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Can virus resistance be acquired through generational exposure?

Can virus resistance be acquired through generational exposure?



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If I have a squash plant that has a mosaic virus of some kind, and I breed its descendants (via seed) for generations, each with exposure to the same virus, will future generations be likely to eventually obtain resistance to the virus, and if so, how long would this typically take?

It seems to me that this might be how the resistant plants would have first developed resistance, but I could be wrong.


Perhaps the answer is in natural selection. Over many generations, if these plants are constantly exposed to the same virus, one of them may obtain a mutation or something similar that allows it to be resistant, thus that plant will have higher survival and growth rate and thus more seeds.

The current plant itself may also adapt to the presence of this virus (perhaps in growth patterns, etc.) over a long period of time.

As for the time for the genetic resistance to take place, it is almost impossible to say as it is almost completely random (and would also depend on what other plants you may pollinate it with as an already resistant plant would, of course, cancel the need for a mutation).

I hope this helps.


Substantial Resistance To HIV Infection Tied To Genetic Mutation

Scientists have found that people who carry one copy of a mutation that protects cells against HIV infection may be partially resistant to the virus causing AIDS. The new finding is reported in a study by a multi-center research consortium that included institutions in New York City, Boston, Seattle, and San Francisco.

"We looked for this mutation in a large cohort of high-risk people who were HIV-negative. We found that bisexual and homosexual Caucasian men with one copy of the mutation had a 70% reduced risk of HIV infection compared with men who didn't carry the mutation at all," says Michael Marmor, Ph.D., Professor of Environmental Medicine and Medicine at New York University School of Medicine, the first author of the study. In previous studies it had been established that men with two mutant copies of the CCR5 gene had even stronger resistance to HIV infection

"Our finding suggests that strategies to prevent HIV infection by blocking receptors used by the virus need not block all of the receptors," says Dr. Marmor. "Reducing the number of receptor sites per cell may be adequate to provide an imperfect but important degree of protection."

There are thousands to tens of thousands of CCR5 receptors on the surface of a subset of immune cells called T-helper cells. In people with two copies of the delta-32 mutation there are no functional CCR5 receptors on these cells.

In order for HIV, the virus causing AIDS, to enter cells it usually must fuse with a receptor called CCR5 that sits on the surface of T-helper immune cells. The delta-32 mutation in the gene encoding the CCR5 protein results in a defective receptor site that blocks entry of the virus. People who carry two copies of the mutation, one from each parent, are resistant to HIV infection despite repeated exposures to the virus. People who carry one copy of the mutation, the study concludes, also may be substantially resistant.

Every gene has two alleles, or forms, one inherited from each parent. People who carry a gene with the same alleles are called homozygotes for a particular trait. People who carry a gene with two different alleles are called heterozygotes.

It has been known for several years that around one percent of Caucasians are genetically resistant to HIV because they are homozygous for the CCR5 mutation, meaning they have inherited two copies of the mutation, one from each parent. "These people, however, are not resistant to all strains of HIV," warns Dr. Marmor. "They should avoid behaviors that might expose them to relatively uncommon HIV strains that use receptors other than CCR5 to gain entry into cells."

Prior research had established that HIV-infected people who are heterozygous for the mutation progress to full-blown AIDS more slowly than people with no copies of the mutation. But it was unclear to what extent people with one copy of the mutation were protected against HIV infection.

The new study suggests that people with one copy of the mutation do have some protection against infection. It prospectively monitored a large cohort of bisexual and homosexual men to see how their CCR5 status correlated with the incidence of HIV infections.

The study, published in the current issue of the Journal of Acquired Immune Deficiency Syndromes, helps fill in the missing information about resistance to HIV infection among men at high risk of infection. The report also contained data on injection-drug users and women at sexual risk of HIV infection.

The study analyzed the prevalence of homozygotes and heterozygotes for the CCR5 mutation among 2,996 individuals, including 1,892 gay men, 474 male injection drug users, 283 female drug users, and 347 women at heterosexual risk of HIV infection. The men in the study were followed for 18 months. They had their blood tested for HIV every six months, and they responded to questionnaires that asked about their behaviors during the course of the study. The women were followed for 24 months, but too few were enrolled to yield statistically significant results.

Among the men, the study found that 40, or 1.3 percent, were homozygous, 387, or 12.9 percent, were heterozygous for the CCR5-delta-32 mutation, and 2,569 had no copies of the mutation. Men who were heterozygotes had a 70 percent reduced risk of HIV infection compared with men who did not carry the mutation. A total of 45 individuals during the course of the study became infected with HIV.

The data also revealed that 10.5 percent of white gay men in the study who were age 45 or older and who lived in San Francisco or New York City, and were HIV negative in 1995, were homozygous for the CCR5-delta-32 mutation. This observation, says Dr. Marmor, underscores the survival advantage provided by the homozygous mutation. Only one percent of Caucasians in the general population would be expected to be homozygous for the mutation.

The study cohort is culled from the larger HIVNET Vaccine Preparedness Study, which enrolled 4,892 people who were HIV negative, but had histories of behaviors that placed them at high risk of infection. Study sites were in Boston, Chicago, New York City, Philadelphia, Providence, San Francisco, and Seattle.

In addition to the lead investigator, Dr. Michael Marmor of the NYU School of Medicine, the study's co-authors include: Haynes W. Sheppard, Ph.D., of the California Department of Health Services, Berkeley Deborah Donnell, Ph.D., of the Fred Hutchinson Cancer Research Center, Seattle Sam Bozeman, Ph.D., of ABT Associates, Cambridge, MA Connie Celum, M.D., of University of Washington, Seattle Susan Buchbinder, M.D., of the San Francisco Department of Health Beryl Koblin, Ph.D., of the New York Blood Center, New York and George R. Seage III, D.Sc., of the Harvard University School of Public Health, Boston.

The study was supported by the National Institute of Allergy and Infectious Diseases, a component of the National Institutes


SARS-CoV-2 Could Evolve Resistance, Rendering COVID-19 Vaccines Ineffective

The series of illustrations on this page are a schematic illustrating three ways that standard samples from COVID-19 clinical trials can be repurposed to assess the risk that vaccine resistance will evolve. 1. The complexity of B-cell and T-cell responses can be measured using blood samples. Different neutralizing antibodies are depicted above in different colors. More complex responses indicate more evolutionarily robust immunity. Credit: Kennedy et al, 2020 (PLOS Biology, CC BY 4.0)

Similar to bacteria evolving resistance to antibiotics, viruses can evolve resistance to vaccines, and the evolution of SARS-CoV-2 could undermine the effectiveness of vaccines that are currently under development, according to a paper published today (November 9, 2020) in the open-access journal PLOS Biology by David Kennedy and Andrew Read from Pennsylvania State University, USA. The authors also offer recommendations to vaccine developers for minimizing the likelihood of this outcome.

“A COVID-19 vaccine is urgently needed to save lives and help society return to its pre-pandemic normal,” said David Kennedy, assistant professor of biology. “As we have seen with other diseases, such as pneumonia, the evolution of resistance can quickly render vaccines ineffective. By learning from these previous challenges and by implementing this knowledge during vaccine design, we may be able to maximize the long-term impact of COVID-19 vaccines.”

2. The effect of vaccination on transmission potential can be assessed by collecting viral titer data using routine nasal swabs. Plaque assays from multiple vaccinated and control individuals are compiled into a histogram. Undetectable viral titers suggest little or no transmission potential, due to either complete immune protection or the absence of exposure. High viral titers suggest high transmission potential due to the absence of a protective immune response. Intermediate viral titers, marked above with an asterisk, suggest moderate transmission potential due to partial vaccine protection. Intermediate titers indicate an increased risk for resistance evolution since pathogen diversity can be generated within hosts and selection can act during transmission between hosts. Credit: Kennedy et al, 2020 (PLOS Biology, CC BY 4.0)

The researchers specifically suggest that the standard blood and nasal-swab samples taken during clinical trials to quantify individuals’ responses to vaccination may also be used to assess the likelihood that the vaccines being tested will drive resistance evolution. For example, the team proposes that blood samples can be used to assess the redundancy of immune protection generated by candidate vaccines by measuring the types and amounts of antibodies and T-cells that are present.

“Much like how combination antibiotic therapy delays the evolution of antibiotic resistance, vaccines that are designed to induce a redundant immune response — or one in which the immune system is encouraged to target multiple sites, called epitopes — on the virus’s surface, can delay the evolution of vaccine resistance,” said Andrew Read, Evan Pugh Professor of Biology and Entomology and director of the Huck Institutes of the Life Sciences. “That’s because the virus would have to acquire several mutations, as opposed to just one, in order to survive the host immune system’s attack.”

3. Pre-existing variation for vaccine resistance can be assessed by recovering genome sequences from nasopharyngeal swabs of symptomatic COVID-19 cases included in the study. In a placebo controlled, double blind study, any significant differences in the genome sequences of samples from vaccinated and control individuals would suggest at least partial vaccine resistance. Credit: Kennedy et al, 2020 (PLOS Biology, CC BY 4.0)

The researchers also recommend that nasal swabs typically collected during clinical trials may be used to determine the viral titer, or amount of virus present, which can be considered a proxy for transmission potential. They noted that strongly suppressing virus transmission through vaccinated hosts is key to slowing the evolution of resistance, since it minimizes opportunities for mutations to arise and reduces opportunities for natural selection to act on those mutations that do arise.

In addition, the team suggests that the genetic data acquired through nasal swabs can be used to examine whether vaccine-driven selection has occurred. For example, differences in alleles, or forms of genes that arise from mutations, between the viral genomes collected from vaccinated versus unvaccinated individuals would indicate that selection has taken place.

“According to the World Health Organization, at least 198 COVID-19 vaccines are in the development pipeline, with 44 currently undergoing clinical evaluation,” said Kennedy. “We suggest that the risk of resistance be used to prioritize investment among otherwise similarly promising vaccine candidates.”


What is transgenerational epigenetic inheritance?

Transgenerational inheritance can occur through epigenetic, ecological, or cultural mechanisms (See Figure 1 of the linked paper below).

Transgenerational inheritance systems. a Offspring inherit from their parents genes (black), the environment (green) and culture (blue). Genes and the environment affect the epigenome (magenta) and the phenotype22. Culture also affects the phenotype, but at present there is no evidence for a direct effect of culture on the epigenome (broken blue lines). It is a matter of debate, how much epigenetic information is inherited through the germline (broken magenta lines). G genetic variant, E epigenetic variant.


Study Shows How Effects of Starvation Can Be Passed to Future Generations

NEW YORK, NY (July 17, 2014) — Evidence from human famines and animal studies suggests that starvation can affect the health of descendants of famished individuals. But how such an acquired trait might be transmitted from one generation to the next has not been clear. A new study, involving roundworms, shows that starvation induces specific changes in so-called small RNAs and that these changes are inherited through at least three consecutive generations, apparently without any DNA involvement. The study, conducted by Columbia University Medical Center (CUMC) researchers, offers intriguing new evidence that the biology of inheritance is more complicated than previously thought. The study was published in the July 10 online edition of the journal Cell.

The idea that acquired traits can be inherited dates back to Jean Baptiste Larmarck (1744–1829), who proposed that species evolve when individuals adapt to their environment and transmit the acquired traits to their offspring. According to Lamarckian inheritance, for example, giraffes developed elongated long necks as they stretched to feed on the leaves of high trees, an acquired advantage that was inherited by subsequent generations. In contrast, Charles Darwin (1809–82) later theorized that random mutations that offer an organism a competitive advantage drive a species’ evolution. In the case of the giraffe, individuals that happened to have slightly longer necks had a better chance of securing food and thus were able to have more offspring. The subsequent discovery of hereditary genetics supported Darwin’s theory, and Lamarck’s ideas faded into obscurity.

“However, events like the Dutch famine of World War II have compelled scientists to take a fresh look at acquired inheritance,” said study leader Oliver Hobert, PhD, professor of biochemistry and molecular biophysics and a Howard Hughes Medical Institute Investigator at CUMC. Starving women who gave birth during the famine had children who were unusually susceptible to obesity and other metabolic disorders, as were their grandchildren. Controlled animal experiments have found similar results, including a study in rats demonstrating that chronic high-fat diets in fathers result in obesity in their female offspring.

In a 2011 study, Oded Rechavi, a postdoctoral fellow in Dr. Hobert’s laboratory, found that roundworms (C. elegans) that developed resistance to a virus were able to pass along that immunity to their progeny for many consecutive generations. The immunity was transferred in the form of small viral-silencing RNAs working independently of the organism’s genome. Other studies have reported similar findings, but none of these addressed whether a biological response induced by natural circumstances, such as famine, could be passed on to subsequent generations.

To address this question, Dr. Hobert’s team starved roundworms for six days and then examined their cells for molecular changes. The starved roundworms, but not controls, were found to have generated a specific set of small RNAs. (Small RNAs are involved in various aspects of gene expression but do not code for proteins.) The small RNAs persisted for at least three generations, even though the worms were fed normal diets. The researchers also found that these small RNAs target genes with roles in nutrition.

Since these small RNAs are produced only in response to starvation, they had to have been passed from one generation to another. “We know from other studies that small RNAs can be transported from cell to cell around the body,” said Dr. Hobert. “So, it’s conceivable that the starvation-induced small RNAs found their way into the worms’ germ cells—that is, their sperm or eggs. When the worms reproduced, the small RNAs could have been transmitted from one generation to the next in the cell body of the germ cells, independent of the DNA.”

The study also found that the progeny of the starved worms had a longer life span than the progeny of the controls. “We have not shown that the starvation-induced small RNAs were responsible for the increased longevity—it’s just a correlation,” said Dr. Hobert. “But it’s possible that these small RNAs provided a means for the worms to control the expression of relevant genes in later generations.”

The findings have no immediate clinical application. “However, they do suggest that we should be aware of other things—beyond pure DNA changes—that may have a long-term impact on the health of an organism,” said Dr. Hobert. “In other words, something that happened to one generation, whether famine or some other traumatic event, may be relevant to the health of its descendants for generations.”


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INNATE IMMUNITY

Innate, or nonspecific, immunity is the natural resistance with which a person is born. It provides resistance through several physical, chemical, and cellular approaches. Microbes first encounter the epithelial layers (physical barriers that line our skin and mucous membranes). Subsequent general defenses include secreted chemical signals (cytokines), antimicrobial substances, fever, and phagocytic activity associated with the inflammatory response. The phagocytes express cell surface receptors that can bind and respond to common molecular patterns expressed on the surface of invading microbes. Through these approaches, innate immunity can prevent the colonization, entry, and spread of microbes.

Figure: An animal&rsquos immune response to a foreign body: Macrophages begin to fuse with, and inject its toxins into, the cancer cell. The cell starts rounding up and loses its spikes. As the macrophage cell becomes smooth. The cancer cell appears lumpy in the last stage before it dies. These lumps are actually the macrophages fused within the cancer cell. The cancer cell then loses its morphology, shrinks up and dies. Photo magnification: 3: x8,000 Type: B & W print


By Gypsyamber D’Souza and David Dowdy | Updated April 6, 2021

When the coronavirus that causes COVID-19 first started to spread, virtually nobody was immune. Meeting no resistance, the virus spread quickly across communities. Stopping it will require a significant percentage of people to be immune. But how can we get to that point?

In this Q&A, Gypsyamber D’Souza, PhD ’07, MPH, MS, and David Dowdy, MD, PhD ’08, ScM ’02, explain how the race is on to get people immune by vaccinating them before they get infected.

What is herd immunity?

When most of a population is immune to an infectious disease, this provides indirect protection—or population immunity (also called herd immunity or herd protection)—to those who are not immune to the disease.

For example, if 80% of a population is immune to a virus, four out of every five people who encounter someone with the disease won’t get sick (and won’t spread the disease any further). In this way, the spread of infectious diseases is kept under control. Depending how contagious an infection is, usually 50% to 90% of a population needs immunity before infection rates start to decline. But this percentage isn’t a “magic threshold” that we need to cross—especially for a novel virus. Both viral evolution and changes in how people interact with each other can bring this number up or down. Below any “herd immunity threshold,” immunity in the population (for example, from vaccination) can still have a positive effect. And above the threshold, infections can still occur.

The higher the level of immunity, the larger the benefit. This is why it is important to get as many people as possible vaccinated.

How have we achieved herd immunity for other infectious diseases?

Measles, mumps, polio, and chickenpox are examples of infectious diseases that were once very common but are now rare in the U.S. because vaccines helped to establish herd immunity. We sometimes see outbreaks of vaccine-preventable diseases in communities with lower vaccine coverage because they don’t have herd protection. (The 2019 measles outbreak at Disneyland is an example.)

For infections without a vaccine, even if many adults have developed immunity because of prior infection, the disease can still circulate among children and can still infect those with weakened immune systems. This was seen for many of the aforementioned diseases before vaccines were developed.

Other viruses (like the flu) mutate over time, so antibodies from a previous infection provide protection for only a short period of time. For the flu, this is less than a year. If SARS-CoV-2, the virus that causes COVID-19, is like other coronaviruses that currently infect humans, we can expect that people who get infected will be immune for months to years. For example, population-based studies in places like Denmark have shown that an initial infection by SARS-CoV-2 is protective against repeat infection for more than six months. But this level of immunity may be lower among people with weaker immune systems (such as people who are older), and it is unlikely to be lifelong. This is why we need vaccines for SARS-CoV-2 as well.

What will it take to achieve herd immunity with SARS-CoV-2?

As with any other infection, there are two ways to achieve herd immunity: A large proportion of the population either gets infected or gets a protective vaccine. What we know about coronavirus so far suggests that, if we were really to go back to a pre-pandemic lifestyle, we would need at least 70% of the population to be immune to keep the rate of infection down (“achieve herd immunity”) without restrictions on activities. But this level depends on many factors, including the infectiousness of the virus (variants can evolve that are more infectious) and how people interact with each other.

For example, when the population reduces their level of interaction (through distancing, wearing masks, etc.), infection rates slow down. But as society opens up more broadly and the virus mutates to become more contagious, infection rates will go up again. Since we are not currently at a level of protection that can allow life to return to normal without seeing another spike in cases and deaths, it is now a race between infection and injection.

What are the possibilities for how herd immunity could play out?

In the worst case (for example, if we stop distancing and mask wearing and remove limits on crowded indoor gatherings), we will continue to see additional waves of surging infection. The virus will infect—and kill—many more people before our vaccination program reaches everyone. And deaths aren’t the only problem. The more people the virus infects, the more chances it has to mutate. This can increase transmission risk, decrease the effectiveness of vaccines, and make the pandemic harder to control in the long run.

In the best case, we vaccinate people as quickly as possible while maintaining distancing and other prevention measures to keep infection levels low. This will take concerted effort on everyone’s part. But if we continue vaccinating the population at the current rate, in the U.S. we should see meaningful effects on transmission by the end of the summer of 2021. While there is not going to be a “herd immunity day” where life immediately goes back to normal, this approach gives us the best long-term chance of beating the pandemic.

The most likely outcome is somewhere in the middle of these extremes. During the spring and early summer (or longer, if efforts to vaccinate the population stall), we will likely continue to see infection rates rise and fall. When infection rates fall, we may relax distancing measures—but this can lead to a rebound in infections as people interact with each other more closely. We then may need to re-implement these measures to bring infections down again.

Will we ever get to herd immunity?

Yes—and hopefully sooner rather than later, as vaccine manufacturing and distribution are rapidly being scaled up. In the United States, current projections are that we can get more than half of all American adults fully vaccinated by the end of Summer 2021—which would take us a long way toward herd immunity, in only a few months. By the time winter comes around, hopefully enough of the population will be vaccinated to prevent another large surge like what we have seen this year. But this optimistic scenario is not guaranteed. It requires widespread vaccine uptake among all parts of the population—including all ages and races, in all cities, suburbs, and countrysides. Because the human population is so interconnected, an outbreak anywhere can lead to a resurgence everywhere.

This is a global concern as well. As long as there are unvaccinated populations in the world, SARS-CoV-2 will continue to spread and mutate, and additional variants will emerge. In the U.S. and elsewhere, booster vaccination may become necessary if variants arise that can evade the immune response provoked by current vaccines.

Prolonged effort will be required to prevent major outbreaks until vaccination is widespread. Even then, it is very unlikely that SARS-CoV-2 will be eradicated it will still likely infect children and others who have not been vaccinated, and we will likely need to update the vaccine and provide booster doses on some regular basis. But it is also likely that the continuing waves of explosive spread that we are seeing right now will eventually die down—because in the future, enough of the population will be immune to provide herd protection.

What should we expect in the coming months?

We now have multiple effective vaccines, and the race is on to get people vaccinated before they get infected (and have the chance to spread infection to others). It is difficult to predict the future because many factors are at play—including new variants with the potential for increased transmission, changes in our own behavior as the pandemic drags on, and seasonal effects that may help to reduce transmission in the summer months. But one thing is certain: The more people who are vaccinated, the less opportunity the virus will have to spread in the population, and the closer we will be to herd immunity.

We have seen that the restrictions needed over time have varied as preventive measures have worked to drive infection rates down, but we have also seen these rates resurge as our responses have relaxed. Once we get enough people vaccinated to drive down infection rates more consistently, we should be able to gradually lift these restrictions. But until the vaccine is widely distributed and a large majority of the population is vaccinated, there will still be a risk of infection and outbreaks—and we will need to take some precautions.

In the end, though, we will build up immunity to this virus life will be able to return to “normal” eventually. The fastest way to get to that point is for each of us to do our part in the coming months to reduce the spread of the virus—continue to wear masks, maintain distance, avoid high-risk indoor gatherings, and get vaccinated as soon as a vaccine becomes available to us.

Gypsyamber D’Souza is a professor and David Dowdy an associate professor in Epidemiology at the Bloomberg School.


Acquired immunity

the condition of being immune the protection against infectious disease conferred either by the immune response generated by immunization or previous infection or by other nonimmunologic factors. It encompasses the capacity to distinguish foreign material from self , and to neutralize, eliminate, or metabolize that which is foreign ( nonself ) by the physiologic mechanisms of the immune response.

The mechanisms of immunity are essentially concerned with the body's ability to recognize and dispose of substances which it interprets as foreign and harmful to its well-being. When such a substance enters the body, complex chemical and mechanical activities are set into motion to defend and protect the body's cells and tissues. The foreign substance, usually a protein, is called an antigen , that is, one that generates the production of an antagonist. The most common response to the antigen is the production of antibody . The antigen--antibody reaction is an essential component of the overall immune response. A second type of activity, cellular response, is also an essential component.

The various and complex mechanisms of immunity are basic to the body's ability to protect itself against specific infectious agents and parasites, to accept or reject cells and tissues from other individuals, as in blood transfusions and organ transplants, and to protect against cancer, as when the immune system recognizes malignant cells as not-self and destroys them.

There has been extensive research into the body's ability to differentiate between cells, organisms, and other substances that are self (not alien to the body), and those that are nonself and therefore must be eliminated. A major motivating force behind these research efforts has been the need for more information about growth and proliferation of malignant cells, the inability of certain individuals to develop normal immunological responses (as in immunodeficiency conditions), and mechanisms of failure of the body to recognize its own tissues (as in autoimmune diseases ).

Immunological Responses . Immunological responses in humans can be divided into two broad categories: humoral immunity, which takes place in the body fluids (humors) and is concerned with antibody and complement activities and cell-mediated or cellular immunity, which involves a variety of activities designed to destroy or at least contain cells that are recognized by the body as alien and harmful. Both types of responses are instigated by lymphocytes that originate in the bone marrow as stem cells and later are converted into mature cells having specific properties and functions.

The two kinds of lymphocytes that are important to establishment of immunity are T lymphocytes (T cells) and B lymphocytes (B cells). (See under lymphocyte .) The T lymphocytes differentiate in the thymus and are therefore called thymus-dependent. There are several types involved in cell-mediated immunity, delayed hypersensitivity, production of lymphokines, and the regulation of the immune response of other T and B cells.

The B lymphocytes are so named because they were first identified during research studies involving the immunologic activity of the bursa of Fabricius, a lymphoid organ in the chicken. (Humans have no analogous organ.) They mature into plasma cells that are primarily responsible for forming antibodies, thereby providing humoral immunity.

Humoral Immunity. At the time a substance enters the body and is interpreted as foreign, antibodies are released from plasma cells and enter the body fluids where they can react with the specific antigens for which they were formed. This release of antibodies is stimulated by antigen-specific groups (clones) of B lymphocytes. Each B lymphocyte has IgM immunoglobulin receptors that play a major role in capturing its specific antigen and in launching production of the immunoglobulins (which are antibodies) that are capable of neutralizing and destroying that particular type of antigen.

Most of the B lymphocytes activated by the presence of their specific antigen become plasma cells, which then synthesize and export antibodies. The activated B lymphocytes that do not become plasma cells continue to reside as &ldquomemory&rdquo cells in the lymphoid tissue, where they stand ready for future encounters with antigens that may enter the body. It is these memory cells that provide continued immunity after initial exposure to the antigens.

There are two types of humoral immune response: primary and secondary. The primary response begins immediately after the initial contact with an antigen the resulting antibody appears 48 to 72 hours later. The antibodies produced during this primary response are predominantly of the IgM class of immunoglobulins.

A secondary response occurs within 24 to 48 hours. This reaction produces large quantities of immunoglobulins that are predominantly of the IgG class. The secondary response persists much longer than the primary response and is the result of repeated contact with the antigens. This phenomenon is the basic principle underlying consecutive immunizations .

The ability of the antibody to bind with or &ldquostick to&rdquo antigen renders it capable of destroying the antigen in a number of ways for example, agglutination and opsonization. Antibody also &ldquofixes&rdquo or activates complement , which is the second component of the humoral immune system. Complement is the name given a complex series of enzymatic proteins which are present but inactive in normal serum. When complement fixation takes place, the antigen, antibody, and complement become bound together. The cell membrane of the antigen (which usually is a bacterial cell) then ruptures, resulting in dissolution of the antigen cell and a leakage of its substance into the body fluids. This destructive process is called lysis.

Cellular Immunity. This type of immune response is dependent upon T lymphocytes, which are primarily concerned with a delayed type of immune response. Examples of this include rejection of transplanted organs, defense against slowly developing bacterial diseases that result from intracellular infections, delayed hypersensitivity reactions, certain autoimmune diseases, some allergic reactions, and recognition and rejection of self cells undergoing alteration, for example, those infected with viruses, and cancer cells that have tumor-specific antigens on their surfaces. These responses are called cell-mediated immune responses.

The T lymphocyte becomes sensitized by its first contact with a specific antigen. Subsequent exposure to the antigen stimulates a host of chemical and mechanical activities, all designed to either destroy or inactivate the offending antigen. Some of the sensitized T lymphocytes combine with the antigen to deactivate it, while others set about to destroy the invading organism by direct invasion or the release of chemical factors. These chemical factors, through their influence on macrophages and unsensitized lymphocytes, enhance the effectiveness of the immune response.

Among the more active chemical factors are lymphokines , which are potent and biologically active proteins their names are often descriptive of their functions: Ones that directly affect the macrophages are the macrophage chemotactic factor , which attracts macrophages to the invasion site migration inhibitory factor , which causes macrophages to remain at the invasion site and macrophage-activating factor , which stimulates the metabolic activities of these large cells and thereby improves their ability to ingest the foreign invaders.

Another factor, a protein called interferon , is produced by the body cells, especially T lymphocytes, following viral infection or in response to a wide variety of inducers, such as certain nonviral infectious agents and synthetic polymers.

A portion of the population of T lymphocytes is transformed into killer cells by the lymphocyte-transforming factor (blastogenic factor). These activated lymphocytes produce a lymphotoxin or cytotoxin that damages the cell membranes of the antigens, causing them to rupture.

In order to ensure an ample supply of T lymphocytes, two factors are at work: lymphocyte-transforming factor stimulates lymphocytes that have already undergone conversion to sensitized T lymphocytes, so that they increase their numbers by repeated cell division and clone formation in the absence of antigens, transfer factor takes over the task of sensitizing those lymphocytes that have not been exposed to antigen.

It is apparent that the immune response brings about intensive activity at the site of invasion it is not only the pathogen that is destroyed, but invariably, there is death or damage to some normal tissues.

Interactions Between the Two Systems. There are several areas in which the cellular and humoral systems interact and thereby improve the efficiency of the overall immune response. For example, a by-product of the enzymatic activity of the complement system acts as a chemotactic factor, attracting T lymphocytes and macrophages to the invasion site. In another example, although T lymphocytes are not required for the production of antibody, there is optimal antibody production after interaction between T and B lymphocytes.

For a discussion of abnormalities of the immune response system, see immune response .

Natural immunity is a genetic characteristic of an individual and is due to the particular species and race to which one belongs, to one's sex, and to one's individual ability to produce immune bodies. All humans are immune to certain diseases that affect animals of the lower species males are more resistant to some disorders than are females, and vice versa. Persons of one race are more susceptible to some diseases than those of another race that has had exposure to the infectious agents through successive generations. One's individual ability to produce immune bodies, and thereby ward off pathogens, is influenced by one's state of physical health, one's nutritional status, and one's emotional response to stress.

In order for an individual to acquire immunity one's body must be stimulated to produce its own immune response components (active immunity) or these substances must be produced by other persons or animals and then passed on to the person (passive immunity). Active immunity can be established in two ways: by having the disease or by receiving modified pathogens and toxins. When an individual is exposed to a disease and the pathogenic organisms enter the body, the production of antibody is initiated. After recovery from the illness, memory cells remain in the body and stand ready as a defense against future invasion. It is possible, through the use of vaccines, bacterins, and modified toxins (toxoids), to stimulate the production of specific antibodies without having an attack of the disease. These are artificial means by which an individual can acquire active immunity.

Sometimes it is desirable to provide &ldquoready-made&rdquo immune bodies, as in cases in which the patient has already been exposed to the antigen, is experiencing the symptoms of the disease, and needs reinforcements to help mitigate its harmful effects. Examples of conditions for which an individual may be given such passive immunity include tetanus, diphtheria, and a venomous snake bite. The patient is given immune serum, which contains gamma globulin , antibodies (including antitoxin) produced by the animal from which the serum was taken.

It is not always necessary that the patient actually suffer from the disease and exhibit its symptoms before passive immunity is provided. In some instances in which exposure to an infectious agent is suspected, immune bodies may be given to ward off a full-blown attack or at least to lessen its severity.

Another way in which immunity can be passively acquired is across the placental barrier from fetus to mother. The maternal antibody thus acquired serves as protection for the newborn until he can actively establish immunity on his own. Although humoral immunity can be acquired in this way, cellular immunity cannot.


Immunity

the condition of being immune the protection against infectious disease conferred either by the immune response generated by immunization or previous infection or by other nonimmunologic factors. It encompasses the capacity to distinguish foreign material from self , and to neutralize, eliminate, or metabolize that which is foreign ( nonself ) by the physiologic mechanisms of the immune response.

The mechanisms of immunity are essentially concerned with the body's ability to recognize and dispose of substances which it interprets as foreign and harmful to its well-being. When such a substance enters the body, complex chemical and mechanical activities are set into motion to defend and protect the body's cells and tissues. The foreign substance, usually a protein, is called an antigen , that is, one that generates the production of an antagonist. The most common response to the antigen is the production of antibody . The antigen--antibody reaction is an essential component of the overall immune response. A second type of activity, cellular response, is also an essential component.

The various and complex mechanisms of immunity are basic to the body's ability to protect itself against specific infectious agents and parasites, to accept or reject cells and tissues from other individuals, as in blood transfusions and organ transplants, and to protect against cancer, as when the immune system recognizes malignant cells as not-self and destroys them.

There has been extensive research into the body's ability to differentiate between cells, organisms, and other substances that are self (not alien to the body), and those that are nonself and therefore must be eliminated. A major motivating force behind these research efforts has been the need for more information about growth and proliferation of malignant cells, the inability of certain individuals to develop normal immunological responses (as in immunodeficiency conditions), and mechanisms of failure of the body to recognize its own tissues (as in autoimmune diseases ).

Immunological Responses . Immunological responses in humans can be divided into two broad categories: humoral immunity, which takes place in the body fluids (humors) and is concerned with antibody and complement activities and cell-mediated or cellular immunity, which involves a variety of activities designed to destroy or at least contain cells that are recognized by the body as alien and harmful. Both types of responses are instigated by lymphocytes that originate in the bone marrow as stem cells and later are converted into mature cells having specific properties and functions.

The two kinds of lymphocytes that are important to establishment of immunity are T lymphocytes (T cells) and B lymphocytes (B cells). (See under lymphocyte .) The T lymphocytes differentiate in the thymus and are therefore called thymus-dependent. There are several types involved in cell-mediated immunity, delayed hypersensitivity, production of lymphokines, and the regulation of the immune response of other T and B cells.

The B lymphocytes are so named because they were first identified during research studies involving the immunologic activity of the bursa of Fabricius, a lymphoid organ in the chicken. (Humans have no analogous organ.) They mature into plasma cells that are primarily responsible for forming antibodies, thereby providing humoral immunity.

Humoral Immunity. At the time a substance enters the body and is interpreted as foreign, antibodies are released from plasma cells and enter the body fluids where they can react with the specific antigens for which they were formed. This release of antibodies is stimulated by antigen-specific groups (clones) of B lymphocytes. Each B lymphocyte has IgM immunoglobulin receptors that play a major role in capturing its specific antigen and in launching production of the immunoglobulins (which are antibodies) that are capable of neutralizing and destroying that particular type of antigen.

Most of the B lymphocytes activated by the presence of their specific antigen become plasma cells, which then synthesize and export antibodies. The activated B lymphocytes that do not become plasma cells continue to reside as &ldquomemory&rdquo cells in the lymphoid tissue, where they stand ready for future encounters with antigens that may enter the body. It is these memory cells that provide continued immunity after initial exposure to the antigens.

There are two types of humoral immune response: primary and secondary. The primary response begins immediately after the initial contact with an antigen the resulting antibody appears 48 to 72 hours later. The antibodies produced during this primary response are predominantly of the IgM class of immunoglobulins.

A secondary response occurs within 24 to 48 hours. This reaction produces large quantities of immunoglobulins that are predominantly of the IgG class. The secondary response persists much longer than the primary response and is the result of repeated contact with the antigens. This phenomenon is the basic principle underlying consecutive immunizations .

The ability of the antibody to bind with or &ldquostick to&rdquo antigen renders it capable of destroying the antigen in a number of ways for example, agglutination and opsonization. Antibody also &ldquofixes&rdquo or activates complement , which is the second component of the humoral immune system. Complement is the name given a complex series of enzymatic proteins which are present but inactive in normal serum. When complement fixation takes place, the antigen, antibody, and complement become bound together. The cell membrane of the antigen (which usually is a bacterial cell) then ruptures, resulting in dissolution of the antigen cell and a leakage of its substance into the body fluids. This destructive process is called lysis.

Cellular Immunity. This type of immune response is dependent upon T lymphocytes, which are primarily concerned with a delayed type of immune response. Examples of this include rejection of transplanted organs, defense against slowly developing bacterial diseases that result from intracellular infections, delayed hypersensitivity reactions, certain autoimmune diseases, some allergic reactions, and recognition and rejection of self cells undergoing alteration, for example, those infected with viruses, and cancer cells that have tumor-specific antigens on their surfaces. These responses are called cell-mediated immune responses.

The T lymphocyte becomes sensitized by its first contact with a specific antigen. Subsequent exposure to the antigen stimulates a host of chemical and mechanical activities, all designed to either destroy or inactivate the offending antigen. Some of the sensitized T lymphocytes combine with the antigen to deactivate it, while others set about to destroy the invading organism by direct invasion or the release of chemical factors. These chemical factors, through their influence on macrophages and unsensitized lymphocytes, enhance the effectiveness of the immune response.

Among the more active chemical factors are lymphokines , which are potent and biologically active proteins their names are often descriptive of their functions: Ones that directly affect the macrophages are the macrophage chemotactic factor , which attracts macrophages to the invasion site migration inhibitory factor , which causes macrophages to remain at the invasion site and macrophage-activating factor , which stimulates the metabolic activities of these large cells and thereby improves their ability to ingest the foreign invaders.

Another factor, a protein called interferon , is produced by the body cells, especially T lymphocytes, following viral infection or in response to a wide variety of inducers, such as certain nonviral infectious agents and synthetic polymers.

A portion of the population of T lymphocytes is transformed into killer cells by the lymphocyte-transforming factor (blastogenic factor). These activated lymphocytes produce a lymphotoxin or cytotoxin that damages the cell membranes of the antigens, causing them to rupture.

In order to ensure an ample supply of T lymphocytes, two factors are at work: lymphocyte-transforming factor stimulates lymphocytes that have already undergone conversion to sensitized T lymphocytes, so that they increase their numbers by repeated cell division and clone formation in the absence of antigens, transfer factor takes over the task of sensitizing those lymphocytes that have not been exposed to antigen.

It is apparent that the immune response brings about intensive activity at the site of invasion it is not only the pathogen that is destroyed, but invariably, there is death or damage to some normal tissues.

Interactions Between the Two Systems. There are several areas in which the cellular and humoral systems interact and thereby improve the efficiency of the overall immune response. For example, a by-product of the enzymatic activity of the complement system acts as a chemotactic factor, attracting T lymphocytes and macrophages to the invasion site. In another example, although T lymphocytes are not required for the production of antibody, there is optimal antibody production after interaction between T and B lymphocytes.

For a discussion of abnormalities of the immune response system, see immune response .

Natural immunity is a genetic characteristic of an individual and is due to the particular species and race to which one belongs, to one's sex, and to one's individual ability to produce immune bodies. All humans are immune to certain diseases that affect animals of the lower species males are more resistant to some disorders than are females, and vice versa. Persons of one race are more susceptible to some diseases than those of another race that has had exposure to the infectious agents through successive generations. One's individual ability to produce immune bodies, and thereby ward off pathogens, is influenced by one's state of physical health, one's nutritional status, and one's emotional response to stress.

In order for an individual to acquire immunity one's body must be stimulated to produce its own immune response components (active immunity) or these substances must be produced by other persons or animals and then passed on to the person (passive immunity). Active immunity can be established in two ways: by having the disease or by receiving modified pathogens and toxins. When an individual is exposed to a disease and the pathogenic organisms enter the body, the production of antibody is initiated. After recovery from the illness, memory cells remain in the body and stand ready as a defense against future invasion. It is possible, through the use of vaccines, bacterins, and modified toxins (toxoids), to stimulate the production of specific antibodies without having an attack of the disease. These are artificial means by which an individual can acquire active immunity.

Sometimes it is desirable to provide &ldquoready-made&rdquo immune bodies, as in cases in which the patient has already been exposed to the antigen, is experiencing the symptoms of the disease, and needs reinforcements to help mitigate its harmful effects. Examples of conditions for which an individual may be given such passive immunity include tetanus, diphtheria, and a venomous snake bite. The patient is given immune serum, which contains gamma globulin , antibodies (including antitoxin) produced by the animal from which the serum was taken.

It is not always necessary that the patient actually suffer from the disease and exhibit its symptoms before passive immunity is provided. In some instances in which exposure to an infectious agent is suspected, immune bodies may be given to ward off a full-blown attack or at least to lessen its severity.

Another way in which immunity can be passively acquired is across the placental barrier from fetus to mother. The maternal antibody thus acquired serves as protection for the newborn until he can actively establish immunity on his own. Although humoral immunity can be acquired in this way, cellular immunity cannot.