cells and the immune system Flashcards

1
Q

what are antigens

A

cell surface membrane contains proteins that act as antigens.

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, including our own body cells
Antigens that aren’t normally found in the body are referred to as foreign antigens - it’s these antigens that the immune system usually responds to

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2
Q

what do antigens allow the immune system to identify

A

antigens allow the immune system to identify:

PATHOGENS

ABNORMAL BODY CELLS

TOXINS

CELLS FROM OTHER INDIVIDUALS OF THE SAME SPECIES

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3
Q

how are pathogens detected by the immune system

A

PATHOGENS
Pathogens are an organism that causes disease, e.g. bacteria, viruses and fungi
All pathogens have antigens on their surface -these are identified as foreign by immune systems, which then responds to destroy the pathogens

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4
Q

how are abnormal cells detected by the immune system

A

ABNORMAL BODY CELLS

Cancerous or pathogen-infected cells have abnormal antigens on their surface, which triggers an immune response

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5
Q

how are toxins detected by the immune system

A

TOXINS
These are poison. They’re also molecules, not cells. Some toxins are produced by bacteria e.g. the bacterium Clostridium botulinum releases a protein toxin that affects the nervous system, causing the symptoms of botulinum

The immune system can respond to toxins, as well as the pathogens released by them.

It’s important to know that the toxin itself is the antigen

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6
Q

how are cells from other individuals ( of the same species) of the same

A

when you receive cells form another person, such as in an organ transport or blood transfusion, those cells will have some antigens that are different to your own ( unless the donor is genetically identical to you)

The foreign antigens trigger an immune response. This response leads to the rejection of transplanted organs if drugs aren’t taken to suppress the recipients immune system

blood transfusion
-most important antigen are the ABO blood group antigens - if the donated blood contains A or B antigens that aren’t recognised by the recipients immune systems, they will generate an immune response

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7
Q

what are the body’s different defence mechanisms

A

if a pathogen is to infect the body, it must first gain entry

the body’s first defence is to form a physical or chemical barrier to entry e.g. skin

the next line ( if this fails) of defence is the white blood cells

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8
Q

what are the two types of white blood cells

A
  1. phagocytes

2. lymphocytes

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9
Q

what is phagocytosis

A

large particles such as some types of bacteria, can be engulfed by cells in vesicles formed from the cell surfaced membrane

This is called phagocytosis

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10
Q

what white blood cell carries out phagocytosis

A

the type of white blood cells that carries out phagocytosis are known as phagocytes

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11
Q

what are the stages of phagocytosis

A
  1. Chemical products/ the foreign antigens of pathogens or dead, damaged and abnormal cells act as attractants, causing phagocytes to move towards the pathogen (e.g. bacterium)
  2. phagocytes have several receptors on their cell - surface membrane that recognise and attach to chemicals/ antigens on the surface of the pathogen
  3. They engulf the pathogen to form a vesicle, known as a phagosome
  4. lysosomes move towards the vesicle and fuse with it
  5. Enzymes called lysozymes are present within the lysosome. These enzymes destroy ingested bacteria by hydrolysis of their walls
  6. the soluble products from the breakdown of the pathogen are absorbed into the cytoplasm of the phagocyte
  7. the phagocyte then presents the pathogen’s antigens on its surface to activate other immune systems. The phagocytes acting as an antigen-presenting cell
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12
Q

what are non- specific immune responses

A

non specific immune responses happen whatever the infection

e.g phagocytosis and skin barrier

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13
Q

what are specific immune responses

A

specific immune responses only react to specific antigens

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14
Q

what does the specific immune response depend on

A

the specific immune response depends on a type of white blood cell called a lymphocyte

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15
Q

how are lymphocytes produced

A

lymphocytes are produced by stem cells in the bone marrow. There are two types of lymphocytes each with its own role in the immune response

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16
Q

what are B lymphocytes (B cells)

A

B lymphocytes (B cells) are so called because they mature in the bone marrow.

They are associated with humoral immunity, that is immunity involving antibodies that are present in body fluids, or humour such as blood plasma

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17
Q

what are T lymphocytes ( T cells)

A

T lymphocytes are so called because they mature in the thymus gland. They are associated with cell - mediated immunity, that is immunity involving body cells

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18
Q

how can T - lymphocytes distinguish invader cells from normal cells

A

phagocytes that have engulfed and hydrolysed a pathogen present some of the pathogen’s antigen on their own cell -the surface membrane

transplanted cells from individuals of the same species have different antigens on their cell surface membrane

cancer cells are different from normal body cells and present antigens on their cell - surfaced membranes

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19
Q

what are antigen - presenting cells

A

cells that display foreign antigens on their surface are called antigen - presenting cells because they can present antigens of other cells on their own cell - surface membrane

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20
Q

what will T lymphocytes only respond to /what is cell - mediated immunity

A

T lymphocytes will only respond to antigens that are presented on a body cell ( rather than antigens within the body fluids)

This type of response is called cell - mediated immunity or the cellular response

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21
Q

why are the receptors on T lymphocytes important

A

receptors on T cells are important as it means that there are a vast number of different type of cells, each one responding to a different antigen

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22
Q

how do T lymphocytes respond to infection by pathogen

A
  1. Pathogens invade body cells or are taken in by phagocytes
  2. the phagocyte places antigens from the pathogen on its cell - surface membrane
  3. receptors on a specific helper T cell (T h cell) fit exactly on to these antigens
  4. this attachment activates the T cell to divide rapidly by mitosis and form a clone of genetically identical cells
  5. The cloned T cells :
    a) develop into memory cells that enable a rapid response to future infections by the same pathogen

b) stimulate phagocytes to engulf pathogens by phagocytosis
c) stimulate B cells to divide and secrete their antibody
d) activate cytotoxic T cells (Tc cells)

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23
Q

how do cytotoxic T cells kill infected cells

A

cytotoxic T cells kill abnormal cells and body cells that are infected by pathogens, by producing a protein called peforin that makes holes in the cell - surface membrane

These holes mean the cell membrane becomes freely permeable to all substances and the cell dies as a result

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24
Q

why is the action of T cells the most effective against viruses

A

the action of T cells is the most effective against viruses because viruses replicate inside cells

As viruses use living cells in which to replicate, the sacrifice of body cells prevent viruses multiplying and infecting

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25
what is the first phase to the specific response to infection infection
the first phase of the specific response to infection is the mitotic division of specific T cells to form a clone of the relevant T cells to build up their numbers some of these T cells produce factors that stimulate B cells to divide. It is these B cells that are involved in the next phase of the immune response humoral immunity
26
what is humoral immunity
Humoral immunity involves antibodies, these antibodies are soluble in the blood and tissue fluid of the body
27
how many different types of B - cells are there
there are many different types of B - cell, possibly as many as ten million
28
what do B cells do
B cells each will produce a specific antibody that responds to a specific antigen. When an antigen (e.g. a protein on the surface of a pathogen, foreign cell, toxin, damaged or abnormal cell) enters the blood or tissue fluid, there will always one B cell that has an antibody on its surface whos shape exactly fits the antigen - they are complementary
29
how do B cells produce antibodies
1. the antigens enters the B - cell by endocytosis and gets presented on its surface of the B - cell 2. The helper T - cells bind to these processed antigens and stimulate this B cell to divide by mitosis to form a clone of identical B cells - all of these B cells produce the antibody that is specific to the foreign antigen ( this is called clonal selection which account s for the body's ability to respond to any vast number of antigens) 3. in each clone, the cells produced develop into one of two cells: - plasma cells - memory cells 4. plasma cells secrete specific antibodies that fits exactly to the antigen on thee pathogen and destroys them 5. the antibody attacks to antigens on the pathogen and destroys them 6. the B - cells that develop into memory cells can respond to future infections by the same pathogen by dividing and developing plasma cells that produce antibodies. This is thee secondary response
30
what are memory cells
memory cells are responsible for the 2nd immune response Memory cells live considerably longer than plasma cells, often for decades They do not produce antibodies directly but circulate in the blood and tissue fluid when they encounter the same antigen at a later date, they divide rapidly into plasma cells and more memory cells in readiness for any future infection memory cells, therefore, provides long - term immunity against the original infection - essentially it ensures that new infection is destroyed before causing any harm. Sometimes the individuals are totally unaware that they have been infected
31
what are plasma cells
plasma cells secrete antibodies usually into blood plasma These cells survive for only for only a few days, but each can make around 2000 antibodies every second during its brief lifespan Therefore plasma cells are therefore responsible for the immediate defence of the body against infection
32
what are antibodies
antibodies are proteins with a specific binding sites it is sythesised by B cells
33
when do B - cells produce antibodies
when the body is infected by non - self material, a B - cell produces a specific antibody this specific antibody reacts with an antigen on the surface of the non - self material by binding to them
34
why is there a massive variety of antibodies
there is a massive variety of antibodies because they are made of proteins. Proteins are molecules that occur in an almost infinite number of forms
35
what is the structure of antibodies
STRUCTURE: 1. antibodies are made up of four polypeptide chains - one of these chains are long - these are called heavy chains - chains of the other pair are shorter - these are called light chains 2. each antibody has a specific binding site that fits very precisely onto a specific antigen to form what is known as an antigen - antibody complex 3. the binding site consist of a sequence of amino acids that form a specific 3D shape that binds directly to a specific antigen
36
how do the antibodies lead to the destruction of the antigen
antibodies do not destroy antigens but rather prepare the antigen for destruction different antibodies lead to the destruction of an antigen in a range of ways e.g. if an antigen is a bacterial cell, antibodies assist in its destruction in two ways: - causes agglutination of the bacterial cells. In this way, clumps of bacterial cells are formed making it easier for the phagocytes to locate them as they are less spread - out within the body -act as a marker that stimulates phagocytes to engulf the bacterial cells when they are attached
37
what are monoclonal antibodies
bacterium or other microorganism entering the body is likely to have many hundreds of different antigens on its surface each antigen will induce a different B cell to multiply and form a clone of itself. Each of these clones will produce a different antibody. these antibodies are called monoclonal antibodies
38
what are the number of different ways in which we can use monoclonal antibodies in medicine
- targeting medication to a specific cell types by attaching a therapeutic drug to an antibody - pregnancy testing - medical diagnosis
39
how can we use monoclonal antibodies to treat cancer | direct monoclonal antibody therapy
as antibodies is very specific to particular antigens (proteins), monoclonal antibodies can be used to target specific substances and specific cells e.g. target cancer cells monoclonal antibodies can be used to treat cancer in a number of ways. By far, the most successful so far is direct monoclonal antibody therapy: - monoclonal antibodies are produced that are specific to antigens on cancer cells - these antibodies are given to are patient and attach themselves to thee receptors on their cancer cells - they attach to the surface of their cancer cells and block the chemical signals that stimulate their uncontrolled growth
40
what is an advantage of direct monoclonal antibody
antibodies are not toxic and highly specific, they lead to fewer side effects than other forms of (cancer) therapy
41
how can we use monoclonal antibodies to treat cancer | indirect monoclonal antibody therapy
indirect monoclonal antibody therapy involves attaching a radioactive or cytotoxic drug ( a drug that kills cells) to the monoclonal antibody when the antibody attaches to the cancer cells, it kills them monoclonal antibodies used this way are referred to as "magic bullet" and can be used in smaller doses, as they are targeted on specific sites
42
what is an advantage of using indirect monoclonal antibody therapy
as the drug is used in smaller doses, usage is cheaper and it also reduces any side effects the drug might have
43
how are monoclonal antibodies used in medical diagnosis
monoclonal antibodies are invaluable tool in diagnosing diseases with over a hundred different diagnostic products based on them: e. g. diagnosis of: - influenza - hepatitis - chlamydia monoclonal antibodies produces a much more rapid result than conventional methods of diagnosis
44
how can monoclonal antibodies be used to produce a diagnosis for cancer
monoclonal antibodies are important in diagnosing certain cancers e.g. a man with prostate cancer often produces more of a protein called prostate specific antigen (PSA) leading to unusually high levels of it in the blood By using a monoclonal antibody that interacts with this antigen, it is possible to obtain a measure of PSA in a sample of blood This therefore gives an earlier warning of its possibility and the need for further tests
45
how can we use monoclonal antibodies in pregnancy testing
it is important to know as soon as possible if a mother is pregnant in order for her to know what actions she can take to ensure the welfare of herself and the born baby but how do pregnancy tests work? METHOD: 1. Pregnancy tests detects the hormone hCG that's found in the urine of pregnant women 2. the application area contains antibodies that are complementary to the hCG protein bound to a coloured bead (blue) 3. when urine is applied to the application area any hCG will bind to the antibody on the beads, forming an antigen- antibody complex 4. the urine moves up the stick to the test strip, carrying any beads with it 5. the test strip contains antibodies to hCG that are struck in place (immoblised) 6. if there is hCG present the test strip turns blue because the immbolised antibody binds to any hCG concentrating the hCG - antibody with the blue beads attached 7. If there is no hCG present, the beads will pass through the test area without binding to anything, and so it won't go blue 6. The hCG - antibody colour complex moves along the strip until it is trapped by a different types of antibody creating a coloured line
46
what are some of the ethics of monoclonal antibodies
monoclonal antibodies development provides society with the power and opportunity to treat diseases However, the use of monoclonal antibodies raises some ethical issues: 1. production of monoclonal antibodies involves the use of mice. These mice are used to produce both antibodies and tumour cells the production of tumour cells involves deliberately inducing cancer in mice and despite the specific guideline drawn up to minimise any suffering, come people still have reservations about using animals in this way 2. monoclonal antibodies have been used successfully to treat a number of diseases, including cancer and diabetes saving many lives However, there have also been some deaths associated with their use in the treatment of multiple sclerosis ( which uses sclerosis). Therefore, it is important that patients have full knowledge of the risks and benefits of these drugs before permission for them to be used ( informed consent)
47
how do we produce monoclonal antibodies
B- cells are short lived and only divide and produce antibodies inside a living organism nowadays, large quantities of a single antibody can produced outside the body METHOD: 1. a mouse is exposed to the non - self material against which the antibody is required 2. the B - cells in the mouse then produce a mixture of antibodies, which are extracted from the spleen of the mouse 3. to enable these B - cells to divide outside the body, they are mixed with cells that divide readily outside the body e.g. cells from a cancer tumour 4. detergent is added to the mixture to break down the cell - surface membranes of both types of cell and enable them to fuse together. The fused cells are called hybridoma cells 5. the hybridoma cells are separated under a microscope and each single cell is cultured to form a clone. Each clone is tested to see whether it is producing the required antibody - because these antibodies come form a clone formed from a single B cell, they are called monoclonal antibodies 7. the hybridoma cell that produces the required antibody is then isolated 8. as these monoclonal antibodies come from mouse tissue, they have to be modified to make them like human cells before they can be used. This process is called humanistaion
48
what is immunity
immunity is the ability of an organism to resist infection
49
what are the two forms of immunity
- passive immunity | - active immunity
50
what is passive immunity
passive immunity is produced by the introduction of antibodies from an outside source. No direct contact with the antigen/ pathogen is required as the antibodies are not being produced by the individuals themselves, the antibodies are not replaced when they are broken down, no memory cells are formed and so there is no lasting immunity
51
what are some examples of passive immunity
- antivenom given to victims of snake bite | - immunity required by the fetus when antibodies pass across the placenta from the mother
52
what is active immunity
active immunity is produced by stimulating the production of antibodies by the individual's own immune systems direct contact within the pathogen or its antigen is necessary Immunity takes time to develop It is generally long - lasting and is of two types
53
what are the two types of active immunity
the two types of active immunity are: - natural active immunity - artificial active immunity
54
what is natural active immunity
natural active immunity results from an individual becoming infected with a disease under normal circumstances The body produces is own antibodies and may continue to do so for years
55
what is artificial active immunity
active immunity forms the basis of vaccination ( immunisation) It involves inducing an immune response in an individual without suffering the symptoms of the disease
56
how do vaccinations work
vaccination is the introduction of the appropriate disease antigens into the body, either by injection or by mouth - this stimulates an immune response against a particular disease the material introduced is called the vaccine and in whatever form (dead or weakened) contains one or more types of antigen form the pathogen these antigens then stimulate the immune response (e.g. T cells and B cells) these response is slight because only a small amount of antigen has been introduced the crucial factor is the memory cells produced, which remain in the blood, and allow a greater and more immediate response to a future infection with the pathogen this results in a rapid production of antibodies and the new infection is rapidly overcome before it can cause any harm and with few, if any symptoms
57
what are the features of a successful vaccination programme
the success of a vaccination programme depends on a number of factors: - a suitable vaccine must be economically available in sufficient quantities in order to immunise most of the vulnerable population - must be a few side - effects. Unpleasant side - effect may discourage individuals in the population from being vaccinated - means of producing, storing and transporting the vaccine must be available e.g. hygienic conditions - it must be possible to vaccinate the vast majority of the vulnerable population to produce herd immunity - there must be means of administering the vaccine properly at the appropriate time
58
what is herd immunity
herd immunity arises when a sufficiently large proportion of the populations has been vaccinated to make it difficult for a pathogen to spread within a population
59
what are the advantages of herd immunity good
if the vast majority of the population is immune, it is highly improbable that a susceptible individual will come in contract with an infected person - it could be dangerous to vaccinate those who are ill or have compromised immune systems therefore herd immunity is the best option
60
how is herd immunity achieved
the percentage of the population that must be vaccinated in order to achieve herd immunity is different for each disease herd immunity is achieved by carrying out vaccination at all one time this means that, for a certain period, there are very few individuals in the population with the disease and the transmission of the pathogen is interrupted
61
why do vaccinations may not eliminate a disease
even when the criteria for successful vaccination are meet, it can still prove extremely difficult to eradicate a disease: The reasons are as follows: -vaccination fails to induce immunity in certain individuals, for example people with defective immune systems - individuals may develop the disease immediately after vaccination but before therm immunity levels are high enough to prevent it. These individuals may harbour the pathogen and reinfect others - the pathogen may mutate frequently, so that its antigens change rather gradually This means that vaccines suddenly become ineffective because the new antigens on the pathogen are no longer recognised by the immune system As a result the immune system does not produce the antibodies to destroy the pathogen This is antigenic variability happens with influenza virus, which changes its antigen frequently. Therefore immunity for influenza is therefore short - lived and individuals may develop repeated boosts of influenza during their lifetime
62
what is HIV
the human immunodeficiency virus (HIV) causes the disease Acquired immune deficiency syndrome (AIDS) it is a relative newcomer in contagious diseases having been first diagnosed in 1981
63
what is the structure of HIV
1. outside is a lipid envelope embedded in which are peg-like attachment proteins 2. Inside the envelope is a protein layer called the capsid that encloses two single strands of RNA and some enzymes -one of these enzymes is reverse transcriptase, so called it catalyses the production of DNA fro RNA (the reverse reaction to that carried out by transcriptase) The presence of reverse transcriptase, and the consequent ability to make DNA from RNA, means that HIV belongs to a group of viruses called retroviruses
64
what is unique to all viruses
all viruses cannot replicate itself Instead it uses its genetic material to instruct the host cell's biochemical mechanisms to produce the components required to make new viruses
65
how do HIV infect helper T - cells
1. following infection HIV enters the bloodstream and circulates the body 2. A protein on the HIV readily binds to a protein called D4 while his protein occurs on a number of different cells HIV most frequently attaches to helper T cells 3. the protein capsid fuses with the cell - surface membrane of the T - cells. The RNA and enzymes of HIV enters the T - cell 4. The HIV reverse transcriptase converts the virus RNA into DNA 5. The nearly made DNA is moved into the helper T cells's nucleus where it is inserted into the cell's DNA 6. The HIV DNA in the nucleus creates messenger RNA (mRNA), using the cell's enzymes. This mRNA contains the instructions for making new viral proteins and the RNA to go into the new HIV 7. The mRNA passes out the nucleus through a nuclear pore and uses the cell's protein syntheses mechanisms to make HIV particles 8. The HIV particles break away from the helper T cell with a piece of cell - surface membrane ( the T - cell surface membrane) surrounding them which from their lipid envelope
66
what happens once a person is infected with HIV
once infected with HIV a person is said to be HIV positive However, the replication of HIV often goes dormancy and only recommences, leading to AIDs, may years later
67
how does HIV causes the symptoms of AIDs
HIV specifically attacks helper T cells HIV causes AIDs by killing or interfering with the normal functioning of helper T cells
68
how low does the number of helper T- cells go when a person is infected with AIDs
any infected person normal has between 800 and 1200 helper in each mm3 of blood a person suffering from AIDs, this number can be as low as 200mm3
69
what happens when a person has an insufficeint number of helper T cells
without a sufficient number of helper T cells, the immune system cannot stimulate B cells to produce antibodies or cytotoxic T cells that kill cells infected by pathogens memory cells may also become infected and destroyed as a result of this the body is unable to produce an adequate immune response and becomes susceptible to other infections and cancers It is these secondary diseases that ultimately cause death
70
what actually kills those infected with HIV
HIV does not kill individuals directly by infecting the immune system ( basically HIV prevents it from functioning normally) As a result those infected by HIV are unable to respond effectively to other pathogens. It is these infections rather than HIV, that ultimately cause ill health ad eventual death
71
what is the ELISA test
ELISA stands for " enzyme linked immunosorbant assay" it uses antibodies to not only detect the presence of a protein in a sample but also the quantity It is extremely sensitive and so can detect very small amounts of a molecule
72
what are the two different types of ELISA tests
indirect ELISA test direct ELISA test
73
what is the indirect ELISA test
in the indirect ELISA test, two different antibodies are used an indirect ELISA test ca be used to see if a patient possesses antibodies to HIV
74
how can an indirect ELISA test be used to detect HIV
1. HIV antigen is bound to the 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 in the plasma, (i.e. antibodies against HIV) these bind to the HIV antigen stuck to the bottom of the well 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 - specifc antibody ( which is also called the primary antibody) the well is washed out again to remove any unbound secondary antibody If there is no primary antibodies present,all the secondary antibodies will be washed because there will be nothing for it to bind to 4. A solution is added as well. This solution contains a substrate, which is able to react with the enzyme attached to the secondary antibody and produce a colored product - If the solution changes colour, it indicated that the patient ha HIV - specific antibodies in there blood and is infected with HIV
75
what is direct ELISA test
A direct ELISA uses a single antibody that is complementary to thee antigen you're testing for
76
how does a direct ELISA test work
1. Antigens from a patient sample are bound to the inside of a well in a well plate ( a plastic tray with loads of little circular pits in it) 2. a detection antibody ( with an attached enzyme ) that is complementary to the antigen of interest is added. If the antigen of interest is present in the patient sample, it will immmobilsed on the inside surface of the well and the detection antibody will bind it 3. The well is then washed out to remove any unbounded antibody and a substrate solution is added If the detection antibody is present, the enzyme reacts with the substrate to give a colour change - this is the positive result for presence of the antigen
77
how do we control the infection of HIV i
there is no vaccine or cure for HIV but antiviral drugs can be used to slow down the progression of HIV infection and AIDs in an infected person Best way to control HIV infection in a population is by reducing its spread HIV can be spread via unprotected sexual intercoure though infected bodily fluids e.g. blood form sharing contaminated needles HIV positive mother could pass on HIV to her fetus so by taking drugs during pregnancy can reduce the baby being HIV - positive
78
what happens on the initial infection of HIV
on the initial infection period of HIV, it replicates rapidly and the infected person may experience severe flu - like symptoms After this period, HIV replication drops to a lower level. This is the latency period During the latency period (which can last for years) the infected person won't experience symptoms
79
what are the symptoms of AIDs
the initial symptoms of AIDs include minor infections of mucous membranes (e.g. the inside of the nose, ears and genitals) and recurring respiratory infections As AIDs progresses the number of immune systems cells decrease further Patients become susceptible to more serious infections including chronic diarrhoea, severe bacterial infections and tuberculosis
80
what are some of the ethical issues that are raised from vaccines
vaccines do raises ethical issues that need to be addressed if such vaccination programmed are to command widespread support The production and use of vaccines raises the following question: 1. the production of existing of production vaccines, and the development of the new ones, often involves the use of animals - How acceptable is this? 2. vaccines have side -- effects that may sometimes cause long - term harm - How can the risk of side effects be balanced against the risk of developing a disease that causes even greater harm 3. On who should vaccines be tested? - How should such trials be carried out? To what extent should individuals be asked to accept accept risk in the interest of the public health? 4. in order for vaccines to be most effective, the majority (preferably all) should be vaccinated. Is it right, in the interest or everyone's health, that vaccination - If so, should this be at any time, or just when there is a potential epidemic? can people opt out? If so, on what grounds: religious belief, medical circumstances, personal belief