The lymphatic system and cancer

Digestive System Anatomy

Human Circulatory System
The CSF fills the space that surrounds the brain, and wastes from inside the brain make their way out to the CSF, which gets dumped, along with the waste, into the blood. The stem cells produce hemocytoblasts that differentiate into the precursors for all the different types of blood cells. The two work together to protect you from illness and disease. Very few viruses can bind to skin cells. Proin semper ultrices tortor quis sodales. This diagram shows the body's lymphatic system, which has evolved to meet this need.

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Right lymphatic duct

The human immune system is a truly amazing constellation of responses to attacks from outside the body. It has many facets, a number of which can change to optimize the response to these unwanted intrusions.

The system is remarkably effective, most of the time. This note will give you a brief outline of some of the processes involved. An antigen is any substance that elicits an immune response, from a virus to a sliver. Parts of the immune system are antigen-specific they recognize and act against particular antigens , systemic not confined to the initial infection site, but work throughout the body , and have memory recognize and mount an even stronger attack to the same antigen the next time.

Any cell not displaying this marker is treated as non-self and attacked. The process is so effective that undigested proteins are treated as antigens.

Sometimes the process breaks down and the immune system attacks self-cells. This is the case of autoimmune diseases like multiple sclerosis, systemic lupus erythematosus, and some forms of arthritis and diabetes. There are cases where the immune response to innocuous substances is inappropriate.

This is the case of allergies and the simple substance that elicits the response is called an allergen. There are two main fluid systems in the body: The blood and lymph systems are intertwined throughout the body and they are responsible for transporting the agents of the immune system. The blood flows from the heart into arteries, then to capillaries, and returns to the heart through veins. The plasma is mostly water All blood cells are manufactured by stem cells, which live mainly in the bone marrow, via a process called hematopoiesis.

The stem cells produce hemocytoblasts that differentiate into the precursors for all the different types of blood cells. Hemocytoblasts mature into three types of blood cells: The leukocytes are further subdivided into granulocytes containing large granules in the cytoplasm and agranulocytes without granules.

The agranulocytes are lymphocytes consisting of B cells and T cells and monocytes. Lymphocytes circulate in the blood and lymph systems, and make their home in the lymphoid organs.

All of the major cells in the blood system are illustrated below. There are —10, WBCs per mm 3 and they live days. About 2,, RBCs are produced each second and each lives for about days They migrate to the spleen to die. Once there, that organ scavenges usable proteins from their carcasses. A healthy male has about 5 million RBCs per mm 3 , whereas females have a bit fewer than 5 million. Normal Adult Blood Cell Counts. Blood type AB means both antigens are present and type O means both antigens are absent.

Type A blood has A antigens and type B blood has B antigens. Some of the blood, but not red blood cells RBCs , is pushed through the capillaries into the interstitial fluid. It flows in the lymphatic vessels and bathes tissues and organs in its protective covering. There are no RBCs in lymph and it has a lower protein content than blood. The lymph flows from the interstitial fluid through lymphatic vessels up to either the thoracic duct or right lymph duct, which terminate in the subclavian veins, where lymph is mixed into the blood.

The right lymph duct drains the right sides of the thorax, neck, and head, whereas the thoracic duct drains the rest of the body.

Lymph carries lipids and lipid-soluble vitamins absorbed from the gastrointestinal GI tract. Since there is no active pump in the lymph system, there is no back-pressure produced. The lymphatic vessels, like veins, have one-way valves that prevent backflow. Additionally, along these vessels there are small bean-shaped lymph nodes that serve as filters of the lymphatic fluid.

It is in the lymph nodes where antigen is usually presented to the immune system. The human lymphoid system has the following: The innate immunity system is what we are born with and it is nonspecific; all antigens are attacked pretty much equally. It is genetically based and we pass it on to our offspring.

Normal flora are the microbes, mostly bacteria, that live in and on the body with, usually, no harmful effects to us. We have about 10 13 cells in our bodies and 10 14 bacteria, most of which live in the large intestine. There are 10 3 —10 4 microbes per cm 2 on the skin Staphylococcus aureus , Staph. Various bacteria live in the nose and mouth. Lactobacilli live in the stomach and small intestine. The urogenitary tract is lightly colonized by various bacteria and diphtheroids.

After puberty, the vagina is colonized by Lactobacillus aerophilus that ferment glycogen to maintain an acid pH. Normal flora fill almost all of the available ecological niches in the body and produce bacteriocidins, defensins, cationic proteins, and lactoferrin all of which work to destroy other bacteria that compete for their niche in the body.

The resident bacteria can become problematic when they invade spaces in which they were not meant to be. This causes an overgrowth of Clostridium difficile , which results in pseudomembranous colitis, a rather painful condition wherein the inner lining of the intestine cracks and bleeds.

A phagocyte is a cell that attracts by chemotaxis , adheres to, engulfs, and ingests foreign bodies. Promonocytes are made in the bone marrow, after which they are released into the blood and called circulating monocytes , which eventually mature into macrophages meaning "big eaters", see below.

Some macrophages are concentrated in the lungs, liver Kupffer cells , lining of the lymph nodes and spleen, brain microglia, kidney mesoangial cells, synovial A cells, and osteoclasts. They are long-lived, depend on mitochondria for energy, and are best at attacking dead cells and pathogens capable of living within cells. Once a macrophage phagocytizes a cell, it places some of its proteins, called epitopes, on its surface—much like a fighter plane displaying its hits.

These surface markers serve as an alarm to other immune cells that then infer the form of the invader. All cells that do this are called antigen presenting cells APCs. The non-fixed or wandering macrophages roam the blood vessels and can even leave them to go to an infection site where they destroy dead tissue and pathogens. Emigration by squeezing through the capillary walls to the tissue is called diapedesis or extravasation.

The presence of histamines at the infection site attract the cells to their source. Natural killer cells move in the blood and lymph to lyse cause to burst cancer cells and virus-infected body cells. They are large granular lymphocytes that attach to the glycoproteins on the surfaces of infected cells and kill them. Polymorphonuclear neutrophils , also called polys for short, are phagocytes that have no mitochondria and get their energy from stored glycogen.

They are nondividing, short-lived half-life of 6—8 hours, 1—4 day lifespan , and have a segmented nucleus. The neutrophils provide the major defense against pyogenic pus-forming bacteria and are the first on the scene to fight infection.

They are followed by the wandering macrophages about three to four hours later. The complement system is a major triggered enzyme plasma system. It coats microbes with molecules that make them more susceptible to engulfment by phagocytes.

Vascular permeability mediators increase the permeability of the capillaries to allow more plasma and complement fluid to flow to the site of infection.

They also encourage polys to adhere to the walls of capillaries margination from which they can squeeze through in a matter of minutes to arrive at a damaged area.

Once phagocytes do their job, they die and their "corpses," pockets of damaged tissue, and fluid form pus. Eosinophils are attracted to cells coated with complement C3B, where they release major basic protein MBP , cationic protein, perforins, and oxygen metabolites, all of which work together to burn holes in cells and helminths worms. Their lifespan is about 8—12 days. Neutrophils, eosinophils, and macrophages are all phagocytes.

Dendritic cells are covered with a maze of membranous processes that look like nerve cell dendrites. Now, just as every cell requires nutrients to fuel it, every cell also produces waste as a byproduct, and the clearance of that waste is the second basic problem that each organ has to solve. This diagram shows the body's lymphatic system, which has evolved to meet this need. It's a second parallel network of vessels that extends throughout the body.

It takes up proteins and other waste from the spaces between the cells, it collects them, and then dumps them into the blood so they can be disposed of.

But if you look really closely at this diagram, you'll see something that doesn't make a lot of sense. So if we were to zoom into this guy's head, one of the things that you would see there is that there are no lymphatic vessels in the brain. But that doesn't make a lot of sense, does it?

I mean, the brain is this intensely active organ that produces a correspondingly large amount of waste that must be efficiently cleared. And yet, it lacks lymphatic vessels, which means that the approach that the rest of the body takes to clearing away its waste won't work in the brain. So how, then, does the brain solve its waste clearance problem? Well, that seemingly mundane question is where our group first jumped into this story, and what we found as we dove down into the brain, down among the neurons and the blood vessels, was that the brain's solution to the problem of waste clearance, it was really unexpected.

It was ingenious, but it was also beautiful. Let me tell you about what we found. So the brain has this large pool of clean, clear fluid called cerebrospinal fluid. We call it the CSF. The CSF fills the space that surrounds the brain, and wastes from inside the brain make their way out to the CSF, which gets dumped, along with the waste, into the blood.

So in that way, it sounds a lot like the lymphatic system, doesn't it? But what's interesting is that the fluid and the waste from inside the brain, they don't just percolate their way randomly out to these pools of CSF. Instead, there is a specialized network of plumbing that organizes and facilitates this process. You can see that in these videos. Here, we're again imaging into the brain of living mice. The frame on your left shows what's happening at the brain's surface, and the frame on your right shows what's happening down below the surface of the brain within the tissue itself.

We've labeled the blood vessels in red, and the CSF that's surrounding the brain will be in green. Now, what was surprising to us was that the fluid on the outside of the brain, it didn't stay on the outside. Instead, the CSF was pumped back into and through the brain along the outsides of the blood vessels, and as it flushed down into the brain along the outsides of these vessels, it was actually helping to clear away, to clean the waste from the spaces between the brain's cells.

If you think about it, using the outsides of these blood vessels like this is a really clever design solution, because the brain is enclosed in a rigid skull and it's packed full of cells, so there is no extra space inside it for a whole second set of vessels like the lymphatic system. Yet the blood vessels, they extend from the surface of the brain down to reach every single cell in the brain, which means that fluid that's traveling along the outsides of these vessels can gain easy access to the entire brain's volume, so it's actually this really clever way to repurpose one set of vessels, the blood vessels, to take over and replace the function of a second set of vessels, the lymphatic vessels, to make it so you don't need them.

And what's amazing is that no other organ takes quite this approach to clearing away the waste from between its cells. This is a solution that is entirely unique to the brain. But our most surprising finding was that all of this, everything I just told you about, with all this fluid rushing through the brain, it's only happening in the sleeping brain.

Here, the video on the left shows how much of the CSF is moving through the brain of a living mouse while it's awake. Yet in the same animal, if we wait just a little while until it's gone to sleep, what we see is that the CSF is rushing through the brain, and we discovered that at the same time when the brain goes to sleep, the brain cells themselves seem to shrink, opening up spaces in between them, allowing fluid to rush through and allowing waste to be cleared out.

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