C17L6 Innate Immunity

The Innate Immune System

When people think of the immune system, the first thing that comes to mind is often antibodies or vaccines or some other aspect of acquired immunity to an infectious agent that the body has already seen. But how does the body protect itself against potentially dangerous bacteria and viruses that it has never seen before? The immune system needs a way to quickly respond to a variety of unknown invaders, whether they've been encountered before or not, and all of the aspects of the immune system that respond to these unknown threats contribute to our bodies' innate immunity or the ability of the immune system to respond to unknown threats.

The innate immune system defends the body against malignant cells, viruses, and other invaders

The innate immune system is capable of mounting a defense against a variety of different threats, including malignant or cancerous cells, viruses that have already infected a cell, multicellular parasites and any other potential pathogens or foreign invaders that are capable of causing disease that might enter the body through an open wound or body orifice. So, let's take a look at how the innate immune system works.

Inflammation

Let's say that our friend Phil is rock climbing when he cuts himself on a sharp edge. It's not a bad cut, so Phil ignores it, but his immune system certainly doesn't! As soon as Phil sustains even the smallest injury, the potential for infection by a foreign invader dramatically increases. In fact, even with the most minor cuts, thousands, if not millions, of foreign entities, most of them bacteria, will enter the wound. So, whenever there is an injury, it is in the body's best interest to mount an immediate immune response to destroy all foreign invaders before they can establish a foothold.

The first response of the body to a localized injury or infection is inflammation or the immediate response of the body to injury or infection that includes an influx of blood plasma and immune cells to a localized area. Injured tissues release a number of signaling molecules, which cause blood vessel dilation, increase blood vessel permeability, and causes endothelial cells that line the blood vessels to present adhesion molecules on their surface. These adhesion molecules are recognized by immune cells in the blood or white blood cells, which bind to the adhesion molecules and stick to the blood vessel wall. The white blood cells then squeeze themselves between endothelial cells of the now more permeable blood vessels and enter the tissue surrounding the vessel.

The signaling molecules are immune cell chemoattractants that cause the immune cells to exit the blood vessel and migrate to the site of injury. One of the best known inflammatory signaling molecules is histamine, which is capable of dilating blood vessels, increasing blood vessel permeability, and causing immune cells to exit the bloodstream and enter the damaged tissue.

Cardinal Signs:

There are five signs that describe an inflammatory response.

Neutrophils

The first immune cells that arrive at an injured site are mostly neutrophils, which are quick-response immune cells that recognize and destroy bacteria. Neutrophils are the most numerous type of white blood cell in the blood, and their job is to immediately respond to inflammation and kill bacteria by phagocytosis, which is the process by which a cell engulfs, destroys and digests another cell, bacteria or cellular debris.

Neutrophils are the first immune cells to arrive at an injured site

Neutrophils have several different types of receptors that recognize several different pathogen-associated molecular patterns that are specific to bacteria and not found on human cells. When the receptors bind to the bacteria-specific patterns, the neutrophil captures the bacteria and engulfs it, surrounding it with its plasma membrane. This intracellular compartment is called a phagosome because it is created during the process of phagocytosis. Lysosomes then fuse with the phagosome to add their digestive enzymes, which kill the bacteria and break it down into its component amino acids, nucleic acids and monosaccharides. These nutrients can then be used by the neutrophil or released into the tissue for use by other cells.

Macrophages

Macrophages are another type of immune cell that phagocytizes foreign organisms, dead cells and cellular debris. Macrophages are a little bigger than neutrophils. They live longer than neutrophils and stay in the tissue even after all of the pathogens are gone. They act like a clean-up crew that phagocytizes leftover debris, bacteria and dead cells.

Complement

So far, most of the components of the innate immune system that we've talked about have been different types of cells, but there are non-cellular components of the innate immune system, too. Complement is a group of serum proteins which mark and destroy foreign microorganisms. Complement proteins are capable of forming a membrane attack complex on plasma membrane surfaces through a series of interactions between the different complement proteins. If the complement proteins are allowed to complete the membrane attack complex, it creates holes in the plasma membrane of its target and destroys it.

Complement proteins form a membrane attack complex on foreign microorganisms

Complement proteins are very non-specific; they will attempt to form membrane attack complexes on any plasma membrane they can. Now this might cause a problem if complement proteins formed membrane attack complexes on the body's own cells and destroyed them, but our cells don't let this happen.

Complement protein complexes that are forming on cell surfaces are fairly unstable and can be disrupted at various stages of completion by at least eight known membrane proteins that are expressed on the surface of all of our cells. So, while complement proteins try to form membrane attack complexes on any membrane surface, the body's own cells easily clear the proteins from themselves, but most bacteria and parasites don't have these complement disrupting proteins, so the membrane attack complex is formed, and the cell is lysed. However, certain types of microorganisms are resistant to lysis. In these cases, the complement proteins remain on the membrane and mark the microorganism as foreign. Neutrophils and macrophages have receptors to complement proteins and will phagocytize the marked invaders.

So, as you can see, complement serves to kill or mark all foreign cells and doesn't rely on recognizing specific organisms or molecules.

Natural Killer Cells

Natural killer cells are a type of immune cell that kills cells not expressing MHC 1 molecules on their surface. Like security guards in a restricted area, natural killer cells check the IDs of cells they come into contact with. For natural killer cells, or NK cells for short, the ID that they need to see is the MHC 1 molecule that normal cells express at all times on their cell surface. But there are three types of cells that do not always express MHC 1 molecules on their surface:

1. Red blood cells, which NK cells ignore for reasons that we won't go into here.

2. Cells infected with a virus

3.Malignant or cancerous cells

But the body doesn't have a quarantine room or a jail where it can put dangerous cells. Instead, the immune system can't take any chances, and the NK cells kill suspicious cells that do not express the correct MHC 1 molecule on their surface.

Eosinophils

Eosinophils are immune cells that attack multicellular parasites. These cells target multicellular parasites like worms by moving into position right up against the parasite and then releasing a host of destructive enzymes from their internal granules directly onto their target. Eosinophils also serve to ramp down the inflammatory response by arriving in the late stages of the response and releasing inhibitors of inflammatory molecules.

Lesson Summary

Let's review. Innate immunity is the ability of the immune system to respond to unknown threats. The innate immune system is capable of mounting a defense against a variety of different threats including any potential pathogens or foreign invaders that are capable of causing disease.

Inflammation is the immediate response of the body to injury or infection that includes an influx of blood plasma and immune cells to a localized area. The first immune cells that respond to inflammation are mostly neutrophils, which are quick-response immune cells that recognize and destroy bacteria. Neutrophils immediately respond to inflammation and kill bacteria by phagocytosis, which is the process by which a cell engulfs, destroys and digests another cell, bacteria or cellular debris. Macrophages are another type of immune cell that phagocytizes foreign organisms, dead cells and cellular debris. Macrophages stay in the tissue even after all of the pathogens are gone and act as a clean-up crew that phagocytizes all left over debris.

Complement is a group of serum proteins that mark and destroy foreign microorganisms. Complement proteins are capable of forming a membrane attack complex on plasma membrane surfaces through a series of interactions between the different complement proteins. If the complement proteins are allowed to complete the membrane attack complex, it creates holes in the plasma membrane of its target and destroys it. The body's own cells have several different membrane proteins that disrupt complement complexes and don't allow the complement proteins to form membrane attack complexes on the body's own cells.

Natural killer cells are a type of immune cell that kills cells that do not express MHC 1 molecules on their surface. Like security guards in a restricted area, natural killer cells check the IDs of cells it comes into contact with. For NK cells, the ID that they need to see is the MHC 1 molecule, which normal cells express at all times on their cell surface. NK cells kill suspicious cells that do not express the correct MHC 1 molecule on their surface, which is usually a sign that the cell is cancerous or infected with a virus.

Eosinophils are immune cells that attack multicellular parasites by releasing a host of destructive enzymes from their internal granules directly onto their target. Eosinophils also serve to ramp down the inflammatory response.