Chapter 2: Defence against disease
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Introduction
No plant or animal lives in isolation. All around, other living things are struggling to survive, and the survival of one individual or group is sometimes at the expense of another individual or group.
One of the major driving forces in biology is the urge to survive so that reproduction can occur and the individual's genes can be passed to the next generation.
For survival to reproductive maturity, plants, animals and other living things need defenses against those who would injure or kill them to ensure their own survival.
Keep this is mind as you study this section.
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Plant Defences
Plant defence mechanisms are not as complex as those of many animals, and most seem to be directed at restricting damage caused by chewing insects, but they are nevertheless, surprisingly successful. They include:
- cells capable of synthesis of antibiotics and various enzymes which can destroy pathogens,
- cellular processes which detect and destroy damaged cells, leaving only healthy cells,
- chemicals with unpleasant tastes/odours which deter all but a few predators,
- chemicals which are skin irritants,
- various drugs and psychedelic compounds which deter predators,
- molecules which mimic predators' hormones and disrupt normal life cycle,
- specialised proteins (lectins) which bind to and inactivate many bacteria, fungi and insects,
- specialised hair like structures on leaves that release a sticky substance when touched by insects. The insects then stick to the hairs and starve to death.
Some of these defence mechanisms rely on the production of particular molecules. If the genes for the production of the molecules can be located and transferred to commercially useful plants, it becomes possible to create plants with increased survival chances.
This is the essence of genetic engineering, and this is the sort of research several of the scientists in Biochemistry at LaTrobe are doing.
This type of topic would be very suitable for your CAT 2 investigation, and more information will be available on it at this Web site when you need it.
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Non-specific and specific defences in animals.
Animal defence mechanisms involve both non-specific mechanisms and specific mechanisms.
Non-specific mechanisms are general in their action, they are not geared to any particular individual or species, but rather they provide barriers or other mechanisms to avoid attack by 'foreign' species.
In invertebrates, the non-specific defence systems are the most important, including
- tough outer coat (exoskeleton or skin) to resist penetration by predators/parasites,
- hairs and scales for protection,
- secretions which either deter or disable predators,
- phagocytic cells that identify and engulf damaged or foreign cells.
As well as the above non-specific mechanisms, specific defence mechanisms (antibody formation) are found in all vertebrates.
There is, however, a gradual increase in the complexity of the immune system as we move from the primitive fish, through the more modern fish, reptiles, amphibians and birds towards the mammals.
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Summary of the mechanisms of fighting disease in humans.
The human body has evolved several mechanisms for surviving an attack by micro organisms and other 'foreign bodies'.
Non-specific defence against foreign bodies.
The logical first line of defence for the body is at the many surfaces through which foreign bodies may enter.
The non specific defences are technically not part of the immune system, but they are a vital way of avoiding the dangers of the external environment to which all our surfaces are exposed.
Since many of our surfaces are warm, moist and bathed in potential nutrients, the best defence is clearly not to allow invaders to remain there for any length of time!
The major non specific defences are:
- physical barrier of skin,
- antibacterial secretions from skin oil glands,
- acid in sweat,
- continual washing of eyes with enzyme containing fluid (tears),
- bacteriostatic secretions in ears,
- sticky mucus and nasal hair in nose,
- mucus and cilia trap and remove debris and micro-organisms from trachea and bronchii,
- acid and commensal organisms in stomach and intestine,
- pH and commensal organisms in vagina,
- antibacterial proteins in semen.
As well as this surface defence, there is a first line of cells and their products always present in low concentrations and rapidly activated in a localised area of infection or tissue damage.
These cells and cell products are able to recognise self and non-self, and work together to inactivate the non-self substances and remove them. The major factors here are:
- complement - a series of proteins which attach to the surface of bacteria, frequently causing them to lyse
- interferons - which aid with virus recognition
- phagocytes - specialised white blood cells (macrophages and granulocytes) which ingest and remove damaged cells and bacterial cells tagged with complement.
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Specific defence mechanisms
The human immune system: phagocytes, antibody-antigen reaction, T and B lymphocytes.
The human body needs a way or ways to protect it from viruses, bacteria, fungi and parasites. It must also provide a mechanism of recognising and inactivating any other large foreign molecules which are potentially damaging.
In spite of all of the surface and other non-specific defences, breaks in our surfaces occur and smart or lucky micro organisms do manage to enter our bodies. Then the specific defences, or more correctly, the immune system, comes to the rescue.
This is a complex system, but careful analysis of the elements of it, and their interactions, will make sense of it. There are several important concepts needed to understand how the immune system works:
- Substances that the body recognises (mainly from surface molecules) as non-self are antigens.
- The cells that carry out many of the functions of the immune system are specialised white blood cells, called lymphocytes. There are two main types of lymphocytes, B lymphocytes and T lymphocytes.
- B lymphocytes make and release antibodies, which are defence molecules that react with and destroy antigens.
- B lymphocytes are mainly produced in the bone marrow.
- T lymphocytes regulate immune responses and can directly attack and kill foreign organisms or infected cells.
- T lymphocytes mature in the thymus gland. There are two types of T cells, the helper cells (TH cells) and the cytotoxic (killer) cells (TC cells).
- TH cells are regulatory cells that produce and secrete lymphokines.
- Lymphokines control the development of other T and B cells as well as macrophages (a type of phagocyte - white blood cell).
- TC cells, when stimulated by antigens and lymphokines, kill foreign organisms or infected body cells.
- B cells are being produced in the bone marrow constantly. Each B cell manufactures antibody that is attached to its surface and acts as a receptor. If the antibody does not interact with its specific antigen within a few days it dies. If the antigen is encountered, in the presence of TH cells, the B cell is stimulated to differentiate. Some of the cells become memory cells, others become plasma cells.
- Memory cells retain the information about the antigen-antibody pair and can rapidly respond if the antigen is encountered again. These are the cells that confer immunity once formed after a first exposure or immunisation to a disease.
- Plasma cells only last a few days, but in that time they release large amounts of antibody (also known as Immunoglobulin or Ig)
- Antibodies circulate in the plasma from where they can be extracted and used across species. Maternal antibodies also enter breast milk and are important in protecting a baby from infection in the first few months of life.
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Cellular and non-cellular (humoral) immune responses.
There are two types of immune response that are usually effective against different types of micro organisms.
The cellular immune response
The cellular response is mediated by T cells against antigens from viruses or parasites. The sequence of events involves macrophages, TH cells, soluble lymphokines, B cells, TC cells and phagocytes.
- Macrophages ingest foreign particles then display foreign protein
on their surfaces as antigens
- TH cells bind to the macrophage, releasing lymphokines
- Lymphokines stimulate B cell antibody production, development of more T cells, development of phagocytes and perhaps lead to fevers and nausea in the patient.
- TC cells lyse the affected cells and kill them.
- Phagocytes remove damaged cells
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The humoral immune response
The humoral ( = in serum) response is mediated by antibodies, produced by B cells in response to antigens from bacteria.
- B cells bind to bacterial antigen (may be cell wall molecule or bacterial toxin)
- B cells differentiate into memory cells and plasma cells
- Plasma cells reproduce to form a clone of cells all releasing the specific antibody for the particular antigen.
- Antibodies combine with antigen
- Phagocytes remove damaged or antibody coated bacteria.
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Some applications of immunology
An understanding of the working of the Immune System has enabled scientists to use this knowledge to explain the mechanisms of some diseases. It also makes it possible for medical research to develop treatments which prevent or reduce the impact of many formerly common diseases. This area of research is well represented in several Institutes in Melbourne.
Immunisation.
It is possible, and usually desirable, to gain immunity (a reasonable level of appropriate memory cells) to a pathogen without actually suffering from the disease caused by that pathogen.
To achieve this, healthy individuals are inoculated with some form of suitable antigen which will initiate an immune response in the person.
So that the person being immunised does not suffer the actual disease, the antigen is modified in some way. This may be by using:
- killed organisms,
- chemically modified organisms
- chemically modified toxins
- antigenic molecules extracted from the organism (such as cell wall components),
- a similar but less virulent (infective) strain of organism,
- a number of small doses of the organism.
However it is done, immunisation builds up the blood memory cell concentration, so that exposure to the pathogen is followed by a large, swift rise in blood antibodies and little if any sign of the disease.
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Mass immunisations of communities has eradicated some diseases (eg. smallpox) as the number of susceptible hosts has declined below the level needed to maintain a viable population of the pathogen.
Recently, in Australia, there have been outbreaks of immunizable diseases such as whooping cough. This has occurred because parents have not had their children immunised and there are now enough susceptible hosts to allow the disease to spread. Several deaths from whooping cough have occurred in this epidemic.
Adverse reactions to immunisation occur occasionally, most often in persons whose immune systems are already impaired (eg. asthmatics, severely allergic people). Some people believe that the slight risks of adverse reactions outweigh the advantages of immunisation. Statistics from times before mass immunisations indicated that the mortality (= death) and morbidity (= illness) rates of epidemics of disease in unimmunised populations are far greater than those of immunisation.
Antigenic variation occurs in some pathogens (eg. influenza virus), so that slight structural variations in strains of the organism can avoid the memory cells stimulated by an earlier infection.
This is the reason that 'new' strains of the common cold and of influenza appear each year.
It also explains why 'at risk' individuls (the elderly and chronically ill) are advised to have annual 'flu shots -last year's antibodies will probably not protect against this year's strain of the virus.
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Passive immunity occurs when antibodies made in a different animal are injected into the infected animal. A short term emergency treatment, as the injected antibodies are recognised as 'foreign' and eventually destroyed. (eg. tetanus antitoxins)
Antivenenes are such antibodies. They are created in animals such as horses or cows, using small amounts of snake or spider venom. The antibodies formed are isolated from the animal's blood, purified and used to stop the effects of the venom in humans unfortunate enough to be bitten. In this situation, the time saved in letting the antivenene neutralise the venom could well save a life.
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Immunological memory relies on memory cells, developed in response to the first exposure to an antigen. Subsequent exposure to the same antigen usually results in more memory cells and a faster, higher antibody response.
Different antigens seem to produce different degrees of memory. One dose of chicken pox usually confers immunity for life, but tetanus 'booster shots' are recommended every ten years.
Auto immune diseases occur when a person's immune system incorrectly identifies that person's cells as 'non-self' and begins to destroy them with the immune system.
This is often seen in joints where connective tissue is broken down in diseases such as arthritis. There are drugs which slow the process, but naturally any drugs which inhibit the immune system leave the patient susceptible to infection.
Allergies occur when the immune system becomes sensitised (in a manner similar to that which occurs in immunisation) to substances which are normally relatively harmless.
The non-specific defences seem particularly triggered here, with the familiar symptoms of 'hay-fever' in mild cases and the more serious asthma in severe cases.
Very rarely, an extreme reaction known as anaphylactic shock occurs and this can be fatal. Anaphylaxis is the most usual reason for people to die of bees stings.
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Tissue transplants and rejection pose a special problem to surgeons. All people have their own characteristic combinations of proteins on their cell surfaces. This is genetically programmed.
This is seen in a simple way with the ABO blood groups, but there are in fact dozens of tissue protein types which can be identified.
When a patient requires a tissue transplant, the lab. needs to 'match' as many of these proteins in the donated tissue as possible. This reduces the risk of rejection of the donor tissue as 'non-self' by the recipient's immune system. The best tissue match comes from identical twins, with close family members the next best.
If close relative donation is not possible, large quantities of immunosuppressive (= anti-rejection) drugs may help whilst the patient's body learns to accept the donated tissue.
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Foetal RH incompatibility may occur when a baby with Rh+ blood is born to a Rh- mother. In this case, the baby has the particular Rh antigen on its red blood cells (inherited from the father), but the mother has no such antigens on hers, and so the antigen is identified as 'foreign' by mother's immune system.
A small amount of foetal blood may enter the maternal circulation during the process of birth, although during a pregnancy the foetal and maternal circulations are separated by membranes at the placenta. This small amount of foetal Rh+ blood will cause the mother to develop antibodies to this particular antigen.
In subsequent pregnancies, if the foetus is again Rh+, there can be severe problems with placental exchange of nutrients and wastes, to the detriment of the developing baby.
Fortunately, it is now routine for Rh- mothers to have their babies tested at birth, and if necessary the mother can be treated to stop the development of anti Rh+ antibodies.
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AIDS (= Acquired Immune Deficiency Syndrome) is the disease caused by the HIV (Human Immunodeficiency Virus).
This virus has a long latent period (symptomless) after infection, but eventually, most persons infected with HIV develop the symptoms of AIDS.
The HIV is a retrovirus (its nucleic acid is RNA, not DNA) containing ssRNA (ss = single stranded).
The virus enters TH cells and forces them to make viral DNA from the code on the ssRNA.
The viral DNA becomes incorporated in the TH cells, which lose their function in the immune system as they manufacture more and more HIV. Eventually, there are too few TH cells to carry out their normal immune function and the patient becomes susceptible to many secondary infections which would otherwise be easily controlled. At this stage the person displays the symptoms of AIDS. Eventually the secondary infections become overwhelming and without a functional immune system the patient dies.
The reason that the HIV is proving so difficult to control with drugs is that, once inside the TH cells, it is as if it was part of 'self', and any drug which attacked the infected TH cells would probably attack unaffected TH cells too, thus hastening the onset of the AIDS symptoms.
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We welcome your comments about this project.
This page is maintained by Jenny Herington, who can be contacted at bio_cat@bioserve.latrobe.edu.au by email.
All of the pages at the VCE Biology Students' site are copyright © Biochemistry, LaTrobe University.
Last update :14 April 97
