Cell Recognition And The Immune System

Question 1

What Is Immunity?

Answer 1

The body becoming better prepared for a second infection from a pathogen that has infected the body before.

This means the pathogen is killed before it does any harm.

Question 2

What Is An Antigen?

Answer 2

An antigen is any part of an organism or substance that is recognised as non-self (foreign) by the immune system and so stimulates an immune response.

Antigens are usually proteins that are part of the cell surface membrane or cell wall of an invading cell.

The presence of an antigen triggers the production of an antibody as part of the bodies defence system.

They’re on pathogens (organisms that cause disease), abnormal body cells (e.g. cancerous or pathogen-infected cells), toxins and cell from other individuals of the same species.

Question 3

Specific And Non-Specific Defence Mechanisms?

Answer 3

Non-specific: Response is immediate and the same for all pathogens.
Defence mechanisms include;
- physical barriers (skin),
- phagocytosis.

Specific: Respnse is slower and specific to each pathogen.
Defence mechanisms include;
- cell mediated response (T lymphocytes),
- humoral response (B lymphocytes).

Question 4

What Are The Steps To Immunity?

Answer 4

Step 1: Non-specific response (phagocytosis and physical barriers).

Step 2: Specific response (cell-mediated immunity and humoral immunity).

Question 5

How Does The Body Recognise Body Cells And Foreign Cells?

Answer 5

Lymphocytes must be able to distinguish the bodies own cells and molecules (self) from those that are foreign (non-self).

Each type of cell, self or non-self, has specific molecules on the surface that can be many different things. However, the immune system recognises the proteins on the cell surface because they are the most identifiable.

Proteins have enormous variety and a highly specific tertiary structure. It is this variety of specific 3-D structure that distinguishes oneself from another. The immune system can identify these proteins and therefore identify:

• Pathogens (e.g. HIV),
• Non-self material such as cells from other organisms of the same species,
• Toxins including those produced by certain pathogens like the bacterium that causes cholera,
• Abnormal body cells such as cancer cells.

Question 6

What Is Tissue Rejection?

Answer 6

When a person has had an organ transplant or tissue transplant, the immune system recognises these transplanted cells as non-self.

The immune system therefore attempts to destroy the transplant.

To minimise the effect of this tissue rejection, donor tissues for transplant are normally matched as closely as possible to those of the recipient.

The best matches often come from relatives that are genetically close.

In addition, immunosuppressant drugs are often administered to reduce the level of the immune response that still occurs.

Question 7

How Lymphocytes Recognise Cells Belonging To Body?

Answer 7

• There are around 10 million different lymphocytes present in the body, each specific to a different chemical shape.
• In the fetus, these lymphocytes are constantly colliding with other cells.
• Infection in the fetus is rare because it is protected from the outside world by the mother and by the placenta.
• Lymphocytes will therefore collide almost exclusively with the bodies own material (self).
• Some of the lymphocytes will have receptors that exactly fit those of the bodies own cells. These lymphocytes either die or are suppressed.
• The only remaining lymphocytes are those that might fit foreign material (non-self).
• In adults, lymphocytes produced in the bone marrow initially only encounter self-antigens.
• Any lymphocytes that show any immune response to the self-antigens undergo programmed cell death (apoptosis) before they can differentiate into mature lymphocytes. No clones of these antiself lymphocytes will appear in the blood, leaving only those that might respond to self non-self antigens.

Question 8

Why Is There Time Lag Between Exposure To Pathogen And Body’s Defences?

Answer 8

When an infection occurs, the one types of lymphocyte that already has complimentary proteins to those of the pathogen is stimulated.

This stimulation causes the lymphocyte to divide and build up its numbers to a level where it can be effective in destroying the pathogen.

This is called clonal selection.

This also explains why there is a time lag between exposure to the pathogen and the bodies defences:

Question 9

Four stages to the immune response?

Answer 9

1. Phagocytosis
2. Activation of T-cells
3. Activation of B-cells and plasma cells
4. Making of antibodies

Question 10

Phagocytosis?

Answer 10

Step 1 of the immune response.

A phagocyte (e.g. a macrophage) is a type of white blood cell that carries out phagocytosis (engulfment of pathogens).

They are found in the blood and in tissues and of the first cells to respond to an immune trigger.

This is a non-specific response.

Steps:
1. A phagocyte recognises the foreign antigens on the pathogen.

2. The cytoplasm of the phagocyte moves around the pathogen, engulfing it.
3. The pathogen is now contained in a phagocytic vacuole (a bubble) in the cytoplasm.
4. A lysosome (an organelle that contains enzymes called lysozymes) fuses with the phagocytic vacuole. The lysozymes break down the pathogen. These lysozymes destroy ingested bacteria by hydrolysis of their cell walls. Larger, insoluble molecules broken down into smaller, soluble ones.
   - The soluble products from the breakdown of the pathogen are absorbed into the cytoplasm of the phagocyte.
5. The phagocyte then presents the pathogens antigens onto its surface to activate other immune system cells.

Question 11

Activation of T-cells?

Answer 11

Step 2 of the immune response.

A t-cell (also called a t-lymphocyte) is another type of white blood cell.

It has receptor proteins on its surface that bind to complimentary antigens presented by phagocytes.
This activates the T-cells.

T-cell stimulate other t-cells.

Helper T cells release chemical signals that activate and stimulate phagocytes.

Cytotoxic T cells kill abnormal and foreign cells.

TH cells also activate b-cells, which secrete antibodies.

The t-cells also develop into memory cells that enable rapid response to future infections by the same pathogen.

Question 12

Activation of b-cells and plasma cells?

Answer 12

Step 3 of the immune response.

B-cells (also called b-lymphocytes) Are also a type of white blood cell.

They are covered with antibodies (proteins that bind with antigens to form an antigen-antibody complex).

Each B-cell has a different shape on its cell-surface membrane, so different ones bind to different antigens.

Steps:
1. When an antibody on the surface of a B-cell meets a complimentary antigen, it’s binds to it.

2. This, together with substances released from helper T-cells, activate the B-cells. This process is called clonal selection.
3. The activated b-cells divide into plasma cells.

Question 12

Making of antibodies?

Answer 12

Step 4 in immune response.

Plasma cells are identical to the b-cell (they’re clones).

Plasma cells secrete lots of antibodies, specific to the antigen. These are called monoclonal antibodies.

Monoclonal antibodies bind to the antigens on the surface of the pathogen to form lots of antigen-antibody complexs.

An antibody has two binding sites, so can bind to 2 antigens at the same time. This means that pathogens become clumped together - this is called 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.

Question 13

What is an antibody?

Answer 13

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 site.

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.

Question 14

What Is Cell-Mediated Immunity?

Answer 14

Immunity that doesn’t involve antibodies.

Involved T lymphocytes that mature in the thymus gland (reason for T).

Immunity in body cells.

Another name for cell mediated immunity is the cellular response.

It is a specific response.

Question 15

What Is Humoral Immunity?

Answer 15

This is immunity that involves antibodies.

Involves B lymphocytes that mature in the bone marrow (reason for B).

Involves antibodies that are present in body fluids (‘humour’ - another name for body fluids) such as blood plasma.

Question 16

Cellular and humoral response?

Answer 16

Cellular - the t-cells and other immune system cells that they interact with, e.g. phagocytosis.

Humoral - b-cells, clonal selection and the production of monoclonal antibodies.

Both types of response are needed to remove a pathogen from the body.

Question 17

The primary immune response?

Answer 17

1. When an antigen enters the body for the first time, it activates the immune system. This is the primary response.
2. The primary response is slow because there are not many B-cells that can make the antibodies needed to bind to it.
3. Eventually, the body will produce enough of the right antibodies to overcome the infection. Meanwhile, the infected person will show symptoms of the disease.
4. After being exposed to an antigen, the t- and b-cells produce memory cells. These memory cells remain in the body for a long time.
5. Memory T-cells remember the specific antigen and will recognise it a second time round. Memory B-cells record the specific antibodies needed to bind to that specific antigen.
6. The person is now immune - their immune system has the ability to respond quickly to a second infection.

Question 18

The secondary immune response?

Answer 18

1. If the same pathogen enters the body again, the immune system will produce a quicker, stronger immune response. This is the secondary response.
2. Clonal selection happens faster. Memory B-cells are activated and divide into plasma cells that produce the right antibodies 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 get rid of the pathogen before the individual shows any symptoms. This shows immunity to that specific pathogen

(Remember that T-cells and B-cells are also called T-lymphocytes and B-lymphocytes).

Question 19

Vaccines?

Answer 19

Whilst b-cells are busy dividing to kill a pathogen (in primary response), an individual will further from the disease. Vaccination stops 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 occurrence of the disease, those not vaccinated are also less likely to catch the disease (because there are fewer people to catch it from). This is called herd immunity.

Vaccines always contain antigens. These may be free or attached to a dead or attenuated (weekend) 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 large to be absorbed into the blood.

Sometimes booster vaccines are given later on to make sure the memory cells are produced.

Question 20

Antigenic variation?

Answer 20

When a person is infected a second time with the same pathogen, the same antigens on its surface will activate the secondary response and so the individual will not get ill.

However, some pathogens can change their surface antigen. This antigen variability is called antigenic variation. This is due to changes in the genes of a pathogen.

This means that when you’re infected a second time, the memory cells produced from the first infection will not recognise the antigen. The immune system must start from the primary response again and so the individual will get ill again.

Antigenic variation also makes it difficult to develop vaccines against some pathogens for the same reason, e.g. HIV and the influenza virus.

Question 21

Influenza virus?

Answer 21

Flu virus.

The influenza vaccine changes every year. That is because the antigens on the surface of the influenza virus change regularly, forming new strains of the virus.

Memory cells produced from vaccination of one strain of the flu will not recognise the stream with different antigens. The strains are immunologically distinct.

Every year, there are different strains of the influenza virus circulating the population, so more vaccines are made.

New vaccines are developed and one is chosen every year that is the most effective against the recent influenza viruses.

Governments and health authorities then implement a programme of vaccination using the most suitable vaccine.

Question 22

Active immunity?

Answer 22

Immunity can be active or passive.

Active - 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 - when your become immune after catching a disease.
2. Artificial - when you become immune after being given a vaccination.

Question 23

Passive immunity?

Answer 23

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 - when a baby becomes immune due to the antibodies it with you from its mother, through the placenta and in breast milk.

2. Artificial - when you become immune after being injected with antibodies from someone else. For example, if you contract tetanus, you can be injected with antibodies against the tetanus toxin, collected from blood donation.

Question 24

Differences between active and passive immunity?

Answer 24

Active immunity:

• Requires expose to antigens.
• 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).

Passive immunity:

• Does not require exposure to antigens.
• Protection is immediate.
• Memory cells are not produced.
• Protection is short-term because the antibodies given are broken down.

Question 26

How Do Cytotoxic T Cells Work?

Answer 26

Cloned T-cells activate cytotoxic T cells (TC cells).

Cytotoxic T cells kill abnormal cells and body cells that are infected by pathogens.

They do this by producing a protein called perforin.

Perforin 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.

The action of T cells is most effective against viruses because of viruses replicate inside living cells. This stops viruses multiplying and infecting more cells.

Question 27

Monoclonal antibodies as target specific substances?

Answer 27

Antibodies are all identical in structure.

Antibodies are specific because their binding sites have a unique tertiary structure that only one particular antigen will fit (one with a complementary shape).

You can make monoclonal antibodies that bind to anything you want, e.g. a cell antigen or other substance, and they will only bind to (target) this molecule.

There are two examples:

1. Targeting drugs to a particular cell type - cancer cells.
2. Targeting a particular substance for medical diagnosis - pregnancy testing.

Question 28

Targeting drugs to a particular cell type - cancer cells?

Answer 28

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 applied to the application area any hCG will bind to the antibody on the beads, forming an antigen-antibody complex.
3. The urine moved up the stick to the test strip, carrying beads with it.
4. The test strip contains antibodies to hCG that are stuck in place (immobilised).
5. If there is hCG present the test strip turns blue because the immobilised antibody binds to any hCG - concentrating the hCG-antibody complexly with the blue beads attached.

If no hCG is present, the beads will pass through the test are without binding to anything, and so it will not go blue.

Question 29

The ELISA test?

Answer 29

The enzyme-linked immundorbent assay (ELISA) allows your to see if a patient has any antibodies to a certain antigen or any antigen to a specific antibody.

It can be used to test for pathogenic infections, for allergies (e.g. nuts or lactose) and for just about anything you can make an antibody for .

In the 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 caused 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 behind tested (e.g. blood plasma). In some types of the test, the quantity of this antigen/antibody can be worked out from the intensity of the colour change.

There are several types of ELISA:

1. Direct ELISA uses a single antibody that is complementary to the antigen you’re testing for.
2. Indirect ELISA is different because it used two different antibodies.

Question 30

Using ELISA as a HIV?

Answer 30

HIV - human immunodeficiency virus.

We use an indirect ELISA test to test for HIV antibodies.

1. The HIV antigen is bound to the bottom of a well in a well plate (plastic test with loads of little circular pits in it).
2. A sample of the patients blood plasma, which might contain several different antibodies, is added to the well. If there are any HIV-specific antibodies. These will bind to the HIV antigen stick to the bottom of the well. The well is the. Washed out to remove unbound antibodies.
3. A secondary antibody, that has a specific enzyme attached to it, is added to the well. The secondary antibody can bind to the HIV-specific antibody (also called the primary antibody). The well is washed out again to remove the 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 indictees that the patient has HIV-specific antibodies in their blood and is infected with HIV.

The washing steps are important to make sure unbound antibodies aren’t left in the wells which could affect the rusults. Unbound secondary antibodies could cause the test to appear positive when there anew no HIV antibodies present.

If the ELISA result was negative, there would be no colour change because there would br no binding.

Question 31

Ethical issues surrounding vaccines?

Answer 31

1. All vaccines are tested on animals before being tested on humans. Some people disagree with animal testing. Animal based substances may be used to produce a vaccine.
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 full protected (e.g. they might have unprotected sex because they have had a new HIV vaccine and think they’re protected - vaccine may not work).
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 - 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 first to receive it.

Question 32

Ethical issues surrounding monoclonal antibody therapy?

Answer 32

They often involve animal rights issues.

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.

Question 33

The MMR vaccine?

Answer 33

1998 - study was published about the safety of measles, mumps and rubella vaccine. The study was based on 12 children with autism (long life development disability), and concluded that there may be a link with MMR and autism.

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.

Studies carried would by different scientists found no link.

There have been further studies to organise conflicting evidence.
2005 - a Japanese study was published about incidence of autism in Yokoham. Looked at 30,000 children brown between 1988 and 1996 and counted number of children that developed autism before 7.

The MMR jag was introduced in 1989, and stopped in 1993.

Question 34

Describing data in the exam?

Answer 34

The graph shows that the number of children diagnosed with autism continued to rise after the MMR vaccine was stopped.

For example, (give example).

Drawing conclusions:
- “there is no link between the MMR vaccine and autism”

Evaluate the methodology:
- “you can be more confident in this study in comparison to the first study conducted in 1998. This is because the sample size for the second study is much larger -30,000 children. A larger sample size means that results are less likely to be due to chance”.

Question 35

Herceptin?

Answer 35

20% of women with breast cancer have tumour that produce more than the usual amount of receptor called HER2.

Herceptin is a drug used to treat this type of cancer - contains monoclonal antibodies that bind to the HER2 receptor on a tumour cell and prevent the cells from growing and dividing.

2005 - study tested Herceptin on women who had undergone chemotherapy for HER2-type breast cancer. 1694 women took the drug for a year after chemo. Another 1694 women were observed for the same time (control). The results are shown on the bar chart.

Describe the data: almost twice as many women in the control group developed breast cancer again or died compared to the group taking Herceptin.

Draw conclusions: a one-year treatment with herceptin after chemo increases the disease-free survival rate for women with the HER2 type breast cancer.

Question 36

What is HIV?

Answer 36

Human immunodeficiency virus - effects the immune system. Eventually leads to AIDS (acquired immune deficiency syndrome).

AIDS deteriorates and eventually causes the immune system to fail. This make someone with AIDS for vulnerable to other infections, like pneumonia.

HIV infects and eventually kills helper t-cells, which acts as the host cells for the virus. Remember helper-t cells send chemical signals that activate phagocytes, Tc and b-cells. Without them, the immune system is unable to mount an effective response to infections because other immune system cells don’t behave how they would.

People infected with HIV develop AIDS when the helper t-cell no Kherson in their body reach a critically low level.

Question 37

HIV structure?

Answer 37

1. A core that contains genetic material (RNA) and proteins (including enzyme reverse transcriptase), which is needed for virus replication.
2. An outer coating of protein called a capsid.
3. An extra outer layer called an envelope. Made of membrane stoked from the cell membrane of a previous host cell.
4. Sticking out from the envelope are lots of copies of an attachment protein that help HIV attach to host helper t-cell.

Attachment proteins are also called envelope proteins.

Question 38

Steps of how HIV replicates inside its host helper t-cells?

Answer 38

HIV and other viruses reproduce in host cells. HIV replicated inside the helper t-cells of the host.

1. The attachment protein attaches to a receptor molecule on the membrane of the host helper t-cell.
2. The capsid is released into the cell, where it uncoates and releases the genetic material (RNA) into the cells cytoplasm.
3. Inside the cell, reverse transcriptase is used to make a complementary strand of DNA from the viral RNA template.
4. 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 to infect other cells.

During the initial infection period, HIV replicated rapidly and the infected person may experience flu symptoms.

After this period, HIV replication drops to a lower level. This is the latency period (could last for years). Symptoms are not experienced during this period.

Question 39

Why are people with AIDS susceptible to a range of illnesses?

Answer 39

People with HIV are classed as having AIDS when symptoms of their failing immune system start to appear or their helper t-cell count drive 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 the infecting with HIV and the development of AIDS varies between individuals (it’s usually 10 years without treatment).

1. The initial symptoms of aids includes minor infections of mucous membranes (inside nose, ears and genitals), and reoccurring respiratory infections.
2. As AIDS progresses, the number of immune system cells decrease further. Patients become susceptible to more serious infection including chronic diarrhoea, secrete 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 taxoplasmosis of the brain (parasite infection) and candidiasis of the respiratory system (fungal infections). It’s these serious infections that kill AIDS patients, not HIV itself.

The length of time people survive with aids varies. Factors that affect progression of HIV and AIDS and survival time with AIDS include existing infections, the strain of HIV they’re infected with, age and access to healthcare.

Question 40

Why don’t antibiotics work for viruses?

Answer 40

Antibiotics kill bacteria by interfering with their metabolic reactions.

They target the bacterial enzymes and ribosomes used in these reactions.

Viruses don’t have their own enzymes and ribosomes - they use the ones in host cells. So because human viruses use enzymes and ribosome ones to replicate, antibiotics can’t inhibits them because they don’t target human processes.

Most antiviral drugs are designed to raged the few virus-specific enzymes that exist. For example, HIV uses reverse transcriptase to replicate. Drugs are designed to inhibit these enzymes because humans don’t use them. The drugs are called reverse-transcriptase inhibitors.

Question 41

Cure for HIV?

Answer 41

There no cure or vaccine for HIV but antiviral drugs can be used to slow down the progression of HIV infection and AIDS.

The best way to control HIV infection in a population is by reducing its spread. HIV can be spread via unprotected sexual intercourse, through inge ted bodily fluids (blood) and from HIV-positive mother to her fetus.

Not all babies from HIV-positive mothered are born infected. Taking antiviral drugs during pregnancy can reduce the chances the baby will have HIV.

Question 42

Targeting drugs - cancer cells?

Answer 42

AntCancer cells have antigens called tumour markers that or not found a normal body cells.

Monoclonal antibodys can be made that will bind to the tumour markers.

You could also attach anti-cancer drugs to the antibodies.

When the antibodies come into contact with the cancer cells, they bind to the tumour markers.

This means the drug will only accumulate in the body where there are cancer cells.

So the side effects of the drug are lower than other drugs because they accumulate near specific cells.