Question

How is a vaccine different from an antibiotic with respect to immune stimulation?

Answer 1

The Immune System and Immunization

The environment contains a wide variety of potentially harmful organisms (pathogens), such as bacteria, viruses, fungi, protozoa and multicellular parasites, which will cause disease if they enter the body and are allowed to multiply. The body protects itself through a various defence mechanisms to physically prevent pathogens from entering the body or to kill them if they do.

The immune system is an extremely important defence mechanism that can identify an invading organism and destroy it. Immunisation prevents disease by enabling the body to more rapidly respond to attack and enhancing the immune response to a particular organism.

Each pathogen has unique distinguishing components, known as antigens, which enable the immune system to differentiate between ‘self’ (the body) and ‘non-self’ (the foreign material). The first time the immune system sees a new antigen, it needs to prepare to destroy it. During this time, the pathogen can multiply and cause disease. However, if the same antigen is seen again, the immune system is poised to confine and destroy the organism rapidly. This is known as adaptive immunity.

Vaccines utilise this adaptive immunity and memory to expose the body to the antigen without causing disease, so that when then live pathogen infects the body, the response is rapid and the pathogen is prevented from causing disease. Depending on the type of infectious organism, the response required to remove it varies. For example, viruses hide within the body’s own cells in different tissues, such as the throat, the liver and the nervous system, and bacteria can multiply rapidly within infected tissues.

Lines of defense:

The body prevents infection through a number of non-specific and specific mechanisms working on their own or together. The body’s first lines of defence are external barriers that prevent germs from entering. The largest of all is the skin which acts as a strong, waterproof, physical barrier and very few organisms are able to penetrate undamaged skin. There are other physical barriers and a variety of chemical defences. Examples of these non-specific defences are given below:

• Skin - a strong physical barrier, like a waterproof wall
• Mucus – a sticky trap secreted by all the surfaces inside the body that are directly linked to the outside, also contains antibodies and enzymes
• Cilia – microscopic hairs in the airways that move to pass debris and mucus up away from the lungs
• Lysozyme – a chemical (enzyme) present in tears and mucus that damages bacteria
• Phagocytes – various cells that scavenge and engulf debris and invading organisms, which form part of the surveillance system to alert the immune system of attack
• Commensal bacteria - bacteria on skin and gut that compete with potentially harmful bacteria for space and nutrients
• Acid - in stomach and urine, make it hard for any germs to survive
• Fever – elevated body temperature making conditions unfavourable for pathogens to survive

The immune response:

An immune response is triggered when the immune system is alerted that something foreign has entered the body. Triggers include the release of chemicals by damaged cells and inflammation, and changes in blood supply to an area of damage which attract white blood cells.

White blood cells destroy the infection or convey chemical messages to other parts of the immune system. As blood and tissue fluids circulate around the body, various components of the immune system are continually surveying for potential sources of attack or abnormal cells.

Antigens and antibodies:

Antigens are usually either proteins or polysaccharides (long chains of sugar molecules that make up the cell wall of certain bacteria). An antigen is a molecule that stimulates an immune response and to which antibodies bind – in fact, the name is derived from “antibody generators.” Any given organism contains several different antigens. Viruses can contain as few as three antigens to more than 100 as for herpes and pox viruses; whereas protozoa, fungi and bacteria are larger, more complex organisms and contain hundreds to thousands of antigens.

An immune response initially involves the production of antibodies that can bind to a particular antigen and the activation of antigen-specific white blood cells.

Antibodies (immunoglobulins; Ig) are protein molecules that bind specifically to a particular part of an antigen, so called antigenic site or epitope. They are found in the blood and tissue fluids, including mucus secretions, saliva and breast milk. There are five classes of antibody – IgG, IgA, IgM, IgD and IgE, which have a range of functions. They can act as ‘flags’ to direct the immune system to foreign material for destruction and form part of the innate / humoral immune response. Normally, low levels of antibodies circulate in the body tissue fluids. However, when an immune response is activated greater quantities are produced to specifically target the foreign material.

Vaccination increases the levels of circulating antibodies against a certain antigen. Antibodies are produced by a type of white blood cell (lymphocyte) called B cells. Each B cell can only produce antibodies against one specific epitope. When activated, a B cell will multiply to produce more clones able secrete that particular antibody. The class of antibody produced is determined by other cells in the immune system, this is known as cell-mediated immunity.

Primary response:

Upon exposure to a pathogen, the body will attempt to isolate and destroy it. Chemicals released by inflammation increase blood flow and attract white blood cells to the area of infection. Specialist cells, known as phagocytes, engulf the target and dismantle it. These phagocytes then travel to the nearest lymph nodes where they ‘present’ the antigens to other cells of the immune system to induce a larger, more specific response. This response leads to the production of antigen-specific antibodies.

Circulating antibodies then find the organism and bind to its surface antigens. In this way it is labelled as the target. This specific response is also called the adaptive or cell-mediated immune response, since the immune system adapts to suit the type of invader.

When the body is first exposed to an antigen, several days pass before this adaptive response becomes active. Upon first exposure to a pathogen, immune activity increases, then levels off and falls. Since the first, or primary, immune response is slow it cannot prevent disease, although it may help in recovery.

Once antigen-specific T and B cells (lymphocytes) are activated, their numbers expand and following an infection some memory cells remain resulting in memory for the specific antigens. This memory can take a few months to fully develop.

Secondary response:

During subsequent exposures to the same pathogen, the immune system is able to respond rapidly and activity reaches higher levels.

The secondary immune responses can usually prevent disease, because the pathogen is detected, attacked and destroyed before symptoms appear. In general, adults respond more rapidly to infection than children. They are able to prevent disease or reduce the severity of the disease by mounting a rapid and strong immune response to antigens they have previously experienced. In contrast, children have not experienced as many antigens and are more likely to get sick.

Memory of the infection is reinforced and long lived antibodies remain in circulation. Some infections, such as chickenpox, induce a life-long memory of infection. Other infections, such as influenza, vary from season to season to such an extent that even an adult is unable to adapt.

Vaccination:

Vaccination utilises this secondary response by exposing the body to the antigens of a particular pathogen and activates the immune system without causing disease.

The initial response to a vaccine is similar to that of the primary response upon first exposure to a pathogen, slow and limited. Subsequent doses of the vaccine act to boost this response resulting in the production of long-lived antibodies and memory cells, as it would naturally following subsequent infections.

The aim of vaccines is to prime the body, so that when an individual is exposed to the disease-causing organism, their immune system is able to respond rapidly and at a high activity level, thereby destroying the pathogen before it causes disease and reduces the risk of spread to other people.

Vaccines vary in how they stimulate the immune system. Some provide a broader response than others. Vaccines influence the immune response through the nature of the antigens they contain, including number and characteristics of the antigens, or through the route of administration, such as orally, intramuscular or subcutaneous injection. The use of adjuvants in vaccines can help to determine the type, duration and intensity of the primary response and the characteristics of resulting antigen-specific memory.

For most vaccines, more than one dose may be required to provide sustained, long-lasting protection – to be fully immunised.

Types of immunization:

Active immunisation – body generates its own response to protect against infection through specialised cells and antibodies, as stimulated by vaccines. Full protection takes time to develop but is long lasting.

Passive immunisation – ready-made antibodies are passed directly to the person being immunised. This allows for immediate protection, but passive immunisation may only last a few weeks or months. Antibodies are passed from mothers to infants across the placenta and in breast milk, to protect the infants for a short time after birth. Antibodies (immunoglobulins) are also purified from blood or in laboratories; these can be directly injected to provide rapid but short lived protection or treatment for certain diseases, such as rabies, diphtheria and tetanus.

Antibiotics and vaccines are in some ways opposites. Antibiotics kill indiscriminately, whereas vaccines are highly targeted. Antibiotics are used to treat severe infection, whereas vaccines prevent infections from ever becoming established. And antibiotics are based on defenses that evolved in microbes, to protect them from bacteria; they are not a natural defense for us, and our bodies are not adapted to cope well with them. Vaccines, in contrast, simply invoke the human body’s natural long-term defense systems, and are therefore far less invasive.

How does nature respond to antibiotics?

Antibiotics create selective pressure on a wide range of bacteria wherever they are used. Humans naturally host large numbers of bacteria. These are essential to our health and killing them off repeatedly risks many long-term health problems, including immune disorders, damage to the gut, and increased vulnerability to infections.

In addition, when you use antibiotics, you put all these bacteria under selection to resist antibiotics. Worse, since antibiotics are often excreted intact, low concentrations of antibiotics are now found in water supplies everywhere, creating a perfect environment for bacteria in general to evolve resistance. Bacteria exchange genetic material with other strains of bacteria, especially via plasmids. So once a mechanism to resist an antibiotic evolves in one strain, we can expect it to spread to many different strains — including those that cause severe disease.

How does nature respond to vaccines?

Vaccines create selective pressure only on the specific infection they target. Due to herd immunity, even some people who cannot be vaccinated receive some protection from widespread use of vaccines (provided everybody else does the right thing). In addition, since vaccines prevent the target replicating at all in the host, they create no bottleneck. In fact, as hosts become more rare, the pathogen is under selection to lie low and avoid harming its host, because it may be a long time before it can spread to a new host. Also, the vaccine does no harm to normal human biota, and therefore does not significantly disrupt the gut, immune system or any other part of the body.

So: the long-term expected effect of vaccines is that (1) vaccines do not affect the evolution of non-targeted strains (2) vaccines cause the targeted strain to evolve to become less severe (3) vaccines are one of the safest medical interventions.

Comparison of long term expected effects on…

Evolution of Resistant Strains: Antibiotics — yes, including non-targeted strains. Vaccines — do not create resistance.

Evolution of disease severity: Antibiotics — unpredictable. Vaccines — make diseases less severe.

Health of treated people: Antibiotics — harmful (but hopefully less so than the infection they treated). Vaccines — harmless.

Health of Untreated People: Antibiotics — none or harmful. Vaccines — beneficial.

Both antibiotics and vaccines are wonderful inventions. They have saved countless lives and spared humanity immense misery. I don’t think current generations can even imagine what life was like without them. Vaccines are vastly preferable to antibiotics; we should use vaccines freely, and antibiotics only when necessary.