Immunity

Applications of Biology

Immunology

Immunity

• This refers to the body’s ability to defend itself against diseases.

• Immunity is provided by the immune system. • The immune system recognizes foreign

material and produces chemicals to destroy it.

• The defence provided by the immune system can be physical, chemical and cellular.

Immunity con’t

• Physical defence includes clotting • Cellular defence includes the barrier created

by epithelia and white blood cells. • Chemical defence include the secretion of

hydrochloric acid to destroy pathogens. • White blood cells play a very important role in

the immune system.

Immunity con’t

• An antigen is a molecule which the body recognizes as foreign.

• Antigens have on their surfaces, large molecules such as proteins, glycoproteins, lipids and polysaccharides.

• White blood cells are able to recognize antigens.

White blood cells

• White blood cells originate in the bone marrow.

• The two main groups involved in defence are phagocytes and lymphocytes.

• Phagocytes can be further classified into neutrophils and macrophages.

Phagocytes

• These are made throughout a person’s lifetime in the bone marrow.

• They are stored in the bone marrow before they are distributed around the body.

• Phagocytes act as scavengers by removing dead cells as well as invasive microorganisms.

Neutrophils

• Approximately 60% of white blood cells are neutrophils.

• They are transported by the blood throughout the body.

• They are often squeezed through the walls of the capillaries (by a process known as diapedesis) to ‘patrol’ the tissues.

Neutrophils con’t

• They are short lived cells and are produced in large amounts during an infection.

Macrophages

• These are larger than neutrophils. • They are usually found in organs such as the

lungs, liver, spleen, kidney and in the lymph nodes.

• They are made in the bone marrow and travel in the blood as monocytes.

• Monocytes develop into macrophages once they settle in the organs.

Macrophages con’t

• Macrophages are long-lived.• They cut up pathogens displaying their

antigens so they can be easily recognized by lymphocytes.

• They therefore play a major role in initiating immune response.

Phagocytosis

• Cells that are being attacked by pathogens produce histamine

• Mast cells are body cells that produce histamine and cause inflammation (see later)

• The pathogens also release chemicals. • These chemicals from the pathogens along

with the histamine attract passing neutrophils to the site of infection.

Phagocytosis con’t

• Neutrophils have receptor proteins (opsonins) on their surfaces which allow them to recognise antibodies and chemicals produced by the bacteria.

• The pathogens may be clumped together and covered in antibodies (secreted by lymphocytes) which would also help to stimulate action by the neutrophils.


• The neutrophils move towards the pathogens and binds with the bacterium.

• The binding stimulates the formation of a pseudopodia and the formation of a vacuole called a phagosome.

• Lytic enzymes are released by lysozomes into the phagosome which break down the bacterium.


• Dead neutrophils collect as a site of infection as pus. (See handout for illustration. Make sure you can illustrate what is there)

• The histamine released by mast cells cause dilation of blood vessels making them leak.

• Plasma and white blood cells flow out into the infected area.


• Pus is formed from dead bacteria and white blood cells (mainly phagocytes).

• The inflamed area thus becomes red, hot and swollen.

• Sometimes a boil is formed which might eventually burst because of the pressure of the pus inside.


• Phagocytosis is enhanced by a group of blood proteins called complement.

• Complement proteins are made by macrophages, monocytes and other cells in the body especially those in the liver.

• They are usually inactive. • When necessary they stick to invading micro-

organisms (mainly yeasts and bacteria)


making them conspicuous to phagocytes as foreign matter.

• Some destroy the membranes of bacteria.

Lymphocytes

• These are smaller than phagocytes and have a large nucleus that fills most of the cell.

• There are two types:1.B lymphocytes2.T lymphocytes

Origin and maturation of B lymphocytes

• As you already know, B cells are made in the bone marrow.

• Here the immature B cells divide by mitosis.• Each B cell is specific to an antigen. • It therefore means that many millions of B cell

types exist in our bodies. • During maturation, each B cell produces

antibodies.

Origin and maturation of B lymphocytes con’t

• The genes that code for antibodies change in a variety of ways to code for different antibodies during maturation.

• Each B cell then divides to give a small number of clones that are able to make the same antibodies.


• The antibodies formed during maturation of the B cells do not leave the cell.

• Rather, they form part of the plasma membrane.

• A part of each antibody forms a protein receptor.

• This receptor can combine with one type of antigen.


• If that antigen enters the body, there will be some mature B cells with cell surface receptors that recognise it. (See hand out for diagram. Make sure you can illustrate what is there)

Action of B lymphocytes

• When pathogens enters the body for the first time, some of them are take up by macrophages (in lymph node etc).

• The macrophages expose the antigens from the pathogens on their surfaces.

• Any B lymphocyte that has cell surface receptors that are specific to the antigens exposed divide repeatedly my mitosis.

Action of B lymphocytes con’t

• Within a few weeks, a huge number of identical B cells are produced.

• Some pathogens have more than one antigen on their surface.

• This means that several B cells are activated on entry of the pathogen.

• As each type B cell divides, a polyclone is formed (each type forms a clone)


• Some of these B cells become plasma cells.• Others become memory cells. • Plasma cells are short lived. • They produce antibody molecules very quickly

(up to several thousand per second)


• The antibody molecules are released into the blood, lymph or onto the linings of the gut or lungs.

• The antibody molecules last longer than the plasma cells. However, their concentrations eventually decrease.


• The memory cells remain in circulation within the body for a very long time.

• If the same pathogen enters the body again, they divide rapidly forming more plasma cells and memory cells.

• This response occurs every subsequent time the pathogen enters the body.


• Thus the pathogen is prevented from causing a disease. (See diagram on hand out – ensure you are able to illustrate what is there)

• The immunity offered by B lymphocytes is called humoral immunity.

• This is because antibodies are produced and transported in body fluids (blood and lymph)

Primary and secondary responses

• When the body encounters an antigen for the first time, the response is slow because there are a few B cells that are specific to the particular antigen.

• This first response is called a primary response.

• During this response, the body experiences symptoms of the disease.

Primary and secondary responses con’t

• When the pathogen tries to enter the body again, the response is much faster.

• This is because there are many memory cells which divide quickly to give plasma cells. Thus more antibodies are produced.

Primary and secondary responses con’t

• This is called a secondary response. The body does not experience symptoms of the disease.

• Memory cells are the basis for immunological memory. (See graph on handout – be able to illustrate what is there)

Antibodies

• So we’ve been talking about antibodies being produced by B lymphocytes.

• What really are antibodies?• They are globular glycoproteins and form the

group of plasma proteins called immunoglobulins.

• All antibodies has a basic strucure.

Structure of an antibody

http://tinyurl.com/77oeght

Antibodies con’t

• All are made up of 4 polypeptide chains: two long or heavy chains and two short or light chains.

• The chains are held together by disulphide bridges.

• Each antibody molecule has two identical binding sites formed by both light and heavy chains.

Antibodies con’t

• The sequence of amino acids form a specific three-dimensional shape which binds to only one type of antigen.

• This is called the variable region and varies for different antibodies.

• There is a hinge region formed between the two heavy chains.

• This provides flexibility.

Antibodies con’t

• Antibodies work in different ways. • Their actions can be summarized into four

groups;1. Agglutination – antibodies have two binding

sites. They can therefore bind to antigens on two different pathogens. This can result in pathogens being clumped together making them more vulnerable to attack.

Antibodies con’t

2. Precipitation – some antigens are soluble. Some antibodies bind them together into large units which are then precipitated out of solution. This way they are more easily digested by phagocytes.

3. Neutralization – some antibodies bind to toxins released by pathogens preventing harm.

Antibodies con’t

4. Lysis – when some antibodies attach to a pathogen, they act as a binding site for a number of blood proteins (complement system). Some of these proteins are enzymes and cause breakdown of the pathogen.

• Immunoglobulin E (IgE) binds to the receptors of mast cells activating them to release histamine.

Origin and maturation of T lymphocytes

• As you already know, T lymphocytes are made in the bone marrow.

• Here the immature T cells dived by mitosis. • They then travel to the thymus gland where

they mature. • They develop specific receptors which are

displayed in the plasma membrane.

Origin and maturation of T lymphocytes con’t

• The mature T cells circulate in the body. (see hand out – be able to illustrate)

• Some form T helper cells, some form T cytotoxic cells, some form T suppressor cells and some form memory T cells.

Action of T lymphocytes

• T cells are activated when they recognize an antigen in contact with a host cell. Eg. A macrophage which has cut up a pathogen displaying its antigen (a help signal).

• The T cell with matching receptors divide by mitosis to form a clone.

• The cells differentiate to form several types of cells, the two main types being T helper cells and killer T cells.

Action of T lymphocytes con’t

• Cytokines are secreted by T helper cells when they are activated.

• Cytokines stimulate appropriate B cells to divide and develop plasma cells which secrete antibodies.

• Some secrete cytokines that stimulate macrophages to carry out phagocytosis more vigilantly.


• The cytokines these T cells secrete belong to a group of proteins called lymphokines.

• Another lymphokine is called interferons. These inactivate the protein making machinery of the infected cell. This therefore inhibits the replication of viruses.


• T cytotoxic cells search for body cells that are invaded with pathogens and are displaying the antigens.

• The killer T cells attach themselves to the infected cells and secrete toxic substances such as hydrogen peroxide killing these infected cells and the pathogens. (see handout – be able to illustrate)


• T suppressor cells – these control the immune system. Once an infection has been eliminated, these cells suppress the activities of the lymphocytes.

• T memory cells – these remain in the body and become very active during a secondary response to antigens.

Active and passive immunity

• Active immunity refers to resistance to disease derived by the body producing antibodies on exposure to antigens.

• Active immunity is long term and can be either natural or artificial.

• When pathogens enter the body by natural means (air borne, food borne etc.), B lymphocytes make antibodies to destroy them.

Active and passive immunity con’t

• As you would remember, memory cells are formed which make the body immune the next time the pathogen invades the body.

• This is natural active immunity.• In some cases antigens are injected or taken

orally into the body. • The body then makes antibodies which

protect the body from those antigens.


• Passive immunity refers to resistance to disease that is short lived and is not derived by any action of the body.

• Passive immunity can also be natural or artificial.

• Natural passive immunity is obtained when antibodies pass by natural means into the body.


• Babies have natural passive immunity. • This is a result of antibodies passing across the

placenta from the mother to the foetus. • After birth, the colostrum which the baby

receives is rich in IgA which prevents the growth of bacteria.

• Because immunity is passive it is short lived.


• Depending on the nature of a disease or infection, antibodies may need to be injected into the body.

• If the body were allowed to make its own antibodies, the person would die. Eg. Tetanus.

• This is artificial passive immunity.

Vaccinations

• A vaccine is a preparation of antigenic material designed to stimulate the production of antibodies and develop immunity within the body.

• Immunity derived from exposure to live pathogens is the best but not always realistic.

• Some vaccines are very effective and one injection is sufficient. Some need vaccinations.

Vaccinations con’t

• The materials used in vaccinations can be grouped:

1.Living attenuated organisms – these are pathogens that are treated (for example, using heat) so that they can multiply but are unable to cause the symptoms of the disease. Even though they are harmless, they stimulate the production of antibodies. Eg. Measles, tuberculosis, poliomyelitis


2. Toxoids – the toxins which result from certain diseases can stimulate the body to produce antibodies. These toxins are modified to prevent them causing symptoms of the disease (eg. Treating it with formaldehyde) and then administered by injection. Eg. Diphtheria, tetanus


3. Dead microorganisms – the pathogens are killed and then injected. Even though they are dead, they are able to stimulate the production of antibodies in the same way they would if they were living. Eg. Typhoid, cholera, whooping cough.


4. Extracted antigens – chemicals with antigenic properties are extracted from the pathogens and injected. Eg. Influenza vaccine

5. Artificial antigens – Genetic engineering is used to transfer genes for the production of antigens from the pathogen to a harmless organism. These are grown in a laboratory for the production of antigens which are later used. Eg. Hepatitis B

Problems with vaccines

• Despite the benefits derived from vaccines, there are several problems associated with them.

1. Poor response – due to weakened immune systems or malnourishment some persons do not develop the necessary B and T cell clones. Persons that are vaccinated with live viruses can pass it to others in faeces. Herd immunity is therefore ideal.

Problems with vaccines con’t

• Antigenic variation – when pathogens mutate causing minor changes in the antigens they produce, this is called antigenic drift. Sometimes the memory cells will still recognise them and cause a secondary response. Sometimes there is an antigenic shift where the mutation is so great that there is a drastic change in antigen structure (eg. Influenza). This results in the vaccine being


changed every year. Also, some pathogens are eukaryotes eg. Plasmodium which causes malaria and Trypanosoma which causes sleeping sickness. Being eukaryotes, they have many more genes than viruses and bacteria and can have many hundreds or thousands of antigens (each stage in the life cycle has different antigens). There are therefore no effective vaccines against these diseases.


• Large invaders like nematodes and platyhelminthes of the body are too large to be dealt with by the phagocytes.

Eosinophils produce materials including enzymes that breakdown the body walls of these parasites and protect the body.

Basophils and mast cells produce chemicals like histamine that stimulate action of the immune system.


• Antigenic concealment – some pathogens are able to hide inside body cells before an immune response can be waged. They are ‘protected’ by being in the body cell eg. Plasmodium in red blood cells. Some remain in the intestines eg. Vibrio cholerae where they cannot be reached by antibodies. To combat this oral vaccines have been developed against cholera


Some pathogens parasitize macrophages eg. Myobacterium tuberculosis. Others parasitize T helper cells eg. HIV. These suppress the immune system.

• Recently, there have been concerns about vaccines influencing the development of autism. There have also been concerns about chemicals used to treat pathogens. Eg. Mercury and chloroform

Monoclonal antibodies

• Since B lymphocytes produce specific antibodies, it would be ideal to be able to produce antibodies outside the body.

• Until recently it was difficult to produce pure cultures.

• In 1975 two persons (Cesar Milsten and Georges Kohler) succeeded in producing pure cultures.

Monoclonal antibodies con’t

• They did this by fusing antibody secreting cells with tumour cells.

• The resulting cells are called HYBRIDOMAS. • These hybridomas secrete antibodies and are

considered ‘immortal’. • These hybridoma cells can be cultured as pure

clones and each type of antibody collected.

Monoclonal antibodies con’t

• The antibodies collected this way are called monoclonal antibodies.

Using monoclonal antibodies

1. They can be used to treat a range of infections.

2. They can be used to separate a particular antigen from a complex mixture – to do this the monoclonal antibodies for the required antigen are immobilized on resin beads which are then packed in a column. When the mixture is passed over the beads, only the required antigen is removed.

Using monoclonal antibodies con’t

• The antigen can then be washed from the beads using a chemical which causes the antibodies to release it.

3. They can be used in immunoassays – this is the use of monoclonal antibodies to determine the amount of a particular antigen in a mixture. The antibodies are labelled eg. With radioactive or fluorescent material for easy detection.


• If they are added to a test sample they will attach to their specific antigen. If the sample is washed in a special solution, the unattached antibodies are removed. The amount of antigens in the sample is revealed by the degree of radioactivity or fluorescence.

4. ELISA (Enzyme Linked Immunosorbant Assay) – this is used in athletes drugs tests, pregnancy test kits and HIV tests.


• The antibodies are immobilized and the test solution passed over them. If the antibody is specific for antigen X and X is present in the test solution, it will bind to the antibody. A second set of antibodies with an enzyme attached is added to the solution. It combines with antibody/antigen X complex. If a substrate is added whose colour the enzyme will change , the amount of chemical X can be


determined. 5.Anticancer drugs are linked to monoclonal

antibodies which are attracted to the cancer cells.

6.ADEPT (Antibody Direct Enzyme Prodrug Therapy) – Monoclonal antibodies are tagged with an enzyme which converts an inactive form of the cytotoxic drug (prodrug) into an active form.


• Once injected these antibodies link with the cancer cells. The inactive form of the drug is administered in large doses. It is only effective on the cancer cells.

• Monoclonal antibodies are used in the cancer treatment Mabthera. The active ingredient is rituximab and is used to treat non-Hodgkins lymphoma which is a cancer affecting B cells.


• Rituximab binds to a specific protein on the surface of the affected B lymphocytes stimulating the immune system to get rid of the cancer cells.

Immunity

Health & Medicine

phagocytosis cells

body cells

neutrophils cont

dead cells

immature b cells

phagocytosis cont neutrophils

phagocytosis cont phagocytosis

macrophages cont macrophages