1. Chapter 11 – immunity

2. Immunity  Immunity is the protection against disease. This is possible because of the immune system and its components. Many pathogens do not cause us harm because we have physical, chemical and cellular defenses that prevent them from entering. If they do enter, these same defenses (white blood cells) will prevent them from spreading through the body. Many pathogens do not cause us harm because we have physical, chemical and cellular defenses that prevent them from entering. If they do enter, these same defenses (white blood cells) will prevent them from spreading through the body. ○ Epithelial cells in the airway passages prevent the entry of pathogens. ○ HCl in the stomach kills bacterial that has been ingested. ○ Blood clotting is a mechanism that prevents blood loss and the entry of pathogens through open wounds.  The immune response is the action of lymphocytes in response to the entry of an antigen into the body. There are different types of lymphocytes that are capable of producing different types of antibodies that acts against a particular antigen. There are different types of lymphocytes that are capable of producing different types of antibodies that acts against a particular antigen. Antigens and antibodies are specific to each other. The lymphocytes will only secrete its antibodies if the proper antigen is encountered. Antigens and antibodies are specific to each other. The lymphocytes will only secrete its antibodies if the proper antigen is encountered. The immune response is slow the first time an antigen is encountered. Sometimes it can take several weeks to build up enough antibodies to destroy the pathogen. The immune response is slow the first time an antigen is encountered. Sometimes it can take several weeks to build up enough antibodies to destroy the pathogen. If a person continues to encounter the same antigen, a response can be rapid enough to entirely prevent symptoms. If a person continues to encounter the same antigen, a response can be rapid enough to entirely prevent symptoms.

3. Cells of the Immune System  The cells of the immune system are produced in the bone marrow. There are 2 types of cells that are involved in the defense of an organism. These cells are visible when a blood smear stained to show nuclei is analyzed. Phagocytes (Neutrophils and macrophages) Phagocytes (Neutrophils and macrophages) Lymphocytes Lymphocytes

4. Phagocytes  Phagocytes are a type of white blood cell that is produced in the bone marrow throughout the life of the organism. These cells are scavengers that remove dead cells as well as invasive microorganisms.  Neutrophils are a type of phagocyte that forms about 60% of the leucocytes in the blood.  They travel all over the body and often leave the blood by squeezing through the walls of the capillaries to ‘patrol’ the tissues.  These cells are released in large numbers during an infection, but they do not live for a long period of time. After they kill and digest some pathogens, they often collect at a site of infection to form pus.  Macrophages are also a type of phagocyte, but they are much larger than neutrophils and are found in organs like the spleen, lungs, liver, kidneys and lymph nodes.  When these cells leave the bone marrow, they travel in the bloodstream as monocytes, which will develop into macrophages once they settle in the organs.  Once in these organs, the macrophages will remove any foreign matter found within them.  These cells live long and play a very important role in initiating the immune responses since they cannot destroy pathogens completely. Instead, they cut up the pathogens to display antigens that can be later recognized by the lymphocytes.

5. Phagocytosis  If a pathogen invades the body and causes and infection, some of the body cells that are under attack will release histamine. This chemical, along any other chemical that is released by the pathogens, will attract neutrophils to the site. The neutrophils then will destroy the pathogens via phagocytosis.  Neutrophils are able to attack certain to attack certain pathogens because pathogens because they have receptor they have receptor proteins on their proteins on their surfaces that surfaces that recognize antibody recognize antibody molecules and attach molecules and attach to them. to them.

6. Lymphocytes  Lymphocytes are much smaller than phagocytes and have a single nucleus that fills most of the cell.  Both types of lymphocytes are produced in the bone marrow before birth.  B lymphocytes (B Cells) are white cells that remain in the bone marrow until they mature. Once they mature, they will spread throughout the body concentrating in the lymph nodes and the spleen. These cells will release antibodies that destroy the antigenic pathogens.  T lymphocytes (T Cells) are white cells that leave the bone marrow and collect in the thymus where they go to mature. Some T cells will coordinate the immune response, stimulating B cells to divide. Others seek out and kill any of the body’s own cells that are infected with pathogens.  Immune responses are only carried out by mature lymphocytes. During the maturation process, millions of lymphocytes develop. Each type is specialized to respond to one particular antigen, giving the immune system the ability to respond to almost any type of pathogen that may enter the body.  Immune responses depend on the interaction of both types of lymphocytes to give an effective defense.

7. B Lymphocytes  Each mature B cell will be capable of producing just one type of antibody.  During the maturation process, the genes that code for antibodies are changed in a variety of ways to be able to code for different antibodies.  Once each cells divides, those cells (clones) will be able to make the same type of antibody. At this stage, the antibody does not leave the B cell, instead it will remain in the plasma membrane. The antibody will then form a protein receptor that will specifically combine with one type of antigen.

8. B Lymphocytes  Some of the B lymphocytes will become plasma cells, which are capable of producing antibodies very quickly. These cells secrete their antibodies into the blood, lymph or onto the linings of the lungs and guts.  Plasma cells do not live very long. Their numbers will decrease within several weeks. However, the antibodies that they secreted into the bloodstream will remain for longer periods of time.  Other B cells will become memory cells. These cells will remain circulating in the body for a long period of time.  If an antigen is reintroduced up to a few months after the first infection, few months after the first infection, the memory cells will divide quickly the memory cells will divide quickly and develop into plasma cells and and develop into plasma cells and more memory cells. more memory cells.  This reaction will reoccur every time there is antigen that is reintroduced there is antigen that is reintroduced into the body. This will destroy and into the body. This will destroy and remove the infection quicker so that remove the infection quicker so that no symptoms of the disease even no symptoms of the disease even develop. develop.

9. Immune Response  The primary response is slow because there are very few B cells that are specific there are very few B cells that are specific to that antigen. to that antigen.  The secondary response is much faster because there are now many memory because there are now many memory cells, which will quickly divide and cells, which will quickly divide and differentiate into plasma cells. Therefore, differentiate into plasma cells. Therefore, there are many more antibodies produced there are many more antibodies produced during the secondary response. during the secondary response.

10. Immune Response  Immunological memory is the ability of the immune system to respond quickly to antigens that it recognizes as having entered the body before. Memory cells are the basis for this and can last for many years.  However, we can suffer from repeated infections because there may be many different strains and new strains that have different antigens.

11. Antibodies  Antibodies are all globular glycoproteins and form the group of plasma proteins known as immunoglobulins.  All antibodies consist of 4 polypeptide chains. (2 long or heavy chains and 2 short or light chains)  There are disulfide bridges that hold the chains together.  Each molecule has 2 identical antigen binding sites that are formed by both light and heavy chains. The sequence of the amino acids is what makes the specific 3-D shape which binds to only one type of antigen. (Variable one type of antigen. (Variable Region) Region)  The hinge region provides the flexibility for the antibody to flexibility for the antibody to bind around the antigen. bind around the antigen.

12. Functions of Antibodies  Antibodies have different functions.  Some antibodies act as labels to identify antigens as targets for destruction by phagocytes.  Antitoxins are a special group of antibodies that group of antibodies that block the toxins released block the toxins released by bacteria. by bacteria.  Some antibodies that have multiple binding have multiple binding sites cause the sites cause the agglutination of bacteria, agglutination of bacteria, which reduces the which reduces the chances of the bacteria chances of the bacteria spreading. spreading.

13. Classes of Antibodies Antibody class Relative Molecular Mass Number of Antigen Binding Sites Sites of ActionFunctions IgG150 0002 Blood Tissue Fluid (can cross the placenta) Enhances activity of macrophages Acts as antitoxins Causes agglutination IgM970 00010 Blood Tissue Fluid (cannot cross the placenta) Causes agglutination IgA160 000 or 320 000 2 or 4 Saliva, tears Bronchial secretions Mucus secretions of small intestine Prostate and vagina secretions Nasal fluid Colostrum/ breast milk Inhibits bacteria adhering to host cells Prevents bacteria forming colonies on mucous membranes IgE180 0002 tissues Heavy chains on IgE activate the release of histamine Involved in response to infections to worms, and allergic responses to harmless substances

14. T Lymphocytes  Mature T lymphocytes have T cell receptors that have a similar structure to antibodies and are each specific to one antigen.  A T cell will become activated when they encounter the antigen in contact with the host cell.  This can occur after a macrophage that engulfs and cuts up a pathogen exposes the surface molecules of the pathogen.  It can also occur by a body cell that has been invaded by a pathogen and displays the antigen on its plasma membrane.  There are 2 types of T cells that respond to pathogens.  T helper cells release cytokines (hormone-like chemicals) that stimulate B cells to divide, so that they may develop into plasma cells and secrete their corresponding antibodies. Other T helper cells secrete cytokines that stimulate macrophages to carry out phagocytosis more vigorously.  Killer T cells look for body cells that have been invaded by pathogens (displaying the antigens on the plasma membrane), attach themselves to the surface of the invaded cell and secrete toxic substances that will kill the pathogens along with the host cell.  There are also memory T cells that remain in the body and can become active quickly during the secondary response.

15. Active Immunity  Active immunity is gained when an antigen enters the body and an immune response occurs where antibodies are produced by plasma cells.  Since the activation of the lymphocytes occurs naturally during an infection, it is known as natural active immunity.  The immune response, however, can also be activated artificially. This can be accomplished by injecting antigens into the body or taking them by mouth (i.e. vaccinations). This is known as artificial active immunity.  The immune response caused by natural or artificial active immunity is similar. The antibody concentrations in the blood provides long-term immunity.  In both types of immunity, it will take time for sufficient active (mature) B and T cells to be produced to give an effective defense. Therefore, if a person becomes infected with a potentially fatal disease, then a more immediate defense is needed.

16. Passive Immunity  Passive immunity is gained without an immune response because the B and T cells have not been activated and plasma cells do not produce antibodies.  Artificial passive immunity occurs when the antibodies come from another person who has encountered the antigen.  Natural passive immunity occurs when antibodies are passed from mother to fetus via the placenta or from mother to child via breast milk.  The antibodies that the mother produces can mother produces can pass across the placenta pass across the placenta and remain in the infant and remain in the infant for several months. for several months.

17. Artificial Passive Immunity  Tetanus is a disease caused by a bacteria that lives in soil, saliva, dust and manure. The bacteria enters the body through a deep cut.  Tetanus kills quickly, so the body’s natural primary response cannot occur. Therefore, people who have a deep cut and may have been infected with the tetanus bacteria will need to be given an injection of antitoxins.  The antitoxins given is a preparation of human antibodies against the tetanus toxin. The antibodies are collected from donated blood from people who had recently been vaccinated against tetanus.  These antitoxins will provide an immediate response, but it is only temporary since the antibodies are not produced by the body’s own cells. Therefore, the antibodies will be attacked as well by phagocytes in the liver and the spleen.

18. Passive vs Active Immunity ImmunityFeatures Antigen Encountered Immune Response Time before antibodies appear in blood Production of memory cells Protection ActiveYes Several weeks during primary response YesPermanent PassiveNo ImmediateNoTemporary

19. Passive vs Active Immunity

21. Vaccines  Vaccines are preparations containing antigenic material. This means that it can contain a whole live microorganism, a dead one, a harmless form (attenuated organism), a harmless form of a toxin (toxoid) or a preparation of surface antigens.  Vaccines can be given via an intravenous or intramuscular injection, or can be taken orally.  Vaccines can be used to mimic an immune response that is caused from a natural infection.  When a vaccine contains living organisms, they reproduce slowly and the immune system will continuously be presented with a large dose of antigens.  These vaccines are highly effective and may give a lifetime’s protection.  However, if a vaccine is made from dead bacteria or viruses, it will not mimic a response caused by a natural infection and therefore be less effective.  These vaccines will need a booster injection(s) to stimulate secondary responses that will give enhanced protection.

22. Problems with Vaccines  Unfortunately, there are many problems that are associated with vaccines.  Some people do not respond very well or at all to vaccinations.  This can be due to a defective immune system, which prevents the production of necessary B and T cell clones.  Also, it may be because the person suffers from malnutrition, especially protein energy malnutrition. This causes the person to not have enough protein to make antibodies or clones of lymphocytes. These people run a high risk of developing infectious diseases and passing them on to people with no immunity.  Some people that are vaccinated with a live virus can pass it out in their faeces during primary response. This can cause others to become infected. This can be avoided by giving herd immunity, when a large number of people / children are vaccinated at the same time.  Antigenic variation is when a pathogen alters its surface proteins so that it may invade a cell. This causes a problem because antibodies that are used to kill a previous strain may not recognize the new antigen produced.  If a minor change occurs to the antigen (antigenic drift) the memory cells can still recognize it and start a secondary response.  If a major change occurs (antigenic shift), a vaccination that was given for a previous strain will not be effective.

23. Problems with Vaccines  The WHO recommends the type of vaccine to be administered based on the antigens that are common at that time. This is why vaccines, like the influenza vaccine, changes every year.  There is no vaccine for the common cold and no effective vaccines against diseases that are caused by protoctists.  The rhinovirus that causes most colds has at least 113 different strains. This makes it impossible to develop a vaccine that can protect a person against all strains.  Protoctists are eukaryotes that have many more genes than bacteria and viruses. This means that they can have up to thousands of antigens on their cell’s surface. Some protoctists even have different antigens during different stages in their life cycle. This means that an effective vaccine would have to contain all antigens present.  Plasmodium passes through 3 stages within the human host, each with a different antigen. In order for a vaccine to be effective, it must be specific to the infective stage and cause an effective response in the time between the mosquito bite and the infection of liver cells.  Trypanosoma (agent that causes sleeping sickness) has a total of a thousand different antigens that change every 4-5 days. This a thousand different antigens that change every 4-5 days. This makes it absolutely impossible for the immune system to respond makes it absolutely impossible for the immune system to respond in an effective manner. in an effective manner.

24. Problems with Vaccines  Another problem is that some pathogens can evade an attack by the immune system by living inside cells.  Some parasitic worms conceal themselves by covering their bodies in host proteins. This makes them invisible to the immune system, which will prevent them from being attacked.  Other pathogens suppress the immune system by parasitizing cells like macrophages and T cells.  Developing vaccines for these types of pathogens is extremely difficult because there is a short period of time for an immune response to occur before the pathogen ends up “hiding”. Vibrio cholerae remains in the intestine where it is not capable of being reached by antibodies. Vibrio cholerae remains in the intestine where it is not capable of being reached by antibodies.  The vaccine for cholera is injected, so it is unable to stimulate antibody production in the intestine. It also cannot stimulate the production of an antitoxin against choleragen.  However, an oral vaccine for cholera has already been developed.

25. Smallpox  Smallpox was an acute, highly infectious disease caused by the variola virus that was transmitted by direct contact.  It caused red spots containing a transparent fluid all over the body. The eyelids became swollen and sometimes the body. The eyelids became swollen and sometimes looked like they were glued shut. If people recovered, they looked like they were glued shut. If people recovered, they would be permanently blind and disfigured by scabs that would be permanently blind and disfigured by scabs that were left when the pustules dried out. were left when the pustules dried out.  Between 12 to 30% of the people who had smallpox died.  The WHO began the smallpox eradication programme in 1956. It was composed of vaccination and surveillance.  Vaccinations of over 80% of populations that were at risk all over the world occurred. By performing ring vaccinations, everyone who may have come into contact with an infected person was protected.  The WHO declared the world free of smallpox in 1980.

26. Smallpox  The eradication programme was successful due to many factors.  The variola virus was stable. It did not mutate and change its surface antigens, so the same vaccine could be used everywhere. That also meant it was cheap to produce.  The vaccine was made from a harmless strain of a similar virus and was effective due to the fact the it was a live vaccine.  The vaccine was freeze-dried and could be kept at high temperatures for as long as 6 months.  Infected people were easy to identify.  The vaccine was easy to administer and was even more effective after the development of a stainless steel, reusable needle.  The smallpox virus did not linger in the body after an infection to become active later and form a reservoir of infection.  The virus did not infect animals, which made it easier to break the transmission cycle.  Many 16- to 17 year olds became enthusiastic vaccinator and suppliers of information about cases.

27. Measles  Measles is caused by a virus that is spread by airborne droplets.  It causes a rash and fever, and could have fatal complications. However, it rarely affects infants under 8 months since they have passive immunity from their mother.  It is a major disease of developing countries because of overcrowding, unsanitary conditions and high birth rates. It will easily infect malnourished infants that suffer from vitamin A deficiency.

28. Measles  Measles has caused many cases of childhood blindness and severe brain damage.  In 1993, there were an estimated 45 million cases of measles and 1.16 million deaths, making it the 9 th leading cause of death worldwide.  Measles is a preventable disease and could be eradicated by a worldwide surveillance and vaccination programme.  However, a one-dose-vaccination programme has not eliminated the disease due to the poor response to the vaccine by children. Some children need several boosters to develop immunity, but it is difficult to give boosters, follow cases of measles and trace contacts.  Measles is very infectious and 93-95% herd immunity must be required to prevent transmission in a population.  The measles vaccines is about 95% effective, so the whole population must be vaccinated and infants must be vaccinated within 8 months of birth to prevent transmission.  Many countries have achieved 80% or more coverage just with the vaccination alone.