The immune system

Draw the general structure of an amino acid.

Which statement describing protein structure is correct?

Antibodies are proteins produced and secreted by plasma cells.

Once activated, a single B cell divides and produces 4000 plasma cells.

Each one of these plasma cells produces 2000 molecules of antibody Q per second.

A human male has a blood volume of 5.4 dm³

Calculate the total number of molecules of antibody Q per cm³ of blood 24 hours after the production of these plasma cells.

Scientists investigated the effect of age on the immune response in healthy female mice.

The scientists used the following method.

1. Infected a large number of young and old mice with the same strain of influenza virus.

2. Removed the lungs from 6 young and 6 old mice on the day of infection (day 0).

3. Repeated step 2 on 8 different days after infection.

4. Determined the mean number of B cells present per gram of lung tissue for young and old mice.

Figure 3 shows the scientists’ results.

The scientists decided that further investigations would be required to conclusively

determine the effect of age on the immune response in healthy female mice.

Using all the information provided, suggest three reasons for the scientists’ decision.

Do not refer to statistical tests, repeats or sample size in your answer.

Figure 1 shows the structure of a fatty acid molecule and the structure of a glycerol molecule.

On Figure 1, draw a circle around the part of the fatty acid molecule and the part of the glycerol molecule that is removed to form a bond in a triglyceride molecule.

Name the bond formed between a fatty acid and glycerol in a triglyceride molecule.

Name the reaction involved in forming a bond between a fatty acid and glycerol in a triglyceride molecule.

Table 1 shows information about three fatty acids.

Name the fatty acid shown in Table 1 that is a saturated fatty acid.

The melting point is the temperature at which a solid changes state to be a liquid.

Use Table 1 to describe the relationship between fatty acid structure and fatty acid melting point.

The ratio of saturated to unsaturated fatty acids in a cell-surface membrane determines the extent of the membrane’s fluidity.

Scientists provided a cell culture of mouse phagocytes with liquid broth rich in unsaturated fatty acids.

The scientists observed:

• an increase in the proportion of phospholipids in the phagocytes containing unsaturated fatty acids

• more phagocytosis.

Suggest and explain why there was more phagocytosis.

In the following passage, each numbered space can be filled with a biological term.

Vaccines can provide protection for individuals and populations against disease. The

Write the correct biological term beside each number below that matches the space in the passage.

There is currently no effective vaccine available for HIV.

Suggest one reason why.

Table 1 shows the action of two antibiotics.

Using the information in Table 1, explain why each antibiotic is not effective against HIV.

Give the three structural features found in all virus particles and describe the function of one of these features.

Function of one named feature

Explain why viruses are described as acellular and non-living.

Give one reason why antibiotics are not effective against viruses.

Some hospital patients suffer from diarrhoea caused by infection with the bacterium Clostridium difficile. The C. difficile bacteria release toxins. These toxins cause the diarrhoea.

The toxins damage the cells lining the ileum, causing them to lose their microvilli. The damage to the cells reduces the absorption of the products of digestion and reduces the absorption of water, resulting in diarrhoea.

Explain why the damage to the cells lining the ileum reduces absorption of the products of digestion and why this reduces absorption of water.

Not all patients in hospital with C. difficile develop diarrhoea.

Scientists measured the anti-toxin antibody concentration in hospital patients with and without C. difficile infection.

They measured the anti-toxin antibody concentration four times:

• on admission to hospital (day 0)

• on day 3

• on day 6

• on the day the patient left the hospital.

Figure 4 shows the scientists’ results.

The scientists suggest that the anti-toxin antibody could be given to some patients as a form of passive immunity.

Use Figure 4 to suggest how this passive immunity would work and which patients should be offered this anti-toxin antibody.

To be used as passive immunity treatment, the anti-toxin antibody would be injected. If it was given by mouth, it would be digested.

Describe how the anti-toxin antibody would be digested.

Dengue fever is a human disease caused by the dengue virus.

Scientists designed an ELISA test to detect antibodies to the dengue virus in a patient’s blood sample.

Figure 10 shows a diagram of this test and some information about how it works.

Figure 11 shows the negative and positive results that were produced 20 minutes after the use of the test shown in Figure 10.

Suggest what is on the test at line T and explain what causes the line to appear in a positive test.

A line at C shows that the test has worked.

Suggest one reason why a line at C shows the test has worked.

Figure 12 shows a flowchart of how the anti-human antibodies with enzyme attached are produced.

Suggest why the fused cells allow continuous production of monoclonal antibodies.

Evaluate the ethics of the production process shown in Figure 12.

Early identification of dengue fever can be difficult as many other diseases produce

the same symptoms. Early identification is important because people suffering with dengue fever can become ill very quickly and may need hospital treatment.

Scientists compared the effectiveness of three diagnostic tests for dengue fever.

• Laboratory-based test – a patient’s blood sample is sent from the doctor’s clinic to a laboratory for testing.

• Current test used in the doctor’s clinic.

• New test to be used in the doctor’s clinic – the ELISA test shown in Figures 10 and 11 (on page 24).

The scientists’ results are shown in Table 3.

A blood sample from each patient with confirmed dengue fever at each time after onset of symptoms was tested with all three diagnostic tests.

The scientists recommend that the new test is used for the identification of dengue fever in all countries around the world.

Discuss this recommendation. Use all the information given.

The dengue virus causes damage to capillaries so that blood proteins move out of the capillaries into the tissue fluid.

Explain how this would affect the return of tissue fluid into the capillaries.

Give two types of cell that can stimulate an immune response.

An autoimmune disease causes the immune system to attack healthy body tissues. Scientists investigated the immune responses of healthy mice and mice with autoimmune disease.

The chemical OXA causes an immune response in mice and can make their skin swell. Mice had olive oil applied to their left ear and OXA in olive oil applied to their right ear.

The immune response was recorded in two ways:

• the cellular response by measuring the mean increase in ear thickness 24 hours after exposure to OXA

• the humoral response by measuring the mean concentration of anti-OXA antibody in blood 14 days after exposure to OXA.

Table 2 shows the results of this investigation. The values in the brackets show ± 2 standard deviations. A value of ± 2 standard deviations from the mean includes over 95% of the data.

Suggest and explain one reason why olive oil was applied to the left ear of the mice.

Plot a suitable graph for mean increase in ear thickness for each group of mice in Table 2.

Include the data for ± 2 standard deviations on your graph.

What can you conclude about the effects of autoimmune disease on the cellular response and the humoral response in male and female mice?

Use the data to justify your conclusions.

Some studies have shown that in humans, oestrogen has the opposite effect on two different autoimmune diseases. Oestrogen:

• accelerates the progression of systemic lupus erythematosus (SLE)

• prevents the progression of rheumatoid arthritis (RA).

The scientists investigated the effect of oestrogen on the immune response in healthy mice and mice with autoimmune disease.

Table 3 shows the scientists’ results.

A student studying these data made the following conclusions.

1. In humans, SLE is caused by an overproduction of antibodies.

2. In humans, RA is caused by an overproduction of cytotoxic T cells (T_C cells).

Evaluate the student’s conclusions.

In mice, one type of autoimmune disease is inherited as a dominant allele. Would the Hardy–Weinberg principle hold true for a population of mice, some of which had this autoimmune disease?

Explain your answer.

Give two features of all prokaryotic cells that are not features of eukaryotic cells.

Many multicellular organisms produce antimicrobial polypeptides (APs) that protect them against prokaryotes. Figure 3 shows how one type of AP acts on the cell-surface membrane of prokaryotes.

This AP has a secondary structure in a helical shape.

Tick () the box to show which type of bond maintains the helical structure of the polypeptide.

The amino acids on one side of each AP helix have hydrophobic properties. The amino acids on the opposite side of each helix have hydrophilic properties. Figure 4 shows this.

Suggest how these properties of the APs allow them to become positioned across the membrane (as shown in Figure 3) and make a channel through which ions can pass.

Figure 5 shows further information about a channel formed in the cell-surface membrane by the APs.

Use Figure 5 to calculate the cross-sectional area of the channel through which ions can pass. Assume the cross-sectional area is circular. Use π = 3.14 in your calculation. Give your answer in nm² and to 1 decimal place.

The APs damage prokaryotic cells but do not damage the eukaryotic cells in the organisms that produce them. Prokaryotic cell membranes do not contain cholesterol.

Assess why the APs do not damage the eukaryotic cells of the organisms that produce them.

Scientists observed these APs on prokaryotes using a transmission electron microscope. They stained the APs using a monoclonal antibody with gold attached to it.

Suggest how these techniques allowed observation of APs on prokaryotes.

ADCs are molecules made of a monoclonal antibody linked to a cancer drug.

Figure 8 shows how an ADC enters and kills a tumour cell.

The process of entering the cell and the breakdown of the antibody to release the drug is very similar to phagocytosis.

Use your knowledge of phagocytosis to describe how an ADC enters and kills the tumour cell.

Some of the antigens found on the surface of tumour cells are also found on the surface of healthy human cells.

Use this information to explain why treatment with an ADC often causes side effects.

Scientists investigated whether one type of ADC could be used to treat human breast

cancer.

This ADC is a monoclonal antibody combined with a drug to inhibit mitosis. The monoclonal antibody binds to a protein found on human breast cancer cells.

The scientists placed small pieces of human breast cancer tissue under the skin of mice.

The scientists then randomly divided the mice into three groups. They treated the groups as follows on day 0.

Group G – control Group H – injected with monoclonal antibody only Group J – injected with ADC (monoclonal antibody + drug).

Every few days, the scientists measured the volume of the tumours formed from the human breast cancer tissue.

Figure 9 shows the scientists’ results.

Figure 9

This source has been removed due to third-party copyright restrictions.

Mice in Group H were injected with 2 mg kg^–1 of monoclonal antibody. The monoclonal antibody was in a solution of concentration 500 mg dm^–3

Calculate the volume of antibody solution that the scientists would have injected into a 23 g mouse. Give your answer in dm³ and in standard form.

Suggest one reason why there are no data for Group G and Group H after day 8

Suggest and explain two further investigations that should be done before this ADC is tested on human breast cancer patients.

Describe how the human immunodeficiency virus (HIV) is replicated once inside helper T cells (T_H cells).

HIV-1 is the most common type of HIV. HIV-1 binds to a receptor on T_H cells called

CCR5.

Current treatment for HIV-1 involves the use of daily antiretroviral therapy (ART) to stop the virus being replicated. Only 59% of HIV-positive individuals have access to ART.

Scientists have found that two HIV-1-positive patients (P and Q) have gone into remission (have no detectable HIV-1). This happened after a blood stem cell transplant (BSCT).

• Patient P was given two BSCTs, and patient Q was given one BSCT.

• All BSCTs came from a donor with T_H cells without the CCR5 receptor.

• In addition, patient P had radiotherapy, and patient Q had chemotherapy. Both of these treatments are toxic.

• Both patients (P and Q) stopped receiving ART 16 months after BSCT.

18 months after stopping ART, both patients had no HIV-1 RNA in their plasma, no HIV-1 DNA in their T_H cells and no CCR5 on their T_H cells.

Use the information given to evaluate the use of BSCT to treat HIV infections.

Alpha-gal is a disaccharide found in red meat.

Alpha-gal is made of two galactose molecules. Galactose has the chemical formula

Give the chemical formula for the disaccharide, alpha-gal, and describe how it is formed from two galactose molecules.

Some people eat red meat for many years without having any reaction, then have an allergic reaction to the alpha-gal in red meat.

An allergic reaction is caused by an immune response.

Draw a labelled diagram of an antibody and identify the specific alpha-gal binding site.

A tick is a small animal that bites humans and feeds on their blood. This results in proteins from the tick saliva entering the human body.

Scientists have suggested one hypothesis for the allergic reaction to alpha-gal in red meat. They think that an earlier immune response to a tick bite can cause a person to have an allergic reaction to alpha-gal in red meat.

Suggest how one antibody can be specific to tick protein and to alpha-gal.

Scientists took blood samples from one man over several weeks and measured the concentration of antibody in the man’s blood. During this time, the man had two tick bites and had an allergic reaction to alpha-gal in red meat.

The scientists’ results are shown in Figure 7.

Figure 7

This figure has been removed due to third-party copyright restrictions.

The scientists’ hypothesis was that an earlier immune response to tick protein causes the allergic reaction.

Consider whether Figure 7 supports this hypothesis.

In Europe, viruses have infected a large number of frogs of different species. The viruses are closely related and all belong to the Ranavirus group.

Previously, the viruses infected only one species of frog.

Suggest and explain how the viruses became able to infect other species of frog.

Name two techniques the scientists may have used when analysing viral DNA to determine that the viruses were closely related.

Determining the genome of the viruses could allow scientists to develop a vaccine.

Explain how.

Describe how the B lymphocytes of a frog would respond to vaccination against Ranavirus.

You can assume that the B lymphocytes of a frog respond in the same way as B lymphocytes of a human.

Do not include details of the cellular response in your answer.

Describe the structure of the human immunodeficiency virus (HIV).

Some people infected with HIV do not develop AIDS. These people are called HIV controllers.

Scientists measured the number of HIV particles (the viral load) and the number of one type of T helper cell (CD4 cells) in the blood of a group of HIV controllers and also in a group of HIV positive patients who had symptoms of AIDS.

The median values and the range of their results are shown in Table 3.

A test sample of 500mm³ of blood is taken from an HIV controller to determine the viral load.

Tick (✓) one box that shows the number of virus particles that would be present in a test sample of blood taken from an HIV controller with the median viral load.

Use the data in Table 3 and your knowledge of the immune response to suggest why HIV controllers do not develop symptoms of AIDS.

Scientists investigated the cell cycle in heart cells taken from mice 6 days before their birth and then at 4, 14 and 21 days after their birth.

Their results are shown in Table 4. Age 0 days = day of birth.

Describe and explain the data in Table 4.

The scientists determined the percentage of heart cells undergoing DNA replication by using a chemical called BrdU. Cells use BrdU instead of nucleotides containing thymine during DNA replication.

Describe how BrdU would be incorporated into new DNA during semi-conservative replication.

Cells with BrdU in their DNA are detected using an anti-BrdU antibody with an enzyme attached.

Use your knowledge of the ELISA test to suggest and explain how the scientists identified the cells that have BrdU in their DNA.

When a person is bitten by a venomous snake, the snake injects a toxin into the person. Antivenom is injected as treatment. Antivenom contains antibodies against the snake toxin. This treatment is an example of passive immunity.

Explain how the treatment with antivenom works and why it is essential to use passive immunity, rather than active immunity.

Figure 8 shows a procedure used to produce antivenom.

A mixture of venoms from several snakes of the same species is used.

Suggest why.

Horses or rabbits can be used to produce antivenoms. When taking blood to extract antibody, 13 cm³ of blood is collected per kg of the animal’s body mass. The mean mass of the horses used is 350 kg and the mean mass of the rabbits used is 2 kg

Using only this information, suggest which animal would be better for the production of antivenoms. Use a calculation to support your answer.

During the procedure shown in Figure 8 the animals are under ongoing observation by a vet.

Suggest one reason why.

During vaccination, each animal is initially injected with a small volume of venom. Two weeks later, it is injected with a larger volume of venom.

Use your knowledge of the humoral immune response to explain this vaccination programme.

Chronic lymphocytic leukaemia (CLL) is a cancer that affects some B cells of a person’s immune system.

Rituximab is a drug used to treat CLL. It binds to a protein called CD20 on the surface of B cells. If enough Rituximab binds to a B cell, it can kill the cell. Rituximab kills both healthy and cancerous B cells. The body then produces new B cells.

The amount of CD20 on the surface of B cells varies from one person to another. Doctors investigated the relationship between the amount of CD20 on the B cells of a patient and the percentage of B cells destroyed by Rituximab.

Figure 2 shows the doctors’ results. Each cross is the result for one patient.

What statistical test could the scientists have used to determine whether there was a significant relationship between the amount of CD20 on the surface of B cells and the percentage of B cells destroyed by Rituximab? Give a reason for your answer.

From these data, what can you conclude about the effectiveness of Rituximab in treating patients with CLL?

Do not include considerations of statistical analyses in your answer.

Approximately 11 percent of people with CLL also have mutations of a gene called NOTCH1. This leads to production of a non-functional transcription factor associated with CD20 production.

The doctors determined the median percentage of B cells destroyed by Rituximab in people with CLL who had the NOTCH1 mutation and those who did not.

The doctors’ results are shown in Table 1.

Human blood contains (approximately) 1.0 10⁹ B cells per dm³.

Use the median values in Table 1 to calculate the difference between the number of B cells per dm³ in the blood of people treated with Rituximab with the NOTCH1 mutation and people without the NOTCH1 mutation.

Express your answer in standard form. Show your working.

Use all of the information to suggest how the mutation of NOTCH1 led to the difference in the percentage of B cells destroyed by Rituximab.

Describe how phagocytosis of a virus leads to presentation of its antigens.

Describe how presentation of a virus antigen leads to the secretion of an antibody against this virus antigen.

Collagen is a protein produced by cells in joints, such as the knee.

Rheumatoid arthritis (RA) is an auto-immune disease. In an auto-immune disease, a person’s immune system attacks their own cells. RA causes pain, swelling and stiffness in the joints.

Scientists have found a virus that produces a protein very similar to human collagen.

Suggest how the immune response to this viral protein can result in the development of RA.