Science Series

Our science series aims to explain in clear terms how the body works in terms of vaccinations and immunity.

How Vaccines Work

What is a vaccine?
Pathogens are microbes such as viruses or bacteria that cause disease. Vaccines include a small amount of weakened or harmless microbe, which when introduced into the body stimulates the immune system to produce antibodies.The immune system is then able to remember the microbe so if the body is invaded by the real pathogen, it is able to fight it instantly and stop the disease developing. With some vaccinations, the immune memory can reduce over several years, which is why booster vaccinations are needed.

When were vaccines discovered?
The term vaccination is derived from ‘vacca' which means cow in Latin and was the name given to the first successful vaccine to be developed in 1796 by Edward Jenner from Berkeley, Gloucerstershire. His inoculation with the cowpox virus gave humans protection against the deadly scourge of smallpox - one of the most contagious and deadly diseases known to man.

As a country doctor, Jenner had always been fascinated by the old wives tale that milkmaids could not get smallpox and believed there was a connection between the fact that they only got cowpox - the non-life threatening weak version of smallpox - but not smallpox itself.

Jenner tried out his theory by vaccinating a healthy young boy with the virus from a dairymaid who had contracted cowpox. The boy proved Jenner's point by surviving repeated attempts to infect him with smallpox.

How are vaccines made?
Vaccines can be made in a variety of ways such as from inactivated (killed) or attenuated (weakened) live organisms or from parts of the bacteria's cell wall. For example the pneumococcal vaccine contains the polysaccharide (carbohydrate) from the cell wall of the pneumococcus bacteria. Some vaccines such as the Hib and Meningitis C vaccines are improved by ‘conjugation' where the polysaccharide outer coat is combined with a protein, which enables the immune system to give a broader response to the invading bacteria.

Do vaccines exist to protect against meningitis?
Vaccines exist to protect against several of the common forms of meningitis such as Hib, Meningitis C and pneumoccoccal meningitis. All of these vaccines are offered to children and other high risk groups through the routine UK immunisation schedule. Individuals who are not vaccinated will still benefit from the routine vaccination programme as those who have been vaccinated are less likely to be a source of infection - this is called herd immunity.

Unfortunately, there is still no vaccine to protect against the most common form of bacterial meningitis in the UK - Meningitis B. Meningitis UK is currently raising money to fund research into this area.

The Immune System - Part 1

The immune system is crucial to human health and consists of a network of interacting cells that work to defend the body against attacks by ‘foreign invaders' such as bacteria and viruses. Its role is to keep invaders out and to seek and destroy those that have already entered the body.

The immune system is very complex and can recognise and remember millions of different enemies, producing secretions and cells to match up with and wipe out each one of them. Once alerted to an invader, the immune cells make changes, producing powerful chemicals to determine how they behave and to signal other immune cells to assist.

The ability to distinguish between the body's own cells (self) and those that do not belong to the body (non-self) is very important. When non-self cells are encountered, an attack is launched and this is called an immune response.

Anything that can trigger this immune response is called an antigen. Tissues or cells from another person (except an identical twin) also carry non-self markers and act as antigens - this explains why tissue transplants may be rejected. In abnormal situations, the immune system can mistake self for non-self and launch an attack against the body's own cells or tissues. The result is called an autoimmune disease, such as some forms of arthritis and diabetes. In other cases the immune system responds to a seemingly harmless foreign substance such as pollen. The result is allergy, and this kind of antigen is called an allergen.

The organs of the immune system are positioned throughout the body. White blood cells are immune cells which are produced in the bone marrow, for example lymphocytes which mature in the thymus gland and then travel around the body via the blood vessels and the lymphatic system. They patrol the whole body searching for antigens being able to pass between the blood and lymphatic vessels. Small lymph nodes are positioned along the lymphatic vessels and are clustered at the neck, armpits, abdomen and groin and this is where immune cells can congregate in specialised compartments to dispose of antigens. The spleen acts in a similar way and the tonsils, adenoids and appendix are also made of lymphoid tissue and protect the body from invaders.

When a vaccine is given, it tricks the immune system into thinking that an infection has occurred. It will launch an attack and develop memory so that if it meets the same infection again the body will recognise it and mount a quicker and stronger response. This prevents the person from getting the disease. This is why vaccine development work is so important.

The Immune System - Part 2

The immune response
Antibodies, phagocytes and the complement system are all part of the immune system. Antibodies attach themselves to bacteria, sending signals to the complement proteins and phagocytic cells to move in and attack. Phagocytes are large white cells that swallow and digest bacteria.

Immune cells are able to communicate with each other either by direct contact or by releasing chemical messengers. The immune system stores just a few of each type of different cells needed to identify the millions of possible enemies and then when an antigen appears the few cells that match it multiply into a full size army to attack the antigen (an antigen is anything that can trigger the immune response).They then fade away leaving just a few sentries behind to guard against further attack.

All immune cells start off as immature stem cells in the bone marrow and then they respond to different cytokines (chemical messengers) and other signals to grow into specific immune cell types. For example, lymphocytes work by secreting antibodies into the bloodstream and lymphatic system, ambushing the antigens that are circulating. Other immune cells then carry out the attack. There is a specific antibody for each antigen and when this antigen is encountered, millions more of those antibodies are produced. The way that an antigen matches an antibody is much the same as how a key matches a lock. Whenever antigen and antibody interlock in this way the antibody marks the antigen for destruction. Antibodies belong to a family of large molecules known as immunoglobulins, each playing different roles in immune defense strategy.

Complement
The Complement system is made up of about 25 proteins that work together to ‘complement' the action of antibodies in destroying bacteria and helps to rid the body of antigens once they have become covered in antibodies. Complement proteins, which cause blood vessels to become dilated and then leaky, contribute to the redness, warmth, swelling, pain and loss of function associated with the inflammatory response. In health, complement are circulating in the blood in a dormant form. Once the first protein in the complement series is activated, usually by antibody that has locked onto an antigen, a domino effect is started with each component taking it in turn in a precise order to become active, known as the complement cascade. They form a cylinder which punctures the cell wall, fluids and molecules then pass through and the cell swells and bursts, thus destroying the bacteria. Part of the complement system also signals other immune system cells to attack the bacteria.

When scientists are carrying out vaccine development work, such as that funded by Meningitis UK, they look for activation of the complement system, as this is a sign of a good vaccine candidate.

The Immune System - The Final Chapter

Immunity
Immunity is the ability of the human body to protect itself from human diseases. There are two types of immunity - Innate or non-specific and Acquired immunity.

Innate or non-specific is present from birth and includes physical barriers (e.g. intact skin and mucous membranes) and chemical barriers (e.g. gastric acid, digestive enzymes).

Acquired immunity is achieved by two methods - active and passive. Active immunity is protection produced by an individual's own immune system and is usually long-lasting. Active immunity can be acquired by natural disease or by vaccination. Vaccines generally provide immunity similar to that provided by the natural infection but without the risk from the disease or its complications. Passive immunity, meanwhile, is protection provided from the transfer of antibodies from immune individuals, most commonly from mother to baby through the placenta or less often from the transfusion of blood. This protection is temporary, commonly only for a few weeks or months.

Immune system diagram

Herd immunity
This is immunity that an entire population enjoys by virtue of the fact that there is too small a population density of susceptible individuals to allow the spread of an infection.

A given case of infection will often give rise to a number of secondary cases, but if the average number of secondary cases falls below a certain level then any outbreak will spontaneously die out, and so everyone is protected, whether they have been immunised or not.

Amongst humans, herd immunity is a phenomenon that relates only to infections that are primarily or exclusively human. If we immunise enough of the population, it is possible to attain herd immunity even to a highly communicable disease like measles, but there can be no such thing as herd immunity to tetanus or salmonellosis.
The beautiful consequence of herd immunity is that once you have achieved it, the disease will just practically disappear from your population and only new cases will be imported. And if this can be achieved on a global scale then the disease is eradicated from the face of the earth. You only need to do it once. This has been achieved with smallpox, a feat that is one of the crowning glories of the history of immunology.

With acquired immunity people who have recovered from a disease largely do not get the same disease again, this is because the activated lymphocytes (called T cells and B cells) become memory cells so that the next time a person meets up with the same antigen the immune system can destroy it. This immunity can be strong, weak, short-lived or long lasting depending on the type of antigen. Immunity can also be affected by inherited genes.

Acquired immunity can also be brought about by immunization with vaccines. Vaccines contain micro-organisms or parts of the micro-organism that have been treated so that they can provoke an immune response but not the full blown disease.

How Meningitis B invades the body

As yet, there is still no vaccine available to protect against meningococcal group B - the most common form of the disease in the UK. Although meningococcal vaccines have been developed in countries such as Cuba and New Zealand, these were mainly to control of outbreaks and will not protect against the most prevalent strains in the UK.

Meningitis B employs particularly cunning ways to avoid the immune system, which in turn present serious challenges for the scientists trying to design a vaccine against it. The capsules of Meningitis B bacteria are decorated with sugar molecules that perfectly mimic molecules found on our own human cells. This means that the bacteria are not recognised as foreign when they are in the body. They effectively slip under the radar of the immune system, camouflaged to look like the host cells.

This clever trick makes vaccine design difficult because the capsule is no good to use as an antigen. Therefore, scientists have been searching for new, different antigens on the surface of Meningitis B bacteria that could be developed as potential vaccine targets. To make things even more difficult for them, Meningitis B continually changes the proteins displayed on its outer surface. It makes constant alterations, choosing from an enormous library of potential combinations. This means that the scientists must look for an antigen that remains the same so that antibodies against it will still work against all the different variations.

A number of potential Meningitis B vaccines are in the pipeline. These vaccines are using not one, but many Meningitis B proteins in an attempt to protect against this variable bacterium. In some cases, scientists have used proteins found on small bubbles of membrane that exist on the outside of the bacterium. Others are targeting specific groups of well-characterised proteins. Researchers are also looking at whether the non-disease causing sister bacterium, Neisseria lactamica, could hold the key to producing an effective vaccine against Meningitis B.

What are bacteria?

Bacteria are tiny single-cell microorganisms and are normally a few micrometers in length. They are neither plant nor animal, being a classification of their own, and usually exist together in millions.

Scientists now say that bacteria were the first life forms on Earth four billion years ago. It is believed that for the next three billion years all life forms on the planet were microscopic in size, dominated by bacteria and archaea (classified as bacteria, but genetically and metabolically different from all other known bacteria).

Bacteriologists say that bacteria are absolutely everywhere except for places that humans have sterilized. Bacteria can survive where no other organism can. Even the most unlikely places where temperatures may be extreme, or where there may be a high concentration of toxic chemicals have bacteria.

Indeed, it is certain that we would not have existed without them. The air we breathe - specifically the oxygen - was most probably created millions of years ago by the activity of bacteria.

Bacteria come in three main shapes:

Spherical (like a ball) which are called cocci (singular coccus).
The meningococcal bacteria which causes meningitis is a diplococcus - a pair of two joined cocci.
Rod shaped known as bacilli (singular bacillus) or vibrio if curved. Spiral known as spirilla (singular spirillum) or spirochetes if their coil is very tight.

Bacteria

There are many variations within each shape group. Unlike the cells of a plant or animal, bacterial cells have no nucleus.

Bacteria reproduce through binary fission which is an asexual form of reproduction which doesn't involve a male and female. The cell continues growing and growing, eventually a new cell wall grows through the center forming two daughter cells, which eventually separate. Each daughter cell has the same genetic material as the parent cell.

The problem with binary fission is that every daughter cell is identical to the parent cell it came from, as well as all its sisters. This makes it harder for bacteria to survive, especially when attacked by antibiotics. To get around this, bacteria use a process called recombination.

The secrets of bacteria have slowly been discovered over the course of human existence - thousands of years ago it was suggested that something too small for the naked eye to see may be the cause of disease, and over the hundreds of years that followed various theories were given. It was not until 1676 that bacteria were properly identified as microorganisms.

Although they can also be dangerous, causing disease, bacteria also play a vital part in keeping all things alive.

Plants, for example, would not survive without bacteria - plants cannot extract nitrogen from the soil, so they benefit from the atmospheric nitrogen which is assimilated by bacteria and released when they die.

We need them too - the human body contains huge amounts of friendly bacteria that are beneficial, e.g. bacteria in the digestive system are essential for the breakdown of certain types of nutrients, such as complex sugars, into forms the body can use.

Friendly bacteria also protect us from pathogenic (disease-causing) bacteria by occupying places in the body where they live and some attack the pathogens.

Whilst acknowledging that bacteria, found in soil, water, plants and animals, have played their part in creating life on earth, it is also true that they have caused some of the most deadly diseases in human history, including the plague, cholera , pneumonia, tuberculosis and of course meningitis.

Despite this, as hygiene has improved over the past 100 years or so, the number of deaths from bacterial diseases has dropped significantly, particularly in developed countries. Vaccines and immunisation programmes have been developed and whilst still devastating, the dangerous effects of bacteria are constantly being hit by modern medicine.