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KA 4: Active immunisation and vaccination and the evasion of specific immune response by pathogens (a) Active immunity, Vaccinations, Herd Immunity KA 4 (b) Pathogenic evasion: antigenic variation, direct attacks KA 4a: Active Immunity, Vaccinations and Herd Immunty By the end of this section you will be able to ….. • • • • • State how active immunity can be achieved Describe what a vaccine is State the 4 types of antigens found in vaccines State the function of an adjuvant Describe the effect of a vaccine on the immune system (how do vaccines work): – a) immediately after vaccination – b) when the body comes into contact with the same pathogen in later life Active Immunity • Immunisation is the process by which a person develops immunity to a pathogen. • Active Immunity is when the protection is gained as a result of a person producing antibodies. • There are 2 types of active immunity: Immunity Naturally Acquired Active Immunity Artificially Acquired Active Immunity Antibodies produced in response to infection / re-infection Antibodies produced after a vaccination Vaccinations • Vaccination is the method of achieving immunisation. • Vaccinations are designed to initiate an immune response without producing the full blown infection, by deliberately introducing the pathogen into the body by: – Injection – Ingestion – Nasal spray • The vaccine is prepared with antigens from infectious pathogens. Antigens in Vaccines 1. Dead pathogens (the pathogen is destroyed and cannot replicate itself) – Hepatitis A, Polio – Rubella, Mumps, Measles – Hepatitis B and HPV – Diphtheria, Tetanus 2. Weakened pathogens (the pathogen has been altered so it cannot cause the disease) 3. Parts of pathogens (only the protein coat of the pathogen is used) 4. Inactivated pathogen toxins (the toxins produced by the pathogen are injected) Adjuvants • Vaccines containing antigens from infectious pathogens are usually mixed with an adjuvant. • This is a chemical that enhances the immune response. • Adjuvants promote the activity of the antigen in order to: – Induce B cells to produce antibodies and cause the primary immune response. – Produce memory cells so that they remain to give a faster secondary immune response if we ever come across the pathogen again. VIDEO: How vaccines work (simplified) NHS definition: • Adjuvants work to boost our immune response to a vaccine and make it more effective and long-lasting. • Using an adjuvant makes it possible to reduce the amount of antigen used in a vaccine, and sometimes the number of doses that need to be given. Meningitis • Meningococcal bacteria can cause meningitis and septicaemia. • There are 6 groups; Men A, Men B, Men C, Men W, Men X and Men Y. • While meningococcal disease affects all age groups, babies and young children, and teenagers and young adults are at a higher risk • They are also more likely to carry meningitis causing bacteria in the back of their throats and the bacteria is transmitted by coughing and sneezing and close contact. • The bacteria is completely harmless most of the time. However, in a susceptible person, these bacteria can cause a wide range of diseases. • Real Story (scroll to bottom of page) Meningitis Vaccines in the UK • Men C: 12-13 months and 3 years – Since the introduction in 1999, cases have fallen by over 90% in all age groups • Men B: new vaccine introduced Sep 2015 – 3 doses to be given at 2, 4 and 12 months old – babies under 1 are most at risk – Most common strain • Men W: from August 2015 1 dose offered by GPs to 17-18 year olds and 1 dose to older university entrants (aged 19 – 25) – Aggressive strain (ST-11) – Historically rare, but cases of meningitis and septicaemia have been increasing in England from 22 cases in 2009 to 117 in 2014. – An increase in all age groups, but there has been a significant increase in university students. Men ACWY • Introduced as a routine vaccine in Aug 2015 • From Spring 2016 it will replace the Men C dose which is currently offered to 13/14 year olds. • The introduction of the Men ACWY for 13 – 18 year olds will improve protection for this high risk group and also help stop the bacteria spreading to the wider population. What’s in your vaccine? The vaccine only contains the sugar coating on the surface of the four groups of meningococcal bacteria and works by triggering the body’s immune system to develop antibodies against the sugar coating without causing disease. http://www.medicines .org.uk/emc/search But what was the first vaccination? The Smallpox Story video Smallpox Exercise • Read the passage and answer the questions that follow • (in folder) Answers 1. When was the first vaccination carried out? (1 mark) 1796 2. What made Jenner think that inoculating people with cowpox would make them immune to smallpox? (1 mark) Folklore suggested that milkmaids who suffered from cowpox never caught smallpox. 3. Why is it preferable to catch cowpox rather than smallpox? (2 marks) Cow-pox is a mild disease. Smallpox was one of the biggest killers of the period, especially of children. 4. How long did it take from the first vaccination to the publication of Jenner’s work? (1mark) 2 years 5. Where does the word ‘vaccine’ come from? (1 mark) From the Latin word for cow – vacca. 6. What evidence from the passage suggests that Jenner truly believed in his work? (1 mark) He tested his theory on his 11-month-old son. 7. Why were Jenner and his discovery mocked? (1 mark) Critics thought it was repulsive and ungodly to inoculate someone with material from a diseased animal. 8. How old was Jenner when he died? (1 mark) 73 9. What would Jenner have had to do to ensure that James Phipps was immune to smallpox? (2 marks) Deliberately expose James to smallpox. Observe to see if he became ill 10. What might have happened to Jenner if his theory had been incorrect? (2 marks) James might have died. Jenner would have been considered a murderer. Quick Questions 1. Describe what is meant by “active immunity” When a person develops immunity against a disease because they have produced antibodies 2. What name is given to the chemical added to vaccine to enhance the immune response? Adjuvant 3. Name 2 types of antigens found in a vaccine Dead pathogen / weakened pathogen / part of a pathogen / inactivated toxin KA 4a: Active Immunity, Vaccinations and Herd Immunty By the end of this section you will be able to ….. State why clinical trials are important Describe what is meant by a randomised, double blind, placebocontrolled protocol. How does a new drug make it your cabinet? Clinical Trials Video • As you watch the video, write down the 6 essential steps to a successful clinical trial Answers… 1. 2. Design should be approved by an ethics committee The people taking part should be split into groups – 1 group should receive the experimental treatment – The 2nd group should receive a placebo, but if there is already an effective treatment, they should receive that, to allow comparison • 3. 4. 5. 6. A placebo is identical to the experimental treatment, but is inactive (will NOT cause any side effects) – Groups should be randomised Double blind research carried (both groups AND the testers should not know who is receiving which treatment) Results should be analysed by unbiased researchers Procedure must be replicated in other independent trials Benefits and risks of experimental treatment must be carefully evaluated before approval can be given (not enough that the treatment is as effective as the old treatment or placebo). Clinical Trials • Vaccines are subjected to clinical trials in the same way as other pharmaceutical medicines to establish their safety and efficacy (capable of producing the intended result) before being licensed for use. • Clinical Trials protocols MUST be: 1. Randomised 2. Double-blind 3. Placebo-controlled • Randomised – Subjects are split into groups in randomised way to eliminate bias • Double Blind – Neither the subjects nor the researchers know who is receiving the active treatment (vaccine). This also eliminates bias. • Placebo controlled – One group of subjects receives the active treatment (vaccine), while the second group receives a placebo control (no medical value) to ensure valid comparisons. • The Power of the Placebo Effect video • Big bang theory Placebo effect Food unwrapped: The power of Beetroot! • 18.30 – 23.15 • Placebo / blind trial • http://www.channel4.com/programmes/ food-unwrapped/on-demand/61830-025 Large Scale Studies • The 2 groups must be of a suitable size to reduce the magnitude of experimental error – For example: one group may have an atypically large number of older people who are overweight and more seriously ill. Thus their health conditions will impact results • 9 out of 14 compared to 41 out of 250 • At the end of the trial, results from the two groups are then compared to determine whether there are any statistically significant differences between the groups, i.e: – Group 1: 50 out of 250 showed improved – Group 2: 224 out of 250 showed improvement KA 4a: Active Immunity, Vaccinations and Herd Immunty By the end of this section you will be able to ….. • State what is meant by herd immunity • Describe the benefit of herd immunity to nonimmune individuals • Describe the importance of herd immunity in reducing the spread of disease • State that the herd immunity threshold depends on a number of factors Give examples of barriers to herd immunity in the developing world Give examples of barriers to herd immunity in the developed world What is Herd Immunity? • http://www.immunisationscotland.org.uk/w hy-immunise/benefits-for-you.aspx (watch the video on “Benefits for you” and also on “Benefits for s all” • https://www.youtube.com/watch?v=CPcC4o GB_o8 (detailed) • https://www.youtube.com/watch?v=UqKPETVvrc (simple) What is Herd immunity? • Herd immunity occurs when a large percentage of a population are immunised. • Non-immune individuals are therefore protected as there is a lower probability they will come into contact with infected individuals • This herd immunity is important in: – Reducing the spread of diseases and – Protecting vulnerable and non-vaccinated individuals. Herd immunity threshold Disease Transmission Average number of secondary infections resulting from single index case Diptheria Saliva 6–7 85% Measles Airborne 12 – 18 83 – 94 % Mumps Airborne droplet 4–7 75 – 86 % Whooping cough Airborne droplet 12 – 17 92 – 94 % Polio Faecal-oral route 5–7 80 – 86 % Rubella Airborne droplet 5–7 83 – 85 % Smallpox Social contact 6–7 83 – 85 % Herd immunity threshold Drop in immunisation rates… 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. • Herd Immunity threshold varies as it depends on: – The disease – The efficacy of the vaccine and – The contact parameters for the population. Snakes & Ladders • Sort the cards into 2 piles – a snake card pile and a ladder card pile • Play the game like you NORMALLY would do EXCEPT… • If you go up a ladder you must read a ladder card out loud AND say if the card relates to the developed world or developing world. • If you go down a snake, you must read a snake card out loud AND say if the card relates to the developed world or developing world. Think… • What colour cards do you think are relevant to the: – Developing world? – Developed world? • Use the cards to make notes on: – Barriers to herd immunity in the developing world – Barriers to herd immunity in the developed world Barriers to herd immunity • In most countries, the policy in public health medicine is to establish herd immunity to a number of diseases. • Difficulties can arise when widespread vaccination is not possible due to malnutrition and poverty (the developing world) or when vaccines are rejected by a percentage of the population (the developed world). House md clip - no vaccine MMR and autism • Example of inadequate research – Sample size – Bias • Example of development of vaccine rejection (barrier to herd immunity) – Led to a series of outbreaks and epidemics in the UK • Example of media influence The MMR Scare • Autism is a condition which affects 1 or 2 people in every 1000, affecting neural development and causing restricted and repetitive behaviour. • It affects social behaviour and language; its causes are unknown. • It is usually diagnosed from the age of three onwards. The MMR Scare • In Britain, as in many countries, the majority of children are vaccinated against measles, mumps and rubella using a combined vaccine (MMR). • A British doctor (Andrew Wakefield) wrote a report on 12 children who had been vaccinated with the MMR vaccine and were subsequently diagnosed as autistic. • The result of this report was that media interest was raised; many anti-MMR stories appeared and there was a significant fall in the number of children given the MMR vaccine. Importance of large scale studies • The Madsen study in Denmark. • Because Denmark tracks patients and the care they receive they have been able to study the correlation between vaccination and illness; the data clearly shows that there is no correlation between MMR vaccination and the incidence of autism. Why is this study more reliable than Dr Wakefields? • The study was based on data from over half a million children • Over 440,000 had been vaccinated and there was no greater incidence of autism amongst children vaccinated as amongst those not vaccinated. • What happened to the MMR vaccination rates of children? • What happened to the incidence of measles? • Is there a causal link? NO Herd immunity to protect those who were not vaccinated, so incidence of measles increases! So… is there a correlation? There is of course a correlation (similar Did the pollen count cause the cream ice cream sales toover rise? •• One graphs shows ice sales • Did the sale of ice cream cause the pollen count to pattern) year and IS theNO other showsTOpollen • arise? BUT THERE EVIDENCE SUGGEST • count. Is thereONE any link? THAT CAUSES THE OTHER No effect of MMR withdrawal on the incidence of autism: a total population study. H Honda et al. Journal of Child Psychology and Psychiatry 2005 COMMENT: The increase in autism and autistic spectrum disorders in this part of Yokohama displays the same increase over time seen in other parts of the world. Here, though, the increase occurred even when the MMR vaccine was withdrawn. This destroys any possible causative link between use of the vaccine and autism The MMR Scare • It was subsequently established beyond reasonable doubt that there is no causal link between MMR vaccination and autism. The doctor had a commercial interest in the alleged link and was subsequently struck off. • The scare affected no other countries; MMR vaccination rates are rising again. Watch the following video on the effect of adverse publicity on the MMR vaccination http://www.youtube.com/watch?v=jfheO9H8CD4 • This is how the paper now appears on the journal website… RETRACTED Quick Questions 1. During clinical trials, one group of test subjects receive the vaccine, but the other group do not. Describe what the 2nd group receive instead. Placebo (has no medical value) 2. What term is used to describe a trail where neither the researchers nor the test Double-blind subjects know who has received the vaccine. 3. Describe how herd immunity is achieved By immunising a large percentage of the population 4. Give one advantage of establishing herd immunity Reduces the transmission rate KA 4a: Active Immunity, Vaccinations and Herd Immunty By the end of this section you will be able to ….. • describe the process of antigenic variation • give examples of pathogens that use antigenic variation • describe why antigenic variation poses a problem to public health • Describe how to set up an experiment to view the antibody-antigen interaction describe how HIV overcomes the immune response describe how TB can avoid the immune response Evasion of specific immune responses • Not all diseases can be eradicated by vaccines. • Some pathogens have evolved mechanisms that evade the immune system. This has great consequences for vaccination strategies. • Pathogens can either: 1. Undergo antigenic variation • Malaria, Influenza, Trypanosomiasis (sleeping sickness) 2. Directly attack the immune system • HIV and TB Re-cap • What is antigen? • Describe the specific immune response • Describe the role of memory cells Let’s play Chinese Whispers! 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. Evolution of the FLU virus • In this diagram, the antigens can change in two ways, but importantly, it means that the antibodies produced by memory cells cannot bind to them and inactivate the pathogen. Trypanosomiasis • A protozoa called Trypanosoma brucei causes the fatal disease called trypanosomiasis or ‘sleepingsickness’. • 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%. Survive and change Survive and change Meningitis B has also evaded our immune system • https://www.theguardian.com/science/o ccams-corner/2015/sep/01/why-is-thenhs-vaccination-for-meningitis-b-notprovided-to-everyone Videos • Malaria: http://www.youtube.com/watch?v=qvlTOhC mxvY • Trypanosomiasis: • http://www.youtube.com/watch?v=4aVUrG O97Zg&list=PLXfKWnjanUc3He0aOwo7Uw 0MuG0jlQjci • Influenza: • http://www.youtube.com/watch?v=ugM1nIhfIA 1. Antigenic variation • Some pathogens can change their antigens, avoiding the effect of immunological memory (memory cells). • Antigenic variation occurs in diseases like malaria and trypanosomiasis, and is one of the reasons why they are still so common in many parts of the world. • Antigenic variation also occurs in the influenza virus, explaining why it remains a major public health problem and why atrisk individuals require to be vaccinated every year. Antibody and Antigen interaction – using agar gel (Experiment) • Agar gel can be used to observe antibodies reacting with antigens. • The agar allows the proteins to diffuse towards each other • When they meet they bind together. This is indicated by a white line in the agar. Antibody and Antigen interaction – using agar gel (Experiment) Antigen X placed in centre well Blood plasma of Pupil A Blood plasma of Pupil B AIM: To observe the presence of antibodies against antigen X in various pupils RESULTS Blood plasma of Pupil F Blood plasma of Pupil E Blood plasma of Pupil D Blood plasma of Pupil C What conclusion can be drawn from these results? Antigen X placed in centre well Blood plasma of Pupil A Blood plasma of Pupil B Blood plasma of Pupil F Blood plasma of Pupil E Blood plasma of Pupil D Blood plasma of Pupil C More Questions! 1. Pupil C wanted to investigate what other antibodies she had. Explain how she could do this. Antigen X placed in centre well Blood plasma of Pupil A Blood plasma of Pupil B Blood plasma of Pupil F Blood plasma of Pupil E Blood plasma of Pupil D Blood plasma of Pupil C More Questions! 2. Antigen X is actually from an Influenza virus. All the pupils have suffered from influenza. Explain why a line did not form between ALL the pupils and antigen X. 3. Explain why a line DID form between 3 of the pupils and antigen X. Antigen H placed in centre well Blood plasma of Pupil A Blood plasma of Pupil B Blood plasma of Pupil F Blood plasma of Pupil E Blood plasma of Pupil D Blood plasma of Pupil C More Questions! 4. Antigen X was replaced with an antigen from a different virus (antigen H). Only Pupils A and E have been vaccinated against this virus. Predict the results that would be observed from this experiment. 2. Direct attack on the Immune System • The absence or failure of some component of the immune system results in increased susceptibility to infection. Direct attacks on the immune system HIV infection • https://www.youtube.com/watch?v=ng2 2Ucr33aw Symptoms of HIV infection • Oral candida is a common symptom • Body cannot defend against the fungus that causes oral thrush • Lesions form on the chest and develop all over the skin Human Immunodeficiency Virus • AIDS is a deficiency disease caused by the HIV virus. • The glycoproteins on the HIV attach to the receptors on the T-helper lymphocytes. • The virus infects the T-helper cell, replicates, leaves by budding and infects more T-helper cells. • The membrane of the T-helper cell becomes punctured, leaving the cell destroyed. • As the number of T-cells decrease, the person becomes more susceptible to infections (pneumonia, rare forms of cancer) Remember, helper T cells are of critical importance to the immune system – they activate B cells and cytotoxic T cells Direct attacks on the immune system TB • http://www.youtube.com/watch?v=IGZLkRN76Dc • http://www.youtube.com/watch?v=gruBIZ0Bm-I • http://www.youtube.com/watch?v=f5uq-ta4km0 – call me maybe version! Symptoms of Tuberculosis TB disease symptoms may include: • A bad cough that lasts 3 weeks or longer. • Pain in the chest. • Coughing up blood or sputum (phlegm from deep inside the lungs) • Weakness or fatigue. • Weight loss. • No appetite. • Chills. • Fever. Tuberculosis Bacteria • TB is an example of where a pathogen hijacks the immune system for themselves. • 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. • The pathogen remains alive inside the phagocyte and avoids immune detection and destruction. How to eradicate a disease? • https://www.youtube.com/watch?v=oBS andHijDc Don’t forget you can do the Key Area 1,2,3 Questions again! Yey Key Area 4: Past Papers Yellow Booklet Paper (new higher human biology) Section Question 2015 1 2 17,20 12,13 specimen 1 2 1 2 19,20 11,12,13 19,20 12 exemplar Don’t forget you can do the Key Area 1,2,3 Questions again! Yey Key Area 4: Past Papers Red Booklet Paper (revised higher human biology) 2014 2013 2012 Section Question 1 2 1 16,28,29,30 12 28,29 2 14 2 13a-f