Cell Recognition And The Immune System Flashcards
what are 3 self-defence mechanisms that the body has
Preventing the entry of pathogens by a variety of physical and chemical defences, such as the skin, mucous membranes, tears (containing the enzyme lysozyme, which destroys bacteria) and saliva
Inflammation (swelling and heating) of the region invaded by the pathogen, a process known as a non-specific inflammatory response
Recognising ‘foreign’ cells and targeting any pathogenic cells, a process known as a specific immune response
what do all cells have in their cell surface membrane
These molecules are usually proteins
They are often proteins that are part of the phospholipid bilayer, such as glycoproteins
However, glycolipids can also act as similar markers
what are the proteins in the CSM known as
cell-surface antigens
what are the role of cell-surface antigens
recognise ‘foreign’ cells enabling them to be identified by the body
They allow the body to recognise its own cells (‘self’) and foreign cells (‘non-self’)
what is the definition of an antigen
A protein that identifies as non-self and stimulates an immune response
what are the 4 ways foreign antigens can end up in the body
Pathogenic cells- microorganisms that cause disease eg bacteria
Abnormal body cells, such as cancerous or pathogen-infected cells
Toxins (these are chemical rather than cellular, in nature)- make us feel ill - pathogens produce these and they are released into the blood stream
Cells from other individuals from the same species (in order for organ transplants to occur successfully the body must not recognise the cells and tissues of the donated organ as foreign, so that no immune response occurs - so use a tissue match eg relative)
what are non-specific defenses
defences that are the same for all pathogens - do not distinguish bwt pathogens and are rapid
what is the difference bwt non-self and self
Antigens produced by the organism’s own body cells (those that the immune system does not recognise as foreign antigens) are known as self antigens
Self antigens do not stimulate an immune response
Antigens not produced by the organism’s own body cells (those that the immune system recognises as being foreign eg. the antigens found on pathogenic bacteria and viruses or if a person receives a different blood type during a transfusion) are known as non-self antigens
Non-self antigens stimulate an immune response
what are specific defences
slow response but longer lasting
highly specific and do distinguish bwt pathogens
give 4 examples of non s defences
-barriers
-commensals
-inflammation and phagocytosis
-interferons
what are barriers
physical barriers that prevent pathogens from gaining entry to the body
give some examples of physical barriers
-Our body cavities (e.g. eyes, nose, mouth, genitals) are lined with a mucus membrane which contain an enzyme called lysozyme. Lysozyme kills bacteria by damaging their cell walls, causing them to burst open.
-Our skin acts as a physical barrier to stop pathogens from getting inside of us. If our skin is cut or wounded, our blood quickly clots to minimise the entry of pathogens.
-the trachea (windpipe) contains goblet cells which secrete mucus. Pathogens that we inhale become trapped in the mucus, which is swept towards the stomach by the action of ciliated epithelial cells.
-Our stomach contains gastric juices which are highly acidic - these will denature proteins and kill any pathogens that have been ingested in our food and drinks.
-The insides of our intestines and the surface of our skin are covered in harmless bacteria which will compete with any pathogenic organisms and reduce their ability to grow.
what are commensals
pop of bacteria that harmlessly live in the body and outcompete negative bacteria
what is the process of inflammation
-damage to the tissues causes the release of chemical mediators such as histamine
-vasodilation of arterioles increasing blood flow - causes redness and swelling
-histamine increases the permeability of the blood vessels
-histamine attracts white blood cells to the area which squeeze’s out of the capillaries and move into the site if tissue damage
what is the process of phagocytosis
-the phagocyte is chemically attracted to the pathogen and binds it
-the phagocyte engulfs the pathogen into a vesicle where it is now known as a phagosome
lysosomes fuse with the phagosome forming a phagolysosome
-hydrolytic enzymes from the lysosomes now digest the molecules of the pathogen which destroy it
what are interferons
-glycoproteins produced by lymphocytes in response to viral infection
-stimulate other blood cells to produce antiviral proteins which stop cells infected by the virus from reproducing
- trigger lymphocytes to identify and destroy cells that have been infected by virus
- they are non-specific but are host-specific eg human interferons only work in humans
what are the 2 types of specific immune response
cell-mediated immunity- T lymphocytes attack pathogens or infected cells directly
humoral response - B lymphocytes produce antibodies to destroy invading pathogens and toxins
what are the 2 types of lymphocytes
B lymphocytes
T lymphocytes
where do T-cells originate from
they are produced by stem cell in the bone marrow and mature and are activated by the thymus gland
what are T cells said to be
competent-a cell’s ability to take up foreign (extracellular) DNA from its surrounding environment
what do t cells respond to
body cells displaying non-self antigens
eg phagocytes that have engulfed and destroyed a pathogen and are displaying some of the pathogen’s antigens on their CSM
body cells that have been infected by a virus
cancer cells displaying unusual antigens
transplant cells
what are antigen-presenting cells
one of the host’s cells that has been invaded by a pathogen and is displaying the antigen on its cell surface membrane- displaying non-self foreign antigens
what is embedded in the CSM of t cells
t cell receptors
what do antigen-presenting cells do
These cells present the antigens from toxins, foreign cells and ingested pathogens
They help to recruit other cells of the immune system to produce a specific immune response
Once the surface receptor of the T cell binds to the specific complementary antigen (on the antigen-presenting cell) it becomes sensitised and starts dividing to produce a clone of cells
how can t lymphocytes recoginse and respond to specific antigens
the t cell receptors have a very specific shape active site which can only bing to a specific antigen
what are the 4 different types of t lymphocytes
Th cells - helper cells
Tc cells -cytotoxic cells
Ts cells- supressor cells
Tm cells - memory cells
what are the t helper cells
when presented to an antigen they release chemicals called cytokines which
activate phagocytic macrophages
activate other types of cell
activate B cells which then go on to produce antibodies
what are t cytotoxic cells
they kill cells displaying specific antigens
what are t supressor cells
regulate the immune response
what are t memory cells
provides immunological memory and facilitates rapid secondary responses to infection
what is the process of the cell-mediated response
- foreign antigens are present to activated t lymphocyte
-specific receptor on surface of t cell combines/ binds to antigen as it has complementary shape - t lymphocyte is stimulated to divide rapidly by mitosis producing many genetically identical cells-clonal expanison
-specific t cells then divide into the 4 types of t cell
what brings about the humoral response
b cells
what are b cells
B-lymphocytes (B cells) remain in the bone marrow until they are mature and then spread through the body, concentrating in lymph nodes and the spleen
Millions of types of B-lymphocyte cells are produced within us because as they mature the genes coding for antibodies are changed to code for different antibodies
describe the process of the humoral response
-antigen enters the blood/ tissue fluid and comes into contact with an inactive b cell with complementary antibody attached on CSM
-antigen binds to surface of antibody and the b cell is stimulated to engulf the antigen
- t helper cell bind to displayed antigen and produces cytokines
- the cytokines activate the b cell to divide by mitosis producing genetically identical cells that produce the same type of antibody
-most of these cell form plasma cells which live in the body for a few days and produce large amounts of the specific antibody which then destroy the pathogen by steps 1-4 - primary response
- the rest of the cell become memory cells which can live in body for many years and respond quickly if they come into contact with the antigen again- by producing large quantities of antibody- secondary response
what is the structure of plasma cells
extremely well-developed endoplasmic reticulum which can produce antibodies at a rated of 2000 molecules per second
what are antibodies
Immunoglobulin proteins that are produced by b cells and are specific to a particular antigen
what is the structure of an antibody
4 chains - 2 longer heavy chains and 2 light shorter chains
with two binding sites
what are the bonds that hold the two chains of an antibody together called
disulfide bridges - creates a hinged region that makes the molecule flexible
what are the bindings sites of an antibody known as
the variable region- it is specific to each individual antibody due to different AA sequence which results in a different tertiary structure
what part of an antibody is the same in all
the constant region
what are the 4 ways in which antibodies work
agglutination
neutralisation of toxins
precipitation
lysis
what happens when an antibody combines with an antigen
forms antibody-antigen complex-An antigen and its complementary antibody have complementary molecular shapes
This means that their molecular structures fit into each other
When an antibody collides (randomly) with a foreign cell that possesses non-self antigens with a complementary shape, it binds with one of the antigens
what is agglutination
bacterial cells clump together with the antibody forming a complex which is easier to phagocytose
what is neutralisation of toxins
complemantary antiboides combine with toxin molecules that are produced by the pathogen and prevent them from binding with the surface of body cells
what is precipitation
antibodies attach to soluble antigens causing them to precipitate out of the solution- they are then destroyed by phagocytosis
what is lysis
Ab-Ag complexes activate a series of blood protiens called complement which bind to the complex and destroy it
what is the primary response system
After clonal selection and expansion, the B-lymphocytes that have become plasma cells secrete lots of antibody molecules (specific to the antigen) into the blood, lymph or linings of the lungs and the gut
These plasma cells are short-lived (their numbers drop off after several weeks) but the antibodies they have secreted stay in the blood for a longer time
The other B-lymphocytes become memory cells that remain circulating in the blood for a long time
This response to a newly encountered pathogen is relatively slow
what is the secondary response system
If the same antigen is found in the body a second time, the memory cells recognise the antigen, divide very quickly and differentiate into plasma cells (to produce antibodies) and more memory cells
This response is very quick, meaning that the infection can be destroyed and removed before the pathogen population increases too much and symptoms of the disease develop
This response to a previously encountered pathogen is, relative to the primary immune response, extremely fast- the person has acquired immunity
what is the latent period
the time between infection and significant antibody production
what happens in the latent period
antigen comes into contact with b cell
activate b cell
b cell divides by mitosis
production of antibody by plasma cells
what are the 4 types of immunity
Natural active immunity
artificial active immunity
natural passive immunity
artificial passive immunity
what is Natural active immunity
develops following natural exposure to an antigen
memory cells develop to produce long lasting immunity
what is artificial active immunity
immunity develops after exposure to an antigen via vaccination
mem cells produce long lasting immunity
what is natural passive immunity
transfer of antibodies from mother to baby via placenta and breast milk
no mem cells develop and short term immunity
what is artificial passive immunity
injection with ready made antibodies
non mem cells develop and short term immunity
what is passive vaccination
intro of ready made antibodies into an individual to establish immediate protections against a pathogen- short term immunity
what is active vaccination
deliberate intro of an antigen into body w intention of stimulating a primary response
so that
secondary response occurs rapidly eliminating the pathogen before it can cause disease
what are some examples of active vaccines
live but attenuated(weakened) form of the pathogen eg polio,measles
dead pathogen eg whooping cough
modified toxins form casual; pathogen eg tetanus and diptheria
purified antigen eg flu
harmless bacteria or yeast that have been genetically modified to carry antigens of vaccine eg hepatitis b vaccine
how can vaccines be effective
Highly effective with one vaccination giving a lifetime’s protection (although less effective ones will require booster / subsequent injections)
Generally harmless as they do not cause the disease they protect against because the pathogen is killed by the primary immune response
what are some of the problems with vaccines
People can have a poor response (eg. they are malnourished and cannot produce the antibodies – proteins or their immune system may be defective) and it could be weakened eg elderly
Antigenic variation – the variation (due to major changes) in the antigens of pathogens causes the vaccines to not trigger an immune response or diseases caused by eukaryotes (eg. malaria) have too many antigens on their cell surface membranes making it difficult to produce vaccines that would prompt the immune system quickly enough
Antigenic concealment – this occurs when the pathogen ‘hides’ from the immune system by living inside cells or when the pathogen coats their bodies in host proteins or by parasitising immune cells such as macrophages and T cells (eg. HIV) or by remaining in parts of the body that are difficult for vaccines to reach (eg. Vibrio cholerae – cholera, remains in the small intestine)
some ethically object to vaccines out of fear or just being a fucking arse
what are the features of vaccines
have to have few side effects
have to make large quantities economically
adequate means of storing,transporting and administering it
what is herd immunity
Herd immunity arises when a sufficiently large proportion of the population has been vaccinated (and are therefore immune) which makes it difficult for a pathogen to spread within that population
Those who are not immunised are protected and unlikely to contract it as the levels of the disease are so low
It is very important as it allows for the individuals who are unable to be vaccinated (e.g. children and those with weak immune systems) to be protected from the disease
The proportion of the population that needs to be vaccinated in order to achieve herd immunity is different for each disease
If vaccination rates fall below the required level then herd immunity can break down
what are monoclonal antibodies
they are produced from a specifc clone of b lymphocyte
have a highly specific antigen binding site and can only recognise and bind to a very unique and specific antigenic sequence.
how are monoclonal antibodies formed
A mouse (or another mammal) is injected with an antigen. The antigen may be a vaccine, and it may be injected several times. This causes an immune response in the mouse i.e. corresponding antibodies are produced by B cells.
Spleen cells which are responsible for producing the lymphocytes are removed from the animal. The spleen produces B cells which are responsible for the antibody production. These spleen cells are removed from the mouse via a small operation.
The spleen cells are fused with tumour cells to form hybridoma cells. The mouse’s spleen cells are fused with myeloma cells (cancerous white blood cells from humans), forming hybridoma cells.
The hybridoma cells continuously produce monoclonal antibodies. These hybridoma cells have both the properties of the lymphocytes and tumour cells i.e. they are able to divide indefinitely and produce many monoclonal antibodies. These cells are checked and grown in culture in the lab.
The monoclonal antibodies are harvested. The monoclonal antibodies produced by the hybridoma cells can be separated and harvested for further use.
why are the hybridoma cells special
they have the characteristics of both the antibody and tumor
- so can divide rapidly and effective in the immune response
what is humanisation of the monoclonal antibody
using genetically modified mice that have human DNA in them so the body does not respond to the antibody as foregin
what can MA be used for
Monoclonal antibodies can be used diagnostically for:
Pregnancy tests
Diagnosing HIV
Detecting the presence of pathogens such as Streptococcus bacteria
Distinguishing between Herpes I and Herpes II
Blood typing before transfusions and tissue typing before transplants
Detecting the presence of antibiotics in milk
Detecting cancer cells
how can MA be used to target cancer cells
cancer cells display abnormal antigens (prescise tertairy structure) and the MA produced is very specific so is complementary and bind to cancer cell
describe process of direct treatment of cancer cells using MA
-alert the immune system to site and stimulating an immune response (phagocytosis) - eg white blood cells engulf
-attach to hormone binding site of the cell so uncontrollable cell division does not occur as hormone cannot bind
-can have a specific drug attached which can kill a specific cancer cell
-activate complement proteins that punch a hole in the cell causing it to burst
-antibody attaches to hormone so it cannot bind
describe the process of indirect cancer treatment
-magic bullet
antibody produced against antigen only found on the cancer cell
coupled with cytotoxic agent
injected into cancer patients and it will only target and kill cancer cells leaving normal cells unaffected
what should the indirect cancer process ensure
antibody has high affinity and avidity for tumor antigen
highly expressed on tumor cell
in patient
stable in circulation
efficiently release the cytotoxin inside the cell
drug - needs to be highly potent since only limited number of molecules can attach to the antibody
how can MA be used to treat other disease
eg heart disease
heart muscle is damaged the myosin - protein- is often exposed
the monoclonal antibody is used as a visualiser to see the affected areas of the heart as it binds to the myosin
the MA also has a radioactive label which enable sit to be seen on a screen so the surgeon can see the damaged area
how do MA diagnostic tests work - pregnancy test
Monoclonal antibodies can be used to detect particular antigens in patient samples of blood or tissue. For example, pregnancy testing uses monoclonal antibodies to detect for human chorionic gonadotrophin (hCG). If a woman is pregnant, hCG will be found in urine, so we can do urine tests using monoclonal antibodies.
We can use fluorescent dyes when doing tests with monoclonal antibodies. We can evoke colour changes to help us detect positive tests. Refer to the diagram below to understand the following steps:
- The person urinates. The person gives a urine sample. If they are pregnant, their urine should contain hCG. the hormone has alpha and beta subunits
- Reaction Site. If hCG is present, it will bind to the free antibody, which has an enzyme attached to it. the antibody beta site is complementary to the hormone beta site so can now carry the dye
- Test Site. hCG bound to the free antibody (and by extension the dye enzyme) enters the test site. Here, the hCG-free antibody complex will bind to another fixed antibody using the hCG. This will bring the enzyme (attached to the complex) close to a dye substrate – a reaction occurs, causing a colour change. binds to alpha unit
- Control site. There is fixed antibody in the control site. This will bind to any free antibody (not bound to hCG), and cause a colour change here.
If a person is not pregnant, the free antibody moves through the test site, and instead binds to the fixed antibody in the control site, causing a colour change here.
If a person is pregnant, the hCG-free antibody complex will form in the reaction site, and this complex binds in the test site, causing a colour change here. Some free antibody will still pass to the control site, so you will see two stripes
how do lateral flow tests work
disease antigen attaches to dye antibody and begins to move up the paper
1st test line - dye is complementary to the virus - antibody complex - so if present changes line colour
2nd test line (control)- if positive dye moves on to this and there is a change in colour
if negative the complex then only moves to control and will bind at control as there is no virus particle on it
if not working - no lines
use of MA in immunosuppressant drugs
stop the t-cells for carrying out cell-mediated response
t-cells will be produced if body thinks new transplant organ is foreign
MA deliver a cytotoxic drug which kills the t-cells
ethics of vaccines and MA
Use of animals:
All vaccines are tested on animals before they can move onto human-trials (testing on humans) but some people think animal testing is unethical
Animal-based substances are sometimes used in the production of vaccines but some people disagree with this
Human testing:
Even at the human-trial stage, a vaccine carries a small risk (the person being tested on may actually suffer from symptoms of the disease or other, unpredicted side-effects)
Volunteers may be at higher risk of contracting the disease if they think the trial vaccine will fully protect them but it actually doesn’t (e.g. they might have unprotected sex because they have had a trial HIV vaccine but they actually end up contracting the disease as a result)
Human volunteers are often paid to take part in vaccine trials. Ethical issues can arise if these volunteers feel pressured into doing this (and potentially being harmed in the process due to the reasons described above) because of their financial status (i.e. people who are struggling financially may be more likely to volunteer themselves)
Side-effects:
Some people refuse to take a particular vaccine due to the (usually very small) possibility of side effects
In fact, these people are often protected due to herd immunity. Other people (who have had the vaccination) may think this is unfair
Some parents refuse to let their children be vaccinated (for various reasons) but this is ethically questionable - should a parent be allowed to put their child at risk (arguably a much greater risk) of contracting the disease instead?
Epidemics:
When new pandemics occur (e.g. Covid-19) there is often a struggle as to who should be vaccinated first (e.g. should the elderly be given priority?)
There is also often a struggle between countries as to who receives the vaccines first and in what quantities (e.g. poorer countries may not be able to afford as many doses of the vaccine as richer countries - should all countries suffering from a pandemic have equal access to a vaccine?)
Ethical issues associated with the use of monoclonal antibodies
Ethical issues around monoclonal antibody therapies often revolve around animal rights issues:
New monoclonal antibody therapies are often tested on animals before they can move onto human-trials but some people think animal testing is unethical
Currently, animals are used to produce the cells from which the monoclonal antibodies are produced but some people think this is an unethical use of animals
some people think creating GM mice is unethical - religus grounds
evaluating the ethics of vaccines and MA
Claims, both negative and positive, are often made about vaccines (e.g. about their success rates or potential side-effects)
These claims need to be validated (confirmed) with scientific evidence before they are accepted (i.e. they need to be backed up by scientific research)
This often involves other scientists repeating the same study (using the same methodology) and trying to reproduce the results
Other scientists may also conduct other studies that try to prove the same theory or find the same results
Even then, it is important to evaluate the data used to support claims or new findings concerning vaccines, as well as the methodology behind this data
The importance of evaluating data behind claims and new scientific findings also applies to monoclonal antibody therapies and treatments
Example: The MMR Vaccine
The MMR vaccine is a vaccine against measles, mumps and rubella that is usually given to young children
A study published in 1998, the findings of which were based on 12 children with autism, concluded that the MMR vaccine might cause autism. It was later found that one of the doctors who worked in this study was acting as a consultant to some parents of autistic children who were suing the pharmaceutical companies that produced the vaccine
Evaluating the study:
The study is not very convincing as it had a very small sample size (just 12 children)
This increases the likelihood that the results were due to chance
The doctor may have been trying to gain evidence for the lawsuit against the vaccine
This would make the study biased (a biased person or a biased study favours one side or issue over another)
In 2005, a study was published on the incidence of autism in 30,000 children in an area of Japan between 1988 and 1996. The MMR vaccine was first introduced in this area in 1989 but stopped being administered in 1993.
Describing the data:
The number of children with autism continued to increase even after the MMR vaccine stopped being administered
For example, in 1992 (when children were given the vaccine) approximately only 75 per 10,000 children were diagnosed with autism by age 7 but in 1994 (when children were no longer given the vaccine) approximately 200 per 10,000 children were diagnosed with autism by age 7
Drawing conclusions:
This study suggests there is no link between the MMR vaccine and autism
Evaluating the study:
We can have greater confidence in the results of this study (compared to the one in 1998) as the sample size was very large (30,000 children)
This improved methodology means that the results are less likely to be due to chance
what is an ELISA test
enzyme-linked immunosorbent assay
what can the ELISA test be used for
ELISA tests can be used to see if a patient has any antibodies to a certain antigen (or any antigens to a certain antibody)
For example, they can be used to test for infections by pathogens or for allergies
how do ELISA tests work
-monoclonal antibody produced that will bind to a specific target antigen and is placed on the assay plate
-sample is added to the well and if antibody is present it will bing due to the specific tertiary structure that is complementary, so will bind to the variable region
-plate washed to remove any unbound material
-2nd monoclonal antibody is produced and this has an enzyme attached to it
- 2nd antibody added to the plate and allowed to attached
-plate washed again
-plate then flooded with enzyme substrate and a colour change is observed if antibody-enzyme complex if present which in turn means antigen is present
why are the ELISA tests useful
quick and reliable and visual
what is HIV
Human Immunodeficiency Virus is a retrovirus- has the ability to make DNA from RNA due to reverse transcriptase enzyme
how is HIV spread
The virus is spread by intimate human contact and can only be transmitted by direct exchange of body fluids
This means HIV can be transmitted in the following ways:
sexual intercourse
blood donation
sharing of needles used by intravenous drug users
from mother to child across the placenta
mixing of blood between mother and child during birth
from mother to child through breast milk
what is the structure of HIV
the HIV virus is made up of several key components:
Two RNA strands
reverse transcriptase
A protein coat (capsid)
A viral envelope consisting of a lipid bilayer and glycoproteins
The lipid bilayer is derived from the cell membrane of the host helper T cell that the particle escaped from
Attachment proteins
how does HIV replicate
When the virus enters the bloodstream it infects a certain type of lymphocyte - helper T cells
Normally lymphocytes seek out and destroy pathogens that enter the body, producing antibodies that attach to pathogens and enhancing phagocytic activity
HIV avoids being recognised and destroyed by lymphocytes by repeatedly changing its protein coat
The virus uses the cell machinery of helper T-cells to multiply:
Viral RNA enters the cell
Viral reverse transcriptase enzymes produce a DNA copy of the viral RNA
The DNA copy is inserted into the chromosomes of the cell
Each time the cell divides it copies the viral DNA
The infected cells remain normal as the viral DNA is inactive
At this stage, the individual is HIV positive and will have antibodies against the virus
After a period of time (possibly years) the viral DNA within the host cells becomes active
It takes control of the helper T cell
More HIV particles are produced
This causes the helper T cell to die
As a result, thousands of new HIV particles are released which are able to infect other helper T cells
Gradually the virus reduces the number of helper T cells in the immune system
B cells are no longer activated
No antibodies are produced
This decreases the body’s ability to fight off infections, eventually leading to AIDS (Acquired immune deficiency syndrome)
how does HIV cause AIDS
Immediately after infection with HIV people often suffer mild flu-like symptoms
These symptoms pass and for a period of time infected people might not know they are infected
After several months or years, the viral DNA replicated by the HIV virus particles becomes active
They gradually destroy and reduce the number of helper T cells present in a host
This is detrimental as helper T cells play an important role in the specific immune response
They stimulate B cells, the production of antibodies and increased rates of phagocytosis
When an individual can no longer produce antibodies they are said to have advanced acquired immunodeficiency syndrome (AIDS)
why are antibiotics not effective against viruses
Do not have bacterial structures/enzymes
OR
Do not have metabolic processes
OR
Do not have a cell wall/murein;
