Unit F222 Module 3: Infectious Disease
What is an infectious disease?
• A disease that can be spread from one organism to ...
• Cell wall – rigid framework of murein
• Plasma membrane – typically phospholipid bilayer
• Flagellum – responsible for m...
The Human Immunodeficiency Virus
Surface glycoproteins
Membrane
Membrane associated /
matrix protein
Protein capsid made o...
As yet there is no vaccine and no cure. There are some drugs that slow down the development of AIDS.
The best way to deal ...
Mutations: some bacteria mutate during cell reproduction. A mutation may cause the bacterium to be
resistant to antibiotic...
Ex-situ conservation
Where habitats have been destroyed and the plant is possibly extinct in the wild, specimens may still...
• Conjunctiva, membrane covering front of eye, is protected by fluid secreted in tear ducts. This
secretion contains lysoz...
• It is specific – it attacks the pathogen, but causes no harm to other cells and tissues. The cells of
the immune system ...
• Agglutination: Antibodies can cause bacterial cells to clump together, which makes it easier for
phagocytes to engulf th...
• T lymphocytes destroy pathogens inside cells by releasing lytic enzymes. Cytokines attract the
phagocytes to engulf cell...
First exposure to pathogen = Primary response
There is a delay before specific antibodies appear in blood because correct ...
Active immunity
Here the organism manufacturers its own antibodies. It is the natural result of infection. It is possible
...
Tests people who have been exposed to TB. A Small amount of serum containing TB antigens is injected
under the skin, If pe...
If you belong to the blood group AB, you have both A and B antigens on the surface of your red blood cells
and no A or B a...
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OCR F222 module 3

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OCR F222 module 3

  1. 1. Unit F222 Module 3: Infectious Disease What is an infectious disease? • A disease that can be spread from one organism to another. These diseases are known as communicable diseases. They are caused by pathogens. Pathogens are organisms that cause diseases and include bacteria, viruses, fungi and protostists, (microorganisms). Definitions • Epidemic – a sudden increase in the incidence in a specified area such as a city or country. • Endemic – an infectious disease which is always present in the population or “prevalence pool” (The proportion of individuals in a population having a disease). • Pandemic – a rise in the incidence of a disease on a global scale. A typical prokaryotic cell (like Mycobacterium tuberculosis) Structure • Genetic material is a circle of DNA not enclosed in a nucleus • Ribosomes – smaller than in eukaryotic cells, not on endoplasmic reticulum • Capsule – layer of mucilage which may unite bacteria into colonies • Plasmids – small pieces of circular DNA which replicate independently of the main genome 1
  2. 2. • Cell wall – rigid framework of murein • Plasma membrane – typically phospholipid bilayer • Flagellum – responsible for motility of many bacteria TB Caused by Mycobacterium tuberculosis, bacterium; Spread by coughs or sneezes of infected droplets of mucus; Infects the lungs, but can spread to other organs (heart, bones, pancreas, thyroid, skeletal muscles); Can also be caught from drinking unpasteurised milk from cows infected with Mycobacterium bovis. Diagnosis • Chest X-ray • Sample of sputum and examined in laboratory. Factors promoting its development • Damp, overcrowded conditions • Abusers of alcohol, drugs • Infected with HIV • Suffering from other conditions that affect immune system Treatment • With antibiotics (e.g. Isoniazid); • Antibiotics must be taken over six to nine months • To prevent resistance developing patients are given a cocktail of 3 to 4 drugs • DOTS – people are watched whilst taking medication • Vaccination – BCG, (Bacillle-Calmet-Guerin) attenuated live strain of Mycobacterium bovis What is a virus like? No cell structure; Many times smaller than a bacteria (generally smaller than 200 nm in diameter); Outside of a living cell they show no signs of life; Can only replicate when inside a living cell. They can be described as obligate intracellular parasites o "Obligate“- the virus (in this case) must do or behave in the specified manner. o “Intracellular parasites” - viruses must carry out their reproduction by parasitizing a host cell. They cannot multiply outside a living cell, they can only replicate inside of a specific host. 2
  3. 3. The Human Immunodeficiency Virus Surface glycoproteins Membrane Membrane associated / matrix protein Protein capsid made of protein subunits / capsomers RNA Enzymes (including reverse transcriptase The facts on HIV • Retrovirus (genetic information is in the form of RNA; DNA copy made using reverse transcriptase). The double stranded DNA inserts itself into the T Helper Lymphocyte • Once in blood infects T helper cells (lymphocytes) • Usually remains dormant for many years, no symptoms but antibodies present • As T helper cells are destroyed, person becomes susceptible to opportunistic infections such as: • TB • Kaposi’s sarcoma • Pneumocystis pneumonia Transmission • Spreads from one infected person to another in body fluids. • Usually spread through sexual intercourse or transfer of infected blood from one person to another (e.g. IV drug abusers who share needles) • It can also be spread from an infected mother to her baby either during pregnancy or in breast milk Controlling the spread 3
  4. 4. As yet there is no vaccine and no cure. There are some drugs that slow down the development of AIDS. The best way to deal with the spread of HIV is to avoid catching it in the first place. The ways of doing this are: • Screening of blood for transfusion • Using condoms for sexual intercourse • Needle exchange schemes for injecting drug abusers so they have fresh, sterile needles available • Educating people about the ways HIV is spread • Offering HIV tests to people at risk (e.g. prostitutes, IV drug abusers • Encouraging people who are HIV positive to contact people they might have infected and advising them to avoid spreading the infection • Encouraging HIV positive mothers not to breast feed • Encouraging people to “take the test”, many people pass on the virus because they are not aware they are HIV positive HIV / AIDS are found in almost every country in the world. Estimations are that 40 million people are infected worldwide. One part of the world that is very badly affected is sub-Saharan Africa. Zimbabwe is the worst affected country where 25% of the adult population are thought to be affected. Life expectancy is only 39 years. Many children are orphaned and many are kept of school because sick parents cannot afford school fees. Antibiotics and MRSA How antibiotics work  Inhibition of cell wall synthesis. Examples: Penicillin’s ; Cephalosporin’s; Carbapenems; Daptomycin Glycopeptides  DNA synthesis: example: Fluoroquinolones  RNA synthesis: example: Rifampin  Protein synthesis: examples: Macrolides ;Chloramphenicol: Tetracycline: Aminoglycosides: Oxazolidonones  Folic acid synthesis: examples: Sulfonamides ; Trimethoprim How do bacteria become resistant to antibiotics? Bacterial populations show some variations in their genetic make-up – some had a gene making them resistant to antibiotics. These bacteria survived and multiplied quickly, all their offspring contained the resistance gene. 4
  5. 5. Mutations: some bacteria mutate during cell reproduction. A mutation may cause the bacterium to be resistant to antibiotics. They multiplied and their offspring are all antibiotic resistant. MRSA - Methicillin-resistant Staphylococcus aureus  Staphylococcus aureus normally lives on the skin or in the nose of many people (harmlessly).  If it gets under the skin or in the lungs it can cause infections like boils or pneumonia.  Carriers are usually totally healthy.  MRSA is a strain of Staphylococcus aureus that is resistant to commonly used antibiotics Why are hospital patients more at risk? • Lots of antibiotics are used in hospital so there is more chance for resistant strains to build up • Patients are already ill and may have a weakened immune system • They may be in close proximity to patients with MRSA • Wards, equipment etc may not be adequately cleaned. • Medical staff may not have adequately washed their hands between patients How can we reduce the spread of MRSA? • Screen new patients for MRSA on admission • Isolate patients with MRSA • Barrier nurse MRSA patients • Use narrow spectrum antibiotics • Ensure patients complete their course of antibiotics • Ensure hospital wards are adequately cleaned. Hands are washed between treating patients Medicines from plants Approx half of the medicines used in the West contain materials that either come from plants or are synthetic forms of plant products. Medicines derived from plants are usually cheaper and generally safer than synthetic varieties. They are obtained either by extracting chemicals from plants and testing them to see if they have therapeutic uses. This is expensive and time consuming. The more efficient approach is to study plants used in folklore – many plants contain very useful medicinal properties. Key definitions: In-situ conservation Aims to preserve the whole habitat that the plant grows in - the plant is conserved where it naturally grows. 5
  6. 6. Ex-situ conservation Where habitats have been destroyed and the plant is possibly extinct in the wild, specimens may still exist. These may be in botanic gardens or as seeds in seed banks Seed banks Many plant species in the world are endangered. Many are becoming extinct before they have even been named! Kew gardens have set up a Millennium Seed Bank. They are collecting seeds from all over the world and storing them. If stored correctly, the seed will last for decades / hundreds of years DNA barcoding  A standard short piece of DNA from a particular locus, on a particular chromosome is chosen. Scientists then find the DNA sequence of this piece of DNA for as many plants as possible. This information is used: • To identify the different life stages of the same plant. E.g. Seeds, seedlings • To identify fragments of plant material • In forensic investigations • In verifying herbal medicines / food stuffs • In biosecurity / trade in controlled species • To build up inventories and ecological surveys • Kew is working with 10 other organisations to select a suitable DNA region to be used as a barcode. • The project intends to build up barcodes for every land plant The immune response The mechanisms or range of defences the body uses to protect it against disease carrying organisms or pathogens. Non-specific defence mechanisms • Unbroken skin – a barrier that is difficult for pathogens to penetrate • Broken skin – blood clotting takes place, this seals the wound and prevents loss of blood • Hydrochloric acid in the stomach; acid pH in vagina make it difficult for most pathogens to survive because their enzymes are denatured in acid conditions. • Epithelium in respiratory tract – covered with mucus, ciliated cells present/ pathogens stick to mucus, cilia beat moving mucus back to throat. It is then swallowed and acid in stomach kills pathogens. 6
  7. 7. • Conjunctiva, membrane covering front of eye, is protected by fluid secreted in tear ducts. This secretion contains lysozyme which digests bacterial cell walls What happens when pathogens enter the body? SECOND LINE OF DEFENCE = phagocytes and inflammation What is phagocytosis?  Carried out by neutrophils and monocytes  Monocytes become macrophages (found in spleen and lungs)  Phagocytes are neutrophils – monocytes – macrophages. They are produced in the bone marrow, inside long bones from stem cells  Damaged cells Release chemicals called cytokines – attract phagocytes  Bacteria become coated in plasma proteins called opsonins.  Phagocytes engulf the bacteria. The bacterium becomes enclosed in a membrane coated vesicle called a phagosome.  Lysosomes, containing digestive enzymes, move towards the phagosome and fuse with it. The digestive enzymes break down the bacterium, soluble products are released, these diffuse into the cytoplasm of the phagocyte What causes inflammation?  It is non-specific  Chemicals, including histamine are released from damaged tissues. These cause vasodilation in the capillaries.  Vasodilation causes more blood flow in the area.  This causes the temperature of the tissue surrounding the wound to rise. This increases the rate of chemical reactions involved in blood clotting.  Higher temperatures also slow down rate of bacterial growth.  Capillaries become more permeable. This means more plasma escapes from the capillaries into the surrounding tissues. This cause the swelling.  The plasma contains neutrophils, monocytes and various proteins that help combat pathogens  People who have serious burns often die of infections. The specific immune response 7
  8. 8. • It is specific – it attacks the pathogen, but causes no harm to other cells and tissues. The cells of the immune system can distinguish “self” cells from “foreign” cells. Antigens They are macromolecules e.g. Glycoproteins. They are present on the surface of organisms / parts of organisms such as cancer cells. The body recognises these as non-self and an immune response is triggered. A specific antibody to that antigen is produced. Antibodies Structure: • 4 polypeptide chains (2 long (heavy), 2 short (light) • 2 binding sites – these fit exactly onto the antigen, they have complimentary shapes. This is the variable portion – it is specific to the antigen • Disulfide bridges hold the chains together • Antibodies are proteins with a quaternary structure • The shape of the variable region changes because the tertiary structure of this region changes • This changes because the primary structure of the amino acids and R groups change in this region How do antibodies destroy pathogens? • Neutralisation: Certain antibodies bind to toxic molecules produced by the pathogen, in doing so they neutralise their harmful effects. • Precipitation: Some antibodies bind together soluble antigens into large units which are thus precipitated out of solution. They are then more easily digested by phagocytes • Lysis: Antibodies which are attached to a pathogen act as binding sites for a number of blood proteins; these are collectively known as the compliment system. Some of these proteins are enzymes which cause breakdown of the pathogen 8
  9. 9. • Agglutination: Antibodies can cause bacterial cells to clump together, which makes it easier for phagocytes to engulf them. • Opsonins: These include antibodies and some other molecules of the immune system. A special attachment site on the antibody’s constant region binds to a receptor site on the plasma membrane of a phagocytic cell, while the variable region binds to the bacterial antigen. The bacterium is held onto the phagocytic cell so it can be engulfed B lymphocytes – Humoral response • Formed from stem cells in the bone marrow, they mature in the bone marrow, hence B lymphocytes. • Approximately 10 million different B lymphocytes, each has a different receptor in its plasma membrane and so is capable of producing a different antibody. • During foetal development the B lymphocytes are constantly meeting other cells – often the foetuses own cells. At this stage the foetus is protected from infection by the placenta. Any B lymphocytes that have receptors matching the body’s own cells will be destroyed or suppressed, this means that by birth, the foetuses B lymphocytes will be capable of attacking foreign or non-self antigens. • When a pathogen enters the body, one kind of B lymphocyte will have receptors that exactly fit the antigens on the pathogen. • The B lymphocyte divides by mitosis, this gives a clone of identical B lymphocytes. • Some of these cells will develop into plasma cells – they secrete specific antibodies against the pathogen. This is the primary response. • B lymphocytes contain very little cytoplasm, differentiation involves the cells becoming much larger to ensure there is room for rough endoplasmic reticulum and golgi apparatus necessary to synthesise antibodies and package them into vesicles for Exocytosis. More mitochondria are also necessary to provide the necessary energy. Plasma cells look very different to B lymphocytes. • Some of the cells become memory B lymphocytes (memory cells). These can survive for decades; they do not secrete antibodies but provide an immunological memory to the antigen. If they encounter the same antigen again they will rapidly divide to produce plasma cells as well as more memory cells. This provides a faster and more intense response. This is the secondary immune response. The role of T lymphocytes – cell mediated response • Produced from stem cells in the bone marrow, they mature in the thymus glands – hence T lymphocytes. • They have different shapes of receptors on their cell surface membrane. A macrophage that has engulfed a pathogen by phagocytosis digests the pathogen and presents the antigen on its cell surface membrane, the T lymphocyte with the right shape of receptor to fit the antigen binds to the macrophage. The T lymphocyte divides to form a clone of T lymphocytes. • The T lymphocytes develop either into T Killer lymphocytes – they kill any cell carrying the specific antigen or T Helper lymphocytes, these cells secrete chemicals that stimulate phagocytosis by phagocytes and antibody production by B lymphocytes. 9
  10. 10. • T lymphocytes destroy pathogens inside cells by releasing lytic enzymes. Cytokines attract the phagocytes to engulf cells. T helper cells also produce cytokines that stimulate B lymphocytes and macrophage cells. Cytokines can also cause T killer lymphocytes to divide by mitosis. • Both T lymphocytes also produce memory cells – these can respond to any later infection by the same pathogen. • T Suppressor lymphocytes “wind down” the action of the immune system after the pathogen has been destroyed. Vaccination This is inducing an individual to produce antibodies even without them suffering the disease. To do this the appropriate antigen most be injected in some way. The antigens stimulate a primary response; this means that B memory cells are made. If the person then encounters the real pathogen there is a faster secondary response. Forms of vaccines Live vaccines – living microorganisms with the same antigen as the pathogen. These microorganisms have been sub-cultured many times in a lab and so do not produce the disease. This is known as an attenuated form of the microorganism.  Examples: measles, TB, poliomyelitis, rubella, mumps Dead microorganisms – killed by chemicals and heat. Although harmless they still carry the antigens necessary to bring about an immune response.  Examples – typhoid, cholera, whooping cough, Hepatitis A A fragment of a pathogen – e.g. viral coat component can be used as a vaccine.  Example – HPV vaccine has viral coat of Human Papilloma Virus What happens to make a person immune? 10
  11. 11. First exposure to pathogen = Primary response There is a delay before specific antibodies appear in blood because correct T lymphocyte has to be selected to divide and produce T helper lymphocytes. Specific B lymphocyte has to be located and activate to divide to form a clone of plasma cells. Specific antibodies are then produced. The secondary response Providing the antigen is the same, memory B cells are already present. They divide very quickly to produce a clone of plasma cells; these produce a large number of antibodies. This is very quick and the pathogen is often destroyed before the patient suffers any symptoms. The person is IMMUNE Herd immunity If enough people in the world are vaccinated against a disease, it is not possible for the disease to spread - everybody is protected. Once a certain proportion of the population is vaccinated against a pathogen, the chances of an infected person meeting a susceptible person and passing it on are very much reduced. If the pathogen is not passed on it cannot multiply in its human host and the pathogen population becomes much smaller Herd immunity – the figures Different diseases have different % of vaccination.  1977 WHO announced the eradication of small pox, 83-85% of world population needed to be vaccinated.  Diphtheria – 85% of population needs to be vaccinated  Whooping cough – 92-94% of population needs to be vaccinated  Measles – up to 94% needs vaccination Passive immunity – the effect is only temporary Antibodies passed into individual rather than the individual producing them.  E.g. Across the placenta (natural)  In mother’s milk (natural)  Artificial injection of antibodies from another individual (tetanus or diphtheria – antibodies come from other mammals), 11
  12. 12. Active immunity Here the organism manufacturers its own antibodies. It is the natural result of infection. It is possible to induce an individual to produce antibodies even without suffering the disease, here the antigen is injected in some way. This is VACCINATION. Developing a vaccine against HIV • Vaccines contain antigens from a pathogen – immune system produces antibodies and memory cells against that pathogen. • HIV keeps mutating, this means antigens with a variety of different shapes are produced and antibodies against one strain of the virus will not bind to antigens that are a slightly different shape. • Antigens of HIV can also change in a person Human Papilloma Virus This is the cause of many cases of cervical cancer. HPV is sexually transmitted, some strains cause genital warts. The HPV vaccine protects against most strains of HPV, hopefully reducing the incidence of cervical cancer. To be effective, girls need to be vaccinated before they become sexually active Why is it difficult to control the spread of a new disease? • No chance to develop immunity to disease • Vaccines not available in advance • Difficult to diagnose as it is new and no research has been done on it. • Lots of foreign travel makes the situation worse Testing for HIV TEST 1 – used to test newborn babies (expensive and complex • Polymerase chain reaction (PCR) • Uses leucocytes from a blood sample, makes copies of DNA present • HIV inserts a DNA copy of its genetic material into T lymphocytes • PCR amplifies sections of this DNA • Control of beta haemoglobin gene is amplified at same time to check PCR system is working ok. Other tests • HIV antibody test – people who are infected will have antibodies against the virus. Test for the presence of HIV antigens – tests use antibodies and enzymes to detect antibodies or antigens What is the Mantoux test? 12
  13. 13. Tests people who have been exposed to TB. A Small amount of serum containing TB antigens is injected under the skin, If person has been exposed to TB there will be an immune response – the greater the immune response the greater the amount of inflammation, 48-72 hrs later. Positive Mantoux test will lead to further investigation to see if they have TB Epidemiology This is the study of the occurrence, distribution and control of diseases in populations. Incidence Number of new cases of a specific illness diagnosed or reported in a stated period of time – usually one year Notifiable disease Doctors in England / Wales have a statutory duty to notify the Local Authority of suspected cases of certain infectious diseases. The local Authority informs the HPA Centre for infections (Cfl) each week with details – local / national trends are established. diseases include – poliomyelitis, anthrax, cholera, food poisoning, malaria, measles, meningitis, mumps, rabies, rubella, TB, viral hepatitis, whooping cough Mortality Refers to deaths. The data might be qualified and is usually expressed as a rate Incidence rate Number of new cases of a specific illness diagnosed or reported in a stated period of time, divided by the number of people at risk for the disease. Also known as the morbidity rate Prevalence The number of current cases of a condition or illness at one time – it doesn’t matter when it started. Usually describes conditions that last a long time (chronic) Prevalence rate The number of current cases of a condition or illness at one time divided by the total number of people who may be at risk for the illness or condition Morbidity Refers to people who are affected. Incidence and prevalence data is this Mortality rate The number of deaths from a specific cause per 1000 people in a population per year ABO blood groups According to the AB0 blood group system there are four different kinds of blood groups: A, B, AB or 0 (null). Blood group A If you belong to the blood group A, you have A antigens on the surface of your red blood cells and B antibodies in your blood plasma Blood group B If you belong to the blood group B, you have B antigens on the surface of your red blood cells and A antibodies in your blood plasma Blood group AB 13
  14. 14. If you belong to the blood group AB, you have both A and B antigens on the surface of your red blood cells and no A or B antibodies at all in your blood plasma. Blood group O If you belong to the blood group 0 (null), you have neither A or B antigens on the surface of your red blood cells but you have both A and B antibodies in your blood plasma. Rhesus factor Many people also have a so called Rh factor on the red blood cell surface. This is also an antigen and those who have it are called Rh+ . Those who haven't are called Rh- . A person with Rh- blood does not have Rh antibodies naturally in the blood plasma. But a person with Rh- blood can develop Rh antibodies in the blood plasma if he or she receives blood from a person with Rh+ blood, whose Rh antigens can trigger the production of Rh antibodies. A person with Rh+ blood can receive blood from a person with Rh- blood without any problems. Who can receive blood from whom? The transfusion will work if a person who is going to receive blood has a blood group that doesn't have any antibodies against the donor blood's antigens. But if a person who is going to receive blood has antibodies matching the donor blood's antigens, the red blood cells in the donated blood will clump or agglutinate. 14

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