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Unit 8: Pharmacological principles of drug actions

The immune system is made up of special cells, proteins, tissues and organs and defends people against microorganisms. In most cases, the immune system does a great job of keeping people healthy and preventing infections. But sometimes problems with the immune system can lead to illness and infection. Through a series of steps called the immune response, the immune system attacks organisms and substances that invade body systems and cause disease. The cells involved are white blood cells, or leukocytes, which come in two basic types that combine to seek out and destroy disease-causing organisms or substances.

On successful completion of this topic you will: • understand the function of the immune system and how drugs may affect

it (LO4).

To achieve a Pass in this unit you need to show that you can: • explain functions of defence mechanisms (4.1).

Defence mechanisms8.6

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8.6: Defence mechanisms

1 Non-specific immune responseInflammationThe non-specific immune response occurs due to tissue damage – mast cells and basophils release substances that cause inflammation. Inflammation is a response to tissue damage causing redness and heat because of dilating blood vessels and an increased blood flow to the area of damage.

Inflammation causes swelling because the extra blood pushes tissue fluid into damaged tissue. This swelling puts pressure on nerves causing pain. White blood cells (or leukocytes) are cells of the immune system involved in defending the body against both infectious disease and foreign materials – they are attracted to the inflamed area to remove dead cells by phagocytosis. The photograph in Figure 8.6.1 shows inflammation of the knee joint – look at the red nature of the inflammation.

PhagocytosisPhagocytes include white blood cells such as neutrophils and monocytes. They engulf pathogens and digest them with lytic enzymes (see Figure 8.6.2). The outer membrane of the neutrophil engulfs the bacteria, which results in the bacteria being contained inside a vacuole. Lysosomes fuse to the vacuole to digest the bacteria with their digestive enzymes. The vacuole breaks into fragments containing parts of the digested bacteria and attaches to proteins of the major histocompatibility complex (MHC).

The vacuole continues to fuse with the cell membrane and the fragments of the bacteria along with the MHC stick out of the surface of the neutrophil. The antigen of the bacteria ends up on the outside of the phagocyte so an immune response is activated against the bacteria.

Figure 8.6.1: A photograph showing the effects of inflammation.

Key termsBasophil: A type of white blood cell that helps you fight infections.

Phagocytosis: The engulfing of foreign particles.

Lytic enzymes: Enzymes that cause lysis (breaking down).

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8.6: Defence mechanisms

Invadingpathogens

NeutrophilWound site

Histamines

Migrate toinfection site Neutrophil engulfs

invader

Bloodvessel

Destroys pathogenusing hypochlorousacid or enzymes

A

B

C

D

2 Specific immune responseAn antigen is a foreign molecule detected by the specific immune system. The immune system responds to this detection by producing specific antibodies (proteins released to the site of infection).

Lymphocytes are a type of white blood cell in the vertebrate immune system (T and B cells). They are produced in the bone marrow and they migrate to the lymph nodes.

The specific immune system responds in two ways that are closely linked – antibody-mediated immune response and cell-mediated immune response.

Antibody-mediated immunityThis response does not directly involve cells; it works through chemicals called antibodies. Antibodies are made by white blood cells called lymphocytes. B cells attack any foreign objects such as bacteria and viruses when they get inside the body.

The primary immune response occurs when B cells are made on the detection of a foreign antibody. One B cell is produced for every antigen detected; they are specific to the particular antigen that has entered the body. Therefore many identical cells are made – they do not directly attack the foreign matter but they make Y-shaped proteins (antibodies) that interact with the antigen on the foreign molecule and stop it being harmful.

Most of the newly synthesised B cells die once the infection is under control but some are left in the body – these are called memory cells. If this particular antigen is detected again the memory cells reproduce and many more are made, enabling the body to defend itself against this foreign bacteria – this is known as the secondary immune defence.

Cell-mediated immunityT cells are activated in the same way as B cells when an antigen invades body cells. Activated T cells differentiate and have various roles in the immune response: T helper cells, T killer cells, T suppressor cells and memory cells.

Figure 8.6.2: Neutrophil engulfing bacteria.

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8.6: Defence mechanisms

T helper cells

These cells help the immune response to take place. They initiate B cells to divide and produce antibodies, and they prepare the macrophages for phagocytosis to digest the foreign pathogens.

T killer cells

These cells directly attack foreign cells – they punch holes into the membranes of the foreign cells causing them to lose cytoplasm and die.

T suppressor cells

These cells help to return the immune system back to normal once the infection has been eliminated. They are necessary so that the body reserves resources.

Memory cells

Some of the activated T cells become memory cells and remain in the body to provide a secondary immune response if the pathogen invades the body again.

3 Immune system stimulationImmune system stimulants encourage the body’s immune system to activate an attack rather than fighting the pathogen themselves. Antiviral drugs and interferons are used to stimulate the immune system to attack pathogens.

Interferons inhibit viral synthesis (production of new viruses) in infected cells. One human interferon, interferon alpha, is the standard treatment for hepatitis B and C.

VaccinationsVaccinations help to speed up the immune response. A dead or inactive form of the pathogen is injected into the body. The body detects the antigens and produces memory cells that are stored in the body ready for a second invasion. The memory cells will then be activated and reproduced in great numbers to protect the body.

Passive immunityBreast milk provides extra immunity to babies because the mother is able to pass on antibodies that are stored in her body to the baby. Babies are able to absorb these large proteins across their porous intestines straight into the bloodstream, helping them to fight common pathogens.

4 Transfusions and transplantsBlood transfusions can be very dangerous because if the donor blood is a different blood group from the recipient blood, the body’s immune system reacts. This immune response can be fatal. Red blood cells have antigens attached to their surface – the antigens present depend on the blood group.

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There are four blood groups: A, B, AB and O. Red blood cells in group O do not contain any antigens, therefore no immune response will be activated if this blood group is transfused into people with other blood groups.

Patients with blood group AB do not contain any antibodies so can receive blood from any blood group. However, their red blood cells have both antigen A and antigen B, so would cause a dangerous reaction if transfused into someone with a different blood group.

People with blood group A contain antigen A on the surface of their red blood cells, and anti B antibodies in their blood.

People with blood group B have antigen B present on the surface of the red blood cells and anti A antibodies in their blood. If a person with blood group A received blood group B during a blood transfusion, the anti B antibodies in their blood would react with the B antigens on the surface of the red blood cells and cause an immune response that could be fatal.

Transplantation involves the placing of tissues and organs into an individual from a donor. However, the problem with transplants is the chance of rejection due to the body’s immune system. Transplanted tissue surfaces are covered in antigens; these foreign antigens activate a cell-mediated immune response. This can cause destruction of transplanted cells and can lead to failure of an organ. The use of drugs and tissue typing can help ensure that rejection does not take place.

5 ImmunosuppressionImmunosuppression is a reduction in activation of the immune system and may happen because of a reaction to a medical treatment. If this did occur, immune system stimulation drugs may be needed to enable the body to fight against disease (see Case study on cancer treatment).

Immunosuppressant drugs are given to prevent the immune system from working. For example, they may be necessary when carrying out an organ transplant – if the recipient has a working immune system then the organ may be rejected. Ciclosporine (cyclosporine, cyclosporin A), a common immunosuppressive drug, is given to inhibit the activity of T cells and cell-mediated immunity.

6 Autoimmune diseasesAutoimmune diseases occur when an immune response is activated against tissues normally in the body because the immune system mistakes some part of the body for a pathogen and attacks its own cells. This is the cause of multiple sclerosis – T cells attack the myelin sheath around neurones, limiting the function of the nervous system. People with insulin-dependent diabetes make antibodies that kill ß cells in the islets of Langerhans in the pancreas, inhibiting the production of insulin and affecting blood glucose levels. Patients suffering with myasthenia gravis make antibodies that attack specialised synapses that connect motor nerves to effectors. This affects the ability of the muscle to contract.

Key termsImmunosuppression: Suppression of the immune system and its ability to fight infection.

Myelin sheath: A layer insulating the axons of nerve fibres.

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CorticosteroidsCorticosteroids are hormones used to relieve inflammation that occurs as part of the immune response due to infection. Inflammation prevents the spread of infection but, in some health conditions, the immune system causes inflammation even though there is no infection. This is known as an autoimmune condition and examples include rheumatoid arthritis and lupus.

Lupus can be treated with nonsteroidal anti-inflammatory drugs (NSAIDs), cyclosporine and steroids. Corticosteroids are prescribed to people with lung conditions, such as chronic obstructive pulmonary disease (COPD), where inflammation occurs in the lungs or airways.

ChecklistIn this topic you should be familiar with the following ideas about the immune system:

the body has specific and non-specific immune responses

parts of the non-specific immune response are the skin, membranes, inflammation and phagocytosis

the specific immune response includes antibody-mediated and cell-mediated responses

antibody-mediated or humoral immunity uses antibodies from B cells to attack foreign objects before they invade the body

cell-mediated immunity activates T cells to attack infected body cells

there are four types of T cells: T helper cells, T killer cells, T memory cells and T suppressor cells

vaccinations are used to stimulate the immune system into producing memory cells to protect the body

blood transfusions and transplants can cause immune responses, which can be dangerous to health. Immunosuppressant drugs are needed to stop any immune response that may be dangerous

autoimmune diseases (such as MS) occur when the body attacks its own body cells

cyclosporine (cyclosporine, cyclosporin A) is a common drug used to suppress the immune system

antiviral drugs and interferons are used to stimulate the immune system.

Case studyIn findings published in 2009 by the British Journal of Cancer, a study by scientists shows that two existing cancer drugs are able to stimulate the body’s immune cells into attacking invading cancer cells.

Current cancer-fighting drugs are known as cytotoxics and they cure patients by killing cells directly and stunting their growth. Experiments have shown that the drugs stimulate the immune system in three stages: firstly, by hijacking the tumour and making it more visible to the body’s immune system. This initiates a signal to the body’s defence system and encourages white blood cells to attack the now visible cancer cells.

Further readingMak, T. and Saunders, M. (2005) The Immune Response: Basic and Clinical Principles, Elsevier Science Publishing.

Schindler, L.W. (1991) Understanding the Immune System, Diane Publishing Co.

Activity1 Research hepatitis C and drugs

that can be used to stimulate the immune system.

2 Research opioids and their suppressive actions.

3 Summarise the body’s defence mechanisms that provide immunity.

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Unit 8: Pharmacological principles of drug actions

8.6: Defence mechanisms

AcknowledgementsThe publisher would like to thank the following for their kind permission to reproduce their photographs:

Shutterstock.com: Photostock 10; Science Photo Library Ltd: Pasieka 2

All other images © Pearson Education

We are grateful to the following for permission to reproduce copyright material:

Diagram of Neutrophil engulfing bacteria, produced by Puricore. Used with permission.

Every effort has been made to trace the copyright holders and we apologise in advance for any unintentional omissions. We would be pleased to insert the appropriate acknowledgement in any subsequent edition of this publication.

About the authorJoanne Hartley-Metcalfe studied Forensic Sciences at UCLAN and is currently Science Vocational Coordinator, teaching KS3 and KS4 Science, level 3 Forensic and Medical Science and A level in a Merseyside school. She has been a Standards Verifier for four years, quality assuring vocational science courses across the country. Joanne has experience authoring and examining, and has made contributions to a number of level 3 resources.