HLA molecules are called antigens because if transplanted, as in a kidney or skin graft, they can provoke an immune response in another person normally, they do not provoke an immune response in the person who has them.
Each person has an almost unique combination of HLAs. The immune system then attacks that cell. HLA molecules are what doctors try to match when a person needs an organ transplant. T cells T lymphocytes , as part of the immune surveillance system, must be able to recognize substances that do not belong to the body foreign antigens. However, they cannot directly recognize an antigen. They need the help of an antigen-presenting cell such as a macrophage or dendritic cell.
The antigen-presenting cell engulfs the antigen. The combined HLA and antigen fragment moves to the surface of the antigen-presenting cell where it is recognized by receptors on the T cell. Some white blood cells—B cells B lymphocytes —can recognize invaders directly. But others—T cells T lymphocytes —need help from cells called antigen-presenting cells:.
The antigen-presenting cell then combines antigen fragments from the invader with the cell's own HLA molecules. A T cell with a matching receptor on its surface can attach to part of the HLA molecule presenting the antigen fragment, as a key fits into a lock. T cells are part of the immune surveillance system. They travel through the bloodstream and lymphatic system. When they reach the lymph nodes or another secondary lymphoid organ, they look for foreign substances antigens in the body.
However, before they can fully recognize and respond to a foreign antigen, the antigen must be processed and presented to the T cell by another white blood cell, called an antigen-presenting cell. Antigen-presenting cells consist of dendritic cells which are the most effective , macrophages, and B cells.
White blood cells are activated when they recognize invaders. For example, when the antigen-presenting cell presents antigen fragments bound to HLA to a T cell, the T cell attaches to the fragments and is activated. B cells can be activated directly by invaders. Once activated, white blood cells ingest or kill the invader or do both.
Usually, more than one type of white blood cell is needed to kill an invader. Immune cells, such as macrophages and activated T cells, release substances that attract other immune cells to the trouble spot, thus mobilizing defenses. The invader itself may release substances that attract immune cells. The immune response must be regulated to prevent extensive damage to the body, as occurs in autoimmune disorders Autoimmune Disorders An autoimmune disorder is a malfunction of the body's immune system that causes the body to attack its own tissues.
Regulatory suppressor T cells help control the response by secreting cytokines chemical messengers of the immune system that inhibit immune responses. These cells prevent the immune response from continuing indefinitely. Resolution involves confining the invader and eliminating it from the body.
After the invader is eliminated, most white blood cells self-destruct and are ingested. Those that are spared are called memory cells. The body retains memory cells, which are part of acquired immunity, to remember specific invaders and respond more vigorously to them at the next encounter. There are two major classes of lymphocytes involved with specific defenses: B cells and T cells. Immature T cells are produced in the bone marrow, but they subsequently migrate to the thymus, where they mature and develop the ability to recognize specific antigens.
T cells are responsible for cell-mediated immunity. The cell-mediated response begins when a pathogen is engulfed by an antigen-presenting cell, in this case a macrophage. After the microbe is broken down by lysosomal enzymes, antigenic fragments are displayed with MHC molecules on the surface of the macrophage. T cells recognize the combination of the MHC molecule and an antigenic fragment and are activated to multiply rapidly into an army of specialized T cells.
One member of this army is the cytotoxic T cell. Cytotoxic T cells recognize and destroy foreign cells and tissues or virus-infected cells. Another T cell is the memory cytotoxic T lymphocyte, which remains in reserve in the body. If, sometime in the future, these T cells re-encounter this specific antigen, they will rapidly differentiate into cytotoxic T cells, providing a speedy and effective defense. Helper T cells coordinate specific and nonspecific defenses.
In large part by releasing chemicals that stimulate T cell and B cell growth and differentiation. Suppressor T cells inhibit the immune response so that it ends when the infection has been controlled. Whereas the number of helper T cells increases almost at once, the number of suppressor T cells increases slowly, allowing time for an effective first response.
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Common Health Topics. Components of the Immune System. Lines of Defense. Physical barriers White blood cells Molecules Lymphoid organs. Plan of Action. Your spleen's main function is to act as a filter for your blood. It recognizes and removes old, malformed, or damaged red blood cells. When blood flows into your spleen, your spleen performs "quality control"; your red blood cells must pass through a maze of narrow passages.
Healthy blood cells simply pass through the spleen and continue to circulate throughout your bloodstream. Blood cells that can't pass the test will be broken down in your spleen by macrophages.
Macrophages are large white blood cells that specialize in destroying these unhealthy red blood cells. Always economical, your spleen saves any useful components from the old cells, such as iron. It stores iron in the form of ferritin or bilirubin, and eventually returns the iron to your bone marrow, where hemoglobin is made.
Hemoglobin is an important protein in your blood that transports oxygen from your lungs to all the parts of your body that need it. Another useful purpose of your spleen is storing blood. The blood vessels in human spleens are able to get wider or narrower, depending on your body's needs. When vessels are expanded, your spleen can actually hold up to a cup of reserve blood.
If for any reason you need some extra blood — for example, if trauma causes you to lose blood — your spleen can respond by releasing that reserve blood back into your system.
Your spleen also plays an important part in your immune system, which helps your body fight infection. Just as it detects faulty red blood cells, your spleen can pick out any unwelcome micro-organisms like bacteria or viruses in your blood. When one of these invaders is detected in your bloodstream, your spleen, along with your lymph nodes, jumps to action and creates an army of defender cells called lymphocytes.
Lymphocytes are a type of white blood cell that produces antibodies, special proteins that weaken or kill bacteria, viruses, and other organisms that cause infection. In the end, rest of the cells would flow out of the spleen along the blood stream Figure 1C. The secretion of these chemokines in SLOs is not constant, but can be regulated by different molecules.
Firstly, previous research shows that the mesenchymal cells of SLOs require continuous signals from many molecules, so as to maintain their secretion of CCL21 and The most-studied molecules are the tumor necrosis factor TNF family members. In addition, these maintaining factors are mainly secreted by lymphocytes Sixt et al. As reported, the deletion of T cells will also lead to the significantly down-regulated secretory volumes of CCL19 and CCL21, and the expression levels of these chemokines can be recovered after the transfusion of T cells.
Even the maintaining effects of these factors have not changed, some molecules also could directly down-regulate the expressions of CCL21 and CCL For instance, upon infection, the reactivated T cells will secrete abundant IFN-r, which will induce the down-regulated expressions of CCL21 and CCL19, and thereby down-regulate the immune response of T cells upon the next infection Mueller et al. This secretion is mainly regulated by LT-B.
These cells were rarely detectable in the spleen of tumor-free mice Ugel et al. Moreover, though not confirmed, we speculate that the blood flow rate in the spleen will also affect the speeds of different cell components entering the spleen.
The reason is that when the expressions of various chemokines are unchanged, the blood flow rate will directly determine the speeds of different cell components entering the spleen, thereby impacting the speed of immune response. In clinic, the key factors that induce the changes of blood flow rate in the spleen are the blood pressure and the size of the spleen. When other conditions are not changed, the blood flow will change with the variation of blood pressure.
When the blood pressure is unchanged, the increase of spleen size will accelerate the blood flow in the spleen. This may also explain why the spleen expands upon the onset of chronic infection in many patients. Therefore, the pathogen clearance rate can be improved by increasing the blood flow in the spleen.
Previous research shows that it is mainly distributed in the marginal zone and red pulp of the spleen Ugel et al. These substances will also accumulate in response to bacterial or parasitic infection, chemotherapy, experimentally induced autoimmunity, and stress. MDSCs are considered as a major contributor to the profound immune dysfunction of most patients with sizable tumor burdens Ostrand-Rosenberg et al. However, recent researches show that these cells also could proliferate in the spleen in certain condition.
This also play an important role in the accumulation of these cells. Moreover, as reported, bone marrow HSPCs can enter circulation in the steady-state. If conditions permit, the circulating HSPCs will produce lineage-descendant cells outside the bone marrow. This so-called extramedullary hematopoiesis occurs predominantly in the liver in the developing embryo, but also in adult tissues including the spleen.
Indeed, under specific disease conditions, splenic HSPCs will profoundly expand. Splenic hematopoiesis has been reported in animal models of several diseases, including cancer, atherosclerosis myocardial infarction, and colitis Cortez-Retamozo et al.
However, there is no report whether these cells are active during immunoregulation. These cells show immunosuppressive properties which could inhibit microphage function Table 2. The spleen undertakes important roles in SLOs, such as clearance of antigens from the blood, and generation of specific immune responses. Moreover, the spleen plays important roles in regulation of immune responses.
Many functions of the spleen are unique and irreplaceable among other SLOs. Finally, more studies on the spleen are needed before dismissing its importance.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Alvarenga, H. Multifunctional roles of reticular fibroblastic cells: more than meets the eye?
Bajenoff, M. Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes. Immunity 25, — Fibroblastic reticular cells guide T lymphocyte entry into and migration within the splenic T cell zone. Bronte, V. The spleen in local and systemic regulation of immunity.
While the function of these structures is unknown, they may represent a degenerative process since they increase over the course of a lifetime. The medulla is also the site of negative selection, in which maturing T cells that react to self-antigens are eliminated by apoptosis in order to prevent autoimmunity.
The gross tissue structure of the thymus depends upon the age of the individual. The organ is large in early life and filled with lymphocytes, but involutes with advancing age, as the parenchyma is gradually replaced by adipose tissue.
Lymph nodes occur along the course of the lymphatic vessels. They filter the lymph as it drains back to the bloodstream. Lymph nodes are important sites of interaction between antigens, antigen presenting cells, and lymphocytes.
Normally, they are only a few millimeters in diameter. However, when an immune response is initiated, the lymphocytes within the lymph nodes undergo activation and proliferation, causing the nodes to enlarge. Lymph nodes are usually bean-shaped, with an indented region known as the hilum. They are covered by a collagenous capsule that extends into the body of the node as trabeculae.
The body of the lymph node is divided into an outer cortex and an inner medulla. The cortex contains a high concentration of lymphocytes while the inner medulla is less cellular.
Lymph from the extracellular space carries antigens and antigen presenting cells such as dendritic cells and macrophages from the tissues to the lymph nodes. The lymph enters the node at several points along the lymphatic system through afferent lymphatic vessels. These vessels pierce through the capsule and drain into the space below, known as the subcapsular sinus. From the subcapsular sinus, the lymph drains toward the medulla via channels called the cortical sinuses. As this occurs, it passes through the lymphoid cell mass in the cortex.
After reaching the medulla, the lymph drains into a complex network of medullary sinuses. The medullary sinuses converge at the hilum and drain into the efferent lymphatic vessels.
The blood supply enters and leaves the lymph node at the hilum. The small arteries enter the lymph node and create a capillary network. Lymphocytes in the blood can then enter the lymph node across the walls of postcapillary venules, which are also known as high endothelial venules, HEV. These HEVs merge into small veins, which then carry blood away from the node. The parenchyma of the lymph nodes is composed of reticular fibers, which support the lymphocytes.
In the cortex, B-lymphocytes are localized in lymphoid follicles just beneath the capsule. In absence of an active immune response, these follicles are known as primary lymphoid follicles. When an immune response is underway, focal points of intense B-cell proliferation known as germinal centers can be found in some follicles.
These follicles then become known as secondary lymphoid follicles. The T-lymphocytes are located deeper within the cortex and are diffusely distributed in the paracortical area.
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