Bovine biology series
Part - 19 Immune system (2/2)
I am remembering the first time I saw I saw a veterinary post a cow. The formative memories are many, but they include the rigidity of the bones. The stiffness and hardness as he took what looked a like a giant hack saw and cut through the spinal column. I recall the very large rib cage. And the bones of the legs. He worked up a sweat to cut through these white bones.
I suppose at this early age I dismissed the multiple functions of the bone. I thought that these white rigid things were dead, serving to support and give structure for the animal as she once was able to stand and eat at the manger.
But in my high school biology class I learned that the bone is really the genesis of many cells; that bones are alive, living tissue, full of biochemical transformations serving life-enhancing roles.
One of them was the production of stem cells in the bone marrow, and thus we continue our journey of the immune system inside the bone exterior.....the marrow of bones.
All blood cells originate from cells found in bone marrow. The bone marrow tissue is found in the medullary cavities of bones, that is, in the center cavity of bones. This soft tissue is fed by blood vessels called the Haversian canals, which are part of the canals of Volkmann. This intricate set of blood vessels supplies the bone marrow with nutrients and take away the by-products and newly formed blood cells.
Stem cells are birth cells, in that they are capable of developing into many types of blood cells. Some of them develop into myeloid cells, which in turn develop into red blood cells (erythrocytes), platelets (blood clotting cells), and monocytes, neutrophils, eosinophils, basophils (white blood cells called leukocytes). Some stem cells develop into lymphoid cells, which are in turn made into B (cells) lymphocytes and T (cells) lymphocytes. Obviously, the importance of healthy bone and bone marrow is significant. And it is here that the basis of immunity arises from the stem cells.
We have learned that the immune system is really comprised of two types of responses: the humoral and the cell-mediated immunities.
The humoral immune system is responsible for the antibodies circulating in the blood system and the lymph system. These antibodies defend against toxins, free bacteria, and viruses in the body’s fluids. B cells that have arisen from bone marrow stem cells have specific receptors that are stimulated by an antigen; these make up the basic lymphocytes of the humoral system. When a foreign bacteria or virus makes its way into the body and finds its way into the blood or interstitial fluid, then if the animal has already prepared a specific antibody to react with this antigen, the humoral system works well. A specific B cell has given rise to an antibody that can deal with this foreign invader, rendering it harmless and no longer is it a threat to the body.
Of significance, here, is the fact that the humoral immune system works with invaders before these foreign substances enter body cells. They have breached the body’s primary defenses and have made their way into the bodies fluids, but not yet have they entered a body cell. The word humoral is derived from the Latin word "fluid".
The B cells stimulate certain plasma cells within the bloodstream to become antibodies. This is the direct result to foreign exposure, of course, as identified by an antigen in the body’s fluid that is not recognized. More specific cells called T-helper cells are involved in turning on the B cells, thus beginning the complex transition of plasma cells to antibodies.
T-helper cells have a sense of memory, as they are specifically designed to remember a specific antigen. Let's say that bacteria A enters the teat end and works its way into the bloodstream. Once here, it comes into contact with a T-helper cell that specifically recognizes it as an antigen for which it was designed to recognize. Well, the T-helper cell binds itself to this invader because its "signature" is recognized as a surface receptor. Once this binding is accomplished, the T-helper cell then binds to a circulating B cell lymphocyte. Together this conglomeration produces an antibody that labels or identifies the invader for destruction.
Once labeled like this, the invader is destroyed by cells that actually engulf and degenerate the invader. This process is called phagocytosis. So antibodies serve the role of identifying foreign invaders (antigens) so they can be destroyed.
Let us assume that the invading bacteria, bacteria A, are dealt with rather severely. That is, it is degraded and consumed by phagocytes after specific antibodies have been made, identifying it as an antigen. On subsequent days and weeks, these antibodies continue circulating in the body fluids, ready to identify any further bacteria A's that happen along. If some do, then another batch of antibodies are made; this is called the secondary immune response. This response serves the animal by protecting it from bacteria A in a stronger, more rapid manner because the level and relative strength of antibodies is greater.
This is why when vaccinations call for booster shots two or four weeks after the initial dose, the antibody titer is greater and thus affording more protection. Additionally is the production of memory cells during the primary stages of antibody production. These cells survive for a long period of time, remembering the receptor site of a particular antigen, such as bacteria A. In this way, memory cells can give rise to further antibody production by stimulating B cell production.
An example of this memory cell importance is the vaccination of a child for chickenpox. The circulating memory cells last the life (in most cases) of the child and adult, protecting the body from the disease.....a lifelong immunity.
Thus the humoral system deals with invading foreign bacteria, viruses and other microbes after they have breached the bodies primary defense mechanisms and have made their way into blood or interstitial fluids. Antibodies are produced that identify these invaders called antigen, and mark them for destruction by phagocytes. Some antibodies remain giving some further protection should this antigen be found again.
The cell-mediated immune response operates a bit differently.
Many pathogens operate by living and reproducing within the cells of a host animal. The humoral immune system dealt with free invaders, but these pathogens require the inner-workings of cells to live and reproduce. So the cell-mediated immune response deals with pathogens already in host cells.
The key components of the cell-mediated immune response system are the T cells, the lymphocytes that are produced in the bone marrow but complete their formative lives in the thymus (an organ found in the chest cavity near the sternum and heart). The T cells leave the thymus, enter the lymph and bloodstream. Interestingly enough, a most remarkable thing happens. Let's assume that bacteria B breaches the primary defense mechanisms of the body, reaching the bloodstream and then enter a body cell. Inside, bacteria B begins to alter the workings of cellular maintenance so that it can survive, grow, reproduce and just plain take over.
Well, this is not desirable for the host animal of course. But the bacteria B has changed the host cell in such a way that a receptor site, as in an antigen marker, is displayed. Since this host cell must be feed nutrients via the bloodstream, along comes a T cell and at once recognizes something very specific. The T cell quickly binds itself to this receptor site.
At this point the host cell is labeled, or marked like a flag. That is, it is now considered foreign ["non-self"] to the body and must be destroyed. The marking of this cell and others that have been infiltrated by bacteria B causes a further production of lymphocytes called helper T cells and Cytotoxic T cells. Together and in wondrous concert, they cause a lysis of the infecting cells. Lysis is a word describing a process of complete destruction of cells.
The Cytotoxic T cells are actually the lymphocytes responsible for destroying the infected host cell. The T cell releases a protein called perforin and this protein causes an open lesion of the host cell's membrane; the cell contents are spilled through the opening, thus cell lysis happens.
The host cell, once a healthy somatic cell of the body, and then an infected one with bacteria B is now sacrificed. This of course deprives bacteria B from growing and taking over.
Cell-mediated immune response is therefore a significant contributor to animal health. Antibodies from the B cells cannot attack foreign invaders like bacteria B once they have gained access into the host cells.
T cells are hardy lymphocytes. They can remain viable in the body fluids for months and years. They simply ply the fluids of the body in their search for distinctive markers, those cells that cannot be identified by "self". When in their travels they come across a cell that is "non-self", it recognizes it as a foreign invader, and it is because the foreigner, bacteria B, had entered the cell and changed it. The T cell then begins the very quick process of killing this host cell. In this way, they are sometimes referred to as killer cells.
Quite remarkable how all this works.
Consider that at each point of barrier, there are defense mechanisms to address substances and foreign invaders. At the primary defense level, the skin and epithelial tissue keeps out the bulk of invaders. If one should secure entrance, say through an orifice or a cut in the skin, then because animals are mostly fluid, they enter a fluid environment. Here, the humoral immune system deals with them. The circulating lymphocytes mark these invaders and they are destroyed by phagocytes, those hungry cells that engulf and destroy the invader. Thus at the fluid barrier, the result is exclusion from the intracellular level, that is, the invader is kept out of the cells themselves.
But if the invader should reach the cellular level, well, the T cells go to work, and the circulating Cytotoxic T cells identify these changed host cells and destroy them through lysis, a process in which a host cell is sacrificed in order that the body may survive.
We might remember the importance of "self" here. The immune system works with the identity of somatic cells, body cells, that are part of the body and not from another animal or specie. Thus the problem of getting a transplant organ to "take" or be accepted. The immune system considers it a foreigner and tries to destroy it. That is why organ matching is at best not absolute but one of closeness. That is why blood types must be matched.
In all this discussion of immunity, the concept of self-preservation or Homeostasis is the foundation of why the system works so well.
But sometimes the immune system does not work as according to plan. Sometimes the battles that must be fought by lymphocytes cannot be won because the immune system is impaired or the invading pathogen can adapt, can change, can alter and can overwhelm the immune system in such a way that homeostasis is compromised.
Any animal can survive the wrath of almost all invading pathogen if its defensive mechanisms are healthy and its immune system can deal with and destroy new pathogens by developing lymphocytes that mark and destroy the invaders. A long statement, I know, but one that aptly describes the relationship between health and immune response.
Perhaps in old age we are really experiencing a slowed immune system, one that does not answer the invading pathogen battle quickly enough. Perhaps we might consider that in our youth, an impaired immune system is caused by a host of stresses, some biological, some environmental, and some psychological. Then there is the case that touches us in so many ways, the cancers that battle the immune system no matter how healthy our immune system may be.
Next month, I'll finish the topic of immunity by writing about life that is not as easy of a read, but one that happens when something is wrong, something does not work, or something that has caused within us a growth of "nonself" cells or tumors. Cancer.
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