Topic 2C - Cells and the immune system DVY * Flashcards
the immune system immunity and vaccines antibodies in medicine interpreting vaccine and antibody data HIV and Viruses
what are antigens?
molecules (usually proteins) that can generate an immune response when detected by the body
where are antigens found?
they’re usually found on the surface of cells
what are antigens used for?
used by immune system to identify pathogens, abnormal body cells, toxins and cells from other individuals of the same species
what are the 4 main stages in the immune response?
- phagocytes engulf pathogens
- phagocytes activate T-cells
- T-cells activate B-cells, which divide into plasma cells
- plasma cells make more antibodies to a specific antigen
what is a phagocyte?
a type of white blood cell that carries out phagocytosis
they’re the 1st cells to respond to an immune system trigger inside the body
where are phagocytes found?
produced throughout life in the bone marrow
they’re found in the blood and in tissues
how do phagocytes engulf pathogens?
- phagocyte recognises foreign antigens on pathogen
- cytoplasm moves round pathogen, engulfing it. and the phagocyte attaches to the pathogen surface using specific receptors
- pathogen now contained in a phagocytic vacuole in cytoplasm of phagocyte called a phagosome
- a lysosome fuses with phagosome, forming phagolysosome. lysozymes break down pathogen via hydrolysis
- phagocytes cytoplasm absorbs soluble products and indigestible debris is excreted by exocytosis. it then presents pathogen’s antigens by sticking them on its surface to activate other immune system cells
what are T-cells (T-lymphocytes)?
another type of white blood cell with receptor proteins on its surface that bind to complementary antigens presented to it by phagocytes. this activates the T-cell
what are the different types of T-cell?
helper T-cells
cytotoxic T-cells
what do helper T-cells do?
release chemical signals that activate and stimulate phagocytes, cytotoxic T-cells and B-cells
what do cytotoxic T-cells do?
kill abnormal and foreign cells
what are B-cells (B-lymphocytes)?
a type of white blood cell covered with antibodies. each B-cell has a different shaped antibody on its membrane, so they’re specific to different antigens
what are antibodies?
globular proteins that are made up of 4 polypeptide chains.
they have a quaternary protein structure
what is clonal selection?
when the antibody on the surface of a B-cell meets a complementary shaped antigen, it binds to it.
this and substances released from helper T-cells, activates the B-cell. it then divides into plasma cells
what are plasma cells?
they’re clones of B-cells so they’re identical to them
what do plasma cells do?
they secrete loads of antibodies specific to the antigen. these are called monoclonal antibodies
what do antibodies do?
they bind to the antigens on the surface of the pathogen to form lots of antigen-antibody complexes
what is agglutination?
an antibody has 2 binding sites, so can bind to 2 pathogens at once, clumping pathogens together
this means they act as markers for phagocytes and they’re less spread out
what happens after agglutination?
phagocytes bind to the antibodies and phagocytose many pathogens at once. this process leads to the destruction of pathogens carrying this antigen in the body
what does the specificity of an antibody depend on?
it depends on its variable regions, which form the antigen binding sites. each antibody has a variable region with a unique tertiary structure that’s complementary to 1 specific antigen. all antibodies have the same constant regions that binds to B-cells
what is the structure of an antibody?
they have heavy chains on the inside of the Y
light, shorter chains on the outside of the V of the Y
constant region at the bottom
variable region at the tips of the antibody
hinge protein at the corners
disulfide bridge between the 2 heavy proteins and the heavy and light chains
what are the 2 types of specific immune response?
cellular (cell-mediated)
humoral (antibody-mediated)
what is the cellular immune response?
involves highly specialised cells that target and kill pathogens inside infected cells
the T- cells and other immune system cells that they interact with, e.g. phagocytes, form the cellular response
what is the humoral response?
attacks pathogens/ toxins in bodily fluids with antibodies before they enter the cell
B-cells, clonal selection and the production of monoclonal antibodies form the humoral response
which immune response is needed to remove a pathogen from the body?
both types are needed 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
what is the primary response?
when an antigen enter the body for the first time and the immune system is activated
why is the primary response slow?
there aren’t many B-cells that can make the antibody needed to bind to it.
what happens in the primary immune response?
an antigen activates the immune system and eventually the body will produce enough of the right antibody to overcome the infection. the infected person will show symptoms of the disease
what do T-cells and B-cells do after being exposed to an antigen to prepare for future infection?
they produce memory cells. these memory cells remain in the body for a long time.
what do memory T-cells do?
they remember the specific antigen and will recognise it a second time around
what do memory B-cells do?
they record the specific antibodies needed to bind the antigen
when is a person immune?
when the infection has been overcome and memory cells have been made - their immune system has the ability to respond quickly to a second infection
what is the secondary immune response?
if the same pathogen enters the body again, the immune system will produce a quicker, stronger immune response
how does clonal selection happen faster in the secondary immune response?
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
does the secondary immune response show symptoms?
the secondary response often gets rid of the pathogen before you begin to show any symptoms
what are the non-specific immune responses?
phagocytosis - cell eating
inflammation - redness + swelling. rush of blood/fluid to infected site
lysozyme action - found in human tears, saliva and lysosomes
interferons
what are interferons?
they’re produced by virus-infected body cells in response to the virus, this triggers the production of a second protein that inhibits viral replication
what do phagocytes do?
remove dead cells as well as infectious micro-organisms
produced in large numbers during infection
what are the 2 types of phagocytes?
neutrophils - leave the blood and ‘patrol’ tissues
macrophages - settle in organs, only partially destroy pathogen
when is histamine produced?
attacked cells release histamine
this attracts phagocytes to the infected area and causes dilation of the blood vessels adding to inflammation
passing neutrophils are alerted and are attracted to the infection site
where are T-cells in the body?
made in bone marrow, migrate via thymus gland to lymph glands
respond to cells altered by cancer, viruses, fungi and parasites in cell-mediated immunity
where are B-cells in the body?
made in bone marrow, migrate directly to lymph glands
respond to bacteria and viruses before they enter our cells in antibody mediated immunity
how are helper T-cells activated?
helper T cell detects antigen and a specific complementary receptor protein on its surface binds to it, this activates the T-cell
what happens after a T-cell is activated?
they divide rapidly by mitosis
this forms a clone of genetically identical cells that cause various things to happen:
stimulate specific B cells to clone and secrete antibodies
stimulate phagocytes
activate cytotoxic (killer) T-cells which kill infected cells
develop into memory cells that circulate in the blood, ready for future infection
how do cytotoxic T-cells kill cells?
they dock onto a target cell
they release the enzyme, perforin, into the target cell
the target cell dies
what happens with B-cells when an antigen has entered the bloodstream?
1 B-cell will have an antibody on its surface with a complementary shape
they bind and the antigen is taken into the B-cell by endocytosis
antigen is processed then presented on its surface
activated T helper cell attaches to the processed antigen
this activated the B-cell which will divide by mitosis and create a clone of plasma cells
the antibodies secreted are all specific to the antigen that was on the pathogens surface
antibodies attach to antigens on pathogens and destroy them
some B-cells develop into memory cells that respond to future infections by the same pathogen
how do plasma cells differ from memory cells?
plasma cells survive a few days then die after doing job, memory cells survive and circulate longer
plasma secrete lots of complementary antibodies quickly into blood and lymph that will disable pathogens and neutralise toxins, but memory divide rapidly if pathogen is reintroduced and develop into plasma cells
plasma are slow primary response
memory is faster and more intense, immunology memory formed
what is neutralisation?
when antibodies bind to the pathogen in such a way that prevent it from causing infection
what are polyclonal antibodies?
naturally produced in immune response
many different antibodies produced by many different plasma cells for every antigen on a pathogens surface
why are polyclonal antibodies produced?
each antigen induces a different B-cell to multiply and clone
what are monoclonal antibodies?
produced from clones of a single plasma cells and so are identical
B-cells are short-lived and only divide inside a living organism
how can monoclonal antibodies be manufactured?
antigenetic material injected into animal, stimulating production of plasma cells
plasma cells produce mixture of antibodies (polyclonal)
antibody producing B-cells extracted from spleen
B-cells mixed with tumour cells to form hybridoma cells that can divide outside the body
each clone is tested and any clone producing the required antibody is grown on a large scale
antibodies extracted from growth medium, are monoclonal because they have come from a clone of a single B-cell
what are magic bullets?
drugs that target specific pathogens without harming the body
how can monoclonal antibodies be used for cancer treatments?
cancer cells have antigens called tumour markers that are not found on normal body cells.
monoclonal antibodies can be made that bind to these markers
these can be attached to anti-cancer drugs
antibodies will bind to tumour markers
the drug will only accumulate in the body where there are cancer cells
what are the different uses of monoclonal antibodies?
magic bullets
medical diagnosis
pregnancy testing
How do pregnancy tests work?
placentas in pregnant women produce hcG so there’s hcG in the urine
Reaction zone - the monoclonal antibody for hcG has coloured particles linked to it, they bind to hcG, forming antigen-antibody complex
results window - they are trapped by another antibody to hcG, immobilising it, creating a blue line
control window - antibodies unbound to hcG bind to final antibody in control window, this proves its working
what do vaccines contain?
free antigens, dead or attenuated pathogens
what do vaccines do?
cause your body to produce memory cells against a particular pathogen, without the pathogen causing disease, so you get immune and build up immunological memory without getting any symptoms.
how do vaccines protect people?
they reduce the occurrence of the disease in the people who get them
people who aren’t vaccinated are less likely to catch the disease due to herd immunity
how can vaccines be administrated?
they can be injected or taken orally
what are the disadvantages of taking a vaccine orally?
it could be broken down by enzymes in the gut
the molecules of the vaccine may be too large to be absorbed into the blood
what might a vaccine be followed up by?
a booster e.g. after several years, to make sure the memory cells are produced
what is antigenetic variability?
when different antigens for the same pathogen are formed due to changes in the gene of a pathogen
what effect does antigenetic variability have?
when you are infected a second time, the memory cells produced from the 1st infection will not recognise the antigens. so the immune system has to carry out the primary response again, which takes time so you will get ill again
examples of pathogens that show antigenetic variation:
HIV and the influenza virus
thats why it is difficult to produce vaccines for them
how does antigenetic variation affect the production of influenza vaccines?
the flu vaccine changes every year because the antigens on the surface of influenza virus change regularly, forming new strains of the virus that are immunologically distinct.
what does immunologically distinct mean?
memory cells produced for one pathogen/strain will not recognise other strains/ pathogens with different antigens
what is done each year in regards to the influenza (flu) vaccine?
every year new strains circulate the population
new vaccines are developed and the most effective is chosen each year
Governments and health authorities then implement a programme of vaccination using this vaccine
what are the 2 types of immunity?
active immunity
passive immunity
within these 2 immunities are natural and artificial types
what is active immunity?
when your immune system makes its own antibodies after being stimulated by an antigen
what is passive immunity?
immunity from being given antibodies made by a different organism - your immune system doesn’t produce any antibodies of its own
what is natural active immunity?
this is when you become immune after catching a disease
what is artificial active immunity?
this is when you become immune after you’ve been given a vaccination containing a harmless dose of antigen
what is natural passive immunity?
this is when a baby becomes immune due to the antibodies it receives from its mother, through the placenta and in breast milk
what is artificial passive immunity?
this is when you become immune after being injected with antibodies from someone else
example of artificial passive immunity:
if you contract tetanus you can be injected with antibodies against the tetanus toxin, collected from blood donation
how do active and passive immunity differ from one another?
- active: requires exposure to antigen, passive: doesn’t
2 . active: takes a while for protection to develop, passive: protection is immediate - active: memory cells produced, passive: memory cells aren’t produced
- active: long-term protection due to antibody production from memory cells in response to complementary antigen, passive: short-term protection because antibodies given are broken down
what is a vaccine?
a preparation containing antigenetic material given by injection or taken by mouth
what is needed for a successful vaccination programme?
sufficient quantities of vaccine to immunise most of vulnerable population
no/few side effects so people aren’t discouraged
a way of producing, transporting and organising vaccine
efficient way to administer vaccine in large population - staff training
possible to create herd immunity
what is herd immunity?
when a sufficiently large proportion are vaccinated
ideal % is different for each disease
this makes it more difficult to spread
what is an example of a successful vaccination programme?
small pox
- herd immunity
- animals weren’t infected
- easy to identify infected
- effective administration of vaccine by volunteers
- few side-effects, easily transported/stored, pathogen didn’t mutate
what are the difficulties of vaccination programmes?
people with weakened immunities pose problem
doesn’t work if person gets disease soon after infection
pathogen can mutate
may be too many strains
objections/ ethical/ religious issues
what is an example of a difficult disease for vaccination?
cholera
-hides in intestines, away from immune system
-oral treatments flushed out by diarrhoea
-frequently mutating antigens
movement of people makes it difficult to track who needs vaccine
what are the advantages of monoclonal antibodies that target cancer cells?
lower side-effects as they only accumulate near specific cells
smaller doses can be used so its cheaper
what medical diagnostic test uses antibodies?
the enzyme-linked immunosorbent assay (ELISA)
what does the ELISA test do?
allows you to see if a patient has any antibodies to a certain antigen or any antigen to a certain antibody
what can the ELISA test be used for?
testing for pathogenic infections, for allergies and anything else that an antibody can be used for
what happens in an ELISA test?
an antibody is used which has an enzyme. this enzyme can react with a substrate to produce a coloured product. this causes the solution in the reaction vessel to change colour
what does a positive result in an ELISA test look like?
if there’s a colour change, it demonstrates that the antigen or antibody of interest is present in the sample being tested. the quantity can sometimes be worked out from the intensity of the colour change
what is a direct ELISA?
it uses a single antibody that is complementary to the antigen you’re testing for
what is an indirect ELISA?
it uses 2 different antibodies
how can an indirect ELISA test be used as an HIV test?
- HIV antigen bound to the bottom of a well in a well plate
- sample of patients blood plasma, is added to well
- well is washed out to remove unbound antibodies
- secondary antibody, with a specific enzyme attached is added to the well
- well washed out to remove unbound secondary antibodies
- solution containing substrate is added to the well
what is a well plate?
a plastic tray with loads of circular pits in it
what happens in the ELISA HIV test if there is a positive result?
patient’s blood plasma contains HIV-specific antibodies that bind to antigens at the bottom of well
secondary antibody binds to HIV-specific antibody
substrate reacts with enzyme attached to secondary antibodies to produce a coloured product
what happens when a study presents evidence for a new theory?
it’s important that other scientists come up with more evidence to validate the theory. other scientists may repeat the study and try to reproduce the results, or conduct other studies to try to prove the same theory
what is an example of new evidence needing to be checked?
a 1998 study carried out on 12 children suggested there was a link between the MMR vaccine and autism
why was the link between MMR and autism unconvincing?
very small sample size, increased likelihood that results were due to chance
study may have been biased because evidence was being gained for a lawsuit against MMR vaccine manufacturer
other studies found no link
what study was carried out that disproves the link between MMR and autism?
Japanese study in 2005 looks at 30,000 children between 1988 and 1996.
the data could be described:
the graph shows number of children diagnosed continues to rise after vaccine stopped
draw conclusions:
there is no link
evaluate methodology:
large sample size, so results are less likely due to chance
what do 20% of women with breast cancer have?
tumours that produce more than the usual amount of a receptor called HER2
what is herceptin?
a drug that treats the type of breast cancer that produces too much HER2,
it contains monoclonal antibodies that bind to the HER2 receptor on a tumour cell and prevent the cells from growing and dividing
how was herceptin tested?
in 2005 a study tested herceptin on 3,388 women who had already undergone chemotherapy. half the women took the drug for a year, the other half were observed
describe the data obtained from the herceptin study:
almost twice as many women in the control group developed breast cancer again or died compared to the group who took herceptin
draw conclusions from the herceptin study:
a 1-year treatment with herceptin, after chemotherapy, increases the disease-free survival rate for women with HER2 - type breast cancer
what are the ethical issues surrounding vaccines?
- all vaccines are tested on animals before being tested on humans
- testing vaccines on humans can be tricky
- some people don’t want to take vaccine due to risk of side effects - but they’re still protected by herd immunity
- if there was an epidemic of a new disease difficult decisions must be made about who gets it first
why does the use of vaccines on animals raise ethical issues?
some people disagree with animal testing. also, animal based substances may be used to produce a vaccine, which some people disagree with
how can testing vaccines on humans be tricky?
volunteers may put themselves at unnecessary risk of contracting the disease because they think they’re fully protected e.g. unprotected sex with the HIV vaccine which might not work
what are the ethical issues surrounding monoclonal antibody therapy?
animals are used to produce the cells from which the monoclonal antibodies are produced.
some people disagree with the use of animals in this way
what does HIV stand for?
human immunodeficiency virus
what does HIV eventually lead to?
AIDS (acquired immune deficiency syndrome)
what is AIDS?
a condition where the immune system deteriorates and eventually fails, making someone more vulnerable to other infections, like pneumonia
when is a person determined as having AIDS?
when helper T-cell numbers in the body reach a critically low level
when is a person determined as having AIDS?
when helper T-cell numbers in the body reach a critically low level, or when symptoms of of their failing immune system start to appear
what does the structure of HIV have?
a core
a capsid
an envelope
attachment proteins
what does the core of HIV contain?
the genetic material (RNA) and some proteins, including the enzyme reverse transcriptase, which is needed for DNA replication
what is a capsid?
an outer coating of protein
what is the HIV’s envelope?
an extra outer layer, made of membrane stolen from the cell membrane of a previous host cell
what do the attachment proteins on HIV do?
loads of copies of an attachment protein stick out from the envelope and help HIV attach to the host helper T-cell
where does HIV replicate?
it can only reproduce inside the cells of the organism it has infected (helper T-cells) because it doesn’t have the equipment, like enzymes and proteins, to replicate on its own
how does HIV replicate?
genetic material released into cytoplasm
reverse transcriptase used to make complementary strand of DNA from viral RNA template
from this, double stranded DNA is made and inserted into human DNA
host cell enzymes used to make viral proteins from viral DNA
viral proteins assembled into new viruses, which bud from the cell and go to infect other cells
how does HIV get into its host cell for replication?
attachment protein attaches to receptor molecules on cell membrane of host helper T-cell
capsid released into cell, where it uncoats and releases genetic material into cell’s cytoplasm
what happens during the initial infection period of HIV?
HIV replicates rapidly and the infected person may experience flu-like symptoms
what happens after the initial HIV infection period?
HIV replication drops to a lower level. this is the latency period, during this time, which can last for years, the infected person won’t experience any symptoms
how long is the latency period of HIV?
around 10 years if left untreated
what are the initial symptoms of AIDS?
minor infections of mucous membranes and recurring respiratory infections
how does AIDS affect people?
people with AIDS generally develop diseases that wouldn’t cause serious problems in people with a healthy immune system
what happens as AIDS progresses from the initial symptoms?
the number of immune system cells decreases further,
patients become susceptible to more serious infections including chronic diarrhoea, severe bacterial infections and tuberculosis
what happens 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. it’s the serious infections that kill AIDS patients, not the HIV itself
what type of disease is toxoplasmosis of the brain?
a parasite infection
what type of disease is candidiasis of the respiratory system?
a fungal infection
what factors affect the progression of HIV to AIDS?
existing infections
the strain of HIV they’re infected with
age and access to healthcare
what do antibiotics do?
they kill bacteria by interfering with their metabolic reactions. they target the bacterial enzymes and ribosomes used in these reactions
how are antibiotics safe for humans?
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
why don’t antibiotics work on viruses?
viruses use the host cells enzymes and ribosomes to replicate, so antibiotics can’t inhibit them because they don’t target human processes
what do antiviral drugs do?
they are designed to target the few virus-specific enzymes that exist. e.g. reverse transcriptase in HIV. human cells don’t use this enzyme so drugs can be designed to inhibit it without affecting the host cell. these are called reverse-transcriptase inhibitors
is there a cure for HIV?
there is 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
what is the best way to control HIV infection in a population?
reducing the spread
how can HIV be spread?
unprotected sexual intercourse, through infected bodily fluids and from a HIV-positive mother to her foetus
how can the chance of babies getting HIV from there mothers be reduced?
taking antiviral drugs during pregnancy can reduce the chance of the baby being HIV-positive
