1. Unit 4 - Immunology and Public Health CfE Higher Human Biology 24. Active Immunisation and Vaccination and the Evasion of Specific Immune Response by Pathogens

2. Learning Intentions I can describe the importance of herd immunity in infectious disease control. I can state that the herd immunity threshold depends on the disease, the efficacy of the vaccine and the contact parameters for the population. I can describe public health immunisation programmes. I can state that establishing herd immunity to a number of diseases. Difficulties when widespread vaccination is not possible due to malnutrition, poverty or vaccine rejected by a percentage of the population. I can describe the evasion of specific immune responses by pathogens. I can state that many pathogens have evolved mechanisms that evade the specific immune system which has consequences for vaccination strategies. Antigenic variation. I can state that some pathogens can change their antigens avoiding the effect of immunological memory. Role and impact in diseases like malaria, trypanosomiasis and influenza. I can describe a direct attack on the immune system. I can state that HIV attacks lymphocytes which are the major cause of AIDS. I can state that Tuberculosis (TB) survives within phagocytes and avoids immune detection.

3. Herd Immunity Vaccines can prevent outbreaks of disease and save lives. When a critical portion of a community is immunized against a contagious disease, most members of the community are protected against that disease because there is little opportunity for an outbreak. This is because their chance of coming into contact with someone with the disease is minimal. Even those who are not eligible for certain vaccines—such as infants, pregnant women, or immunocompromised individuals — get some protection because the spread of contagious disease is contained. This is known as “herd immunity."

4. Herd Immunity Box 1 shows a community in which no one is immunized and an outbreak occurs. Box 2, some of the population is immunized but not enough to confer herd immunity. Bow 3, a critical portion of the population is immunized, protecting most community members. Watch the following video on the effect of adverse publicity on the MMR vaccination http://www.youtube.com/watch?v=jfheO9H8CD4

5. Absence of herd immunity Some populations do not have herd immunity and this may be because of very different reasons; In developing countries, malnutrition and poverty prevent mass vaccination programmes In developed countries, adverse publicity about vaccines leads to parents choosing to not have their child vaccinated.

6. Herd immunity threshold This is the percentage of the population who need to be immunised by the vaccine to offer protection for people who are not vaccinated. DiseaseTransmission Average number of secondary infections resulting from single index case Herd immunity threshold DiptheriaSaliva6 – 785% MeaslesAirborne12 – 1883 – 94 % MumpsAirborne droplet4 – 775 – 86 % Whooping coughAirborne droplet12 – 1792 – 94 % PolioFaecal-oral route5 – 780 – 86 % RubellaAirborne droplet5 – 783 – 85 % SmallpoxSocial contact6 – 783 – 85 %

7. Herd Immunity The principle of herd immunity applies to control of a variety of contagious diseases, including – influenza, – measles, – mumps, – rotavirus, – pneumococcal disease.

8. Public Health Immunisation Programmes In most countries, policy in public health medicine is to establish herd immunity to a number of diseases.

9. Public Health Immunisation Programmes

10. Difficulties can arise when widespread vaccination is not possible due to – malnutrition and poverty (the developing world),

11. Developed World – Difficulties carrying out widespread vaccination arise when large numbers of the population reject immunisation programmes – This this is a result of adverse publicity about vaccinations eg Media attention and consequent public concerns about vaccine safety followed publication of a small case-series of children who developed autism after receipt of the measles-mumps-rubella (MMR) vaccine. Many well-controlled studies performed subsequently found no evidence that MMR vaccine causes autism. However, despite these studies, some parents remain concerned that the MMR vaccine is not safe. http://news.bbc.co.uk/1/hi/health/3041225.stm

12. Public Health Immunisation Programmes Because of vaccines, small pox is now eradicated globally, polio nearly, and, in countries where children are regularly vaccinated, we don’t worry too much about diphtheria, measles, whooping cough, and rubella. Vaccination may be the most effective public health intervention of all time— that’s especially true in developing countries, where many families can’t find or afford health care when they get sick. The prevention offered by vaccines can be lifesaving.

13. Evasion Of Specific Immune Response Just as vertebrates have developed many different defences against pathogens, so pathogens have evolved elaborate strategies to evade these defences. One way in which an infectious agent can evade immune surveillance is by altering its antigens; this is particularly important for extracellular pathogens, against which the principal defence is the production of antibodies against their surface structures. Pathogens can change their antigens so that antibodies and memory cells are useless. The influenza virus is typical of this, and this is why you need a new ‘flu jag every year.

14. Antigenic Variation Antigenic variation is a change in surface antigens on an infectious organism to help the organism evade the immune systems of potential hosts. Organisms use a variety of tactics for changing the composition of the antigens on their surface. This evolutionary trick allows them to continue growing and spreading in populations, perpetuating their existence. Antigenic variation is of interest for people in charge of developing vaccines and medications to prevent and treat infection.

15. Antigenic Variation Organisms like viruses, bacteria, and parasites all have an external envelope, with a series of surface proteins. When an organism enters a host for the first time, the immune system does not recognize any of the proteins and may allow the organism to multiply, creating an infection. The immune system will learn that those proteins are dangerous, and when the organism appears in the future, the body will go on the attack. It sees the proteins, recognizes them as a threat, and sends out immune cells to kill the organism.

16. Antigenic Variation Without antigenic variation, infectious organisms would quickly become extinct. Numbers of vulnerable people in the population would drop and the organisms would not be able to survive. If, however, the organism can change the proteins in future generations, it can adapt and start evading the immune system again.

17. Antigenic Variation Some organisms experience random mutations, which can occur at any time. Others actually program in antigenic variation. These organisms can switch proteins on and off to present a completely different antigen to the immune system.

19. Antigenic Variation Antigenic variation can happen through mutation. Some organisms are better at it than others. – The influenza viruses are a notorious example; they change so much that people must design a new vaccine every year to inoculate people against the flu. – malaria – antigenic variation occurs within a population – Trypanosomiasis - Trypanosomes are insect-borne protozoa that replicate in the extracellular tissue spaces of the body and cause sleeping sickness in humans. They select from a range of genes for antigen production

20. Trypanosomiasis A protozoa called Trypanosoma brucei causes the fatal disease called trypanosomiasis or ‘sleeping-sickness’. It has a glycoprotein coat which can contain one of many different antigens. About 1% of them can vary the antigen and replace the whole ‘coat’ when the immune system attacks. The new coat has different antigens so the immune system has to start again, giving it time to reproduce before destroying another 99%.

21. Survive and change

22. Malaria To prevent the red blood cells, which the malaria protozoa hide in, from being destroyed they present a protein on the cell’s surface which causes it to stick to a blood vessel wall. It is also able to switch between many genes for this protein preventing the immune system producing appropriate antibodies in time.

23. Tuberculosis T.B. Mycobacterium tuberculosis causes T.B. It interferes with the body’s phagocytic response The pathogen is able to survive inside phagocytes When a macrophage engulfs the BT bacterium, the microbe prevents lysosomes fusing with the vesicle If fusion does occur, the pathogen is not easily attacked by lysosomal enzymes because it is protected The pathogen remains alive inside the phagocyte and avoids immune detection Tuberculosis bacteria (green) within a phagocyte of the immune system

24. Direct attack on the immune system Some microorganisms hijack the immune system for themselves, e.g. tuberculosis bacteria They allow themselves to be engulfed by phagocytes but prevent the lysosomes fusing with the vacuole they are in. They also have a waxy coat to prevent them being digested even if they did come into contact with it. This means they are able to hide amongst the immune system and evade destruction.

25. Direct attack on the immune system AIDS is a deficiency disease caused by the HIV virus. The virus enters helper T cells by using a glycoprotein anchor. It changes the genetic makeup of the host cell and inserts genes for making new virus particles. In the case of HIV, the virus can remain dormant for several years before releasing new virus particles. The immune system does release antibodies against HIV but they are ineffective against those hiding inside the helper T cells. After many years, the number of helper T cells has diminished significantly and the person is now at more risk of opportunistic infections such as pneumonia.

27. AIDS (acquired immune deficiency syndrome) is a disease caused by HIV (human immunodeficiency virus) HIV attacks helper T lymphocytes The envelope surrounding the HIV particle fuses with the membrane of the helper T cells and the virus enters the host cell It can remain dormant for years before directing the synthesis of new viral particles New viral particles escape from the helper T cell by ‘budding’

28. B cells do make antibodies but these are ineffective against viral particles ‘hiding’ inside helper T cells As number of helper T cells decreases, immunological activity decreases leaving the person susceptible to infection Remember, helper T cells are of critical importance to the immune system – they activate B cells and cytotoxic T cells

30. Retrovirus HIV is a retrovirus, it contains RNA Along with RNA it introduces ‘reverse transcriptase’ into the host cell This produces viral DNA from viral RNA Eventually, viral DNA directs the synthesis of new viral RNA

31. Case study on HIV-page 344. 1.Explain how HIV can be transmitted. 2.What public health measures have been put in place to control the spread of aids? 3.Is there a cure for aids? 4.What can some drugs do? 5.What’s the problem with developing countries? 6.What are anti-retroviral drugs? 7.What do combinations of the drugs available do? 8.Why has a successful vaccine not been discovered?

32. Clonal selection-may need. These produce Y-shaped protein molecules in response to the surface antigens of bacteria and viruses. The proteins produced are antibodies. It is the shape of the protein of the antibody that makes it specific to a specific antigen Production of cell products such as antibodies in response to an antigen is called the humeral response. The stages in the humeral response shown by B lymphocytes are in the diagram. 1.The B lymphocyte comes into contact with a specific antigen from a bacteria or virus 2.The B cell divides rapidly to form a group of identical cells 3.Some cells develop into plasma cells that produce the antibody specific to the antigen 4.The released antibody leads to the destruction of cells with the antigen 5.Other cells develop into memory cells and if the same antigen enters the body again, the memory cells quickly produce more of the plasma cells.

33. Chapter 24 herd immunity and antigenic variation. questionanswer What is herd immunity? This is protection given indirectly to the non- immune minority by the immune majority because a certain amount of people have been vaccinated against a pathogen. How does this work? Most of a population is immunised against a pathogen and some are not. This reduces the chances of a non- immune individual coming into contact with an infected person. This also gives protection to vulnerable groups. Name some diseases that mass vaccination in herd immunity has eradicated. Tuberculosis, poliomyelitis, smallpox. What is the herd immunity threshold? This is the percentage of immune individuals above which a disease can’t take hold and it changes for each disease. Name some factors that this threshold depends on. The virulence of the pathogen, the efficacy(effectiveness) of the vaccine, the populations contact parameters(population density).

34. Chapter 24-antigenic variation. questionAnswer. Name two protozoans that can operate antigenic variation. Trypanosomiasis and malaria. What disease is caused by Trypanosomiasis? A neurological disease called Trypanosomiasis (sleeping sickness). What is trypanosma brucei?The protozoan(single celled animal) that causes this disease. What is the pathogen that causes this surrounded by that can vary in chemical composition depending on which genes are switched on? A coat of glycoprotein molecules. What is made by the infected host in response to the antigen (the pathogen’s coat) and kills 99% of the protozoa? Antibodies. What happens to the other 1%? Get rid of their coat, switch on other genes and get a new antigenic coat so the hosts immune system makes a new set of antibodies that deals with 99% again and 1% shed their coat and survive etc. until host dies.

35. Chapter24 antigenic variation-malaria. Question.Answer. What pathogen causes malaria?A protozoan called plasmodium falciparum. Describe its life cycle.Complex.Found in humans and mosquitoes and humans and mosquitoes are called the hosts. Found for longer in humans in their red blood cells. What allows the pathogen to evade the hosts immune system? Great genetic variation exists in the pathogen that it switches between. It makes a protein that sticks to Red blood cells surface and stops it from being moved or destroyed by the body to allow the pathogens to survive in the RBC. Have scientists been able to produce an effective vaccine against it? No and malaria kills many people every year.

36. Chapter 24 direct attack on the immune system questionAnswer. From which cells are phagocytes derived?Bone marrow stem cells. Do they exert a specific or non-specific attack on pathogens? Non-specific. How do they destroy pathogens?Engulf and digest using enzymes in lysosomes. What are larger phagocytic cells called?Macrophages and are found in connective tissue. Where are the smaller phagocytes found?In the blood stream. What can some bacteria do to succeed?They can interfere with the phagocytic response and stop it. Name the bacteria that causes tuberculosis. Mycobacterium tuberculosis. Why is it called an intracellular pathogen?It can survive inside phagocytes. How can it do this? Once inside a vesicle in the macrophage it stops lysosomes fusing with the vesicle and if fusion does happen it is protected by a waxy cell wall and can’t be digested-other macrophages may surround it.

37. Chapter 24 immunodeficiency disease. Question.Answer. Define immunodeficiency disease.Some part of the immune system does not work and the person is open to infection. What does AIDS stand for?Acquired immune deficiency syndrome. What does HIV stand for?Human immunodeficiency virus. How does HIV work?The virus attacks helper T cells by becoming attached by glycoprotein on its surface to specific receptors on the helper T cells. The HIV particle fuses with the membrane of the helper T cell and the virus enters the cell. Why is HIV described as a retrovirus?Because it contains RNA and not DNA. How does the virus make viral DNA? It uses the enzyme reverse transcriptase to reverse normal transcription and makes viral DNA from viral RNA. This can stay in the host cell’s DNA for many years before making new viral particles inside the host cell and then leaving by budding to infect other cells. The host cell gets destroyed by apoptosis.

38. HIV continued. questionanswer Why are the antibodies against HIV made by B cells not effective against viral particles? Viral particles are inside the helper T cells and antibodies can’t get to them. Why are helper T cells important for the immune system? They activate B cells and cytotoxic T cells. What happens as the number of helper T cells drop? The immune system does not work as well and the person is susceptible to opportunistic infections such as pneumonia. The person develops aids after several years of infection.

39. Chapter 24 herd immunity and antigenic variation. QuestionAnswer. What is the public health policy for combating common diseases in many countries? They carry out mass vaccination programmes that create herd immunity to the pathogens. What is this policy in the UK?Vaccination for diphtheria, tetanus, polio, whooping cough, flu begins at 2 months and continues for many years. Where may herd immunity be absent?Developing countries where many people are poor and malnourished, developed countries where vaccination preventable diseases are compromised due to people believing bad publicity about the vaccine. i.e. the level of herd immunity is below threshold and non-vaccinated people do not get protection.

40. Chapter 24-evasion of specific immune responses. questionanswer How can a pathogen evade specific immune response? They do this by evolving into new versions of the pathogen to stay one step ahead of the vaccination programme. How can pathogens change their genotype? By mutations and genetic recombination which is a combination of genetic material from two different strains. What is antigenic variation?This is where pathogens have antigens on their surface different from the original strain. How does the influenza virus avoid the body’s immune system? It produces new antigens which re-infect the body because its new antigens are not recognised by the body’s memory cells. At risk individuals are vaccinated every year with a new version of the vaccine. Apart from viruses and bacteria what other pathogens can operate antigenic variation? Pathogenic protozoa (unicellular animals).