Defence against infectious diseases 9/28/10 8:39 PM

6: Human Health and Physiology6.3 Defence against infectious diseases

Orange book: pg. 217-227Green book: pg. 95-97

6.3.1 Define pathogen (pg. 217, 101 )

6.3.2 Explain why antibiotics are effective against bacteria but not against viruses (pg. 218, 101)

6.3.3 Outline the role of skin and mucous membranes in defence against pathogens (pg. 218-219, 101 )

6.3.4 Outline how phagocytic leucocytes ingest pathogens in the blood and in body tissues (pg. 219, 102 )

6.3.5 Distinguish between antigens and antibodies (pg. 219, 102 )

6.3.6 Explain antibody production (pg. 220, 102 )

6.3.7 Outline the effects of HIV on the immune system (pg. 224, )

6.3.8 Discuss the cause, transmission and social implications of AIDS (pg. 224, )

6.3.1 Pathogens 9/28/10 8:39 PM

6.3.1 Define pathogen

Orange book pg. 217Green book pg. 101

To doWrite out a definition for the term ‘pathogen’.List examples of common pathogens.Ensure you read the relevant sections in the textbooks and complete a brief summary in your green exercise books.

Out bodies are exposed to many disease-causing agents. Any living organism or virus that is capable of causing a disease is called a pathogen. Pathogens include: viruses, bacteria, protozoa, fungi and worms of various types. Yet exposure to the vast majority of the pathogens does not result in a disease. Primarily, this is because we are too well defended for most pathogens to enter our bodies and, in the case of those that do enter, we have often previously developed an immunity to that pathogen. For some, such as bacteria, there are chemicals, called antibiotics that can work against the living bacteria cells but do not affect our body cells.

6.3.2 Antibiotics 9/28/10 8:39 PM

6.3.2 Explain why antibiotics are effective against bacteria but not against viruses

Orange book pg. 218Green book pg. 101

To doEnsure you read the relevant sections in the textbooks.Read and highlight keywords only in the text below.Summary in your green books to include:definition of an antibioticwhat is different about a ‘therapeutically’ useful antimicrobial agent compared to other chemicals that might destroy microbes?explain the difference between ‘cidal’ and ‘static’explain why antibiotics are effective against bacteria but not viruses.

Antibiotics are antimicrobial agents produced naturally by other microbes (usually fungi or bacteria). The first antibiotic was discovered Alexander Flemming in 1928 from the filamentous fungus Penicilium notatum. Flemming did not appreciated the importance of what he had found, and the antibiotic substance, named penicillin, was not purified until the 1940s, just in time to be used at the end of the second world war. Today there are hundreds of different antibiotics, though many are modified forms of naturally-produced antibiotics (semi-synthetic antibiotics).

Action of AntibioticsMany chemicals kill microbes. But a therapeutically useful antimicrobial agent must be selectively toxic i.e. it must kill pathogenic microbes already growing in human tissue, without also killing the host human cells.

Some antibiotics are cidal (bacteriocidal, fungicidal, etc.), which means they kill the microbes, while others are static (bacteriostatic, fungistatic, etc.), which means they stop further growth, but don't kill existing cells. Both are useful medically, because if the growth of an infective pathogen is stopped, the body's immune system will be able to kill it.

Antibacterial DrugsIn order to understand how antibiotics work against bacteria, you need to recall that bacteria are prokaryotic cells. Prokaryotes, have many unique features not present in eukaryotes, so antibiotics can be selectively toxic by targeting such features as the bacterial cell wall, 70S ribosomes, and enzymes that are specific to bacteria. In this way the human eukaryotic cells are unaffected. There are also differences in biochemical reactions and pathways. For example, proteins synthesis is similar in both types of a cell, but not exactly the same. Some antibiotics may selectively block protein synthesis in bacteria, but have no effect on our cells’ ability to manufacture proteins. Another type may inhibit the production of a new cell wall by bacteria, thus blocking their ability to grow and divide.

Viruses do not have any form of cell structure or metabolism – hence, antibiotics are ineffective against viruses. Viruses replicate only within living host cells and make use of the living host cell’s transcription and translation mechanisms. These are eukaryotic mechanisms and thus are not affected by any antibiotics, which affect only prokaryotic mechanisms. The absence of any sort of cell wall means that penicillin has not effect on viruses.

6.3.3 Defence 9/28/10 8:39 PM

6.3.3 Outline the role of skin and mucous membranes in defense against pathogens

Orange book pg. 218-219Green book pg. 101

To doEnsure you read the relevant sections in the textbooks.Read and highlight keywords only in the text below.Complete the following tables as a summary in your green exercise book:SkinStructure Function in DefenceClosely packed cellsShedding of epidermal cellsSebaceous glandsAcidity (pH3-5)Perspiration & lysozyme

Mucous MembranesStructure Function in DefenceMucusNose hairsTrachea ciliaTearsSalivaGastric JuiceVaginal secretions

The best way to stay healthy is to prevent pathogens from having the chance to cause disease. One way you can do this is to try and stay away from sources of infection. This is why it is still common to isolate (or quaratine) people who have certain transmittable diseases. Obviously, it is not possible to isolate yourself from every possible source of infection. The human body harbours a huge number of microorganisms. Indeed, we contain about 10,000 times as many bacterial cells than we do human cells! We are constantly exposed to countless organisms in the food and water we consume, in the air we breathe and on the objects we touch. Without means of defense, the human body would be an ideal place for microorganisms to live – however the human body has some ingenious ways to make it difficult for pathogens to enter and start an infection.

First line of defence: Skin and Mucus MembranesThe skin and mucus membranes of the body are the first line of defence against pathogens (a pathogen is a disease causing organism). Both physical and chemical barriers discourage pathogens and foreign substances from penetrating the body and causing disease.

With its many layers of closely packed cells, the outer layer of the skin – the epidermis – provides a formidable barrier to the entrance of microbes. In addition, periodic shedding of epidermal cells helps remove microbes at the skins surface. Bacteria rarely penetrate the intact surface of healthy epidermis. If this surface is broken by cuts, burns or punctures however, pathogens can penetrate the epidermis and invade adjacent tissues or circulate in the blood to other parts of the body.

Certain chemicals also contribute to the high degree of resistance of the skin and mucus membranes to microbial invasion. Sebaceous (oil) glands of the skin secrete an oily substance called sebum that forms a protective film over the surface of the skin. The chemicals in sebum inhibit the growth of certain pathogenic bacteria and fungi.

The acidity of the skin (pH3-5) is caused in part by the secretion of fatty acids and lactic acid. Perspiration helps flush microbes from the surface of the skin and it also contains lysozyme, an enzyme capable of breaking down the cell walls of certain bacteria. Lysozyme if also present in tears, saliva, nasal secretions and tissue fluid, where it also exhibits antimicrobial activity.

Mucus membranes which line the body cavities, secrete a fluid called mucus that lubricates and moistens the cavity surface. Because mucus is slightly viscous, it traps many microbes and foreign substances. The mucus membranes of the nose have hairs that trap and filter microbes, dust and pollutants form inhaled air. The mucus membranes of the respiratory tract contain cilia, microscopic hair-like projections. The waving action of the cilia propels inhaled dust and microbes that have become trapped in mucus towards the throat. Coughing and sneezing accelerate movement of mucus and its entrapped pathogens out of the body.

Other fluids by various organs also help protect surfaces of the skin and mucus membranes. In the eyes, tears are manufactured and drained away in response to irritants. Blinking spreads tears over the surface of the eyeball, and the continual washing action of tears helps dilute microbes and keep them from settling on the surface of the eye.

Saliva, produced by the salivary glands, washes microbes form the surfaces of the teeth and from the mucus membranes of the mouth, much as tears wash the eyes. The flow of saliva reduces the colonisation of the mouth by microbes.

Gastric juice, produced by the glands of the stomach, is a mixture of hydrochloric acids, enzymes and mucus. The strong acidity of gastric juice (pH 1.2-3.0) destroys many bacteria and most bacterial toxins.

6.3.4 Phagocytes 9/28/10 8:39 PM

6.3.4 Outline how phagocytic leucocytes ingest pathogens in the blood and in body tissues

Orange book pg. 219Green book pg. 102

To doView the two animations on phagocytes:http://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter2/animation__phagocytosis.html

http://www.sp.uconn.edu/~terry/Common/phago053.html

Read through the process of phagocytosis in the textbooks and below

In your green exercise books simplify and annotate a diagram of the process of phagocytosis

What happens when pathogens do get in ?Our bodies have yet another line of defence for when pathogens do successfully enter.

Role of phagocytic leucocytesLeucocytes, also known commonly as white blood cells, are the cells in our bloodstream that help us fight off pathogens that enter our bodies and also provide us with an immunity for many pathogens we encounter a second time. There are many different types of leucocytes and they have many different roles in keeping us healthy.

One type of leucocyte that gets involved very early in the process of fighting off a pathogen is called a macrophage. Macrophages are large white blood cells that are able to change their cellular shape to surround an invader and take it in through the process of phagocytosis. This movement of the cell membrane is very similar to the movement an amoeba makes and is quite often referred to an amoeboid motion. Even though we think of blood cells as being within the blood vessels, that is not always true for these macrophages. Because macrophages can easily change their shape by amoeboid movement, they are able to squeeze their way in and out of small blood vessels. Therefore, it is not unusual for macrophages to first encounter an invader completely outside the bloodstream.

When a macrophage does meet a cell, it recognizes whether the cell is a natural part of the body and therefore “self”, or not part of the body and therefore ‘not-self’. This recognition is based on the protein molecules that make up part of the surface of all cells and viruses. If the collection of proteins the macrophage encounters is determined to be ‘self’ , then the cell is left alone. If the determination is ‘not-self’, the macrophage engulf the invader by phagocytosis. All phagocytes typically contain many lysosome organelles in order to help chemically digest whatever has been engulfed. This types of response by the body is called non-specific because the identity of the pathogen has not been determined at this point, just the fact that it is something that is ‘not-self’ and therefore should be removed.

Phagocytosis by LeukocytesThe diagram below is TOO detailed however it illustrates the process of phagocytosis.Phagocytosis occurs by the following process:1. The pathogen becomes surrounded by pseudopodia. 2. Pathogen is ingested forming a "phagosome," which moves toward the lysosome. 3. Fusion of the lysosome and phagosome, releasing lysosomal enzymes into the phagosome. 4. Digestion of the ingested material. 5. Release of digestion products from the cell.

* Too much info, but - MHC II – major histo-compatibility complex – label every cell in the body as belonging to you – so it is important in cell recognition (i.e. recognizing ‘self’ cells over ‘foreign’ cells).

6.3.5 Antigen & Antibodies 9/28/10 8:39 PM

6.3.5 Distinguish between antigens and antibodies

Orange book pg. 219Green book pg. 102

To doEnsure you read the relevant sections in the textbooks.Read and highlight keywords only in the text below.Summary in your green books to include:definition of an antigenexamples of typical antigensdefinition of antibody

AntigensSubstances that are recognised as foreign and provoke immune responses are called antigens. Some antigens are free molecules such as venoms and toxins; others are components of plasma membranes and bacterial cell walls. Entire microbes or parts of microbes may act as antigens.

Chemical components of bacterial structures such as flagella, capsules, and cell walls are antigenic, as are bacterial toxins.

Non-microbial examples of antigens include chemical components of pollen, egg white, incompatible blood cells and transplanted tissues and organs.

Typically, just certain parts of a large antigen molecule act as the triggers for immune responses. Antigens are large, complex molecules such as nucleic acids, lipoproteins, glycoproteins and polysaccharides. Some universal molecules such as glucose and amino acids are not antigenic; if they were, our immune systems would attack the nutrients and other molecules essential to our very survival. The uniqueness of antigen molecules enables the body to distinguish its own (“self”) molecules from those of any other individual or organism (“non-self”). The immune system “learns” to distinguish self from non-self antigens prior to birth; thereafter, it normally attacks only non-self antigens.

AntibodiesAn antibody is a protein found in the blood plasma and body secretions. A particular region of the antibody forms an antigen-binding site, which attached to the antigen molecule. The antibody’s structure matches its antigen much as a lock fits a specific key. In other words, if you has a measles infection, you would produce one type of antibody and another types if you contract a virus that gives you flu like symptoms. Each type antibody is different because each type has been produced in response to a different pathogen. The immune system is thought to produce as many as 2 million different antibodies! Antibodies are produced by certain white blood cells.

6.3.6 Antibody Production 9/28/10 8:39 PM

6.3.6 Explain antibody production

Orange book pg. 220Green book pg. 102

To doEnsure you read the relevant sections in the textbooks.Read and highlight keywords only in the text below.Use the second diagram to describe the process of antibody production but TRY not to look back at the first set of notes.Summary in your green books (try to complete it from memory)

Antibodies occur in the body fluids and bind to bacteria, toxins and extracellular viruses, ‘tagging’ them for destruction by other cells. The type of cells involved in antibody production are B-lymphocytes which, synthesis and secrete the antibodies.

The essential features of antibody production are:Recognition. B-lymphocytes recognise an antigen and divide repeatedly; most of the cells produced differentiate into plasma cells, which synthesise antibodies to that antigen.

Attack. Plasma cells release their antibodies, which bind to the antigen, render it harmless, and “tag” if for destruction by other agents.

Memory. Some B-lymphocytes differentiate into memory cells, which provide lasting protection against future exposures to the same pathogen.

(Try to remember these three stages as the three ‘R’s – Recognise, React and Remember).

The diagram below illustrates the steps in an antibody-mediated response.

Different B-lymphocytes have thousands of different surface receptors; some of these B-lymphocytes should recognise the antigen.

Once a B-lymphocyte recognises an antigen it will bind to it.

The B-lymphocyte multiply, so producing many identical B-lymphocytes which will recognise the specific antigen. This process is called clonal selection, as only the B-lymphocyte which recognises the antigen is cloned.

Some of the clones differentiate into plasma cells – these cells produce antibodies. Some of the B-lymphocytes do not differentiate into plasma cells and instead become memory cells that are ready to respond more rapidly and forcefully should the same antigen reappear at a future time.

The antibodies can launch their attack on the antigens.

Different antigens stimulate different B-lymphocytes to develop into plasma cells and their accompanying memory B-lymphocytes. The B-lymphocytes of a particular clone are capable of secreting only one kind of antibody, which will attack only one particular type of antigen. However that does not mean that each antigen only triggers one type of B-lymphocyte! Antigens may have many sites on them, which are recognised as being ‘foreign’ and each of these sites can trigger a response by different B-lymphocytes and there may be many different B-lymphocytes launching an antibody attack on one foreign invader.

The diagram below is the same sequence of events shown on the previous diagram for antibody production. Try to go through the stages

explaining in your own words what is happening. (Parts of the diagram are too detailed).

1. Recognition

2. Binding

3. Replication (multiplication)

4. Plasma cells and Memory Cells

5. Antibodies attack

6.3.7 Effects of HIV 9/28/10 8:39 PM

6.3.7 Outline the effects of HIV on the immune system

Orange book pg. 224Green book pg. 102

To do: Read the relevant pages in your textbooks Outline the effects of HIV on the immune system in your green exercise books.

Human immunodeficiency virus (HIV) is the virus that eventually results in the set of symptoms collectively called acquired immune deficiency syndrome (AIDS). All viruses must find a type of cell in the body that matched their own proteins in a complementary way. This is why only certain body cells are damaged by certain viruses as is typically reflected in the symptoms associated with the particular infection. For example, a cold virus locates the proteins on mucous membrane cells in you nasal region and ultimately damages those cells. This results in symptoms including swelling of the areas and excessive mucus production. Other cells of the body do not have the same protein and therefore the cold virus does not affect them.

The same specificity concept holds true for HIV. Only certain cells in the body have the protein in their membranes that HIV recognizes. One of those is a cell type that functions as a communicator cell in the bloodstream. This cell is known as a helper-T cell and this is the cell that HIV infects. Because HIV is a type of virus that has a latency period (infection occurs, but cells remain alive), it is usually many years after HIV infection that the symptoms called AIDS develop. Helper-T cells are the cells that communicate which cells need to undergo the cloning process and begin antibody production, When the helper-T cells begin to die, the communication between cells no longer occurs and antibodies do not get produced. At this stage, the individual no longer fights off pathogens as they did before and the symptoms of AIDS start to appear. It is one or more of the secondary infections that ultimately takes the life of someone with AIDS.

1. Recognition

2. Binding

3. Replication (multiplication)

4. Plasma cells and Memory Cells

5. Antibodies attack

6.3.8 AIDS 9/28/10 8:39 PM

6.3.8 Discuss the cause, transmission and social implications of AIDS.

Orange book pg. 224Green book pg. 103

To do: Read the relevant pages in your textbooks Discuss the cause, transmission and social implication of AIDS.

AIDS has been and will probably continue to be a difficult disease for humans to deal with. In the previous section we looked at the cause of AIDS, specifically HIV. It continues to be very difficult to find a vaccine or cure for the infection caused by this virus. HIV ‘hides away’ inside its host cells for years. During this time, the body’s immune responses continue to work against other pathogens, but not to combat the HIV because it is already inside body cells waiting for some chemical signal(s) to become active. The virus also mutates relatively quickly for a virus. The body’s immune responses or vaccines may not even recognise HIV after it has mutated several times.

Adding to the difficulty of developing medication is the association of HIV with sexual activity and drug abuse. This initially led to some reluctance in allocating money for HIV research. Today, huge sums of money are allocated for HIV/AIDS research, but this is a relatively new development.

The transmission of HIV has another historical significance which has affected how society responded to the disease. HIV is transmitted from person to person by body fluids. This includes body fluid exchanges during sex and ill-advised practice of re-using unsterile syringe needles for legal or illegal drug injections. At one time, blood for transfusions was not tested for blood-borne diseases like HIV. Unfortunately, more than a few people became HIV positive from blood transfusions. Today, at least in countries with reasonable medical care, blood is routinely tested for the presence of blood-borne diseases and immediately destroyed if pathogens are found.

AIDS was originally labelled as a disease affecting homosexuals and drug abusers. We now know AIDS is rapidly spreading by way of heterosexual encounters and everyone is at risk. Individuals who have been diagnosed with being HIV positive may be discriminated against in terms of employment, insurance, education access, social acceptance and many other forms of discrimination.

We should also remember that not every country has the education and medical facilities to deal with this disease. In some countries, inadequate medical care sometimes leads to an increase in infection rates as patients with a variety of ailments are often grouped together in large ‘wards’ and this leads to an exchange of diseases between them.

Until a cure for AIDS is found, perhaps the best that can be accomplished is to continue to lengthen the life-span of those infected, and to educate people on how to decrease their risk of exposure to HIV. This disease is truly a global problem and effective treatment and education must not be limited to certain countries.