Immunity

• Non-specific--- do  not distinguish between two types of pathogen, but respond to all of them in the same way.
• there are two forms 1) a barrier to the entry of pathogens 2)phagocytosis
• Specific---they are mechanisms that distinguish between types of pathogens. The response is less rapid but it provides long-lasting immunity.
• specific respnses involve white blood cells called lymphocytes.
• it takes two forms 1) cell- mediated response involving T cells. 2)humoral responses involving B cells.  

• lymphocyytes cant distinguish between tghe body's own cells and chemicals and foreign pathogens.
• own cells are known as self and foreign microorgansims are known as non-self.
• if the lymphocytes could not do this they would destroy the organism's own tissues.
• Specific lymphocytes are not produced in response to an infection - they already exist.
• there are around 10 million already existing in the body.
• due to the huge number of lymphocytes there is a high probability that when a foreign pathogen enters the body there will be a lymphocyte that has a protein on its surface that is complementary to an antigen on the surface of the pathogen.
• the lymphocyte 'recognises' the pathogen.
• the lymphocyte is then stimulated to build up its numbers to a l;evel where it can be effective in destroying the pathogen.
• this explains why there is a time lag between exposure to the pathogen and the body's defences bringing it under control.

• A protective covering - the skin covers the body's surface, providsing a ohysical barrier that most pathogens find hard to penetrate.
• Epithelia covered in mucus - many epithelial layers produce mucus, which acts as a further defecne against invasion. In the lungs, pathogens stick to this mucus, which is then transported away by the cilia, up the trachea, to be swallowed into the stomach.
• Hydrochloric acid in the stomach - this provides such a low pH that the enzymes of ,most pathogens are denatured and therefore the organisms are killed.

Some phagocytes travel in the blood but can move out of blood vessels into other tissues.

1) Chemical products of the pathogen act as attractants, causing phagocytes to move towards the pathogen.

2) Phagocytes attach themselves to the surface of the pathogen.

3) They engulf the pathogen to form a vesicle which is known as a phagosome.

4) Lysosomes move towards the phagosome and fuse with it.

5) Enzymes witrhin the lysosomes break down the pathogen. The porcess is the same as that for  the digestion of food in the intestines, namely the hydrolysis of larger, insoluble molecules into  smaller, soluble ones.

6) The soluble products from the breakdown of the pathogens are absorbed into the cytoplasm of the phagocyte. 

Phagocytosis causes inflammation at the site of infection.

This swollen area contains dead pathogens and phagocytes, which are know as pus.

Inflammatrion is the result of the release of histamine, which causes dilation of the blood vessels.

This speeds up the delivery of the phagocyte to the site of infection.

An antigen is any part of an organsim or substance that they body recognises as non-self by the immune system and stimulates an immune response.

Antigens are usualy proteins that are part of the cell-surface membranes or cell-walls of invading cells, such as microorganisms, or diseased cells, such as cancer cells.

The presence of an antigen triggers the production of an antibody as part of the body's defence system.

• B Lymphocytes (B cells) are associated with humoral immunity.
• Immunity involving antibidies that are present in body fluids or 'humour.'
• T lymphocytes (T cells) are associated with cell-mediated immunity.
• Immunity involving body cells.
• Both are formed from stem cells in the bone marrow.
• However B cells mature in the bone marrow.
• T cells mature in the thymus.

T cells respond to an ornganism's own cells that have been invaded by non-self material (e.g. a virus). They also respond to transplanted material, which is genetically different.

They can distinguish these invader cells from normal cells because:

• Phagocytes that have engulfed and broken down a pathogen present some of the pathogen's antigens on their own cell-surface membrane.
• Body cells invaded by a virus present some of the vairal antigens on their own cell- surface membrane as a sign of distress.
• Cancer cells likewise present antigens on their cell-surface membranes.

These cells are called antigen-presenting cells because they can present antigens of other cells on their own cell surface membrane. 

As T cells will only respond to antigens that are attached to a body cell this type of response is called cell-mediated immunity. There are a number of different T lymphocytes. The stages of response of T cells to infection by a pathogen are as follows:

1) Pathogens invade body cells or are taken in by phagocytes.

2) The phagocyte places antigens from the pathogen onto its cell-surface membrane.

3) Receptors on certain T helper cells fit exactly onto these antigens.

4) This activates other T cells to divide rapidly by mitosis and form a clone.

5)  The cloned T cells:

                                   a)develop into memory cells.

                                   b)stimulate phagocytes to engulf pathogens by phagocytosis.

                                   c)stimulate b cells to divide.

                                   d)kill infected cells.

• They do not kill by phagocytosis.
• They produce a protein that makes holes in the cell-surface membrane.
• These holes means that the cell becomes freely permeable to all substanv=ces and dies as a result.
• The action of T cells is tha most effective against viruses because they live inside cells.
• As viruses need living cells in which to reproduce, this sacrifice of the body cells prevents them from multiplying and infecting more cells.

• When an anitgen enters the blood or tissue fluid, there will be one type of B cell that has an antibody on its surface whose shape exactly fits the antigen, they are complementary.
• The antibody therefore attaches to the complementary antigen.
• This type of B cell divides by mitosis to form a clone of Identical B cells which all rpoduce an antibody which is specific to that foreign antigen.
• A typical pathogen has many different antigens on its surface it might also produce toxins which act as antigens. Therefore many different B cells make clones, each of which produces its own antibody that is specfifc to each foreign antigen.

Plasma cells

• Secrete antibodies directly .
• These cells survive for a few days , but each make around 2000 antibodies each second.
• These antibodies destroy the pathogen and any toxins it produces.
• Theses plasma cells are therefore responsible for the immediate defence of the body against inffection.
• This is known as the primary immune response.

Memory cells

• Often live for decades.
• They do not produce antibodies directly, but circulate in the blood and body fluid. When they encounter the same antigen but at a later date they divide rapidly and develop into plasma and memory cells.
• The plasma cells produce the antibodies needed to destroy the pathogen while the new memory cells circulate in readiness for future infection.
• Memory cells provide long lasting immunity against the original infection. This is known as the secondary immune response.
• It is more rapid and of greater intensity than the primary immune response.
• It emsures that the infection is repulsed before it can cause any harm.

1) The surface antigens of the invading pathogen are taken up by the B cells.

2)The B cells process the antignes and present them on their surfaces.

3) T helper cells attach to the processed antigens on the surface of the B cells thereby activating them.

4) The B cells are now activated to divide by mitosis to give a clone of the plasma cells.

5) The cloned plasma cells produce antibodies that exactly fit the antigens on the pathogen's surface.

6) The antibodies attach to the antigens on the pathogen and destroy them. This is the primary immune response.

7) Some B cells develop into memory cells they can respond to future infections by the same pathogen by dividing rapidly and developing into plasma cells that produce antibodies. This is the secondary immune response.

• Some viruses have over 100 different strains.
• The antigens that these viruses are made out of are constantly changing. This is known as antigenic variability.
• Any subsequent infections are therefore more likely to be caused by different varieties of the pathogen.
• There antigens will not correspond to the antibodies or meory cells formed during previous infections.
• This means that there must be a primary immune response to the pathogen.

• They are proteins synthesised by B cells
• When the body is invaded by non-self material a B cell poduces antibodies
• These antibodies react with the antigens on the surface of the foreign material by binding to them precisely, in the same way as the lock and key model.
• Antibodies are very specific, each antigen having its own antibody.
• This massive variety is possible because they are made of proteins, which occur in nearly an infinite number of forms.

• They are made up of 4 polypeptide chains.
• One pair are made up of long chains, they are called heavy chains.
• The other pair are made up of shorter chains, they are called light chains.
• They have a binding site that fits very precisely onto the antigen to form an antigen-antibody complex.
• The binding site is different on different antibodies and is therefore called the variable region.
• Each site consists of a sequence of amino acids that form a specific 3-D shape that binds directly to a single type of antigen.
• The rest of the antibody is the same in all antibodies and is known as the constant region.
• This binds to all receptors on cells such as B cells.

• Each antigen will induce a different B cell to multiply and clone itself.
• Each of these clones will produce a different antibody, collectively known as polyclonal antibodies.
• It is of considerable medical value to be able to produce antibodies outside of the body.
• It is even better to be able to isolate a saingle antibody and to be able to clone it.
• These antibodies are known as monoclonal antibodies.

• Seperation of a chemical mixture.
• Immunoassay - This is the method of calculating the amount of a substance in a mixture. It is used in pregnancy testing kits, testing for drugs in urine and detecting the human immunodeficiency virus (AIDS test).
• Cancer Treatment - Monoclonal antibodies can be made that attach themselves only to cancer cells. These monoclonal antibodies can then be used to activate a cytotoxic drug (one that kills cells). This drug will only be activated by cells to which the monoclonal antibody is attached. The cancer cells will then be destroyed, causing little if any damage to other cells.
• Transplant surgery - Even with close matching, a transplanted organ will normally suffer some rejection because of the action of the T cells. Monoclonal antibodies can be used to 'knock out' these specific T cells.

• 1) A mouse is exposed to the non-self material against which an antibody is required.
• 2) The B cells in the mouse then produce a mixture of antibodies (polyclonal antibodies), which are extracted from the spleen of the mouse.
• 3) To enable these B cells to divide outside the body, they are mixed with cells that divide readily outside the body, e.g. cells from a cancer tumour.
• 4) Detergent is added to the mixture to break down the cell-surface membrane of both types of cell and enable them to fuse together.
• 5) The fused cells are seperated under a microscope and each single cell is cultured to form a group (clone). Each clone is tested to see whether it is producing the required antibody.
• 6) Any clone producing the required antibody is grown on a large scale and the antibodies are extracted from the growth medium.
• 7) Because these antibodies come from cells cloned from a single B cell, they are called monoclonal antibodies.

As they come from a mouse they must be modified to ake them like human cells before they can be used. This process is called humanisation.

• Is produced by the production of antibodies into individuals form an outside source.
• The antibodies aren't produced by the person themselves and so aren't replaced when they are broken down in the body.
• This means that the immunity is short-lived.

• Produced by stimulating the production of antibodies by the individual's own immune system.
• It is generally long-lasting.

• A suitable vaccine must be economically available in sufficient quantities to immunise all the vulnerable population.
• There must be few side-effects, if any, from the vaccination. Unpleasant side-effects may discourage individuals in the population from being vaccinated.
• Means of producing, storing and transporting the vaccine must be available. This usually involves technologically advanced equipment, hygienic conditions and refrigerated transport.
• There must be the means of administering the vaccine properly at the appropriate time. This involves training staff with appropriate skills at different centres throughout the population.
• It must be possible to vaccinate the vast majority (all, if possible) of the vulnerable population. This is best done at one time so that, for a certain period, there are no individuals with the disease and the transmission of the pathogen is interrupted. This is known as herd immunity.

• Vaccination fails to induce immunity in some individuals.
• Some may develop the disease after vaccination. These individuals may harbour the pathogen and reinfect others.
• The pathogen may mutate frequently, so the antigens change suddenly. Immunity is therefore short-lived as the immune system does not produce the antibodies to destroy the pathogen.
• There may be varieties of a pathogen that it is almost impossible to develop a vaccine that is effective against them.
• Certain pathogens 'hide' from the immune system, either by concealing themselves inside cells, or by living in places out of reach such as within the intestines.
• Individuals may have objections to vaccination for religious, ethical or medical reasons.

The control of cholera is difficult because:

• It is an intestinal disease and therefore not easily reached by the immune system.
• The antigens change rapidly, making it difficult to develop a long-lasting and effective vaccine.
• Mobile populations, resulting from global trade, tourism and refugees, spread cholera and make it difficult to ensure that individuals are vaccinated.

It is difficult because:

• The increase in HIV infection means that there are more people with impaired immune systems. Tgis meakes them more likely to contract TB.
• Circumstances mean that in some countries there are refugees who move around frequently and are often housed in overcrowded, temporary accomodation.
• Mobile populations, resulting from global trade, tourism and refugees, spread TB and make it difficult to ensure that individuals are vaccinated.
• Tge proportion of elderly people in the population is rising. These people have less effective immune systems and so vaccination is less effective at stimulating immunity.