4.2 Immunity Flashcards

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1
Q

4.2 Immunity

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2
Q

Defence Mechanisms

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The body has a range of defences to protect itself from pathogens. There are two main types:

Non-specific mechanisms do not distinguish between one type of pathogen and another, but respond to all of them in the same way. These mechanisms act immediately and take two forms:
1. A barrier to prevent entry of pathogens

  1. Phagocytosis

Specific mechanisms do distinguish between one pathogen and another. They respond less rapidly but provide long lasting immunity. The response involves a type of white blood cells called and lymphocyte which can take two forms:
1. Cell mediated immunity involving T lymphocytes

  1. Humoral response involving B lymphocytes
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3
Q

What is a pathogen?

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A pathogen is a disease causing microbe/ microorganism

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4
Q

Non- Specific Defence Mechanisms

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Natural Defence barriers
Most microorganisms find it difficult to get inside the body. There are four main ways in which the body prevents potential pathogens from entering.

1.Physical Defence
This skin provides a physical barrier to the entry of pathogens. The tough outer layer of dead cells contains keratin and very little water, which microorganisms need for growth. The skins also secretes various chemicals which inhibit the growth of bacteria such as:
•tears - the lachrymal glands secrete tears which dilute and wash away microorganisms
•sebum - secreted by the sebaceous glands and contains fatty acids that have antimicrobial action
•mucus - a sticky secretion produced by goblet cells that line the air passages, the mucus traps many airborne pathogens

  1. Mechanical Defence
    Nasal hair filter the air that is drawn into the nasal passages. Bacteria and other particles trapped in the mucus are swept away from the lungs by the cilia.
    Cilia are tony hair that beat with a wave-like motion.
  2. Chemical Defence
    Tears, mucus, saliva and sweat all contain chemicals that inhibit the growth of microorganisms.
    Lysozyme is an enzyme found in many of these secretions. It catalyses the hydrolysis of molecules in the cells walls of bacteria.
    In addition to lysozyme, sweat contains lactate which also slows bacterial growth.
    Hydrochloride acid present in gastric juices kills almost all microorganisms that get as far as the stomach.
    The vagina contains harmless bacteria that convert carbohydrate to lactate, which kills pathogenic bacteria.
  3. Biological defence
    There are natural populations of harmless bacteria living on the skin and mucous membranes that inhibit the growth of many pathogenic microbes.
    They protect us by competing with pathogenic bacteria for nutrients.
    Wide-spectrum antibiotics can destroy these useful bacteria and so remove some of the body’s defence.

*The natural defence barrier is the first line of defence, if the microorganisms breach this the second line of defence occurs;

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5
Q

Diagram of Phagocytosis

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6
Q

The Immune Repsonse

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The immune response is another aspect of our body’s defence against pathogen- this time is involves the B and T lymphocytes. The immune response depends on the concept of ‘Self and Non-Self’ and on the recognition of antigens. Antigens act as biological markers/ labels and they provide a way in which the body can recognise something that should not be present and therefore may be harmful.

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7
Q

What is an Antigen?

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• A chemical capable of provoking the production of specific complementary antibodies - KNOW

Antigens are usually chemicals, particularly proteins or carbohydrates, found on the surface of a cell. When they enter the body, the antigen is recognised by the immune system and trigger an immune response from lymphocytes.

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8
Q

Self and Non-Self

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All organisms are genetically different (except for clones and twins) and have different molecules on the surface of their cells. Each different molecule has a very different shape which is determined genetically.

Due to molecules being specific to each individual, the body can distinguish between its own molecules (self) and different molecules (non-self). Normally the body does not respond to ‘self’ cells. However, ‘non self’ cells act as antigens. The body recognises the ‘non self’ cells and this triggers an immune response which will usually destroy the cells carrying antigens.

This reaction to ‘non self’ is one of the main problems in transplanting organs or tissues from one individual to another. The recipient is likely to ‘reject’ to donated organ.

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9
Q

How do Lymphocytes know what is Self and Non-Self?

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During foetal development, lymphocytes make contact with foetal ‘self’ cells and are switched off if they are complementary. The remaining ‘switched on’ lymphocytes are those that are not complementary to the ‘self’ cells.

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10
Q

Self and Non-Self Diagram

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11
Q

Lymphocytes

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The body contains thousands of different B and T lymphocytes. Each has specific protein receptor sites on its cell surface membrane whose molecular shape in complementary to the shape of one particular antigen. The shapes match by a ‘lock and key’ mechanism. This allows the recognition of and response to a huge range of different antigens.

Summary

B lymphocytes:
•Formed in stem cells within bone marrow
•Development within the bone marrow
•Provide antibody mediated immunity
•Antibodies are produced which responds to antigens found in the body fluids. Usually bacterial and viral infections

T lymphocytes
•Formed in stem cells within bone marrow
•Developed within the thymus gland
•Provides cell mediated immunity
•Responds to antigens attached to body cells. Usually body cells affected by viral infections

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12
Q

How do lymphocytes become sensitised or activated?

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When a complementary antigen makes contact with receptors on the surface of a lymphocyte it will become sensitised.

-After being sensitised, the B lymphocyte activates certain genes that set in motion the process which leads to the production of antibodies

-After being sensitised, the T lymphocytes produces different types of T- cells

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13
Q

Antibody-mediated Immunity
- B lymphocytes

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Antibody-mediated immunity combats ‘free’ pathogens in blood or tissue fluid. The antibody-mediated immunity is initiated by an activation phase. This is where macrophages (a type of phagocyte) engulf and digest microbes through phagocytosis. This is non specific immunity because the macrophages engulf all foreign cells without specificity. Some of the digested antigens are then displayed on the surfaces of the macrophages as a way of alerting B lymphocytes to act. This display provides other cells of the immune system with an opportunity to recognise the invader and become activated. This is called antigen presentation.

While antigen presentation is taking place B lymphocytes are circulating throughout the bloodstream. Some of the B cells will have cell surface receptors which fits the antigens being presented on the surface of the macrophages. These cells then become activated and respong by dividing repeatedly by mitosis to produce clones of itself, and therefore forming huge numbers of identical B cells over a period of a few weeks.

Note: The period of time between contact with the antigen and the cloning of the B lymphocytes is when the person will suffer the symptoms of the disease.

Some of these activated B cells become plasma cells which produce antibody molecules very quickly. Plasma cells secrete antibodies into the blood, lymph or onto the lining of the lungs and gut. These cells do not live longer than a few weeks before they are destroyed, although the antibodies that they produce can stay in the body for longer.

Other B cells become memory cells that remains circulating in the blood for a long time. If the same antigen is reintroduced a few weeks or months after the first infection, these memory cells divide rapidly and develop into plasma cells and more memory cells. This is respected on every subsequent invasion by the same antigen, which means the infection can be destroyed before the symptoms develop. I.e. the person has become immune to this specific disease.

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14
Q

Antibody-Mediated Immunity
- B lymphocytes
Diagram

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15
Q

Antibodies

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Antibodies form a crucial part of the body’s defence against disease.
Antibodies are specific; different antibodies are produced to deal with different pathogens.

Definition of Antibody:
Globular proteins which are specific and complimentary to particular antigens and which can feast to antigens leading the their destruction.

Note: Antibodies being globular structures is good as small changes in the primary structures will result in different globular shapes to allow millions of different antibodies

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16
Q

Action of Antibodies in forming an Antigen-Antibody Complex

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17
Q

Antigen-Antibody Reaction

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18
Q

The Action of Antibodies

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•Agglutination- complementary antibodies attach to antigens clumping the bacteria together. Typically, the build up of antibodies in the body fluid will enable a sufficient number to be present to immobilise the bacteria causing their affluent clumping as an antigen-antibody complex. In due course the antigen-antibody complex (clump of bacteria and antibodies) is engulfed by polymorphs and other phagocytes.

•Precipitation- some antibodies bind together soluble antigens into large units which are then precipitated out of solution. As such they are more easily infected by phagocytes (I.e. the antibodies act as opsonins by attaching to pathogens and marking them for phagocytosis)

•Antibodies can also destroy invading cells directly.

Note: Opsonins are molecules which enhance phagocytosis

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19
Q

Cell- Mediated Immunity
-T lymphocytes

A

In an immune response, the production of T lymphocytes is stimulated by the body’s own cells that have been changed due to the presence of non-self material within them. These cells are referred to as antigen-presenting cells. Examples include:

Macrophages that have engulfed and broken down pathogens, to then present some of the pathogenic antigens on their own cell surface

Any type of body that has been invaded by a virus of which antigen are presented on the cell surface membrane of the body cell

Cancer cells (tumours) may present abnormal antigens on their cell surface membrane

•T lymphocytes will also be activated by transplants, due to the fact that the donated tissue comes from a genetically different individual and will have proteins on its cell surface which the recipients body will recognise as non-self and therefore attack

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20
Q

Antigen-Presenting Cells Bringing about a Response
-Diagram

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21
Q

The Resultant Cloned T-cells

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The cloned T cells produced from this response can develop into:

Killer T-cells (Tc)- Directly destroy infected cells by attaching to the antigens on the cell surface membrane. Killer T-cells can destroy cells by releasing toxic substances such as hydrogen peroxide or nitric acid, or through a protein perforin which creates holes in the cell membrane causing lysis

Helper T-cells (Th)- When T helper cells are activated they release hormone-like cytokines that stimulate appropriate B cells to divide, develop into plasma cells and secrete antibodies. They also release and attach opsonins to pathogens which marks them to get the attention of phagocytes. They secrete proteins (interferon) which helps limit the ability of viruses to replicate

Suppressor T-cells (Ts)- Suppresses the immune response of other immune cells. They “switch off” immune responses after invading microbes and infected cells have been destroyed. Also prevents autoimmune response (when the body attack ‘self’ cells in the body)

Memory T-cells (Tm)-Remain in the body fluid and respond quickly to future infections by the same pathogen

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22
Q

Summary

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23
Q

Summary of Immune Response Involving B and T cells

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24
Q

Active and Passive Immunity

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There are 2 basic types of immunity, active and passive. In addition both types may be acquired naturally or artificially.

Active Immunity occurs when the body produces its own antibodies to a particular antigen.
-Natural active immunity occurs as a results of having an infection which causes the primary immune response (T cells and antibodies produced by plasma cells) and the production of memory cells (T and B cells). Further contact does not cause disease because memory cells respond quickly enough and produce antibodies. This type of immunity is very effective and may last for life, however, it does involve suffering from the disease the first time.
-Artificial active immunity (immunisation). Small amounts of a weakened form of the pathogen are injected into a person in a way that largely avoids the individual becoming ill. The antigen present present stimulates the primary response and the production of memory cells. The immune system is tricked into responding as if it is a real infection. Different types of vaccine include living pathogens that have been treated so they are safe (eg tetanus) or just extracted antigen (eg hepatitis B). A booster injection can be given which is similar to a secondary response. Long term immunity can be achieved due to the production of memory cells.

Passive Immunity occurs when the body receives antibodies from someone else and therefore doesn’t make its own antibodies. This gives immediate protection, however, the protection does not last very long because the antibodies break down and aren’t replaced as there are no memory cells for the body to then produce more of these specific antibodies.
-Passive immunity may be gained naturally when antibodies are made by a mother and cross the placenta to the foetus, the baby also receives antibodies in the first breast milk in the colostrum. The mother supplies antibodies that she has produced during her lifetime to disease which she has come in co tact with. Both the antibodies passed in the placenta and the colostrum provide the baby with some protection until it’s own immune system matures.
-In artificial passive immunity, antibodies are obtained from another person and are injected to give immediate protection or to give rapid help in treating the condition. An example would be the injection of tetanus antibodies after some wounds to prevent the disease developing. Sources of ready made antibodies for transfer include; from individuals recovering from an infection or from another mammal which has produced antibodies as a results of an inoculation , eg snake venom when introduced to mammals causes the production of antibodies. The serum from these mammals which contains the antibodies can be injected into a snakebite victim. (These methods have been superseded by monoclonal antibody production).

Note:
*Serum is blood plasm without clotting factors

Definitions:
- Active immunity is when the body produces its own antibodies and memory cells
-Passive immunity is the donation of antibodies from a different source

25
Q

Summary of the Types of Immunity

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26
Q

Comparison of Different Types of Immunity

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27
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28
Q

Monoclonal Antibodies
-Involving B lymphocytes

A

The removal of sensitised B lymphocytes from a mouse that has been infected with a specific antigen. The B cells (short lived) are hybridised with cancer cells (long lived and rapidly cloned) to produce cells that can produce the required antibody in a fur enter in a commercial setting.

Advantages:
-Produced in large quantities
-Can produce a single type of antibody

29
Q

Monoclonal Antibody Production

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30
Q

Transplanting Tissue

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The Stages of Transplant Rejection:

• T lymphocytes are sensitised by the non self antigen on the transplant cells

•In response the T cells will clone to produce killer T cells which destroy the transplanted cells

3 Strategies for Reducing Transplant Rejection:

1.Tissue Typing
A match between donor and recipient antigens is looked for so that there is a small difference in self and non-self. Close relatives are a good source while an identical twin is the best source.

  1. Immunosuppression Techniques
    This involves weakening the immune system using drugs that reduce DNA replication, therefore reduce the chance of lymphocytes cloning. This will limit the production of Killer T-cells.
    These drugs would have to be taken for life to prevent future rejection. The disadvantage to this strategy is that it will compromise the immune system therefore making the recipient susceptible to every day diseases and infections.
  2. X-rays
    This inhibits the production of lymphocytes through ration of bone marrow and lymph tissue.
    Bad side effects include sickness and hair loss.
31
Q

ABO Blood Grouping

A

ABO Blood Grouping
• The ABO system of blood grouping is based upon two different antigens- A and B found on the surface of RBC
• There are also two different antibodies, a and b which are found in the blood plasma
• If antibody a comes into contact with antigen A then it causes the red blood cells carrying antigen A to agglutinate. This also happens if antibody b comes into contact with antigen B

The ABO group of a person is determined genetically. In addition, unlike other antibodies, antibodies a and b are not produced in response to an antigen rather they are present in the blood at all times.

Note:
Agglutination is very dangerous as it can cause blockage in capillaries and blood vessels, and muscles won’t receive the oxygen they require.

32
Q

Which Antigen do the Blood Groups Contain?

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33
Q

Which Antibody do the Blood Groups Contain?

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34
Q

Note on Blood Groups Antigen- Antibody content

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35
Q

The ABO Blood Groups Table

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36
Q

Blood Transfusion

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• Blood group information becomes vital when blood needs to be transfused (donated) from one person to another, e.g. after loss of blood. The wrong combination of donor’s and recipient’s blood could kill the recipient due to agglutination (the blood or oxygen supply can become blocked).

•The recipient’s blood is checked carefully before the transfusion.

•When a blood transfusion is given, it is the type of red blood cell, with their particular antigens, that is crucial. YOU CANNOT RECEIVE A FOREIGN ANTIGEN. THE RECIPIENT MUST NOT HAVE ANTIBODIES THAT MATCH THE DONATED ANTIGENS.

Note:
Blood group O is the universal donor as it doesn’t have any antigens on its cell surface

Blood group A is the universal recipient as it doesn’t have any antibodies in its plasma

37
Q

Blood Transfusion Table

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38
Q

How Blood Groups are Tested

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39
Q

Rhesus Systems

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• The rhesus system involves an antigen other than antigen A or B, sometimes called antigen D or rhesus antigen. This antigen is also found on the cell surface membrane of erythrocytes.

• If an individual possesses this antigen, they are said to be rhesus positive (Rh+). If someone does not possess the antigen, they are rhesus negative (Rh-).

• There are no naturally occurring antibodies to the rhesus antigen in the blood of a Rh- person but an immune response will be triggered if Rh+ blood is given to a Rh- person and they will produce anti-D (anti-rhesus) antibodies.

40
Q

Rhesus Factors and Pregnancy

A

• There is a potential problem if a foetus is Rh+ and the mother is Rh- because at the end of pregnancy and during birth, foetal cell fragments (containing antigen D) can pass
across
to the mother.

• In this event, the mother’s blood will be triggered to produce anti-D antibody (the rhesus antibody).

• Like all antibodies, these can pass across the placenta to the foetus. However, the production of the antibodies and the passing of them across the placenta takes time and as cell fragments will only pass to the mother at the end of pregnancy, the foetus will not be affected.

• The problem arises during subsequent pregnancies. Because the mother’s immune response has been triggered, her blood will contain rhesus antibodies and memory cells. Another pregnancy involving a Rh+ foetus will produce a much faster secondary response. The rhesus antibodies will be produced very quickly and in large numbers and can pass to the foetus before it is born, breaking down it’s red blood cells which will be fatal to the foetus without several foetal blood transfusions.

• This potential problem is now easily dealt with: After the birth of the first Rh+ baby, a Rh- mother receives donor anti-D antibodies at around 30 weeks (i.e. passive immunity). These antibodies destroy the foetal cell fragments before the mothercan make her own antibodies actively. This means that no memory cells are made and so the next Rh+ pregnancy will not be affected.

Note:
-Once baby is born she gets another dose 72hrs after birth

  • Anti-D antibodies could also be produced in a Rh- individual if there was a blood transfusion error where an Rh- individual is given Rh+ blood.
41
Q

Antibiotic Resistance

A

What are Antibiotics?
•Antibiotics are drugs that are developed to kill bacteria.

How do Antibiotics stop Bacterial Growth?
•They disrupt cell wall formation by inhibiting an enzyme involved in the process. The bacteria are killed as the cell bursts by lysis as it cannot resist the osmotic pressure due to it’s weakened cell wall. Penicillin works in this way.
•They inhibit metabolic processes including protein synthesis, for example, erythromycin destroys the ribosomes in prokaryotic cells.

How does Antibiotic Resistance occur?
•Bacteria are antibiotic resistant when one or more antibiotics no longer have an effect
•Mutations in the bacterial genome lead to metabolic changes that results in antibiotics no longer being effective. As bacteria can reproduce v. rapidly by binary fission, one resistant bacterium can rapidly results in a large population of antibiotic resistant bacteria

How do Bacteria get Antibiotic Resistant Genes from Other Bacteria?
•Transformation- ‘Jumping Genes’

How are some Bacteria not Destroyed by Antibiotics?
•They can prevent antibiotics from getting to its target by changing the permeability of the membrane
•They can change the tragedy to antibiotics no longer recognise and attach
•Produce enzymes to destroy target

42
Q

Antimicrobial

A

An antimicrobial is an agent that kills microorganisms or stops their growth, they include: disinfectants, antiseptics, antibiotics, antibacterial, antifungals and antivirals.

The recent rise of antibiotic resistance has increased the need to find or produce new antibiotics. Plants have natural antimicrobial properties. One of the many concerns regarding the destruction of rainforests, include the loss of unknown species of plant which may have important antimicrobial properties.

43
Q

Factors Affecting Disease Spread

A

Factors include:
1. How easily it spreads from one person to another
2. How likely someone will fall sick to a disease once infected
3. If there is a vaccine
4. The % uptake of the vaccination
5. The bacterial resistance to antibiotics

A disease outbreak is the occurrence of cases of disease in excess of what would normally be expected in a defined community, geographical area or season.
An outbreak may occur in a restricted geographical area, or may extend over several countries. It may last for a few days or weeks, or for several years.

Pandemic:
Spread rapidly in a small region at higher levels than normal

Pandemics:
Affecting many thousands of people or several countries at the same time

44
Q

Viruses

A

Most major epidemics and pandemics are caused by viruses.

There are many factors that make viruses the more likely casual agents of widespread infections. These include:

1) Viruses have very small genomes prone to mutation

2) Many are retroviruses with RNA genome. Less stable than those with a genome as DNA

3) Antibiotics are not effective against viruses

Influenza, SARS, rabies and Ebola are all caused by viruses with RNA as the genetic material. It is thought that AIDS (arising from HIV infection) has been responsible for 30 million plus deaths over the last few decades. The ‘Spanish’ flu virus killed between 30-50 million people in a worldwide pandemic in 1918-1919.

45
Q

HIV/AIDS

A

HIV/AIDS

• The virus that causes HIV is a retrovirus (converts its RNA to DNA in host cells)

• Infection of the HIV virus leads to a weakened immune system

• This eventually leads to the patient suffering from one or more of the diseases associated with AIDS (e.g. pneumonia, TB, some cancers)

HIV positive is a term used to describe someone infected with the HIV virus (i.e. they produce antibodies to the antigen of the virus)

• The HIV virus is thought to have mutated from a similar virus (SIV) that causes the same type of immunodeficiency in chimpanzees that HIV does in humans

• The virus transferred to humans in the early 1900s in central Africa possibly through a human being bitten by a chimp or through handling chimp meat

• For decades AIDS was restricted to isolated pockets in central Africa

• AIDS spread to western populations in the 1980s mainly because of globalisation, increased use of air travel and the development of a more casual approach to sex in many societies.

• Until recently it has been very difficult to produce drugs to treat this virus. It meets many of the criteria associated with disease-causing microbes that can potentially cause epidemics or pandemics, i.e. it is an unstable retrovirus that has a high rate of mutation, it is not controlled by antibiotics, it cannot be vaccinated against.

• New antiretroviral drug treatments have significantly reduced death rates from HIV, greatly extending the life expectancy of patients with the condition.

46
Q

Animals as Reservoirs of Disease-Causing Viruses

A

Before crossing over into humans the SIV virus had almost certainly co-existed with its primate hosts for a very long time. Animal species that harbour viruses that subsequently cause disease in humans are described as reservoirs for that virus. Reservoirs species are not vectors as they are not adapted to transfer the pathogen to another species; if a transfer occurs, it is usually a chance event. Terms such as ‘bird flu’ and ‘swine flu’ give a clue to the reservoir origins of the viruses responsible for causing these conditions.

There are many examples of viruses transferring from other animal species to humans and then causing epidemics and pandemics. A range of bat species have had a very significant role in this inter-species spread. Bats are reservoirs for the viruses that cause Marburg, SARS and Nipah and are an initial reservoir for rabies before its transfer into dogs and then into humans.

Bats make suitable reservoirs for disease causing pathogens that subsequently infect humans because:

1) They are mammals and therefore have similar physiology to humans

2) Social animals/ are in close contact with large numbers of other bats. Increasing the possibility of cross infection

3) Can fly large ranges and therefore are potentially in contact with other organisms considerable distances from their base

Urbanisation and the clearing of woodland for housing and agriculture has resulted in humans interfering with habitats frequented by bats. This has led to an increase in the inter species transfer of some viruses from bats to humans in recent decades.

47
Q

Diagnosing Infection

A

Earlier and more accurate diagnosis of infection can lead to more effective treatment at an earlier stage of disease progression. The use of ELISA techniques and the detection of cytokines as biomarkers are examples of recent development in this area of medicine.

ELISA (Enzyme-linked immunosorbent assay)
This is a lab technique that uses antibodies, enzymes and
other molecules as biomarkers to detect the presence of particular molecules in the body.
Body fluids from a patient are added to a number of wells on a plate and a range of antibodies are added to these wells. Reactions between antibodies and antigens trigger an enzyme linked to the antibody into causing a colour change thus identifying the antigens or other molecules present.

ELISA diagnostic kits can be used to detect:
Pathogens in the body/Disecs testing
Cancer cell markers
Cardiac disease markers
Pregnancy (in home pregnancy kits)

They have the advantage of enabling early, rapid screening and can provide a wide range of diagnostic feedback from the one test.

Pregnancy testing - Following the implantation of an egg in the uterine wall, increased levels of the hormone hG can be detected in the blood or urine. In a pregnancy test, hG antigens are detected by complementary hG (monoclonal) antibodies immobilised on the ELISA plate. The formation of this antigen-antibody complex results in a linked enzyme reacting to produce the characteristic colour change associated with pregnancy kits.

Testing for viral pathogens- An ELISA plate impregnated with viral antigens is coated with blood serum from the patient. If the patient’s blood contains complementary antibodies (evidence of infection), then the antigen-antibody complex triggers an enzyme reaction that leads to a colour change.

What are Cytokines?
Cytokines are chemicals released by T-helper and other cells as part of the immune response during infection. They are small proteins that help coordinate the immune response. They can be found in the blood and are used as biomarkers to identify a number of conditions including TB and rheumatoid arthritis.

48
Q

ELISA

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49
Q

Definitions

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50
Q

Bio Fact Sheet

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51
Q

Bio Fact Sheet (next page)

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52
Q

Lymphocytes Fact Sheet

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53
Q

Lymphocytes Fact Sheet (next page)

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54
Q

The Immune System Overview

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