Different things can make different cells produce different kinds of interferons (IFNs). IFNs are a group of natural proteins, sugars, and small chains that are found in many animals with backbones. There are three main kinds of IFNs: alpha (?), beta (?), and gamma (?). They have different shapes and work in different ways. IFN-? and IFN-? have one part, but IFN-? has more parts. IFN-? and IFN-? use the same receiver, but IFN-? uses a different one. IFN-? and IFN-? can make natural killer (NK) cells stronger, but IFN-? can make big eaters stronger. IFN-? and IFN-? can stay the same in acid, but IFN-? cannot. IFN-? is not made all the time, but IFN-? and IFN-? are. This article mainly talks about IFN-? because it affects the hormone system and the brain system a lot and can help with many sicknesses and cancers.
IFN-? was first thought to be made by big eaters, white cells, and one-cells and to stop viruses from growing and make the immune system better. Later, IFN-? was found to do more things, like stopping tumors from growing and changing how other things work in the body. Besides making the immune system better, IFN-? also makes the body do other things when there is an infection. These things include feeling and moving differently, getting hot, not wanting to eat, and having brain problems like being mixed up, sad, or not sleeping well. In the body, IFN-? is always made at a low level.
The brain is mostly separate from the hormone system and the immune system because there is a wall of blood vessels that stops many cells and things from going into the brain. Only a little bit of IFN-? can go into the deep parts of the brain after it is given into the spine or into the body in the fluid around the brain. It is thought that IFN-? that is given into the body goes into the brain through places where the wall is not there.
So, only some places near where the wall is not there get a lot of IFN-?, but other places far from where the wall is not there do not get much IFN-?. In fact, IFN-? gets a lot in the bridge and the control center, where the wall is not very strong. Also, there are seven places that can make IFN-?, and two of these places (glue cells and nerve cells) are in the brain because there are places for IFN-? to stick to in the brain. These places for sticking are in the brain in general, and in the control center especially (because it connects the brain and the hormone system), as well as in the hormone system. These places for sticking may be how IFN-? connects with the brain and the hormone system.”
How atoms stick together
Atoms can stick together to make small groups called molecules. The number of atoms in each group is always the same for a certain kind of molecule. For example, every water molecule has two hydrogen atoms and one oxygen atom. This makes water different from mixtures of atoms that are not stuck together. For example, hydrogen and oxygen can be mixed in any amounts, but they will only stick together in certain amounts to make water (H2O). Sometimes, the same atoms can stick together in different ways to make different molecules. For example, two hydrogen atoms and one oxygen atom make water, but two hydrogen atoms and two oxygen atoms make hydrogen peroxide (H2O2).
Also, sometimes different molecules can have the same atoms but in different places. These molecules are called isomers. For example, ethyl alcohol (CH3CH2OH) and methyl ether (CH3OCH3) both have one oxygen atom, two carbon atoms, and six hydrogen atoms, but they are arranged differently. Not all things are made of small groups of atoms. Some things are made of big grids of atoms that are all stuck together. For example, table salt is made of sodium atoms and chlorine atoms that are arranged in a pattern. Each sodium atom is next to six chlorine atoms and each chlorine atom is next to six sodium atoms. The force between any sodium and any chlorine atom is the same.
So there is no small group of atoms that we can call a salt molecule. For things like salt, we use a formula that shows the simplest ratio of the atoms, like NaCl for salt.Atoms stick together by sharing pairs of electrons, or covalent bonds. These bonds make the atoms stay in certain positions around each other so that the bonds are strong. This means that each molecule has a fixed shape that does not change easily. The shape of the molecule affects how it behaves; for example, the water molecule is bent and has a positive end and a negative end, but the carbon dioxide molecule is straight and has no charge. It is important to know how atoms change their positions when they react with other atoms. In some molecules, the shape can change; for example, in ethane (H3CCH3) the two carbon atoms can rotate around each other.
Some molecules have no electric charge, which means they have the same amount of negative and positive parts. These parts can be arranged in different ways. If they are arranged evenly around the molecule, the molecule is nonpolar. If they are arranged unevenly, with more positive parts on one side and more negative parts on the other, the molecule has a dipole moment (i.e., it can spin when there is an electric or magnetic field) and is polar. When polar molecules can spin freely, they tend to line up in ways that make them attract each other.
Nonpolar molecules usually like to mix with fats, while polar molecules like to mix with water. Fat-soluble, nonpolar molecules can easily cross a cell membrane because they blend with the nonpolar part of the fat layer. Water (a polar molecule) can also cross the cell membrane, but many other polar molecules cannot, such as charged particles or those that have many polar groups. Polar molecules need special transport systems to cross the fat layer.”
What antibodies do
human B cell
When something that doesn’t belong in the body gets in, the body’s defense system knows it is different because it has different molecules on its surface than the ones in the body. To get rid of the intruder, the body’s defense system uses many ways, including one of the most important—making antibodies. Antibodies are made by special white blood cells called B cells. When something that doesn’t belong in the body sticks to the B cell, it makes the B cell split and grow into a group of identical cells called a clone. The grown-up B cells, called plasma cells, send out millions of antibodies into the blood and lymph.
antigen, antibody, and lymphocyte
As antibodies move around, they attack and stop things that don’t belong in the body that are the same as the one that started the body’s defense response. Antibodies stop things that don’t belong in the body by sticking to them. The sticking of an antibody to a poison, for example, can change the poison’s chemical makeup and make it harmless; such antibodies are called antitoxins. By attaching themselves to some invaders, other antibodies can make them unable to move or get into body cells. In other cases the antibody-covered thing that doesn’t belong in the body is part of a chemical chain reaction with complement, which is a group of proteins in the blood. The complement reaction either can make the invader break open or can bring invader-eating cleaner cells that swallow up or eat up the invader. Once started, antibody making goes on for several days until all things that don’t belong in the body are gone. Antibodies stay in the blood for several months, giving longer protection against that specific thing that doesn’t belong in the body.”
How antibodies are used for health and science
Antibodies are very useful for health and science. They are made by the body’s defense system to fight off harmful things like germs or poisons. Sometimes, doctors can give people antibodies from someone else who has already fought off the same harmful thing. This can help protect them quickly from things like snake venom or a bad infection. Vaccines are another way to protect people from harmful things. They make the body’s defense system learn how to fight off a specific harmful thing, so that it can be ready if it ever comes back.
Scientists can also make special kinds of antibodies in the lab, called monoclonal antibodies. These antibodies can stick to one part of any molecule, such as a drug, a hormone, a germ, or a cell receptor. This makes them very good at finding and measuring different things in the body or in the lab. They can also help tell different kinds of cells apart by finding new markers on their surfaces. For example, monoclonal antibodies can find cancer cells in a tissue sample by sticking to cancer markers.
Monoclonal antibodies can also be used to try to kill cancer cells. They can carry drugs or radiation to the cancer cells and destroy them. They can also help the body’s defence system attack the cancer cells better, by blocking some signals that stop it from working well. One way to do this is with ipilimumab, a monoclonal antibody that works against advanced skin cancer. It blocks a signal called CTLA4 that normally stops the defence system from killing cancer cells.
By blocking this signal, ipilimumab makes the defence system stronger and able to fight off the cancer better. Another way to do this is with inhibitors of PD-1, a signal that is found on defense cells and that makes them less active. Some cancers have too much PD-1 and make the defense system weaker. Anti-PD-1 therapies, such as nivolumab and pembrolizumab, stop PD-1 from working and make the defense system more active against the cancer. These therapies have helped some people with skin cancer and other types of cancer.
How enzymes work
Enzymes are special molecules that help speed up chemical reactions in living things. They can do this many times without being used up or changed. A small amount of an enzyme can make a big difference in how fast a reaction happens. An enzyme molecule can change 1,000 other molecules every second. The more molecules that need to be changed, the faster the enzyme works, until it reaches its maximum speed. At this point, all the parts of the enzyme that do the work are busy and cannot take any more molecules.
Some things can stop enzymes from working well. Some molecules look like the ones that the enzyme changes, but they are not. They can trick the enzyme and take the place of the real ones. This blocks the enzyme from doing its job. For example, penicillin is a medicine that does this to stop some bacteria from making their cell walls.
Some molecules can stop enzymes from working by attaching to them somewhere else. This can make the enzyme change its shape and lose its ability to work. This is called allosteric inhibition, and the place where these molecules attach is called the allosteric site. Sometimes, a molecule that is made by an enzyme later on can come back and attach to the allosteric site. This stops the enzyme from making more of that molecule when there is enough already. This is a way of controlling how much of something is made by an enzyme.
Allosteric control can also make enzymes work better. Some molecules can attach to the allosteric site and make the enzyme change its shape so that it can work with other molecules that it could not before. These molecules are called activators. They can be hormones or other things that are made by earlier enzymes. Allosteric activation and inhibition let the cell make energy and materials when they are needed and stop making them when there is enough.
How Interferons Work
Interferons (IFNs) are proteins that help the immune system fight infections and diseases. They are part of a group of molecules called cytokines that send signals to other cells. Interferons are especially good at stopping viruses from spreading, but they also help prevent tumors, make cells show their identity better, and turn on immune cells like natural killer cells and macrophages. There are three main types of interferons: interferon-alpha, beta, and gamma. Interferon-alpha and beta are similar and belong to Type 1, while interferon-gamma is different and belongs to Type 2. Scientists have also found a new type of interferons, called Type 3, which includes interferon lambda.
Interferons change how the immune system works by starting a chain of events that leads to making new proteins such as MHC class 1, B2 microglobulin, and others. Alpha and beta interferons attach to the IFNA receptor, which has two parts, IFNAR1 and IFNAR2. IFNAR1 does not hold onto interferon very well by itself, but it does better when IFNAR2 is there. Some enzymes called SHP-1 and 2 stick to IFNAR1 and slow down the activation of JAK signaling. IFNAR2 has three forms, short, soluble, and long. The long form makes the JAK-STAT pathway and antiviral response work. When interferon activates the receptor, protein complexes form and move to the nucleus and turn on STATs. This makes IFNAR1 and IFNAR2 stick together, which causes a series of changes.
First, the JAK enzyme, Tyk 2, which is linked to IFNAR1, is changed by JAK1, another JAK enzyme attached to IFNAR2. Tyk2 then changes JAK1, which changes IFNAR1 and 2. Next, STAT2 binds to IFNAR1 at specific changed spots. Then, STAT2 is changed by JAK enzymes, making a place for STAT1, which is also changed. After being changed, the STATS separate and bind to the interferon regulatory factor 9, which makes the main interferon transcription factor, ISGF-3. IGSF-3 then moves to the nucleus and binds to ISRE, starting the making of interferon-induced genes. For interferon-gamma, there are different DNA control sequences called gamma-activated sequence elements, which are in the start of interferon-gamma stimulated genes.
Interferons stop viruses from multiplying at many steps of the viral life cycle, such as entering, copying, RNA stability, making proteins, maturing, and leaving. This action depends on the making of antiviral genes. Interferons make more PKR through an ISRE and GAS in the start of the PKR gene. The kinase activity of the PKR gene changes the translation start factor eIF2-a at Ser51. eIF2-a-GTP is needed for the start of viral protein making.
PKR also has roles in cell growth, tumor prevention, and signal transmission through the control of serine change of STAT1 and the change of IkB, which makes NF-kB-dependent genes work. Also, the 2-5 A oligosynthetase/RNAse L system is strongly made by interferons. RNAse Ls are turned on by double-stranded RNAs and break down all single-stranded RNA, stopping viral multiplication. The Mx proteins are a family of GTPases made by interferons that stick together and interfere with copying in negative-sense virus multiplication. Another protein that stops viral multiplication that is made by interferons is the guanylate binding protein.
Besides the antiviral effects of interferons, they also have antiproliferative effects. Scientists think that these antiproliferative effects of interfer
How Interferons Work and What They Do
Interferons are a kind of protein that sends signals inside cells. They make two copies of a receiver stick together to start the signal. Interferons are not very big proteins. Interferon-gamma has two same parts that twist around each other. Two receivers bind on both sides of IFN-gamma. Interferon-alpha has one part, and two different receivers bind to different parts of the protein.
Alpha-interferons can change how the immune system works and gamma-interferon helps fight off invaders. They also help control abnormal cell growth, and help normal cells grow at the right rate. The signals are not very clear and can mean different things when mixed with other signals between cells. This makes it hard to use interferon as a medicine. Some hormones like insulin have easy, direct actions, so insulin works well when given to patients. But the fake signals from interferon treatment can be misunderstood, causing bad side effects. Sometimes, though, interferon can send the right messages, telling the immune system to kill cancer cells or stopping the growth of blood vessels that feed a tumor.”
Different types of immune proteins blocked the new coronavirus in different ways in the lab.
We did this study from December 2020 to March 2021. We got samples of the new coronavirus from four groups (B, B.1, B.1.1.7, and B.1.351) (Fig. 1 and SI Appendix, Table S1). We got these samples from a website and grew them once in human lung cells (A549) that we changed to have the protein that the virus uses to enter cells (ACE2) (A549-ACE2) (SI Appendix, Fig. S1A). We treated the A549-ACE2 cells with 17 kinds of immune proteins (PBL Assay Science) overnight in the same way and three times each, then added a small amount of virus for 2 h (SI Appendix, Fig. S1B).
We used the same amount of immune proteins based on how many molecules they have, like we did before with HIV-1 (3, 30). To test how well the different immune proteins stopped the different live samples of the new coronavirus, we used a method to measure how much virus was made 24 h after infection (Fig. 2A). We first tried different amounts of immune proteins and found that a 2-pM amount was good for showing the difference between immune proteins that were very good or very bad at stopping the virus (like IFN? and IFN?1) (SI Appendix, Fig. S1C). The IFN? and IFN?1 amounts we used did not hurt the cells much (SI Appendix, Fig. S1D). So we used 2 pM amounts for more testing.
We also compared our method with another method using VeroE6 cells that makes spots where the virus grows using three times less or more virus of one sample (B.1.351). The results from these two methods were very similar (SI Appendix, Fig. S2A). But our method could measure more virus; we think that 1 spot equals about 900 copies of the virus gene (SI Appendix, Fig. S2A). The number of virus copies also matched the number of lung cells from people that were infected with different samples of the new coronavirus as seen by a microscope (SI Appendix, Fig. S2B). So we used our method to see how well the different immune proteins worked.
