ALLERGIES AND THE DEFENCE AGAINST DISEASES #3

A pleasant greetings to all my readers once again. I want to say a big thanks to you for all the support and encouragement. Today, I will continue from where I stopped in my last post on the series of ALLERGIES AND THE DEFENCE AGAINST DISEASES.

So, I’ll be raising the curtain with the term “transplantation” and “grafting”, before going further to discuss on “antibiotics” and its resistance.

TRANSPLANTS AND GRAFTS

Transplantation involves taking cells, tissues or organs from one individual and placing them into another individual. Since the first organ transplant operations in the 1950s, patients have received hearts, lungs, skin, corneas, kidneys and various other organs. The success rate of these operations has improved steadily.

Pixabay

The biggest problem facing most transplant recipients is that of rejection. The cells of transplanted tissue are covered in antigens that stimulate the specific immune response of the recipient, notably the cell-mediated response brought about by T cells. Symptoms of rejection include the degeneration of blood vessels in the transplanted organ and the destruction of whole cells, followed by their replacement with ‘scar’ tissue. A patient whose transplant is rejected becomes seriously ill: he or she loses the function of the organ concerned and the massive immune response puts an incredible amount of stress on an already weakened body.

Rejection can be minimized by tissue typing or by using drugs to suppress the immune system.

Tissue typing

Like red blood cells, other body cells also have surface antigens that are different in different people. Body cells, such as cells in the kidney or liver, have many antigens that differ, from person to person. This is why matching the tissue type of the donor and recipient is much more complex than matching blood groups. In practice, the cells from two people are never identical, so the aim is to match people who have as few differences as possible.

Immunosuppression

If the recipient of a transplant has a fully functional immune system, even a closely matched organ will be rejected to some extent. To counter this, transplant patients are given immunosuppressive drugs. The most effective is currently cyclosporin. This chemical, isolated from a fungus, inhibits the action of T cells and so has a profound effect on cell-mediated immunity. Since the introduction of cyclosporin in the early 1980s, the success rates of some transplants have risen to over 90 per cent.

The problem with immunosuppressive drugs is, of course, that they reduce the body’s ability to fight off infection. Transplant patients are more prone to infection from normally harmless microorganisms, particularly viruses. Although the dose of immunosuppressive drugs can be reduced after a few months if there is little sign of rejection, transplantees must continue to take them for life.

ANTIBIOTICS AND THE TREATMENT OF INFECTION

Throughout human history, millions of people have died from bacterial infections. Today, we still suffer from such infections but we now have antibiotics – safe and effective drugs that can be used against the bacteria that cause disease.

The first antibiotics developed in the 1930s and 1940s were chemicals that one microorganism produced to kill another. For example, penicillin, the first antibiotic to be produced in large enough quantities to be used in combating bacterial infections, is produced by a type of fungus. Since then, antibiotics have been extracted from a range of unusual sources including snowdrop bulbs and toad skin: yet others can be synthesized.

PRODUCING PENICILLIN ON A LARGE SCALE

Penicillin is produced commercially using a strain of fungus called penicillium chrysogenum. This is an aerobic organism that needs a high level of oxygen to grow in culture. For this reason, it is grown commercially in fermenters with a relatively small volume of 40-200 dm³. These are easier to aerate effectively than much larger fermentation tanks.

Chemical structure of Penicillin

G. Cacycle; public domain

In the commercial production of penicillin, the fungus produces most penicillin at temperatures between 25 and 27 °C. During the first 40 hours or so, the fungus is growing in the culture and increasing in biomass. Once it has reached a certain concentration in the culture, it starts to produce large amounts of penicillin, but this continues for only a short time before the fungus starts to run out of nutrients and begins to die. To get the most out of each fermentation, new nutrients are added after 40 hours to stimulate a further increase in biomass. About 20-40 per cent of the culture is removed, to be processed so the penicillin can be purified, and new culture medium replaces it. This process, called batch fill and draw, can be carried out up to ten times before the fermentation tank needs to be cleaned out completely.

ANTIBIOTICS AND ANTIBIOTIC RESISTANCE

Before the 1940s. Having a serious bacterial infection often meant death. Antibiotics such as penicillin seemed to be wonder drugs at first, bringing people back from the brink of death. Today we have thousands of different antibiotics that work in hundreds of different ways.

Antibiotics are, however, no longer seen as wonder drugs. Since the 1940s, resistant strains of bacteria have arisen that can case infections that are very difficult to treat, as they no longer respond to an antibiotic. One of the best-known antibiotic-resistant bacteria is MRSA – methicillin-resistant Staphylococcus aureus.

But how did this happen? Bacteria, like all living organism, vary. In any population of bacteria, the majority will be killed by an antibiotic. But it only takes one bacterium to have a gene mutation that enables it to survive the effect of an antibiotic to create billions of descendant bacteria all antibiotic resistant. Bacteria also swap antibiotic resistance genes by passing plasmids containing the genes from one bacterium to another – so the resistance spreads even more quickly.

Molecular targets of antibiotics on the bacteria cell.

Original: J Raghu Vector: Mrmw - Own work based on: Antibiotics action.png; CC0

WHAT ARE THE TYPES OF ANTIBIOTIC RESISTANCE?

A bacterium becomes resistant to an antibiotic when one of its alleles becomes altered. There are four main mechanisms by which this can lead to resistance:

The altered allele occurs in the gene that codes for the protein that is a target for the antibiotic. If the altered protein is a different shape, it can no longer bind to the antibiotic. If there is no binding, the antibiotic can have no effect on any biochemical pathways inside the bacterium.
Some antibiotic-resistant bacteria stop the antibiotic reaching its target molecule inside the cell either by preventing the antibiotic from entering the cell or by pumping it out faster than it can get in. This can happen if the mutation occurs in an allele that codes for a membrane receptor or transport protein.
If the target of an antibiotic is an enzyme, bacteria that produce an alternative version of the enzyme can bypass the antibiotic. This enzyme still carries out the same function as the original in the cell, but the antibiotic does not affect it. Having both forms of the same enzyme gives the bacteria a great advantage – it can survive equally well whether or not the antibiotic is present.
A mutation might enable the bacterium to produce an altered enzyme that is then able to react with the antibiotic and disable it. These types of mutation are happening all the time in bacteria – normally, they just arise and are lost. However, when antibiotics are present in large amount for a long time, this exerts a selection pressure that results in lots of antibiotic-resistant bacteria.

HOW MUCH OF A PROBLEM IS ANTIBIOTIC RESISTANCE?

Globally, antibiotic resistance is now a major public health problem. Over-prescribing of antibiotics by doctors is thought to be a major cause. Many still give antibiotics, particularly to children, for sore throats and earache, which are mostly caused by viruses. Another factor is that people don’t finish courses of antibiotics – they stop taking them as soon as they feel better. This allows bacteria even with partial resistance to re-establish an infection. Antibiotics used in farming that get into the human food chain also do not help.

Hospitals now face serious problems as MRSA and other antibiotic-resistant strains of bacteria can cause terrible infections in elderly patients and in those in intensive care, who are already weak. The UK has one of the highest rates of hospital-acquired infection in Europe: MRSA costs the NHS £1 billion per year and, together, MRSA and antibiotic-resistant Clostridium infections killed 16 500 people between 2004 and 2007.

Choosing Wisely antibiotics poster small English

Wikipedia Commons

SUMMARY

After reading all these series of mine on ALLERGIES AND THE DEFENSE AGAINST DISEASES, we should know and understand the following:

We are surrounded by potential pathogens (disease-causing organisms) such as bacteria and viruses which can cause disease if allowed to enter and multiply inside the body.
The body’s defence system consists of barriers to keep microorganisms out, and mechanisms to detect and destroy those that do enter. Together, these mechanisms are the immune response.
The immune system is capable of non-specific responses and specific responses. Non-specific mechanisms (inflammation and phagocytosis) occur in response to any invading microorganism. Specific mechanisms allow the body to recognize and fight individual types of microorganism. There are two specific responses: cell-mediated immunity and humoral immunity.
Lymphocytes (types of white cells) are responsible for the specific immune response. T cells mature in the thymus gland and B cells come directly from bone marrow. Both are able to recognize foreign antigens that come from pathogens.
B cells are responsible for humoral immunity: they secrete specific proteins called antibodies.
T cells are responsible for cell-mediated immunity and help to control the overall specific response. T killer cells attack pathogens or infected cells. T helper cells activate B cells, telling them to secrete antibodies. T suppressor cells damp down the immune response when the infection is over.
Autoimmune diseases occur when the body’s immune system attacks its own tissues. Examples include rheumatoid arthritis, multiple sclerosis and myasthenia gravis. Allergies occur when the body ‘over-reacts’ to a normally harmless substance such as pollen.
When cells or tissues are taken from one individual and given to another, they may be recognized as ‘foreign’ and destroyed. This process is often called graft rejection. To minimize the chance of rejection in blood transfusions and organ transplants, it is important to match blood and tissue types.
Antibiotics are important drugs for treating infections caused by bacteria. In the time since antibiotics were first developed and used in the 1940s, bacteria have evolved to become resistant to them. Antibiotic-resistant strains of many bacteria are becoming common and represent a problem for doctors and researchers.