KEEPING HEALTHY - The bodies defence against infection

and ways of fighting infectious diseases

e.g. vaccination-immunisation, drugs, antibiotics, monoclonal antibodies

See also Culturing microorganisms like bacteria - testing antibiotics

Doc Brown's Biology Revision Notes

Suitable for GCSE/IGCSE/O level Biology/Science courses or equivalent

 This page will answer many questions e.g.

 How does our body defend itself when it becomes infected?

 What are the physical and chemical methods of protection?

 What is a pathogen?   What is our immune system?  What is a vaccine?

How does vaccination-immunisation protect us?



How our bodies defend themselves against infectious diseases?

Be aware that our bodies provide a good environment for many microbes to live and multiply at our expense and can make us ill once they are inside our body.

Our bodies need to be capable of stopping most microbes from getting in and dealing with any microbes which do get in.

Starting with a historic note

A simple example of how science works - cleanliness reduces the incidence of infection!

Appreciate the contribution of Semmelweiss in controlling the rate of patient infection to solving modern problems with the spread of infection in hospitals.

Semmelweis worked in Vienna General Hospital in the 1840s and witnessed large numbers of women dying after childbirth from a puerperal fever disease.

He thought that the staff of the hospital were spreading the disease via unwashed hands.

After instructing doctors and nurses to wash their hands in an antiseptic solution, the mortality rate was considerably reduced.

Although Semmelweis didn't realise it at the time, the antiseptic solution was killing the infecting bacteria.

Apparently, when he left the Vienna hospital, the practice of washing hands in the antiseptic solution was relaxed, and the death rates rose again!

With the advent of new strain of bacteria today, there is now an even greater need for emphasis on hospital hygiene than ever before - so, if on a hospital visit, PLEASE WASH YOUR HANDS in the antiseptic gel provided.


What are the dangers?

Microorganisms that cause infectious disease are called pathogens.

Bacteria and viruses may reproduce rapidly inside the body and may produce poisons (toxins) that make us feel ill.

What is a bacteria?

Bacteria and certain protozoa are very small cells which can rapidly reproduce by cell division in your body making you feel ill by damaging your body's cells and producing toxins (poisons produced as a by-product of the bacteria's cell chemistry).

What is a virus?

Viruses are NOT cells and much smaller than bacteria, but damage the cells in which they reproduce. Viruses replicate by invading a cell and using the cell's genetic machinery to reproduce themselves ie copies of the original virus. The virus 'invaded' cell then bursts releasing lots of new viruses which go on to invade more healthy cells. The cell damage makes you feel ill as your body (temporarily) fights back to make as many good cells as it can to replace those destroyed by the virus.

Fungi are also pathogens and includes microorganisms like yeasts and moulds (so don't eat mouldy food!).


How do our bodies defences work?

The body has different physical and chemical ways of protecting itself against pathogens.

Physical mechanisms of protection from pathogens

Your skin and hairs and mucous in the respiratory tract can stop a lot of the pathogen cells from entering your body.

The whole of the respiratory tract from the nasal passage, down the trachea and into the lungs is covered with mucous and lined cilia (fine hairs that can move freely at their ends).

The hairs and mucous in your nose traps dust and any other particles that might contain pathogens like bacteria  before they can get down  into the lungs.

Cells in the trachea and bronchi secrete mucous to trap pathogens.

The hair-like structure of the cilia then move-push the mucous up to the back of the throat where it can be swallowed,

and the cilia can also move the mucous along from the lungs up to the nasal passage -and then you can blow your nose!

The stomach produces strong hydrochloric acid, a strong acid that kills most pathogens, and a safe distance from the sensitive tissue of the mouth and tongue!

Skin in good condition acts as a very effective physical barrier against pathogens.

As well as acting as a physical barrier, your skin also secretes antimicrobial molecules that can kill pathogens.

What happens if the skin is damaged?

When a cut in the skin occurs, small sections of cells called platelets help the blood to clot quickly to seal the wound (seal = scab when dry) and prevent microorganisms entering the skin tissue or blood stream. Clotting also reduces blood loss.

The greater the concentration of platelets in the blood the faster the clotting process ('sealing') can occur.

Chemical protection by killing pathogens

In tears our eyes produce a chemical called lysozyme that kills bacterial microorganisms on the surface of the eye.

Lysozyme is an enzyme that breaks down the cell walls of bacteria, so destroying the bacteria on the surface of the eye.

As already mentioned, your stomach contains quite concentrated strong hydrochloric acid which kills the majority of pathogenic bacteria - sadly not all of them at times!

The saliva produced in your mouth contains molecules that can kill some of the pathogens that enter the mouth.

 

Beyond the stomach

Not all the remaining pathogens that reach the stomach from the mouth are killed by the hydrochloric acid.

Some pathogens enter the intestines and have to compete with the 'local' bacteria for food to survive.

Your gut is full of bacteria - the gut is their natural habitat.

 

These physical and chemical defences are non-specific and can counteract a variety of types of pathogens.

 


The IMMUNE SYSTEM

What is the immune system?

The immune system 'kicks in' if pathogens do get inside your body.

The white blood cells are present throughout your body in your blood system and therefore are always at hand to defend you from invading pathogens and the do so in three main ways - see sections (a) to (c) below.

If your white blood cell count is low you are more susceptible to disease and infection, because this equates to a weakening of your immune response system

For example, HIV/AIDS weakens white cell action and hence the body has a weaker responding immune system that allows pathogens to have a more devastating effect on the body - sometimes with fatal consequences from a disease that in a healthy body would not have proved fatal.

The immune system of the body produces specific antibodies to kill a particular pathogen.

This leads to immunity from that pathogen.

In some cases, dead or inactivated pathogens stimulate antibody production.

If a large proportion of the population is immune to a pathogen, the spread of the pathogen is very much reduced.

More details on the functions of the white blood cells of the immune system

What is the function of white blood cells?

What is an antibody? What is an antigen? What is an antitoxin?

If pathogens like harmful bacteria actually get into your body your immune system responds to destroy them to defend you from their harmful effects.

The most important feature of your immune system is the function of the different types of white blood cells.

These white blood cells are travelling around the whole of your body in your bloodstream and so are always available to tackle an infection.

More of the types of white blood cells can be made to tackle any major infection, but infections may take time to be cleared up completely.

When white blood cells meet an invading pathogen (bacteria, virus etc.) they can respond in three different ways.

(a) The ingesting of pathogens by white blood cells - phagocytes

White cells can surround 'foreign' invasive microorganisms and break them up, effectively digesting them.

The white blood cells that do this are called phagocytes and the process is called phagocytosis.

Phagocytes are made and stored in the bone marrow - the soft tissue at the centre of bones.

When an infection happens more phagocytes are released and travel through the blood to the point where the pathogen (e.g. bacteria) has entered the body and the diagram shows what happens next.

1. The phagocyte detects the presence o pathogens and moves towards them.

2. Phagocytes have a flexible membrane that changes shape and surrounds a clump of the pathogens.

3. The pathogens then become completely enclosed in the cytoplasm of the phagocyte cell and can then be digested.

4. Enzymes in the cytoplasm of the phagocyte break the pathogens down and the products absorbed into the phagocyte's cytoplasm.

 

(b) Producing antibodies, which destroy particular bacteria or viruses.

All invading cells have unique molecules ('molecular structure') on their surface called antigens.

When white cells encounter a 'foreign' antigen on a pathogen they don't recognise, they produce proteins called antibodies which lock onto the antigens of the pathogen making them more susceptible to phagocytosis - described above.

The white blood cells that perform this task are called B-lymphocytes and the overall process is described using the diagram below. These cells are involved with specific immune responses.

1. Large numbers of B-lymphocyte white blood cells (grey) are always present in the blood and they can recognise OR not recognise, different types of pathogens - bacteria and viruses.

2. All invading pathogens (green O) have unique molecules on their surface called antigens (blue -, often proteins). If the surface of the lymphocyte detects the antigens (blue) on the surface of a 'foreign' pathogen they don't recognise, a response is triggered by the lymphocyte cell.

3. The lymphocyte cell begins to produce protein molecules called antibodies (black Y).

4. The antibodies move out of the cell to 'confront' the invading pathogen and will not lock onto any other pathogen.

5. The antibodies lock onto the antigens on the surface of the pathogen (e.g. invading bacteria cell).

6. The invasive pathogen is then more easily found and destroyed by another type of white blood cell - the phagocytes, which destroy them by phagocytosis - described in section (a) above.

The antibodies often cause the pathogens to clump together making it easier for the phagocyte cells to find and ingest them by phagocytosis.

The white blood cells that detect the pathogen then divide to produce more copies (clones) of the same white blood cell, which in turn make more of the antibody.

The antibodies are produced quite rapidly and move all around the body in the bloodstream to find other similar pathogens.

Memory lymphocyte white blood cells (memory cells) are also produced in the immune response to a pathogen and the harmless forms you are vaccinated with.

They stay in the body for a long time and 'remember' a specific antigen on the surface membrane of a specific pathogen. This means if you get re-infected, your body's response is much faster and more effective - you might not even notice any symptoms!

The antibodies produced are specific to that type of antigen, they will not lock onto any other type of antigen, hence they are specific to a particular pathogen.

e.g. the antibody for the measles virus is different to the antibody of chickenpox virus.

The production of antibodies by the body in recognition of foreign material is called the immune response.

One the 'blueprint' antibody is made, it is rapidly reproduced, carried round the body in the bloodstream, and lock onto the specific invasive pathogens and kill them.

The immune response mechanism of the white blood cells is the same in fighting either bacterial or viral infections.

If a person becomes infected with the same pathogen microorganism, the appropriate type of white blood cell will automatically, and quickly, produce the correct specific antibodies to kill the pathogen because of the first invasion of a particularly pathogen the person has become naturally immune to the specific infection.

This is because once the white blood cells have made an antibody in response to a particular infection, they can easily recognise the specific bacterium or virus and produce the same antibody again - see below - more on memory lymphocytes.

This immunity helps prevent the immune person becoming ill again, or at least minimises the chance of 2nd attack of the specific pathogen having any significant effect.

More on memory lymphocytes

Memory lymphocytes are naturally produced in the immune response to a pathogen.

When a pathogen enters your body for the first time, the immune response is slow because there are relatively few of the B-lymphocytes around capable of making the antibody to combat a particular pathogen.

Eventually, your body will produce enough of specific antibody to overcome the infection, but in the mean time, you will display symptoms of the disease.

As well as antibodies, memory lymphocytes are also produced by your immune response to a foreign antigen of a pathogen. They stay around in the body for some time and 'remember' a specific antigen on the surface membrane of a specific pathogen.

The person is now got some immunity to respond much more quickly to a second infection.

See also section on vaccination-immunisation

If the same pathogen enters your body again there are far more white blood cells around to recognise the pathogen and produce antibodies to combat it.

In other words, the secondary response is faster and stronger than the first immune response, an, in many cases, destroys the pathogen before you exhibit any symptoms.

need graph

 

Epidemics are large scale outbreaks of an infectious communicable disease. Mass vaccination programmes help reduce the chances of an epidemic, but, a high percentage of a population needs to be vaccinated to avoid the infection spreading rapidly.

 

(c) White blood cells also help to defend against pathogens by:

Producing antitoxins, which counteract the toxins released by the pathogens.

You can think of these antitoxins as a sort of antibody that combines with the poisonous waste product molecules produced by e.g. by bacteria to form a harmless product - a sort of chemical 'neutralising' effect (but NOT the acid-alkali variety!).

These antitoxins are very specific chemicals that remove the toxicity effect of the toxins produced by pathogen cell action.


How can our health be further protected from pathogens? fighting infections!

Be able to explain how the treatment of disease has changed as a result of increased understanding of the action of antibiotics and immunity.

Be able to evaluate the consequences of mutations of bacteria and viruses in relation to epidemics and pandemics - data provided.

Be able to evaluate the advantages and disadvantages of being vaccinated against a particular disease - data provided.

As already mentioned, Semmelweiss recognised the importance of hand-washing in the prevention of spreading some infectious diseases.

By insisting that doctors washed their hands before examining patients, he greatly reduced the number of deaths from infectious diseases in his hospital.

Some medicines, including painkillers, help to relieve the symptoms of infectious disease, but do not kill the pathogens.

As we have seen, our immune system of the body produces specific antibodies to kill a particular pathogen.

This leads to immunity from that pathogen.

In some cases, dead or inactivated pathogens stimulate antibody production.

If a large proportion of the population is made immune to a pathogen by vaccination-immunisation, the spread of the pathogen is very much reduced - which is what the next section is all about

 


VACCINATION-IMMUNISATION

If you become infected with a new ('foreign') pathogen that your immune system doesn't recognise as 'friendly', it takes your white blood cells a few days to produce the antibodies to protect you.

In the mean time you are unfortunately ill and not feeling well to a greater (fatal) or lesser (a bit poorly) degree.

Vaccination is a successful method to drastically reduce the response time of your immune system and usually prevents the onset of the disease.

People can be immunised against a disease by introducing small quantities of dead or inactive forms of the pathogen into the body (vaccination).

The process of vaccination has radically changed the way we fight disease because it is not about treatment of a disease, it is all about preventing the effects of an infection.

(c) doc b Know that vaccination is an important method of preventing infection.

What is vaccination? What is a vaccine? What is immunisation?

Vaccination protects the individual from future infections and mass scale vaccination can greatly reduce the incidence of disease.

Protection is better than cure! If you become infected with a pathogen, it takes a few days for your white cell immune system to deal with the microorganism, and you can become quite ill in a few days.

Vaccination is the process of injecting the individual with small amounts of specific harmless dead/inactive microorganisms (pathogens) which carry the antigens that cause the immune system to produce the corresponding protective antibodies - even though the pathogen is in a harmless form.

The MMR vaccine contains weakened versions of the viruses that cause measles, mumps and rubella (German measles).

So, vaccines automatically stimulate the white blood cells to produce antibodies that destroy the invading 'foreign' pathogens.

This makes the person immune to future infections by the microorganism ie gives the individual immunity from further attacks - the overall process is referred to as immunisation.

If the same type of pathogen, that you have been vaccinated against, enters your body, your body can respond by rapidly making the correct antibody, in the same way as if the person had previously had the disease.

(c) doc bVaccination is when the vaccine is administered to you (usually by syringe injection).

Immunisation is what happens in your body after you have the vaccination.

The vaccine stimulates your immune system so that it can recognise the disease (invasive pathogen - bacteria or virus) and protect you from future infection (i.e. you become immune to the infection).

The diagram and notes below what happens on vaccination to complete the immunisation effect.

1. You are injected by vaccination with a weakened/inactive/dead form of the pathogen - although harmless, your body will respond to the 'new' antigens detected - an immune response.

2. Your lymphocyte white blood cells recognise the pathogen as harmful and produce the antibodies to counteract 'what is perceived' as an active pathogen.

3. If the same actually active pathogen enters your body, it is quickly recognised by its antigen molecules and attacked by the specific antibodies already present and more can be made too, quite rapidly.

4. The effect of the pathogen is 'neutralised' so you don't become ill.

5. When the pathogens are combined with the antibodies they are much more susceptible to be ingested by the phagocyte white blood cells and destroyed.

MMR vaccine is used to triple protect children against measles, mumps and rubella (German measles).

The vaccine contains weak inactive versions of three viruses that cause measles, mumps and rubella.

The effects of vaccination can 'wear off' over time, and booster injections maybe necessary to increase the levels of the protective antibodies.

There are arguments for and against vaccination (the 'pros and cons').

For vaccination-immunisation:

Vaccines have resulted in the large scale control of many infectious diseases that were once common and often fatal eg measles, mumps, polio, rubella, smallpox, tetanus, whooping cough etc.

These communicable diseases were once common in the UK but smallpox has been completely eradicated and polio infections are very rare these days (down as much as 99%)

Epidemics are less likely with mass vaccination - spread of the disease is less likely as there are fewer infected people carry an active form of the disease - but a large percentage of the population needs to have been vaccinated - less people around to carry and pass on the pathogen.

Without mass vaccination an outbreak of epidemic proportions is much more likely - many more people potentially to carry and transmit the disease which can spread rapidly, particularly in densely populated areas where lots of people are in close contact.

Against vaccination-immunisation:

Some vaccines do not always give you immunity but development work goes on all the time to make more effective vaccines - especially as different strains of viruses and bacteria are constantly evolving.

There may also be side-effects in which the 'patient' has a bad reaction to a particular vaccine eg swelling, fever, seizure (serious!), but such reactions and complications are rare and the mass good effect of large scale immunisation should be balanced against the very rare negative effect - however serious this might be.

There are some concerns over using 'whole' pathogens so that the vaccine actually causes disease in the person. Therefore some vaccines only use parts of the pathogen cells which must include the antigens for the white blood cells to react to.

Producing vaccines and carrying out mass vaccination programmes can be expensive - the disease may be rare or the vaccine proves to be not that effective.

The benefits of vaccination must outweigh the development and production costs involved.

There is a very small risk involved with most medical treatments and although side-effects are not uncommon, without vaccination some of these diseases are fatal or have very serious non-fatal outcomes - people can die of from measles, rubella has serious consequences for pregnant women, there can be serious complications for infected people who have not been vaccinated.

Following a seaside accident - cut on knee, as an eleven year old, I collapsed unconscious after a tetanus injection at a local hospital. I was ok within half an hour BUT my parents got a bit of a shock!

Parents of young children are always given details of vaccination schedules and where appropriate, warned of side effects associated with specific vaccines.

Sadly in some countries, including in the UK, a lot misinformation was put about on social media about the supposed ill-effects of taking the MMR (mumps, measles and rubella) vaccine e.g. causing autism. The information was not backed up by real scientific data and as a result was hundreds of thousands of young children were not vaccinated with three medical conditions with potentially serious consequences.


More on fighting disease.

See also

Keeping healthy - communicable diseases - pathogen infections   gcse biology revision notes

Keeping healthy - non-communicable diseases - risk factors for e.g. cancers   gcse biology revision notes

 

DRUGS - medicines to treat disease

Drugs are substances that affect how the body works.

Most drugs are proven safe medicines to use, but some are potentially dangerous if misused.

Many drugs can be bought directly from a pharmacy, but others can only be obtained from a doctors prescription.

The first thing you should appreciate is the difference between 'feeling better' and being 'cured'!

Some drugs like aspirin or paracetamol relieve pain and reduce discomfort i.e. reduce the symptoms, but they do not counteract the disease you are suffering from e.g. a virus giving you a headache.

Such drugs do NOT cure you because they do NOT kill the pathogen causing the disease in the first place.

Lots of other drugs e.g. cold remedies, decongestants, analgesic pain killers etc., cannot destroy e.g. the cold or flue virus but do make you feel a lot better and help you get a better nights sleep!

Other drugs e.g. the antibiotic penicillin do kill or inhibit the growth of certain bacterial infections.

(See next section on antibiotics and drug development)

However, they are not a 'blanket cure', different types of bacteria require different types of antibiotic and the correct match is required to effect a cure.

ANTIBIOTICS

See also Culturing microorganisms like bacteria - testing antibiotics  gcse biology revision

Unlike 'symptom relievers' like aspirin, antibiotics like penicillin do kill or inhibit the growth of certain bacterial infections.

However, they are not a 'blanket cure', different types of bacteria require different types of antibiotic and the correct match is required to effect a cure.

Never-the-less, the widespread use of antibiotics has greatly reduced the number of deaths from communicable diseases caused by bacteria.

Unfortunately, antibiotics do NOT destroy viruses infections from e.g. flue or cold viral infections.

Virus attacks can be treated with very specialised and expensive anti-viral drugs, but since viruses reproduce in your own body cells, its difficult to avoid damage to you own healthy body cells.

 

Antibiotics, including penicillin, are medicines that help to cure bacterial disease by killing infectious bacteria inside the body, without killing your own body cells.

What is an antibiotic? How do they work?

NOTE: An antibiotic kills bacteria in the body.

An antiseptic kills bacteria outside the body e.g. on the skin or disinfecting a worktop in the kitchen.

Antibiotics cannot be used to kill viral pathogens, which live and reproduce inside cells.

Antibiotics do NOT destroy viruses, typified by the cold and flue viruses we all suffer from.

Viruses make your own body cells reproduce the invasive virus and unfortunately anti-viral drugs may attack good cells too!

It is quite difficult, and costly, to develop and market anti-viral drugs that will only kill the virus and not your own body's healthy cells.

Antibiotics like penicillin kill or prevent the growth of harmful pathogens, they kill the bacteria but not your own healthy body cells.

Antibiotics work by inhibiting processes in bacterial cells, they do NOT affect the cells of the host organism.

Some antibiotics inhibit the building of the cell walls of bacteria, which prevents cell division - these antibiotics do not affect human cells which do not have cell walls.

Different antibiotics attack different bacteria, so it is important that specific bacterial infections should be treated with the appropriate specific antibiotics.

The use of antibiotics has greatly reduced deaths from infectious bacterial diseases.

However, overuse and inappropriate use of antibiotics has increased the rate of development of antibiotic resistant strains of bacteria.

You need to be aware that it is difficult to develop drugs that kill viruses without also damaging the body’s tissues.

Explaining the use of antibiotics to control infection:

Antibiotics are taken internally e.g. intravenous syringe injection, or orally taken by tablet or liquid suspension.

Antibacterials to treat bacterial infections

Probably the most well known antibacterial is the antibiotic penicillin which is effective against many bacterial infections BUT NOT viruses like the common cold or flue.

An antibiotics can kill bacteria or prevent them growing and reproducing.

Many strains of bacteria, including MRSA, have developed resistance to antibiotics due to mutations, which cause stronger more resilient strains of bacteria to survive as a result of natural selection.

To prevent further resistance arising it is important to avoid over-use of antibiotics.

Knowledge of the development of resistance in bacteria is limited to the fact that pathogens mutate, producing resistant strains.

Mutations of pathogens produce new strains.

Antibiotics and vaccinations may no longer be effective against a new resistant strain of the pathogen.

The new strain will then spread rapidly because people are not immune to it and there is no effective treatment.

Can bacteria become resistant to antibiotics?

Unfortunately the answer is yes! Bacteria will sometimes quite naturally mutate into forms that are resistant to current antibiotics, so if you are infected with a new strain of bacteria, your resistance from your 'current' antibiotic is not as effective.

If an infection is treated with an antibiotic, any resistant bacteria from any mutations will survive and this means more resistant bacteria can survive and reproduce to infect other people, while the non-resistant strains will tend to be reduced.

This bacterial mutation is an example of natural selection at the individual cell level and drug companies are constantly trying to develop new antibiotics to combat the new evolving strains of harmful bacteria - but new harmful 'superbugs' are becoming more common the more we use antibiotics and new epidemics can break out!

MRSA, methicillin-resistant staphylococcus aureus causes serious wound infections (including after surgery in a hospital), can't be treated with many current antibiotics and causes serious wound infections that can be fatal to young babies or elderly people in particular.

Misuse by over-prescribing antibiotics is believed to be causing the rise of mutant resistant strains of bacteria, so doctors are being advised to avoid over-prescribing antibiotics to reduce the mutation rate and not treating mild infections with antibiotics.

Symptoms like headaches or sore throats are not a justification for being prescribed antibiotics. Unfortunately, many patients (for various reasons) are prescribed antibiotics when they are actually suffering from a viral infection.

BUT, if an antibiotic is appropriately prescribed, you should always complete the course, even if you feel a lot better, this is to maximise killing the bacterial infection and minimise the chance of passing on of the infection.

It isn't just bacteria that can mutate, viruses can also evolve via new mutations. Viruses are notable for the rapidity with which they can mutate which makes it difficult to develop new vaccines. The reason being that changes in the virus (or bacteria) DNA leads to different gene expression in the form of different antigens, so different antibodies are needed. The flue virus is a never ending problem and in the past pandemics (epidemics across many countries at the same time) have killed millions of people, mercifully this rarely happens these days thanks to antibiotics.

Understand that antibiotics kill individual pathogens of the non-resistant strain.

Individual resistant pathogens survive and reproduce, so the population of the resistant strain increases.

Now, antibiotics are not used to treat non-serious infections, such as mild throat infections, so that the rate of development of resistant strains is slowed down.

The development of antibiotic-resistant strains of bacteria necessitates the development of new antibiotics.

 

ANTISEPTICS

See also Culturing microorganisms like bacteria - testing antiseptics  gcse biology revision

Antibiotics kill pathogens in your body, antiseptics kill pathogens outside of your body e.g. on the surface of your skin or disinfecting surfaces in the kitchen.

Antiseptics are used to clean wounds by killing microorganisms or stopping them multiplying.

The use of antiseptics in hospitals and GP surgeries is vital to prevent the spread of infectious diseases like MRSA.

You should always cleanse-disinfect your hands with the facilities provided before visiting someone in hospital.

There are many commercial antiseptic cleaning substances available for your kitchen, toilets etc.

Most claim to 'kill 99% of all germs' !!!!

 

ANTIVIRALS

Antivirals are drugs used to treat viral infections.

Most antivirals do not kill the virus but stop them reproducing.

They are not easy to develop as effective anti-virus agents because it is difficult to target the virus without damaging the host cells.


DEVELOPING and TESTING NEW DRUGS

See also Products of the Chemical & Pharmaceutical Industries & impact on us (GCSE chemistry notes)

It has been known for some time that plants produce a wide range of chemicals to defend themselves against attack from e.g. insect pests or pathogen microorganisms.

Historically, currently and in the future, these substances provide a basis for developing drugs to treat human diseases.

Even some of our current medications come from knowledge of plants giving us many traditional herbal recipes e.g.

(i) The painkiller aspirin was developed from chemicals in willow plants that reduce fever and reduce pain in childbirth.

(ii) Drugs like digitalis have developed from chemicals found in foxglove plants and are used to treat heart conditions.

Many antibiotics are made from growing microorganisms (first found by 'accident'!) e.g.

(i) The famous scientist Alexander Fleming noticed in some petri dishes used for investigating bacteria, a mould had grown, but the area around the mould was free of bacteria.

He realised that the mould (in this case Penicillium notatum), was producing a chemical that killed the bacteria.

This chemical was extracted and named penicillin, and proved to be a very effective antibiotic in killing various bacterial infections.

(ii) These days pharmaceutical companies grow fungi and other microbes on a large scale and extract the antibiotic molecules in the laboratory.

 

These days drugs are manufactured on a huge scale in the pharmaceutical industry.

Chemists can synthesis molecules based on naturally found organic compounds from plants and also lots of molecules that have never existed in nature until synthesised in a modern chemical laboratory.

Historically, most effective drugs were discovered by accident e.g. somebody by chance notices some effect of a chemical which might have a medical application.

However, these days, research is very systematic and we have an extensive database of knowledge about the structure and properties of molecules AND how diseases work.

Some drugs have been successfully designed by computer software that can construct and display molecular structure e.g. design a molecule with a shape to fit into the active site of an enzyme to inhibit its action.

See also Products of the Chemical & Pharmaceutical Industries & impact on us (GCSE chemistry notes)

Developing a new drug - a lengthy and costly process!

The drugs developed and produced by the pharmaceutical industry are often very costly in the making for several reasons

You have to carry out a lot of research and development to find a suitable compound that performs an effective medical treatment for some condition e.g. to reduce blood pressure, kills cancer cells, slows down the development of dementia etc.

The compound must be tested, often modified and retested.

All new potentially useful drugs must be fully tested in trials including animal trials (controversial) and human trials and this all takes time and money.

Until a drug has fully passed all safety and effectiveness tests it cannot be marketed and sold to medical institutions from hospitals to high street pharmacies etc. The manufacturer must prove that any pharmaceutical product like a drug does meet all legal requirements that it does actually work and is safe to use.

The stages in the testing of a new drug-medicine is summarised below:

Stage 1 Preclinical testing (non-living animal testing):

Computer models can be used initially to simulate a human's responses to a drug and can identify possible effective drugs, but cannot possibly be as accurate as actually using cell tissue cultures or live animals.

In preclinical testing the drugs are tested on human tissue cells in the laboratory.

However, these procedures cannot be used to test drugs that affect a complex body system.

e.g. a drug for controlling blood pressure must be tested on the whole live animal with its complete circulatory system.

Stage 2 Preclinical testing (live animal testing):

If the stage 1 tests prove satisfactory, and no potential harmful effects are detected, you can then move onto testing the drug on live animals.

This is to see whether the drug works and producing the desired medical effect (this is known as testing the efficacy of the drug).

You are also looking for potential harmful effects, including toxicity.

You are also investigating the appropriate dosage in terms of concentration/amount and frequency of administering the drug.

According to UK law, any new drug must be tested on two different live mammals, but there are objections to this on several grounds:

(i) Many people object on the grounds it is cruel and unethical to use animals in tests, but others think drug safety should override these considerations i.e. avoid the use of a potentially dangerous drug.

(ii) Animals used in testing drugs are not quite the same as humans. Could their biological differences give us false results in terms of the efficacy of the drug when used on humans?

Stage 3 Clinical testing on humans:

If the drug has passed all the preclinical tests, you can then test it on human volunteers in what is called a clinical trial - which is just as complicated as any research laboratory testing.

Initially, the drug is tested on healthy volunteers - this is the only way to find out if there are any harmful side effects on a healthy body working normally. Initially it is unsuitable to test the drug on sick people who are likely to be more vulnerable to side effects.

At first very low doses of the drug are administered to healthy people and then the dose is gradually increased.

If the results of the tests on healthy individuals are good and meet any health and safety criteria, the drug can then be tested on patients suffering from the illness-disease the drug is designed to combat.

From these tests the optimum dose is found - that is the dose that is most effective with the fewest side effects.

The safety and effectiveness of the new drug must be thoroughly checked out.

This takes some time, human drug trials may last for months or even years.

Sometimes this is due to the long term progression of a disease e.g. cancer and the time taken for the treatment to be shown to be effective.

It might also be a long time before the symptoms of side effects show up.

We now get into the practice of how to get statistically valid results from real patients.

To test the effectiveness of a drug a group of patients are randomly selected into two groups.

One group is given the new drug and the other group a placebo - a substance that is like the drug being tested, but has no effect - it can be just a sugar pill.

Using a placebo ensures the doctors can see the real difference the drug is having on the patient's condition. This also allows for where the patient does expect an improvement in their medical condition and might actually feel better - even though unknowingly, nothing is suppose to improve!

In some trials on seriously ill patients, placebos are not used - it would be unethical not to allow all patients the same chance of benefiting from the new drug.

In other trials doctors might test new drugs against the best existing treatment instead of testing against a placebo.

Note that that clinical trials must be blind, meaning, the patient in the trial doesn't know whether they are getting the new drug or a placebo.

Sometimes the clinical trials are double-blind where neither the patients nor the doctors know who has the drug or placebo until all the results have been gathered and analysed. This ensures the doctors administering, monitoring and analysing the drug trial are not subconsciously influenced by their knowledge of the patients.

Before any drug is approved for use in our healthcare systems, the results of drug testing trials must be peer reviewed by other equally qualified medical practitioners.

This is essential to avoid false or biased claims of the new drug's performance in real patients.

Peer reviewers check the validity of the drug trial e.g. has it been correctly designed and rigorously carried out to the highest scientific standards.

Finally, the drug can only be approved for patients of the general public after permission is granted by the appropriate medical agency if all health and safety criteria are met. The rules are strict to ensure the drugs are as effective and safe to use as possible.

 


MONOCLONAL ANTIBODIES - production and uses

You need to have read about antibodies before studying this section.

How do you make monoclonal antibodies?

As we have seen, antibodies are produced by the type of white blood cell called B-lymphocytes. It is proving useful to medicine to produce lots of a specific antibody from multiple clones of a single white blood cell. The antibodies will be identical and only target one specific antigen protein molecule. Unfortunately, lymphocyte cells do not divide easily, but tumour cells can be readily cultured to undergo rapid cell division.

The process starts by (i) injecting a mouse with a specific antigen and then extracting the B-lymphocytes produced and (ii) culturing tumour cells.

(iii) You then fuse a mouse B-lymphocyte with a tumour cell to create a 'hybrid' cell called a hybridoma cell - which can be cloned to make lots of identical cells. It is these cells that produce identical monoclonal antibodies, which can be collected and purified for research or direct medical use.

If possible, you can produce monoclonal antibodies that bind to anything you want e.g. an antigen that is only found on the surface of a one specific type of cell e.g. a target cancer cell.

Because monoclonal antibodies only bind to a specific antigen molecule, you can therefore target a specific cell and destroy it (e.g. a cancer cell) or 'neutralise' a chemical in the body to inhibit its poisonous action.

 

Uses of monoclonal antibodies

 

1. Treating diseases using monoclonal antibody techniques

As we have seen, different cells in the body have different antigen molecules on their surface, which gives them a unique molecular signature.

This means you can make monoclonal antibodies that will bind to ('target') specific cells with that specific antigen.

Cancer cells have antigens on their cell membranes that you do not find on normal healthy body cells and they are known as tumour markers.

In the laboratory you can culture cells to produce monoclonal antibodies (see above) that will bind to these tumour marker antigens, but the real trick is other things you can do with the monoclonal antibody e.g.

an anticancer drug-agent can be attached to the monoclonal antibody - see the diagram below.

The anti-cancer agent might be a toxic drug or radioactive substance (radioisotope) or chemical that inhibits the growth and division of cancer cells. Any toxic effect will only kill the cancer cells, not the healthy non-cancerous cells, because the anti-cancer agent is only attached to the cancer cell antibody, which itself, will only attach itself to the cancer cells - that's the way the antigen-antibody mechanism works.

Advantages and problems with using monoclonal antibodies

Despite the wonderful advantages of applying monoclonal antibodies to medical treatments, there are the 'usual' pros and cons.

In other cancer treatments e.g. chemotherapy and radiotherapy you inadvertently damage neighbouring healthy cells as well as killing the cancer cells because of the high energy of the radiation (often gamma radiation). This doesn't happen with monoclonal antibody drug cancer treatment where the side effects are much less.

Unfortunately, monoclonal antibodies do cause more side effects than expected.

Symptoms exhibited include fever, low blood pressure and vomiting.

These side effects have limited the use of monoclonal antibody drug treatments.

 

2. Tests for tracing and measuring specific substances to help in medical diagnosis

e.g. monoclonal antibody applications include ...

(a) Binding them to a specific hormone or other molecule in the blood to measure the concentration ('level' of chemical).

(b) Testing blood samples for the presence of specific pathogens.

(c) Tracing and locating specific molecules on cell or tissue.

You first make monoclonal antibodies that bind to the specific molecule X you are investigating.

The antibodies are then reacted to bind with a fluorescent dye molecule to facilitate an analysis.

If the molecule X is present in your analysis sample, the monoclonal antibody will attach itself to it.

Therefore the presence, location and concentration of molecule X can be obtained using uv light to cause a fluorescent effect.

(d) Testing for cancer.

You first make the specific antibody that will bind to the cancer cells, but this antibody is labelled with a radioisotope.

The radioactive labelled antibody is fed into the patient through a drip into the bloodstream and carried all the way around the body.

When the antibody encounters a cancer cell it will bind to it because it recognises the antigen of the cancer cell (the tumour marker).

The radiation emitted from the radioactive tracer is monitored by a special camera (linked to a computer and screen) and where the cancer cells are concentrated, the emitted radiation will be the greatest - this will show up as a bright 'hot spot' on the screen.

Therefore doctors can see exactly where the cancer is, the size of the tumour and, from previous scans, whether the cancer is spreading e.g. secondary cancers from prostate cancer i.e. cancer spreading out of the prostate gland.

See also using monoclonal antibodies to treat cancer in section 1.

(e) Using monoclonal antibodies to find blood clots

Blood clots form when proteins in the blood join together to form a solid mesh that restricts `blood flow.

You can make monoclonal antibodies, labelled with a radioactive tracer, that bind to these particular proteins.

After injection of these monoclonal antibodies into the bloodstream, a special camera (linked to a computer and screen) can pick out where the blood clot is where there is a high concentration of the radioisotope - shown by a bright 'hot spot' on the screen.

Blood clots are very potentially dangerous and this technique is able to detect them and allow the doctor to remove them before the patient comes to harm.

 

3. Pregnancy testing using monoclonal antibodies

Monoclonal antibodies are used in a pregnancy test strip/stick which can detect the HCG hormone which is present in the urine of pregnant women. The science behind the test is illustrated in the diagram below.

1. You wee onto the end of the strip or dip it into a collected sample of urine - the method is upto you!

2. The reaction zone is impregnated with the HCG antibody which has been modified with an enzyme (e) to facilitate a colour effect if HCG hormone is present.

As the urine diffuses up the strip this 1st antibody combines with any HCG hormone in the urine and continues moving along the strip.

3. In the test zone the HCG combination encounters and attaches itself to a 2nd, but immobile antibody.

If the HCG hormone is present in the urine the enzyme triggers a chemical reaction to give a colour change e.g. the appearance of blue colour would signify a positive pregnancy test.

If the HCG hormone is not present, no colour change is seen, indicating a negative pregnancy result

4. The control zone is to check that the strip is working correctly, irrespective of a positive result.

As the urine diffuses further up the strip it carries along some of the first HCG antibody (with enzyme e) that has not combined with the HCG hormone. It then encounters an immobile version of the 2nd antibody which already has the HCG hormone attached to it

If the pregnancy stick is behaving correctly, you should get the same colour change as if it was a positive pregnancy test.

 

Note: You can impregnate the strip with different antibodies to test for the presence of other substances in the urine e.g. the antigens on other pathogens.

 


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