I mean the immunity that covers only one body part or skin area after exposure to the infection but does not cover the whole organism.
Immune systems of healthy adults 'remember' germs to which they’ve never been exposed, Stanford study finds
Mark Davis and his colleagues found that key immune cells in our bodies have "memories" of microbes they've never encountered.
It’s established dogma that the immune system develops a “memory” of a microbial pathogen, with a correspondingly enhanced readiness to combat that microbe, only upon exposure to it — or to its components though a vaccine. But a discovery by Stanford University School of Medicine researchers casts doubt on that dogma.
In a path-breaking study published online Feb. 7 in Immunity, the investigators found that over the course of our lives, CD4 cells — key players circulating in blood and lymph whose ability to kick-start the immune response to viral, bacterial, protozoan and fungal pathogens can spell the difference between life and death — somehow acquire memory of microbes that have never entered our bodies.
Several implications flow from this discovery, said the study’s senior author, Mark Davis, PhD, professor of microbiology and immunology and director of Stanford’s Institute for Immunity, Transplantation and Infection. In the study, newborns’ blood showed no signs of this enhanced memory, which could explain why young children are so much more vulnerable to infectious diseases than adults. Moreover, the findings suggest a possible reason why vaccination against a single pathogen, measles, appears to have reduced overall mortality among African children more than can be attributed to the drop in measles deaths alone. And researchers may have to rethink the relevance of experiments conducted in squeaky-clean facilities on mice that have never been exposed to a single germ in their lives.
“It may even provide an evolutionary clue about why kids eat dirt,” said Davis. “The pre-existing immune memory of dangerous pathogens our immune systems have never seen before might stem from our constant exposure to ubiquitous, mostly harmless micro-organisms in soil and food and on our skin, our doorknobs, our telephones and our iPod earbuds.”
CD4 cells are members of the immune club known as T cells. CD4 cells hang out in our circulatory system, on the lookout for micro-organisms that have found their way into the blood or lymph tissue.
In order to be able to recognize and then coordinate a response to a particular pathogen without inciting a Midas-touch overreaction to anything a CD4 cell bumps into (including our own tissues), our bodies have to host immensely diverse inventories of CD4 cells, each with its own narrow capacity to recognize one single pathogenic “body part” or, to be more scientific, epitope — and, it’s been believed, only that epitope. Contact with that epitope can cause a CD4 to whirr into action, replicating rapidly and performing the immunological equivalent of posting bulletins, passing out bullets and bellowing attack orders through a bullhorn to other immune cells. This hyperactivity is vital to the immune response. (It is CD4 cells that are targeted and ultimately destroyed by HIV, the virus responsible for AIDS.)
In the early 1980s, Davis, now the Burt and Marion Avery Family Professor of Immunology at Stanford, unraveled the mystery of how organisms such as ourselves, equipped with only 20,000 or so genes, can possibly generate the billions of differing epitope-targeting capabilities represented in aggregate by T cells. He found that highly reshufflable “hot spots” in a rapidly dividing T cell’s DNA trigger massive mix-and-match madness among these genetic components during cell division, so each resulting T cell sports its own unique variant of a crucial surface receptor and, therefore, is geared to recognizing a different epitope.
That variation accounts for our ability to mount an immune response to all kinds of microbial invaders, whether familiar or previously unseen. But it doesn’t account for the phenomenon of immune memory. CD4 cells, like other T cells, can be divided into two groups: so-called “naïve” CD4s randomly targeting epitopes belonging to pathogens they haven’t encountered yet and CD4s that, having had an earlier run-in with one or another bug, have never forgotten it. These latter CD4 cells are exceptionally long-lived and ultra-responsive to any new encounter with the same pathogen.
“When a naïve CD4 cell comes across its target pathogen, it takes days or even weeks before the immune system is full mobilized against that pathogen. But an activated-memory CD4 cell can cause the immune system to mount a full-blown response within hours,” said William Petri, MD, PhD, chief of infectious diseases and international health at the University of Virginia.
That’s why Petri, who was not involved in the study, thinks the newfound abundance in healthy adults, and total absence in newborns, of memory CD4 cells targeting microbes those individuals have never encountered before is so important. For the past 20 years, he has led a team conducting medical interventions in an urban slum in Dacca, the capital of Bangladesh. There, the average infant experiences a half-dozen diarrhea-inducing infections and as many upper-respiratory-tract infections within the first year of life, many of them within the first few months. The consequence, Petri said, is rampant malnutrition, with corresponding cognitive deficits and high mortality — this, despite the fact that Petri’s group provides free health-care and education services and visits homes twice a week.
“If I had lived in such a slum as a kid, I probably would have died of infection,” Petri said.
A sophisticated technique invented by Davis in 1996 and since refined in his and others’ laboratories permitted the Stanford team to identify a single CD4 cell targeting a particular epitope out of millions. Using this method, his team exposed immune-cell-rich blood drawn from 26 healthy adults, as well as from two newborns’ umbilical cords, to various epitopes from different viral strains. They were able to fish out, from among hundreds of millions of CD4 cells per sample, those responsive to each viral epitope.
Nearly all of the 26 adult blood samples contained cells responsive to HIV to HSV, the virus that causes herpes and to cytomegalovirus, a common infectious agent that often produces no symptoms but can be dangerous to immune-compromised people. This wasn’t surprising, given humans’ exhaustive inventories of divergent CD4-cell affinities.
What was surprising was that, on average, about half of the virus-responsive CD4 cells in each adult sample bore unmistakable signs of being in the “memory” state: a characteristic cell-surface marker, gene activation patterns typical of memory T cells, and rapid secretion of signature biochemical signals, called cytokines, that communicate with other immune cells — even though highly sensitive clinical tests showed that these individuals had never been exposed to any of these viruses in real life.
The newborns’ blood contained similar frequencies of CD4 cells responsive to the same three viruses. However, all these cells were in the “naïve” rather than memory state. “This could explain, at least in part, why infants are so incredibly susceptible to disease,” said the study’s first author, Laura Su, MD, PhD, an instructor in immunology and rheumatology.
Another surprise: About one-fifth of the adult samples boasted “cross-reactive” memory CD4 cells responsive to other harmless environmental microbes. For example, CD4 cells selected specifically for their reactivity to HIV turned out to be able to recognize a large number of common environmental microbes, including three gut-colonizing bacteria, a soil-dwelling bacterial species and a species of ocean algae. Considering that the investigators tested only a negligible fraction of all the microbes a person might encounter, it’s a sure bet that this measure of CD4-cell cross-reactivity was an underestimate.
Next, the researchers recruited two adults who hadn’t been vaccinated for flu in five years or longer, and then vaccinated them. In these volunteers, memory CD4s proliferated and otherwise became activated in response to exposure to certain components of the influenza virus, but also to epitopes of several different bacterial and protozoan microbes.
This cross-reactivity could explain why exposure to common bugs in the dirt and in our homes renders us less susceptible to dangerous infectious agents.
Which raises another point. “We grow and use experimental lab mice in totally artificial, ultra-clean environments,” Davis said. “That’s nothing like the environment that we live in. The CD4 cells from adult mice in the lab environment are almost entirely in the naïve state. They may be more representative of newborns than of adults.”
Petri described the new study as paradigm-shifting. “It was one of those rare, seminal findings that changes the way I think about the immune response,” he said.
Davis’ study offers hope that some of the immunity conferred by a vaccine extends beyond the specific microbe it targets, Petri said. “This adds support to the impetus to vaccinate infants in the developing world,” he said. As many as 30 different pathogens can cause diarrhea, so vaccinating small children against all of them — even if those vaccines existed — would require so many separate injections as to be logistically hopeless. Understanding the mechanism by which cross-reactivity occurs might further allow immunologists to develop “wide-spectrum vaccines” that cover a number of infectious organisms.
The study was funded by the National Institutes of Health (grants AR059760, DK007056-36 and AI057229) and the Howard Hughes Medical Institute. Other Stanford co-authors were senior bioinformatics specialist Brian Kidd, PhD clinical fellow Arnold Han, MD, PhD and biology undergraduate student Jonathan Kotzin.
Not so novel coronavirus?
At least six studies have reported T cell reactivity against SARS-CoV-2 in 20% to 50% of people with no known exposure to the virus.5678910
In a study of donor blood specimens obtained in the US between 2015 and 2018, 50% displayed various forms of T cell reactivity to SARS-CoV-2.511 A similar study that used specimens from the Netherlands reported T cell reactivity in two of 10 people who had not been exposed to the virus.7
In Germany reactive T cells were detected in a third of SARS-CoV-2 seronegative healthy donors (23 of 68). In Singapore a team analysed specimens taken from people with no contact or personal history of SARS or covid-19 12 of 26 specimens taken before July 2019 showed reactivity to SARS-CoV-2, as did seven of 11 from people who were seronegative against the virus.8 Reactivity was also discovered in the UK and Sweden.6910
Though these studies are small and do not yet provide precise estimates of pre-existing immunological responses to SARS-CoV-2, they are hard to dismiss, with several being published in Cell and Nature. Alessandro Sette, an immunologist from La Jolla Institute for Immunology in California and an author of several of the studies (box 1), told The BMJ, “At this point there are a number of studies that are seeing this reactivity in different continents, different labs. As a scientist you know that is a hallmark of something that has a very strong footing.”
Swine flu déjà vu
In late 2009, months after the World Health Organization declared the H1N1 “swine flu” virus to be a global pandemic, Alessandro Sette was part of a team working to explain why the so called “novel” virus did not seem to be causing more severe infections than seasonal flu.12
Their answer was pre-existing immunological responses in the adult population: B cells and, in particular, T cells, which “are known to blunt disease severity.”12 Other studies came to the same conclusion: people with pre-existing reactive T cells had less severe H1N1 disease.1314 In addition, a study carried out during the 2009 outbreak by the US Centers for Disease Control and Prevention reported that 33% of people over 60 years old had cross reactive antibodies to the 2009 H1N1 virus, leading the CDC to conclude that “some degree of pre-existing immunity” to the new H1N1 strains existed, especially among adults over age 60.15
The data forced a change in views at WHO and CDC, from an assumption before 2009 that most people “will have no immunity to the pandemic virus”16 to one that acknowledged that “the vulnerability of a population to a pandemic virus is related in part to the level of pre-existing immunity to the virus.”17 But by 2020 it seems that lesson had been forgotten.
Researchers are also confident that they have made solid inroads into ascertaining the origins of the immune responses. “Our hypothesis, of course, was that it’s so called ‘common cold’ coronaviruses, because they’re closely related,” said Daniela Weiskopf, senior author of a paper in Science that confirmed this hypothesis.18 “We have really shown that this is a true immune memory and it is derived in part from common cold viruses.” Separately, researchers in Singapore came to similar conclusions about the role of common cold coronaviruses but noted that some of the T cell reactivity may also come from other unknown coronaviruses, even of animal origin.8
Taken together, this growing body of research documenting pre-existing immunological responses to SARS-CoV-2 may force pandemic planners to revisit some of their foundational assumptions about how to measure population susceptibility and monitor the extent of epidemic spread.
Studies suggest people who recovered from COVID could have long-lasting immunity
NEW YORK -- Two encouraging studies suggest that people who recovered from COVID-19 had immune responses to the virus long after antibodies faded, even up to one year later.
The findings may help put to rest lingering fears that protection against the virus will be short-lived.
Researchers in both studies examined bone marrow in volunteers who had been exposed to the coronavirus about a year earlier. They found that a part of the immune system called "B cells" seemed to stick around, providing the body with a biological "memory" of a coronavirus infection.
The study published online at BioRxiv, a site for biology research, found that these B cells continued to grow and strengthen at least 12 months later.
Health officials have emphasized for months that COVID-19 vaccinations turbo-charge the body's antibody response. In essence, a shot gives the body more antibodies than a natural infection would, and more antibodies are usually associated with longer protection, said Dr. William Schaffner, a professor in the Department of Health Policy at Vanderbilt University.
Experts, however, have no way to definitely know now how long protection from coronavirus lasts, as the virus is new and therefore hasn't been studied over long periods of time. While the findings are optimistic, these studies also don't take virus variants into account, Schaffner said.
And just because the studies show evidence of long-lasting immune responses doesn't mean experts know how long complete protection lasts, said Dr. Dan Barouch from Beth Israel's Center for Virology and Vaccine Research.
This means that despite promising results, booster shots may still be needed.
"I don't anticipate that the durability of the vaccine protection is going to be infinite. It's just not, so I would imagine we will need at some time a booster," Dr. Anthony Fauci, the nation's top infectious disease expert, said Wednesday during a Senate hearing.
Instead, blood levels of antibodies fall sharply following acute infection, while memory B cells remain quiescent in the bone marrow, ready to take action when needed.
Dr. Ellebedy’s team obtained bone marrow samples from 19 people roughly seven months after they had been infected. Fifteen had detectable memory B cells, but four did not, suggesting that some people might carry very few of the cells or none at all.
“It tells me that even if you got infected, it doesn’t mean that you have a super immune response,” Dr. Ellebedy said. The findings reinforce the idea that people who have recovered from Covid-19 should be vaccinated, he said.
Five of the participants in Dr. Ellebedy’s study donated bone marrow samples seven or eight months after they were initially infected and again four months later. He and his colleagues found that the number of memory B cells remained stable over that time.
The results are particularly noteworthy because it is difficult to get bone marrow samples, said Jennifer Gommerman, an immunologist at the University of Toronto who was not involved in the work.
A landmark study in 2007 showed that antibodies in theory could survive decades, perhaps even well beyond the average life span, hinting at the long-term presence of memory B cells. But the new study offered a rare proof of their existence, Dr. Gommerman said.
Dr. Nussenzweig’s team looked at how memory B cells mature over time. The researchers analyzed blood from 63 people who had recovered from Covid-19 about a year earlier. The vast majority of the participants had mild symptoms, and 26 had also received at least one dose of either the Moderna or the Pfizer-BioNTech vaccine.
So-called neutralizing antibodies, needed to prevent reinfection with the virus, remained unchanged between six and 12 months, while related but less important antibodies slowly disappeared, the team found.
As memory B cells continued to evolve, the antibodies they produced developed the ability to neutralize an even broader group of variants. This ongoing maturation may result from a small piece of the virus that is sequestered by the immune system — for target practice, so to speak.
A year after infection, neutralizing activity in the participants who had not been vaccinated was lower against all forms of the virus, with the greatest loss seen against the variant first identified in South Africa.
Vaccination significantly amplified antibody levels, confirming results from other studies the shots also ramped up the body’s neutralizing ability by about 50-fold.
Senator Rand Paul, Republican of Kentucky, said on Sunday that he would not get a coronavirus vaccine because he had been infected in March of last year and was therefore immune.
But there is no guarantee that such immunity will be powerful enough to protect him for years, particularly given the emergence of variants of the coronavirus that can partially sidestep the body’s defenses.
The results of Dr. Nussenzweig’s study suggest that people who have recovered from Covid-19 and who have later been vaccinated will continue to have extremely high levels of protection against emerging variants, even without receiving a vaccine booster down the line.
“It kind of looks exactly like what we would hope a good memory B cell response would look like,” said Marion Pepper, an immunologist at the University of Washington in Seattle who was not involved in the new research.
The experts all agreed that immunity is likely to play out very differently in people who have never had Covid-19. Fighting a live virus is different from responding to a single viral protein introduced by a vaccine. And in those who had Covid-19, the initial immune response had time to mature over six to 12 months before being challenged by the vaccine.
“Those kinetics are different than someone who got immunized and then gets immunized again three weeks later,” Dr. Pepper said. “That’s not to say that they might not have as broad a response, but it could be very different.”
Macrophages: The 'defense' cells that help throughout the body
The term "macrophage" conjures images of a hungry white blood cell gobbling invading bacteria. However, macrophages do much more than that: Not only do they act as antimicrobial warriors, they also play critical roles in immune regulation and wound-healing. They can respond to a variety of cellular signals and change their physiology in response to local cues.
David Mosser, Professor of Cell Biology and Molecular Genetics at the University of Maryland's College of Chemical and Life Sciences, will discuss the three primary duties of macrophages at the 2010 American Physiological Society conference, Inflammation, Immunity, and Cardiovascular Disease, in Westminster Colorado, August 25-28. The full conference program can be found at http://the-aps.org/meetings/aps/inflammation/.
"There has been a huge outpouring of research about host defense that has overshadowed the many diverse activities that these cells do all the time," said Dr. Mosser. "We'd like to dispel the narrow notion that most people have that macrophages' only role is defense, and expand it to include their role in homeostasis."
Macrophages exist in nearly all tissues and are produced when white blood cells called monocytes leave the blood and differentiate in a tissue-specific manner. The type of macrophage that results from monocyte differentiation depends on the type(s) of cytokines that these cells encounter. Cytokines are proteins produced by immune cells that can influence cell behavior and affect interactions between cells. For example, macrophages that battle microbial invaders arise in response to interferon-&gamma, a cytokine that is produced during a cellular immune response involving helper T-cells and the factors they produce. These macrophages are considered to be "classically activated."
However, when monocytes differentiate in response to stimuli such as prostaglandins or glucocorticoids, the resulting macrophages will assume a "regulatory" phenotype. Alternately, wound-healing macrophages arise when monocytes differentiate in response to interleukin-4, a cytokine which is released during tissue injury.
According to Dr. Mosser, macrophages can change their physiology and switch types. For example, in healthy, non-obese people, macrophages in fat tend to function as wound-healing macrophages. They are also thought to maintain insulin sensitivity in adipose cells. However, should an individual become obese, macrophages in fat will instead promote inflammation and cause the adipose cells to become resistant to insulin.
Immune-regulating macrophages produce high levels of the cytokine interleukin-10, which helps suppress the body's immune response. Suppressing an immune response may seem counter-intuitive, but in the later stages of immunity it comes in handy because it limits inflammation.
According to Dr. Mosser, immune-regulating macrophages may hold the key to developing treatments for autoimmune diseases such as multiple sclerosis or rheumatoid arthritis. The focus of new research is on reprogramming the macrophages to assume a regulatory phenotype and prevent autoimmunity, he said.
There is broad potential for exploiting different stages of macrophage activation, Dr. Mosser added. "It might be possible to manipulate macrophages to make better vaccines, prevent immunosuppression, or develop novel therapeutics that promote anti-inflammatory immune responses."
The release of interleukin-4 in response to tissue injury not only results in macrophages that specialize in wound-healing, it allows the macrophages to convert arginine to ornithine, which is a precursor of polyamines and collagen. Both polyamines and collagen are instrumental to the formation and maintenance of extracellular matrix, the material between cells that gives them structural support.
Certain harmful microbes, such as the tropical parasite Leishmania spp., can exploit wound-healing macrophages, said Dr. Mosser. "If you have a macrophage whose job it is to promote wound-healing, that macrophage will not be capable of killing microbes," he said. "The microbe can enter the macrophage and survive inside, which is not good for the human host."
Infection with Leishmania spp. causes leishmaniasis, which is characterized by skin sores and ulcers and can enlarge the spleen, damage the liver, and cause anemia. At worst, it can decrease immunity and leave victims vulnerable to potentially fatal opportunistic infections. Survivors can suffer from immune reconstitution inflammatory syndrome, in which their recovering immune systems go overboard in response to infection and create an inflammatory response that makes symptoms even worse. Understanding how Leishmania exploits macrophages has led to a better understanding of how macrophages function in health and disease. It has also stressed the importance of treating infections early, before the bugs can wreak havoc on the immune system.
Materials provided by American Physiological Society. Note: Content may be edited for style and length.
Seeking medical attention
Naturally, it's important that you still take precautions to avoid contracting coronavirus, even if you have a really healthy immune system. Follow the latest guidance from Public Health England which currently states that people who are well should only leave their home for few, very specific reasons. If you do have to go out, practise social distancing to avoid coming into contact with people who may be ill.
If you need to see a GP, take note of the latest guidance from your practice or local pharmacy or on their website. Some surgeries have stopped face-to-face appointments and are turning to video or telephone appointments. Others have switched off online appointment booking. Many non-urgent appointments will be cancelled as GP practices are overrun as a result of the pandemic.
If you need medication, pharmacies are functioning as usual but will be busier than they normally are. If you are self-isolating or can't attend in person to pick up your prescription, ask someone to pick it up on your behalf. Some pharmacies are still able to offer a home delivery service.
If you experience any symptoms of fever or new, continuous cough, self-isolate and avoid all contact with other people until you have used Patient's coronavirus checker tool to find out what to do next.
Natural and acquired immunity
Every animal species possesses some natural resistance to disease. Humans have a high degree of resistance to foot-and-mouth disease, for example, while the cattle and sheep with which they may be in close contact suffer in the thousands from it. Rats are highly resistant to diphtheria, whereas unimmunized children readily contract the disease.
What such resistance depends on is not always well understood. In the case of many viruses, resistance is related to the presence on the cell surface of protein receptors that bind to the virus, allowing it to gain entry into the cell and thus cause infection. Presumably, most causes of absolute resistance are genetically determined it is possible, for example, to produce by selective breeding two strains of rabbits, one highly susceptible to tuberculosis, the other highly resistant. In humans there may be apparent racial differences, but it is always important to disentangle such factors as climate, nutrition, and economics from those that might be genetically determined. In some tropical and subtropical countries, for example, poliomyelitis is a rare clinical disease, though a common infection, but unimmunized visitors to such countries often contract serious clinical forms of the disease. The absence of serious disease in the residents is due not to natural resistance, however, but to resistance acquired after repeated exposure to poliovirus from infancy onward. Unimmunized visitors from other countries, with perhaps stricter standards of hygiene, are protected from such immunizing exposures and have no acquired resistance to the virus when they encounter it as adults.
Natural resistance, in contrast to acquired immunity, does not depend upon such exposures. The human skin obviously has great inherent powers of resistance to infection, for most cuts and abrasions heal quickly, though often they are smothered with potentially pathogenic microorganisms. If an equal number of typhoid bacteria are spread on a person’s skin and on a glass plate, those on the skin die much more quickly than do those on the plate, suggesting that the skin has some bactericidal property against typhoid germs. The skin also varies in its resistance to infectious organisms at different ages: impetigo is a common bacterial infection of children’s skin but is rarer in adults, and acne is a common infection of the skin of adolescents but is uncommon in childhood or in older adults. The phenomenon of natural immunity can be illustrated equally well with examples from the respiratory, intestinal, or genital tracts, where large surface areas are exposed to potentially infective agents and yet infection does not occur.
If an organism causes local infection or gains entry into the bloodstream, a complicated series of events ensues. These events are described in detail in the article immune system, but they can be summarized as follows: special types of white blood cells called polymorphonuclear leukocytes or granulocytes, which are normally manufactured in the bone marrow and which circulate in the blood, move to the site of the infection. Some of these cells reach the site by chance, in a process called random migration, since almost every body site is supplied constantly with the blood in which these cells circulate. Additional granulocytes are attracted and directed to the sites of infection in a process called directed migration, or chemotaxis.
When a granulocyte reaches the invading organism, it attempts to ingest the invader. Ingestion of bacteria may require the help of still other components of the blood, called opsonins, which act to coat the bacterial cell wall and prepare it for ingestion. An opsonin generally is a protein substance, such as one of the circulating immunoglobulins or complement components.
Once a prepared bacterium has been taken inside the white blood cell, a complex series of biochemical events occurs. A bacterium-containing vacuole (phagosome) may combine with another vacuole that contains bacterial-degrading proteins (lysozymes). The bacterium may be killed, but its products pass into the bloodstream, where they come in contact with other circulating white blood cells called lymphocytes. Two general types of lymphocytes—T cells and B cells—are of great importance in protecting the human host. When a T cell encounters bacterial products, either directly or via presentation by a special antigen-presenting cell, it is sensitized to recognize the material as foreign, and, once sensitized, it possesses an immunologic memory. If the T cell encounters the same bacterial product again, it immediately recognizes it and sets up an appropriate defense more rapidly than it did on the first encounter. The ability of a T cell to function normally, providing what is generally referred to as cellular immunity, is dependent on the thymus gland. The lack of a thymus, therefore, impairs the body’s ability to defend itself against various types of infections.
After a T cell has encountered and responded to a foreign bacterium, it interacts with B cells, which are responsible for producing circulating proteins called immunoglobulins or antibodies. There are various types of B cells, each of which can produce only one of the five known forms of immunoglobulin (Ig). The first immunoglobulin to be produced is IgM. Later, during recovery from infection, the immunoglobulin IgG, which can specifically kill the invading microorganism, is produced. If the same microorganism invades the host again, the B cell immediately responds with a dramatic production of IgG specific for that organism, rapidly killing it and preventing disease.
In many cases, acquired immunity is lifelong, as with measles or rubella. In other instances, it can be short-lived, lasting not more than a few months. The persistence of acquired immunity is related not only to the level of circulating antibody but also to sensitized T cells (cell-mediated immunity). Although both cell-mediated immunity and humoral (B-cell) immunity are important, their relative significance in protecting a person against disease varies with particular microorganisms. For example, antibody is of great importance in protection against common bacterial infections such as pneumococcal pneumonia or streptococcal disease and against bacterial toxins, whereas cell-mediated immunity is of greater importance in protection against viruses such as measles or against the bacteria that cause tuberculosis.
How one local man's immunity to ticks could save us all
Richard Ostfeld says he is lucky to have been bitten by ticks so much.
That's because now, when a tick bites him, it usually dies.
Ostfeld is a disease ecologist at the Cary Institute of Ecosystem Studies in Millbrook. For decades, he has studied ticks and tick-borne diseases, primarily in the forests and fields of the mid-Hudson Valley.
Dr. Richard Ostfeld surveys ticks collected on a white drag cloth at a field site on the Cary Institute’s campus. (Photo: Sam Cillo/Cary Institute of Ecosystem Studies)
During the Poughkeepsie Journal's forum on Lyme disease last month, Ostfeld told the overflow audience at Marist College that he has been bitten so frequently by ticks over the years, he has developed an acquired immunity to the bite itself.
"I develop a burning, itching feeling that wakes me up in the middle of the night, even if it is just a tiny, little larva," he said.
Most of the time, the offending tick is dead. If not, its minutes are numbered.
All of this happens just as the tick is beginning to feed, he said.
Ostfeld ends up with a welt lasting for days. But the ticks never get much of a chance to pass along any disease.
Ostfeld said there are studies suggesting the same thing happens in animals. Some critters develop an immune response that attacks certain proteins in the ticks' saliva.
"And the feeding success by the ticks goes plummeting," he said. "It goes down at different rates depending on the host, and depending on how many times the host has been exposed."
All of this suggests, Ostfeld said, that there is potential for a vaccine to trick our immune system into thinking that it has been exposed in the past.
"That is what vaccines do," he said. "So there is every biological reason to expect that an anti-tick vaccine could be developed for people."
In 2013, scientists funded by the European Union began an effort to do just that.
The idea here is to create a vaccine that will stop the tick from being able to transmit the disease by undermining proteins in its saliva.
If you can do that, you can potentially stop not only the spread of Lyme disease, but also the increasing number of more deadly diseases such as those caused by the Powassan virus.
Vaccines, as Ostfeld warned, are tricky things.
It's hard not only to predict how a potential vaccine may behave, but also how it will be received by the public.
There remains, among many, an aversion to vaccines of any kind, based on an often misguided belief that the vaccines cause dangerous side effects. The debate following the recent measles outbreak comes to mind here.
That's what happened with the last Lyme vaccine.
Lymerix was approved and released in 1998 and gone — off the market — in fewer than four years.
Some believed the vaccine caused early onset arthritis, and that in turn led to a class-action lawsuit.
Its maker pulled the vaccine, citing poor sales, despite the fact that a 2001 U.S. Food and Drug Administration study found no link between Lymerix and early or late onset arthritis.
Sometimes, it doesn't matter what the science says.
During the Journal's forum, it was fascinating to watch how much of the discussion was focused on all of the issues surrounding the treatment of Lyme disease.
You had questions about doctors, treatment guidelines, medical politics, insurance coverage — you name it.
It’s human nature, after all. You are in pain. You want the pain to go away.
But far too few of the audience's questions were aimed at how to ensure the pain never gets there in the first place.
These include not only a vaccine that would defeat a tick's ability to transmit the disease, but other efforts such as tick-control measures or even longer-term things like fostering biodiversity, which has been linked to lower rates of tick-borne diseases.
So how much lower is the herd immunity threshold when you’re talking about a virus spreading in the wild, like the current pandemic?
According to the standard models, about 60% of the U.S. population would need to be vaccinated against COVID-19 or recover from it to slow and ultimately stop the spread of the disease. But many experts I talked to suspect that the herd immunity threshold for naturally acquired immunity is lower than that.
“My guess would be it’s potentially between 40 and 50%,” Pitzer said.
Lipsitch agrees: “If I had to make a guess, I’d probably put it at about 50%.”
These are mostly just educated estimates, because it’s so hard to quantify what makes one person more susceptible than another. Many of the characteristics you might think to assign someone — like how much social distancing they’re doing — can change from week to week.
“The whole heterogeneity problem only works if the sources of heterogeneity are long-term properties of a person. If it’s being in a bar, that’s not in itself sustained enough to be a source of heterogeneity,” Lipsitch said.
Heterogeneity may be hard to estimate, but it’s also an important factor in determining what the herd immunity threshold really is. Langwig believes that the epidemiological community hasn’t done enough to try and get it right.
“We’ve kind of been a little sloppy in thinking about herd immunity,” she said. “This variability really matters, and we need to be careful to be more accurate about what the herd immunity threshold is.”
Some recent papers have tried. In June the journal Science published a study that incorporated a modest degree of heterogeneity and estimated the herd immunity threshold for COVID-19 at 43% across broad populations. But one of the study’s co-authors, Tom Britton of Stockholm University, thinks there are additional sources of heterogeneity their model doesn’t account for.
“If anything, I’d think the difference is bigger, so that in fact the herd immunity level is probably a bit smaller than 43%,” Britton said.
Another new study takes a different approach to estimating differences in susceptibility to COVID-19 and puts the herd immunity threshold even lower. The paper’s 10 authors, who include Gomes and Langwig, estimate that the threshold for naturally acquired herd immunity to COVID-19 could be as low as 20% of the population. If that’s the case, the hardest-hit places in the world may be nearing it.
“We’re getting to the conclusion that the most affected regions like Madrid may be close to reaching herd immunity,” said Gomes. An early version of the paper was posted in May, and the authors are currently working on an updated version, which they anticipate posting soon. This version will include herd immunity estimates for Spain, Portugal, Belgium and England.
Many experts, however, consider these new studies — not all of which have been peer-reviewed yet — to be unreliable.
In a Twitter thread in May, Dean emphasized that there’s too much uncertainty around basic aspects of the disease — from the different values of R0 in different settings to the effects of relaxing social distancing — to place much confidence in exact herd immunity thresholds. The threshold could be one number as long as a lot of people are wearing masks and avoiding large gatherings, and another much higher number if and when people let their guard down.
Other epidemiologists are also skeptical of the low numbers. Jeffrey Shaman of Columbia University said that 20% herd immunity “is not consistent with other respiratory viruses. It’s not consistent with the flu. So why would it behave differently for one respiratory virus versus another? I don’t get that.”
Miller added, “I think the herd immunity threshold [for naturally acquired immunity] is less than 60%, but I don’t see clear evidence that any [place] is close to it.”
Ultimately, the only way to truly escape the COVID-19 pandemic is to achieve large-scale herd immunity — everywhere, not just in a small number of places where infections have been highest. And that will likely only happen once a vaccine is in widespread use.
In the meantime, to prevent the spread of the virus and lower that R0 value as much as possible, distancing, masks, testing and contact tracing are the order of the day everywhere, regardless of where you place the herd immunity threshold.
“I can’t think of any decision I’d make differently right now if I knew herd immunity was somewhere else in the range I think it is, which is 40-60%,” said Lipsitch.
Shaman, too, thinks that uncertainty about the naturally acquired herd immunity threshold, combined with the consequences for getting it wrong, leaves only one path forward: Do our best to prevent new cases until we can introduce a vaccine to bring about herd immunity safely.
“The question is: Could New York City support another outbreak?” he said. “I don’t know, but let’s not play with that fire.”