Topic 2C - Cells and the Immune System - complete

- antigens are molecules (usually proteins) that can generate an immune response when detected by the body
- they are usually found on the surface of cells and are used by the immune system to indentify: pathogens (organisms that cause disease), abnormal body cells (e.g. cancerous or pathogen-infected cells, which have abnormal antigens on their surface), toxins and cells from other individuals of the same species (e.g. organ transplants)

- a phagocyte (e.g. a macrophage) is a type of white blood cell that carries out phagocytosis (engulfment of pathogens)
- they're found in the blood and in tissues and are the first cells to respond to an immune system trigger inside the body
1) a phagocyte recognises the foreign antigens on a pathogen
2) the cytoplasm of the phagocyte moves round the pathogen, engulfing it
3) the pathogen is now contained in a phagocytic vacuole (a bubble) in the cytoplasm of the phagocyte
4) a lysosome (an organelle that contain enzymes called lysozymes) fuses with the phagocytic vacuole
- the lysozymes break down the pathogen
5) the phagocyte then presents the pathogen's antigens
- it sticks the antigens on its surface to activate other immune system cells

- a t-cell (t-lymphocyte) is another type of white blood cell
- it has receptor proteins on its surface that bind to complementary antigens presented to it by phagocytes
- this activates the t-cell
- different types of t-cells respond in different ways
- for example, helper t-cells (T_H cells) release chemical signals that activate and stimulate phagocytes and cytotoxic t-cells (T_c cells) which kill abnormal and foreign cells
- helper t-cells also activate b-cells, which secrete antibodies

- b-cells (B-lymphocytes) are also a type of white blood cell
- they're covered with antibodies (proteins that bind antigens to form an antigen-antibody complex)
- each b-cell has a different shaped antibody on its membrane, so different ones bind to different shaped antigens
1) when the antibody on the surface of a b-cell meets a complementary shaped antigen, it binds to it
2) this, together with substances released from helper t-cells, activates the b-cell
- this process is called clonal selection
3) the activated b-cell divides into plasma cells

- plasma cells are identical to the b-cell (they're clones)
- they secrete lots of antibodies specific to the antigen
- these are called monoclonal antibodies
- they bind to the antigens on the surface of the pathogen to form lots of antigen-antibody complexes
- an antibody has two binding sites, so can bind to two pathogens at the same time
- this means that pathogens become clumped together (agglutination)
- phagocytes then bind to the antibodies and phagocytose many pathogens at once
- this process leads to the destruction of pathogens carrying this antigen in the body

- antibodies are proteins & are made up of chains of amino acids
- the specificity of an antibody depends on its variable regions, which form the antigen binding sites 
- each antibody has a variable region with a unique tertiary structure (due to different amino acid sequences) that's complementary to one specific antigen
- all antibodies have the same constant regions

- the immune response is split into two (cellular response and humoral response)
1) cellular - the t-cells and other immune system cells that they interact with, e.g. phagocytes, form the cellular response
2) humoral - b-cells, clonal section and the production of monoclonal antibodies form the humoral response
- both types of response are needed to remove a pathogen from the body and the responses interact with each other 
- e.g. t-cells help to activate b-cells, and antibodies coat pathogens making it easier for phagocytes to engulf them

1) when an antigen enters the body for the first time it activates the immune system
- this is called the primary response\
2) the primary response is slow because there aren't many B-cells that can make the antibody needed to bind to it 
3) eventually the body will produce enough of the right antibody to overcome the infection
- meanwhile, the infected person withh show symptoms of the diease
4) after being exposed to an antigen, both t-cells and b-cells produce memory cells
- these memory cells remain in the body for a long time
- memory t-cells remember the specific antigen and will recognise it a second time around
- memory b-cells record the specific antibodies needed to bind the antigen
5) the person is now immune
- their immune system has the ability to respond quickly to a second infection

1) if the same pathogen enters the body again, the immune system will produce a quicker, stronger immune response 
- this is know as the secondary response
2) clonal selection happens faster
- memory b-cells are activated and divide into plasma cells that produce the right antibody to the antigen
- memory t-cells are activated and divide into the correct type of t-cells to kill the cell carrying the antigen
3) the secondary response often gets rid of the pathogen before you begin to show any symptoms 
- this is because you are immune to the pathogen

- while your b-cells are busy dividing to build up their numbers to deal with a pathogen (i.e. the primary repsonse), you suffer from the disease
- vaccination can help avoid this
- vaccines contain antigens that cause your body to produce memory cells against a particular pathogen, without the pathogen causing disease
- this means you become immune without getting any symptoms
- vaccines protect individuals that have them and, because they reduce the occurence of the disease, people who aren't vaccinated are also less likely to catch the disease (herd immunity)
- vaccines always contain antigens, these may be free or attached to a dead ot attenuated pathogen 
- vaccines may be injected or taken orally
- the disadvantages of taking a vaccine orally are that it could be broken down by enzymes in the gut or the molecules of the vaccine may be too larger to be absorbed into the blood
- sometimes booster vaccines are given later on (e.g. after several years) to make sure that memory cells are produced

- antigens on the surface of pathogens actiavte the primary response
- when you're infected a second time with the same pathogen they activate the secondary response and you don't get ill
- however, some pathogens can change their surface antigens
- this antigen variability is called antigenic variation (different antigens are formed due to changes in the genes of a pathogen)
- this means that when you're infected for a second time, the memory cells produced from the first infection will not recognise the different antigens
- so the immune system has to start from scratch and carry out a primary response agaisnt these new antigens
- this primary response takes time to get rid of the infection, which is why you get ill again
- antigenic variation also makes it difficult to develop vaccines against some pathogens for the same reason
- examples of pathogens that show antigenic variation include HIV and the influenza virus 

1) the flu vaccine changes every year
- thats because the antigens on the surface of the flu virus change regularly, forming new strains of the virus
2) memory cells produced from the vaccination with one strain of the flu will not recognise other strains with different antigens
- the strains are immunologically distinct
3) every year there are different strains of the flu virus circulating in the population, so a different vaccine has to be made
4) new vaccines are developed and one is chosed every year that is the most effective against the recently circulating influenza viruses
5) governments and health authorities then implement a programme of vaccination using the most suitable vaccine

- this is the type of immunity you get when your immune system makes its own antibodies after being stimulated by an antigen
- there are two different types of active immunity:
1 - natural - this is when you become immune after catching the disease
2 - artificial - this is when you become immune after you've been given a vaccination containing a harmless dose of antigens

- requires exposure to antigens
- it takes a while for protection to develop
- memory cells are produced
- protection is long-term because the antibody is produced (after activation of memory cells) in repsonse to a complementary antigen being present in the body

- this is the type of immunity you get from being given antibodies made by a different organism 
- your immune system doesn't produce any antibodies of its own
- there are two types:
1 - natural - this is when a baby becomes immune due to the antibodies it receives from its mother, through the placenta and in breast milk
2 - artificial - this is when you become immune after being injected with antibodies from someone else e.g. if you contract tetnus you can be injected with antibodies against the tetanus toxin, collected from blood donations

- doesn't require exposure to antigen
- protection is immediate
- memory cells aren't produced
- protection is short-term because the antibodies given are broken down

- monoclonal antibodies are antibodies produced from a single group of genetically identical b-cells (plasma cells)
- this means that they're all identical in structure
- antibodies are very specific because their binding sites have a unique tertiary structure that only one particular antigen will fit into (one with a complementary shape) 
- you can make monoclonal antibodies that bind to anything you want and they will only bind to this molecule
- e.g. a cell antigen or other substance

1) different cells in the body have different surface antigens
2) cancer cells have antigens called tumour markers that are not found on normal body cells
3) monoclona antibodies can be made that will bind to the tumour markers
4) you can also attach anti-cancer drugs to the antibodies
5) when the antibodies come into contact with the cancer cells they will bind to the tumour markers
6) this means the drug will only accumulate in the body where there are cancer cells
7) so, the side effects of an antibody-based drug are lower than other drugs because they accumulate near specific cells

- pregnancy tests detect the hormone human chorionic gonadotropin (hCG) that's found in the urine of pregnant women
1) the application area contains antibodies for hCG bound to a coloured bead (blue)
2) when urine is appllied to the application area any hCG will bind to the antibody on the beads, forming an antigen-antibody complex
3) the urine moves up the stick to the test *****, carrying any beads with it
4) the test ***** contains antibodies to hCG that are stuck in place (immobilised)
5) if there is hCG present the test ***** turns blue because the immobilised antibody binds to any hCG, concentrating the hCG-antibody complex with the blue beads attached
- if no hCG is present, the beads will pass through the test area without binding to anything, and so it won't go blue

- the enzyme-linked immunosorbent assay (ELISA) allows you to see if a patient has any antibodies to a certain antigen or any antigen to a certain antibody 
- it can be used to test for pathogenic infections, for allergies (e.g. to nuts or lactose) and for just about anything you can make an antibody for
- in an ELISA test, an antibody is used which has an enzyme attached to it
- this enzyme can react with a substrate to produce a coloured product
- this causes the solution in the reaction vessel to change colour
- if there's a colour change, it demonstrates that the antigen or antibody of interest is present in the sample being tested (e.g. blood plasma)
- in some types of ELISA, the quantity of the antigen/antibody can be worked out from the intensity of the colour change
- there are several different types of ELISA
- direct ELISA uses a single antibody that is complementary to the antigen you're testing for
- indirect ELISA is different because it uses two different antibodies

1) HIV antigen is bound to the bottom of a well in a well plate 
2) a sample of the patient's blood plasma, which might contain several different antibodies, is added to the well
- if there are any HIV-specific antibodies (i.e. antibodies against HIV) these will bind to the HIV antigen stuck to the bottom of the well
- the well is then thoroughly washed out to remove any unbound antibodies 
3) a secondary antibody, that has a specific enzyme attached to it, is added to the well
- this secondary antibody can bind to the HIV-specific antibody (which is also called the primary antibody)
- the well is washed out again to remove any unbound secondary antibody
- if there's no primary antibody in the sample, all of the secondary antibody will be washed away 
4) a solution is added to the well
- this solution contains a substrate, which is able to react with the enzyme attached to the secondary antibody and produce a coloured product
- if the solution changes colour, it indicates that the patient has HIV-specific antibodies in their blood and is infected with HIV

1) in 1998, a study was published about the safety of the measles, mumps and rubella (MMR) vaccine 
- the study was based on 12 children with autism and concluded that there may be a link between the MMR vaccine and autism
2) not everyone was convinced by this study because it had a very small sample size of 12 children, which increased the likelihood of the results being due to chance
- the study may have been biased because one of the scientists was helping to gain evidence for a lawsuit against the MMR vaccine manufacturer
- also, studies carried out by different scientists found no link between autism and the MMR vaccine
3) there have been further scientific studies to sort out the conflicting evidence
- in 2005, a Japanese study was published about the incidence of autism in Yokohama
- they looked at the medical records of 30,000 children born between 1988 and 1996 and counted the number of children that developed autism before the age of 7
- the MMR jab was first introduced in Japan in 1989 and was stopped in 1993
- during this time, the MMR vaccine was administered to children at 12 months old

- the graph shows that the number of children diagnosed with autism continued to rise after the MMR vaccine was stopped
- for example, from all the children born in 1992, who did receive the MMR jab, about 60 out of 10,000 were diagnosed with autism before the age of 7
- however, from all the children born in 1994, who did not receive the MMR jab, about 160 out of 10,000 of them were diagnosed with autism before the age of 7
- in conclusion, there is no link between the MMR vaccine and autism
- you can be much more confident in this study, compared to the 1998 study, because the sample size was so large (30,000)
- a larger sample size means that the results are less likely to be due to chance

- about 20% of women with breast cancer have tumours that produce more than the usual amount of a receptore called HER2
- herceptin is a drug used to treat this type of breast cancer
- it contains monoclonal antibodies that bind the HER2 receptor on a tumour cell and prevent the cells from growing and dividing
- in 2005, a study tested Herceptin on women who has already undergone chemotherapy for HER2-type breast cancer
- 1694 women took the drug for a year after chemotherapy and another 1694 women were observed for the same time (the control group)
- almost twice as many women in the control group developed breast cancer again or died compared to the group taking herceptin
- a one-year treatment with herceptin, after chemotherapy, increases the disease-free survival rate for women wih HER2-type breast cancer 

Vaccines
1) all vaccines are tested on animals before being tested on humans
- some people disagree with animal testing
- also, animal based substances may be used to produce a vaccine, which come people disagree with
2) testing vaccines on humans can be tricky (e.g. volunteers may put themselves at unnecessary risk of contracting the disease because they think they're fully protected)
3) some people don't want to take the vaccine due to the risk of side effects, but they are still protected because of herd immunity & some people think this is unfair
4) if there was an epidemic of a new disease there would be a rush to receive a vaccine and difficult decisions would have to be made about who would be the first to receive it

Monoclonal Antibody Therapy
- animals are used to produce the cells from which the monoclonal antibodes are produced
- some people disagree with the use of animals in this way

- HIV is a virus that affects the immune system
- it eventually leads to AIDS
- AIDS is a condition where the immune system deteriorates and eventually fails
- this makes someone with AIDS more vulnerable to other infections, like pneumonia
- HIV infects (and eventually kills) helper T-cells, which act as the host cells for the virus
- helper t-cells send chemical signals that activate phagocytes, cytotoxic t-cells and b-cells so they're hugely important cells in the immune response
- without enough helper t-cells, the immune system is unable to mount an effective response to infections because other immune system cells dont behave how they should
- people infected with HIV develop AIDS when the helper t-cell numbers in their body reach a critically low level

- a core that contains the genetic material (RNA) and some proteins, including the enzyme reverse transcriptase, which is needed for virus replication
- an outer coating of a protein called a capsid
- an extra outer layer called an evelope
- this ^ is made of membrane stoled from the cell membrane of a previous host celll
- sticking out from the envelope are loads of copies of an attachment protein that help HIV attach the to host helper t-cell

- viruses can only reproduce inside the cells of the organism it has infected
- HIV replicated inside the helper t-cells of the host
- it doesn't have the equipment to replicate on its own, so it uses those of the host cell
1) the attachment protein attaches to a receptor molecule on the cell membrane of the host helper t-cell
2) the capsid is released into the cell, where it uncoats and releases the genetic material (RNA) into the cell's cytoplasm
3) inside the cell, reverse transcriptase is used to make a complementary strand of DNA from the viral RNA template
4) from this, double-stranded DNA is made and inserted into the human DNA
5) host cell enzymes are used to make viral proteins from the viral DNA found within the human DNA
6) the viral proteins are assembled into new viruses, which bud from the cell and go on to infect other cells
- during the initial infection period. HIV replicated rapidly and the infected person may experience severe flu-like symptoms
- after this period, HIV replication drops to a lower level (latency period) whch can last for 10 years & the person wont experience any symptoms

- people with HIV are classed as having AIDS when symptoms of their failing immune system start to appear on their helper t-cell count drops below a certain level
- people with AIDS generally develop diseases that wouldn't cause serious problems in people with a healthy immune system
- the length of time between infection with HIV and the development of AIDS varies between individuals but without treatment it's usually around 10 years
1) the initial symptoms of AIDS include minor infections of mucous membranes (e.g. inside the nose, ears and genitals), and recurring repiratory infections
2) as AIDS progresses the number of immune system cells decreases further
- patients become susceptible to more serious infections including chronic diarrhoea, severe bacterial infections and tuberculosis
3) during the late stages of AIDS patients have a very low number of immune system cells and can develop a range of serious infections such as toxoplasmosis of the brain and candidiasis of the respiratory system
- its these serious infections that kill AIDS patients, not HIV itself 
- the length of time that people with AIDS survive varies a lot
- factors include existing infections, the strain of HIV they're infected with, age and access to healthcare

- antibiotics kill bacteria by interfering with their metabolic reactions
- they target the bacterial enzymes and ribosomes used in these reactions
- bacterial enzymes and ribosomes are different from human enzymes and ribosomes 
- antibiotics are designed to only target the bacterial ones so they don't damage human cells
- viruses don't have their own enzymes and ribosomes
- they use the ones in the host's cells
- because human viruses use human enzymes and ribosomes to replicate, antibiotics can't inhibit them because they don't target human processes
- most antiviral drugs are designed to target the few virus-specific enzymes (enzymes that only the virus uses) that exist
- for example, HIV uses reverse transcriptase to replicate
- human cells don't use this enzyme so drugs can be designed to inhibit it without affecting the host cell
- these drugs are called reverse-transcriptase inhibitors

- there's currently no cure or vaccine for HIV but antiviral drugs can be used to slow down the progression of HIV infection and AIDS in an infected person
- the best way to control HIV infection in a population is by reducing its spread
- HIV can be spread via unprotected sex, through infected bodily fluids (e.g. like blood from sharing contaminated needles) and from a HIV-positive mother to her fetus
- not all babies from HIV-positive mothers are born infected with HIV and taking antiviral drugs during pregnancy can reduce the chanc of the baby being HIV-positive