Cells (Immunity) - Antigens and Self Tolerance

Question 1

What is an infection?

Answer 1

Any infection is an interaction between the pathogen and the body’s various defence mechanisms. Sometimes the pathogen overwhelms the defences and the individual dies. Sometimes the body’s defence mechanisms overwhelm the pathogen and the individual recovers from the disease.

Question 2

What is immunity?

Answer 2

Having overwhelmed the pathogen, however, the body’s defences seem to be better prepared for a second infection from the same pathogen and can kill it before it can cause any harm. This is known as immunity and is the main reason why some people are unaffected by certain pathogens.

Question 3

What are defence mechanisms?

Answer 3

The human body has a range of defences to protect itself from pathogens. Some are general and immediate defences whereas others are more specific, less rapid but longer-lasting. These responses involve a type of white blood cell called a lymphocyte.

Question 4

How does the body distinguish its own cells from foreign material?

Answer 4

To defend the body from invasion by foreign material, lymphocytes must be able to distinguish the body’s own cells and molecules (self) from those that are foreign (non-self). If they could not do this, the lymphocytes would destroy the organism’s own tissues.

In the fetus, the lymphocytes are constantly colliding almost exclusively with the body’s own material. These lymphocytes are destroyed or suppressed so that the only remaining lymphocytes are those which recognise foreign material.

Each type of cell, self or non-self, has specific molecules on its surface that identify it. While these molecules can be of a variety of types, it is the proteins that are the most important. This is because proteins have enormous variety and a highly specific tertiary structure. It is this variety of specific 3D structure that distinguishes one cell from another.

Question 5

What do antigens allow the immune system to identify?

Answer 5

• pathogens
• non-self material such as cells from other organisms of the same species
• toxins including those produced by certain pathogens
• abnormal body cells such as cancer cells

Question 6

What are the disadvantages of this response?

Answer 6

Although this response is clearly advantageous to the organism, it has implications for humans who have had tissue or organ transplants. The immune system recognises these as non-self even though they have come from individuals of the same species. It therefore attempts to destroy the transplant.

Question 7

How can you minimise the effect of tissue rejection?

Answer 7

Donor tissues for transplant are normally matches as closely as possible to those of the recipient. The best matches often come from relatives that are genetically close as they share similar antigens. In addition, immunosuppressant drugs are often administered to reduce the level of the immune response that still occurs.

Question 8

How many types of lymphocytes are there? What is clonal selection?

Answer 8

Specific lymphocytes are not produced in response to an infection, they already exist - all ten million different types. Given that there are so many different types of lymphocytes, there is a high probability that, when a pathogen gets into the body, one of these lymphocytes will have a protein on its surface that is complementary to one of the proteins of the pathogen. With so many different lymphocytes, there are very few of each type.

When an infection occurs, the one type already present that has the complementary proteins to those of the pathogen is stimulated to divide to built up its numbers to a level where it can be effective in destroying it. This is called clonal selection, and explains why there is a time lag between exposure to the pathogen and body’s defences bringing it under control.

Question 9

What is a non-specific defence mechanism?

Answer 9

Response is immediate and the same for all pathogens.

• physical barrier
• phagocytosis

Question 10

What is a specific defence mechanism?

Answer 10

Response is slower and specific to each pathogen.

• cell-mediated response (T lymphocytes)
• humoral response (B lymphocytes)

Question 11

How do lymphocytes recognise cells belonging to the body?

Answer 11

• There are probably around ten million different lymphocytes present at any time, each capable of recognising 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, in particular, the placenta.
• Lymphocytes will therefore collide almost exclusively with the body’s own material (self).
• Some of the lymphocytes will have receptors that exactly fit those of the body’s own cells.
• These lymphocytes either die or are suppressed.
• The only remaining lymphocytes are those that might fit foreign material (non-self), and therefore only respond to foreign material.
• In adults, lymphocytes produced in the bone marrow initially only encounter self-antigens.
• Any lymphocytes that show an immune response to these self-antigens undergo programmed cell death (apoptosis) before they can differentiate into mature lymphocytes.
• No clones of these anti-self lymphocytes will appear in the blood, leaving only those that might respond to non-self antigens.

Question 12

What is health?

Answer 12

A state of complete physical, mental and social well-being and not merely the absence of disease or infirmity.

Question 13

What is disease?

Answer 13

A description of symptoms which suggest a malfunction of body or mind.

Question 14

What is a pathogen?

Answer 14

A microorganism that causes disease.

Question 15

What are the different types of pathogens?

Answer 15

• bacteria
• virus
• fungi
• protist/plasmodium

Question 16

What is the difference between epidemics and pandemics?

Answer 16

Epidemic - widespread outbreaks of disease

Pandemic - epidemics that spread internationally

Question 17

What are some examples of barriers to disease?

Answer 17

• epidermis of skin: layers of dead cells prevent invasion (skin is a tough physical barrier consisting of keratin)
• mucus membranes: protective mucus layer secreted by goblet cells (invaders get trapped in the mucus)
• ciliated epithelia: sweeps invaders away so they can be removed, e.g. in the lung
• gut and skin flora: natural bacterial flora competes with pathogens for food and space
• hydrochloric acid in stomach: low pH so the enzymes of pathogens are denatured

Question 18

What is a problem with barriers?

Answer 18

Some pathogens can penetrate barriers:

• malaria is caused by Plasmodium, which passes through the skin when a mosquito bites
• bubonic plaque enters the skin through flea bites
• influenza virus passes through lining of trachea and lungs

Question 19

How do pathogens cause disease?

Answer 19

Bacteria and Fungi:

1. damaging cells by releasing digestive enzymes
2. damaging cells by releasing toxins

Question 20

Why do we feel ill?

Answer 20

Pathogens colonise and reproduce in tissue and body fluids causing:

• Physical damage to cell structure
• Disruption of cell metabolism and function
• Release of toxins
• Stimulation of the body’s immune system

Question 21

What are the two types of toxins?

Answer 21

Exotoxins – secreted by or leak from bacteria.

Endotoxins – complex compounds released when bacterial cell dies.

Question 22

What is an antigen?

Answer 22

Any part of an organism (often a protein on the surface of a cell) that is recognised as foreign by our immune system.

Question 23

Give an example of a bacterial disease.

Answer 23

An example of a bacterial disease is tuberculosis. TB is caused by a bacteria which infects phagocytes in the lungs. The first infection is symptomless as the infected phagocytes are sealed in tubercles as a result of inflammatory response in the lungs.

However, the bacteria lie dormant inside the tubercles as they are not destroyed by the immune system due to the tubercles being covered with a thick waxy coat. When the immune system becomes weakened, the bacteria become active again and slowly destroy the lung tissue thus leading to breathing problems, coughing, weight loss as well as fever. TB can potentially lead to death.

Question 24

Given an example of a viral infection.

Answer 24

An example of a viral infection is HIV which causes AIDS. The first symptoms of HIV include fevers, tiredness and headaches. After several weeks HIV antibodies appear in blood thus making a person HIV positive. After this period, the symptoms disappear until the immune system becomes weakened again thus leading to AIDS. Symptoms of AIDS include weight loss, diarrhoea, dementia, cancers and opportunistic infections such as TB.

Question 25

What is lysozyme action?

Answer 25

Lysozyme are enzymes found in secretions such as tears and mucus which kill bacterial cells by damaging their cell wall.

Question 26

What is interferon?

Answer 26

Interferons prevent viruses spreading to uninfected cells by stopping protein synthesis in viruses.

Question 27

What is phagocytosis?

Answer 27

A process in which white white blood cells engulf pathogens thus destroying them. They do this by fusing to a pathogen and enclose them in a phagocytic vacuole with a lysosome. After the pathogen is engulfed and destroyed, its chemical markers called antigens are then presented on the surface of the phagocyte. The phagocyte then becomes an antigen presenting cell which activates an immune response if the antigen is recognised as foreign.

Question 28

Why doesn’t the body develop long-term immunity against the flu?

Answer 28

• Antigen proteins change: antigenic variability.

Antigenic drift: mutation of DNA (frequent small changes)
Antigenic shift: mixing of DNA between different strains (rare large changes leading to epidemics)

• If the shape of the antigen changes then the person will no longer be immune to that strain.

Question 29

What is the difference between active immunity and passive immunity?

Answer 29

Active Immunity:

• requires exposure to antigen
• it takes a while for protection to develop
• memory cells are produced
• protection is long-term because the antibody is produced (after activated memory cells) in response to complementary antigen being present in the body

Passive Immunity:

• does not require exposure to antigen
• protection is immediate
• memory cells are not produced
• protection is short-term because the antibodies given are broken down

Question 30

What is actively acquired immunity?

Answer 30

Actively acquired immunity is when an individual develops immunity to a specific antigen due to exposure to it. Memory cells are formed which provide long term immunity to that antigen. This type of immunity may develop as a result of accidental exposure to the antigen during infection, or by deliberate exposure to the antigen during vaccination. Because second and even third exposures to antigens will cause even larger populations of memory cells to form and much higher levels of circulating antibodies to be produced, vaccinations are often repeated (booster vaccinations).

The time scale for vaccinations and for the persistence of immunity varies according to the antigen involved.

Question 31

What is passively acquired immunity?

Answer 31

Passively acquired immunity is when an individual becomes immune to an antigen due to receiving ready-made antibodies against the antigen or an infusion of actual activated immune cells from a compatible donor. For instance, antibodies from the mother may pass to the foetus via the placenta. The antibodies will only persist in the baby for a few weeks and so this type of immunity is short term. People who have possibly been exposed to tetanus spored are given antibodies to protect them in case their own acquired immunity has weakened if booster immunizations have been missed. Passive immunity in the form of antibodies is also given to people who have been bitten by rabid dogs, to prevent the development of rabies.

Question 32

What is non-specific resistance?

Answer 32

Unlike the development of immunity, which is specific to particular antigens, non-specific resistance is inherited and consists of a wide variety of body reactions which provide a general response against invasion.

Question 33

What is the function of phagocytosis?

Answer 33

Ingestion and digestion of foreign particles/microbes by neutrophils, eosinophils, monocytes and macrophages.

Question 34

Why do we get fevers?

Answer 34

Raised body temperature inhibits microbial enzymes and growth, and speeds up the processes of repair.

Question 35

What are some primary defence mechanisms?

Answer 35

1. Skin
   - The skin forms a physical barrier (made of dead cells) stopping pathogens entering the blood.
   - Keratin strengthens this barrier.
   - The chemical defence is the secretion of antimicrobial fluid (sebum) on to the surface of the skin.
2. Mucous Membranes
   - Exposed parts of the body are at risk of pathogen entry.
   - Goblet cells secrete mucous, which traps pathogens.
   - Ciliated cells sweep pathogens back out.
3. Innate Immune System Cells
   - Cells of the innate immune system can be found in many areas: exposed areas of the body near mucous membranes, and deep inside tissues.
   - Cells of the innate immune system can travel the body via the lymphatic system.
   - This has vessels that extend throughout the body.

Question 36

What are neutrophils?

Answer 36

• They are found in blood and tissue fluid.
• They are the more common phagocyte out of the two.
• Neutrophils are made in the bone marrow, and reside in blood and tissue fluid.
• They are short-acting and initiate the immediate response.

Question 37

What are macrophages?

Answer 37

• They are found in blood and lymph nodes.
• They are bigger than neutrophils.
• They develop in lymph nodes, and are made in bone marrow.
• Macrophages are involved in the adaptive, specific immune response.

Question 38

How does the immune system work?

Answer 38

• The immune system works through a system of recognition mechanisms.
• It can distinguish between native cells (self) from pathogens (foreign bodies), and eliminates these pathogens.

Question 39

What is the innate immune system?

Answer 39

• Line of defence: First line.
• Specificity: It is non-specific, so is a general mechanism of defence against disease causing threats to an organism.
• Cells involved: Involves lymphocytes, which break down pathogens via phagocytosis.

Question 40

What is the adaptive immune system?

Answer 40

• Line of defence: Second line.
• Specificity: It is a long term, highly specific and targeted response against a particular pathogen.
• Cells involved: It involves antibodies, B cells and T cells.

Question 41

What are autoimmune disorders?

Answer 41

• The immune system does not want to attack the body’s own native cells (self), as it can lead to autoimmune diseases.
• Autoimmune disorders are caused when the body’s own immune system destroys its own tissues.
• These autoimmune disorders can often be fatal for an organism.
• They can be acute or chronic.

They can be:

• long term treatable diseases, i.e. type 1 diabetes.
• sudden and lead to rapid deterioration of the organism.

Question 42

What is clonal deletion?

Answer 42

Deleting any immune cells that respond to self-antigens.

Question 43

What is central tolerance?

Answer 43

• During maturation, all B-cells and T-cells travel through a tissue matrix containing all the self-antigens that can be found in the body.
• If a T-cell or a B-cell reacts with any self-antigen, it is killed off via apoptosis.
• This overall process is clonal deletion.
• It leaves immune cells which do not respond to self-antigens.

Question 44

What is peripheral tolerance?

Answer 44

• It is very similar to central tolerance but occurs when the T-cells and B-cells are still immature.
• Clonal deletion removes immature T-cells and B-cells which respond to self-antigens.

Question 45

Which lymphocytes are destroyed?

Answer 45

Any lymphocytes which have a very high affinity for self-cells are destroyed.

Question 46

What is clonal anergy?

Answer 46

Activating any immune cells that bypass clonal deletion.