Greetings Bored Surfer!

March is now upon us and brings unpredictable weather, basketball mania and green beer. It also brings other instances worthy of being celebrated.

March 8th is National Proofreading Day. I, for one, need to express my appreciation for these patient souls (both the amateurs and professionals – you know who you are) who toil endlessly to protect us from the scourge of bad grammar. To honor these humble language servants, please practice the correct use of the apostrophe. It’s for making contractions and possessives – not plural’s.

Don’t forget that Pi day comes around every year on 3-14.

March 28 is National Respect Your Cat Day. I don’t know who thought this up, because your average cat is not satisfied with being disrespected 364 days a year.

March 30 is billed as National Doctor Day. It appears to be targeted towards physicians, but does not specifically preclude displaying your affection for your favorite PhD, dentist, optometrist or veterinarian (hint, hint).

The world is full of many dangers including wars, lobstrosities, fires, floods, famines, droughts, Plymouth Furys, Greek Furies, unregulated electrical grids, Skynet, low men in yellow coats, predators and Predators. As horrifying as these threats to human life may seem, they pale in comparison to the power of pathogens, the many mighty microbes that cause disease. Luckily, the immune system is there to detect foreign material, eliminate it and remember it, in case it is encountered again.

This edition of BLOG blog is meant to provide a basic understanding of the mechanisms that protect us (humans and animals) from disease. A complete explanation of the extremely complex network of cells and chemical messengers that constitute the mammalian immune system is well beyond any blog’s scope. Although it is incredibly difficult to adequately and accurately describe the

immune system without going into excruciating detail, I shall try to provide a brief overview. Please note that while most of this information is geared toward humans, it applies to our canine and feline companions as well.

The body’s first line of defense against the germs that surround you every day is physical barriers. Skin does a good job of keeping your insides in and outside stuff out. There are also antimicrobial proteins and immune cells on the surface to intercept potential invaders. When skin cells die and flake off, they take bacteria with them. The sloughed cells mix with soil particles, pollen, hair, textile fibers, pet dander and paper fibers (among other things) in varying amounts to form house dust.

In locations where a body cavity needs to connect to the outside world, you have mucous membranes to provide protection. In addition to being a physical barrier, mucous membranes secrete mucus that traps small particles (yes, that’s where boogers come from). Please note that mucous is an adjective and mucus is a noun. In the respiratory tract, there are cilia (tiny hair-like projections from cells) that move foreign material out of the nose and throat through coordinated movements. There are also bacteria-fighting molecules present in your saliva and tears as well as in the skin and mucous membranes themselves.

If your outer protective layer (including the tissue boxes on your feet) proves unsuccessful in preventing a microbial invasion, an all-purpose inflammatory response is activated to neutralize the threat. The main respondents to the germ breach are white blood cells.

Neutrophils, the most common type of white blood cells, are usually the first to respond. They are normally found in the bloodstream, but have the ability to enter other tissues when needed. Their job is to detect, kill and eat antigens (material considered foreign). When their task is completed, they self-destruct. The remains of the mass neutrophilic hara-kiri are the main ingredient of pus.

Mast cells also respond, but in a manner unrelated to sailing. This type of white blood cell is responsible for visible signs of inflammation. Mast cells release the chemical histamine, which in turn causes the blood vessels in the area to dilate and become more permeable. The increased blood flow causes redness and swelling at the site of injury. It also causes an increase in temperature, which increases the metabolic rate, which allows cells to repair themselves faster.

In some cases, an invading pathogen requires a specific response in addition to the usual preventative measures. The white blood cells primarily responsible for this function are called lymphocytes. There are two major classifications of lymphocytes (B cells and T cells). There are several subtypes of B cells and T cells and multiple interactions between them. For the sake of simplicity, just know that T cells control the immune reaction (regulatory t cells), assist the B cells (helper T cells) or have the ability to destroy cells that are infected or cancerous (cytotoxic T cells). B cells have the task of making antibodies, which are proteins (often y-shaped) that bind to a specific antigen. The antibodies cover the surface of the pathogen, which not only prevents it from binding to a healthy cell, but also marks the invader for destruction. Upon the first encounter with a germ, it can take several days to mount a full response. There are, however, memory cells of both the B and T varieties, which command a much faster and more impressive immune response when they encounter a repeat offender.

Sometimes the immune system responds to stimuli in an undesirable fashion. It may overreact to a non-pathogenic substance, like pollen, cat dander or peanut butter and cause an allergic reaction. There are also instances where the immune system mistakenly identifies certain normal cells as foreign material and runs amok attacking them. This results in autoimmune diseases like rheumatoid arthritis, lupus, and inflammatory bowel disease. Treatment of these conditions frequently relies on suppressing the immune system. The obvious downside to immunosuppression is increased susceptibility to other diseases. This is also a topic that deserves its own in-depth analysis – Immune Cells Gone Wild, so to speak.

What if you could receive the benefits of immunity without actually being exposed to disease-causing organisms? Believe it or not, your immune system can be trained in advance to recognize pathogens and produce antibodies at a moment’s notice if a particular germ is encountered. It’s the reward of memory cells without the risk of illness! This is the concept of vaccination, and it prevents serious illness (and, in some cases, death) for millions and millions and millions of people.

You already know that a vaccine is a substance used to stimulate the immune system and provide protection against a particular disease. You may also be aware that the name comes from the Latin name of cowpox (Variolae vaccinae). This is because the British physician Dr. Edward Jenner used pus from a cowpox lesion on a milkmaid’s hand to experimentally infect a child with that mild disease. This led to the boy (and subsequently millions of others based on this premise) to be protected from the deadly smallpox.

You are undoubtedly already aware that there have been some new developments in the vaccine realm. You may even be reading this while you are waiting in line to receive one. And while you may be relieved vaccines have become available to fight the latest pandemic, you may have some reservations regarding the speed of development. I would like to provide some insight on the processes involved.

Vaccines are often classified based on the particular particles they present to the immune system.

The modified live (also known as live attenuated) type contains a weakened version of the pathogen. While not strong enough to cause disease, it does trigger a response similar to that of a real infection. This results in the formation of the all-important memory cells. This creates strong and long-lasting protection as long as the recipient’s immune system is not compromised by other factors (for example if your entire immune system takes a holiday to watch Immune Cells Gone Wild). However, creating, mass producing and storing an appropriately disabled pathogen can be a difficult process. Vaccines of this type are the Measles/Mumps/Rubella combination used in people and canine parvovirus.

Inactivated vaccines use a killed germ. This eliminates the possibility of getting the disease from the shot, which is very important for diseases like rabies. It also does not elicit as robust a response as a live vaccine, so additional doses over time (booster shots) are usually necessary. The less than overwhelming response should come as no surprise to fans of Swiss Army Man.

Recombinant (or subunit) vaccines are genetically engineered to contain only part of the target pathogen. They usually require periodic boosters, but can be used safely in people with weakened immune systems. Included in this category are Hepatitis B and HPV in humans and canine Lyme disease.

In some cases, the vaccine does not target the germ itself. Toxoid vaccines are made from harmless versions of certain proteins (toxins) caused by things like tetanus and western diamondback rattlesnake venom.

The latest approaches to artificially providing immunity are the mRNA (messenger RNA, which is a single strand of DNA that contains the directions for making one type of protein) and DNA. These concepts have actually been in development for years but only recently found their niche. They work in a slightly different way than the previously mentioned types. These new vaccines contain viral genetic material that instructs your cells to make a protein found on the surface of the virus. They do not enter the nucleus of your cells or interact with your DNA, because that could potentially change your number of eyes or give you superpowers. You cannot get the actual disease, but responding to these proteins prepares your immune system for an encounter with it. One downside is that mRNA is meant to be used on a short-term basis and broken down by the cell after the code is read and the protein in question is produced; it is easily degraded and requires special maintenance. Vaccine preparation requires the mRNA be encased in a protective fatty barrier to be delivered into a cell. It also needs to be stored at a very low temperature so the mRNA does not break down before performing its intended task.

In the past, vaccine technology took years of research, development, preparation and testing before becoming available for mass distribution. The mumps vaccine went from virus isolation (from the researcher’s then 5-year-old daughter) to FDA approval in a mere four years. It also held this speed record until the Emergency Use Authorization for Covid-19 vaccine was issued in Dec 2020. Please note that an Emergency Use Authorization is not the same as a traditional approval. It is designed to make a product available to the public as soon as possible, based on the best available risk-vs-benefit data. The complete approval process usually entails following tens of thousands of clinical trial participants for a minimum of six months as well as inspection of the production facilities, a review of manufacturing plans, assessing the product’s stability and scrutinizing vast amounts of trial data. This investigation often takes a year or longer. This begs the question of whether the FDA’s approval process is too long and tedious or did companies cut corners and potentially endanger people by rushing a vaccine to market.

It is important to note that some of the increased speed of development is due to relatively recent technological advances. Isolation of a virus followed by the determination of its complete DNA sequence is routine nowadays. A vaccine based on genetic material instead of the whole virus also has some temporal advantages. It simply takes longer to grow enormous amounts of live pathogens in a lab than to reproduce a single strand of DNA on a large scale. There is also greater risk of the live pathogen infecting people in the lab (or escaping from the Army base where it is being developed). This applies to the research stage as well as the manufacturing of the finished product.

The new Covid-19 vaccines also followed a different timeline when it came to testing. Under normal circumstances, a vaccine is first subjected to pre-clinical tests in the lab (in both test tubes and in lab animals) to show safety and efficacy before advancing to clinical trials in humans.

In Phase I of the clinical trials the vaccine is administered to a small group of healthy adults who are at a low risk of getting the disease. While the primary objective of this stage is to assess safety, data relating to the immune response is also vital to the process. If the results are favorable, the vaccine candidate progresses to the next phase of trials.

Phase II takes place on a larger scale, using hundreds (or thousands) of people at multiple sites. The objective is to determine the optimal dose and schedule for administration of the vaccine, while continuing to monitor for side effects.

Phase III is designed to test the effect of the final formulation of the vaccine. They are conducted on thousands of subjects under conditions similar to the vaccines expected use.

Each of these phases normally takes at least a few months and each new phase does not begin until the previous one has been completed. In order to get vaccines distributed sooner, the pharmaceutical companies conducted the Covid- 19 trials concurrently instead of consecutively. They also started manufacturing the vaccines on a large scale before the customary point in the process, which could have been a large financial setback if their particular vaccine did not work as planned. Rest assured, Big Pharma came through unscathed.

The benefits of vaccines are well documented. They are, quite simply, decreased illness, suffering and death from certain diseases. In the case of smallpox, the disease has been eliminated from the face of the Earth. Polio, for which a vaccine has been available since 1955, could potentially be eradicatedwithin a few years. That would make it an endangered species, but it’s not nearly cute enough to be a World Wildlife Fund poster child. There may also be some nonspecific effects of vaccines, particularly the modified live variety. The stimulation of immune system in youngsters may help fight a range of diseases, not just the target of the vaccine, and decrease overall mortality.

Of course, no medical procedure is completely without risk. For vaccines, the most common side effects are mild and include things like pain, swelling and/or redness at the vaccination site. One may also experience mild fever, muscle or joint pain, headache, lethargy or chills. Severe reactions such as a life- threatening allergic reaction (anaphylactic shock), seizures and thrombocytopenia (lack of platelets in the blood) rarely occur.

There is also a small segment of the population for whom vaccination is ill- advised. This is primarily people whose immune systems cannot respond appropriately to a vaccine due to underlying disease or certain medications. Like a certain fading Southern belle, they depend on the kindness of strangers. They need all the healthy people around them to be vaccinated, which limits the disease’s potential to spread to them.

Thank you for joining me on this venture into the immunization process. I hope you enjoyed reading this and gleaned some useful information along the way.

Until next time, be excellent to each other.

Dr. Debbie Appleby