaced in the long bones by fat so that in adults it is found only in the central bones, such as the ischium.
The key cells in bone marrow are the hematopoietic stem cells, which give rise to the lymphoid stem cells and the myeloid stem cells. Lymphoid stem cells give rise to the lymphocytes, which specifically identify foreign molecules and cells. The myeloid stem cells give rise to all of the other blood cells, including red blood cells.
Let's make of list of the important cells to use for reference as we talk further about each of the types. No need to memorize them now, because you will become familiar with all of them as a move along. (But we put off red blood cells until the spring.)
Now is a good time to outline the main fluid compartments in the body:
Intracellular fluid is very different in composition to the others and is very carefully regulated by the plasma membrane of each cell.
The blood plasma and interstitial fluid are similar, but not identical. The wall of a capillary consists of only the endothelium, which consists of one layer of flat cells. The endothelium in most capillaries (with some important exceptions) are quite permeable to molecules smaller than proteins. Thus, if you take blood and subtract the blood cells and blood proteins, you have the composition of most interstitial fluid. However, this breaks down in a region of inflammation, which entails a significant increase in the permeability of blood capillaries.
Lymph is derived directly from the interstitial fluid and thus has exactly the same composition. Lymphatic capillaries are found in the tissues throughout the blood and accept interstitial fluid directly. They have flap-like openings in their walls, which allow even cells to enter.
The lymphatic vessels drain away the small, net excess of interstitial fluid that forms as fluid leaves the circulatory capillaries. This is quite variable, but totals roughly 2 liters per day in a healthy person. By contrast, the heart pumps 2 liters of blood in about 20 seconds in a resting person.
Observe in the above figure that microbes infecting the interstitial fluid slowly find their way into the lymph, which then slowly flows through ever largers lympatic vessels towards a big vein in the chest. The lympathic vessels are very thin-walled, have occasional valves, and a small amount of smooth muscle. The slow, steady formation of lymph and simple, ordinary compressions of the tissues are usually enough to create the slow flow.
But as the lymph flows from the lymphathic capillaries to the circulatory system, it inevitably must percolate through one or more lymph nodes. These are found especially in the neck, armpits, groin, and all along the back of the abdomen and thorax.
We will study the structure of lymph nodes in lab. Here, note that lymph enters the node around its periphery in the subcapsular space and then percolates through the lymph node to its concave side, where it leaves in another lymphatic vessel. Note the microbe entering the lymph node. Also, a type of cell called a dendritic cell phagocytizes microbes in the tissues and then travels via the lymph to the lymph nodes.
As lymph moves through the lymph node, it encounters huge numbers of lymphocytes, and it is usually here that a specific immune response develops; this is where the various events take place that will soon be our main topic.
The B cell response takes place in the lymphoid follicles, which are shown as circles in the figure. On the other hand, T cells are found mainly in the paracortical area just beyond the follicles.
While not shown in the figure, lymph nodes have circulatory capillaries just like other tissues. In the paracortical area, the small thin-walled vessels just after the capillaries are called high endothelial venules. Here is where lymphocytes in the blood bind cell adhesion molecules, cross the endothelium, and enter a lymph node. Lymphocytes need to move between the various lymph nodes of the body, so that immunity developed in one lymph node spreads to lymph nodes throughout the body. Also, a lymph node encountering an active infection will recruit additional lymphocytes by expressing more cell adhesion molecules that bind lymphocytes moving through the blood.
The white pulp of the spleen has the same types of cells as a lymph node. But it is focused on microbes in the blood rather than microbes in the interstitial fluid. The red pulp destroys aged red blood cells. More later.
Epithelia lined by mucus are a logical place for pathogens to gain entry to the internal environment of the body. Unlike the skin, with its dry, keratinized stratified squamous epithelia, epithelia in the digestive, respiratory and urinary systems are lined by living cells.
Because these epithelia are such likely sites for colonization by pathogens, special aggregations of lymphoid tissue are closely associated with the epithelia. These aggregations are called mucosal associated lymphoid tissue (MALT). Microscopically, most of this are clusters of cells in the interstitial fluid directly below the epithelia. These cells are much like those in a lymph node, with a preponderance of lymphocytes.
Some of these aggregations are quite large, such as the tonsils and the Peyer's patches in the distal part of the small intestine. The tonsils and Peyer's patches have follicles, just like the lymph nodes. In other places, the MALT consists of small, simple, scattered aggregations. Cells move between all types of MALT and lymph nodes, especially those in the abdomen. In this way, the immunological capabilites are spread throughout the MALT and even throughout the body.
Mucosal surfaces have one challenge that is not present in other areas of the body. For a moment, take the point of view of a pathogen. One option might be to cross the epithelium and enter the interstitial fluid. But here you immediately encounter phagocytes and other heavy hitters of the immune system. Why not simply bind to the apical surface of the epithelium and remain there, enjoying your metabolism and reproduction? Here you are somewhat separated by the immune system. Indeed, this is a logical move and many microbes do just that.
Because of this, MALT has some additional special mechanisms to deal with pathogens in the lumen. Refer to the figure to the right. Their moist apical surfaces are covered by mucus, which provides a first line of defense. The first step for an effective pathogen is to bind somehow to the epithelial cells.
In order for the immune system to respond to these microbes, their molecules need to be transported to the other cells of the MALT or a nearby lymph node. Notice the dendritic cell in the figure with one of its long, characteristic extentions capturing a microbe in the lumen. Also, the epithelium itself may have special M cells. These also engulf a microbe and transfer its molecules to the MALT.
While not shown in the figure, there are also some lymphocytes embedded in the epithelium lining the intestines. These are programmed to respond to some of the more commonly encountered microbes.
The B lymphocytes in the MALT tend to make IgA. This is because a dimer of this antibody can bind to the basal surface of the epithelium, can be transfered to the apical surface and then can be released. In the lumen it binds to the surface of a microbe. This can prevent the microbe from binding to the epithelium and agglutinate it with other identical microbes into clumps.
The epidermis of the skin contains a network of Langerhans cells, which are a type of dendritic cell. These phagocytes capture antigen, release from the epidermis and migrate to lymph nodes to start an adaptive (specific) immune response. Under the epidermis there are macrophages and T cells, much like elsewhere in the body.
The thymus is a nondescript appearing organ that lies just above the heart. It is here that T cells develop their surface molecules and are selected. Again, more later.
QUESTION: What is the difference between blood and typical interstitial fluid?
QUESTION: What are the permeability characteristics of most capillary endothelia?
QUESTION: What type of antibody is typically made by lymphocytes in MALT?
QUESTION: What main type of cell phagocytizes microbes in the tissues and then travels to a lymph node via the lymph?
QUESTION: From what type of blood cell does not develop from myeloid stem cells?