AS Level Biology - Immunity Notes
Immunity Learning Outcomes
Outline the origin of white blood cells.
Explain the immune system's distinction between self and non-self (e.g., pathogens, transplanted tissues).
Describe the responses of phagocytes and lymphocytes during infection.
Explain the significance of increased white blood cell counts in infections and leukaemias.
Describe the occurrence of autoimmune diseases.
Explain the relationship between antibody structure and function.
Outline the production and use of monoclonal antibodies in diagnosis and treatment.
Distinguish between the four types of immunity.
Describe the use of vaccination to control infectious diseases.
Discuss the success of smallpox eradication and reasons for the persistence of measles, cholera, malaria, and TB.
Polio Eradication
Polio vaccination programs started in the 1950s, leading to the elimination of polio in the Americas by 1994.
In 2013, only 369 cases worldwide, mainly in Nigeria, Somalia, and Pakistan.
India mobilized medical staff and volunteers to vaccinate children multiple times.
Vaccination programs faced resistance and attacks on medical staff in some countries like Pakistan.
Smallpox Eradication
Smallpox was declared eradicated in 1980 by the World Health Organization (WHO).
Polio is a likely candidate to be the next eradicated infectious disease.
Immunity Overview
Immunity is the protection against disease provided by the body’s internal defense or immune system.
External cellular and chemical barriers are part of the defense system.
Some people exposed to infectious diseases experience few or no symptoms due to immunity.
Most people only contract measles once because the body develops a way to recognize and prevent harm from the measles virus again.
External Defense System
Physical, chemical, and cellular defenses prevent pathogens from entering the body.
Examples include epithelia lining airways, hydrochloric acid in the stomach, and blood clotting.
Internal Defense System
White blood cells recognize and destroy pathogens that enter the body.
Pathogens are recognized by distinctive molecules on their surfaces, such as proteins, glycoproteins, lipids, and polysaccharides, as well as waste materials.
Any molecule recognized as foreign by the body is an antigen.
Two types of white blood cells: phagocytes and lymphocytes.
Immune System Distinguishing Self from Non-Self
Each individual has unique molecules on their cell surfaces, called cell surface antigens.
These antigens do not stimulate antibody production in the same individual but will in others.
Example: ABO blood group system. If type A blood is given to someone with type B blood, the recipient's immune system recognizes the type A blood cells as non-self and produces antibodies.
If blood of the correct type (e.g., type B to a type B recipient) is used, the immune system recognizes the antigens as self and produces no antibodies.
Immune Response
The response of lymphocytes to a foreign antigen.
Lymphocytes may produce antibodies or kill infected cells.
Cells of the Immune System
Originate from the bone marrow.
Two main groups: phagocytes (neutrophils and macrophages) and lymphocytes.
Phagocytes
Produced throughout life in the bone marrow and stored there before distribution in the blood.
Act as scavengers, removing dead cells and invasive microorganisms.
Neutrophils:
Form about 60% of the white cells in the blood.
Travel throughout the body, squeezing through capillary walls to patrol tissues.
Released in large numbers during an infection, but are short-lived.
Macrophages:
Larger than neutrophils.
Found in organs like the lungs, liver, spleen, kidney, and lymph nodes.
Originate in bone marrow, travel as monocytes, and develop into macrophages in organs.
Long-lived cells that initiate immune responses by displaying antigens to lymphocytes.
Phagocytosis
Cells under attack release chemicals like histamine, attracting neutrophils (chemotaxis).
Neutrophils are stimulated to attack pathogens, especially when they are covered in antibodies.
Neutrophils have receptor proteins on their surfaces that recognize antibody molecules.
The neutrophil engulfs the pathogen, trapping it within a phagocytic vacuole (endocytosis).
Digestive enzymes are secreted into the phagocytic vacuole, destroying the pathogen.
Neutrophils die after killing and digesting pathogens, forming pus at the site of infection.
Lymphocytes
A second type of white blood cell that plays a crucial role in the immune response; smaller than phagocytes and have a large nucleus.
Two types: B-lymphocytes (B cells) and T-lymphocytes (T cells).
B-lymphocytes:
Remain in the bone marrow until mature, then spread throughout the body, concentrating in lymph nodes and the spleen.
T-lymphocytes:
Leave the bone marrow and collect in the thymus, where they mature.
The thymus gland, located in the chest beneath the sternum, doubles in size between birth and puberty and then shrinks.
Only mature lymphocytes can carry out immune responses.
The maturation process produces many different types of B- and T-lymphocytes, each specialized to respond to one antigen.
Mature B and T cells circulate between the blood and the lymph, ensuring they encounter pathogens and each other.
Immune responses depend on B and T cells interacting to provide an effective defense.
Some T cells coordinate the immune response by stimulating B cells to divide and secrete antibodies.
Other T cells kill infected cells by making direct contact with them.
B-Lymphocytes
As each B cell matures, it gains the ability to make just one type of antibody molecule.
Many different types of B cells develop, potentially as many as 10 million.
The genes that code for antibodies are changed in various ways to code for different antibodies.
Each cell divides to give a small number of cells that can make the same type of antibody, called a clone.
Antibody molecules remain in the B cell surface membrane, forming a glycoprotein receptor that can combine with one type of antigen.
If that antigen enters the body, there will be mature B cells with cell surface receptors that will recognize it.
B Cells During the Immune Response:
When an antigen enters the body for the first time, the small numbers of B cells with receptors complementary to the antigen are stimulated to divide by mitosis (clonal selection).
The clone of cells divides repeatedly by mitosis (clonal expansion) to produce large numbers of identical B cells over a few weeks.
Some activated B cells become plasma cells that produce antibody molecules very quickly (up to several thousand a second).
Plasma cells secrete antibodies into the blood, lymph, or onto the linings of the lungs and the gut.
Plasma cells are short-lived, lasting several weeks, and then their numbers decrease, but the antibody molecules they secrete stay in the blood longer.
Other B cells become memory cells that circulate in the body for a long time.
If the same antigen is reintroduced later, memory cells divide rapidly and develop into plasma cells and more memory cells.
This is repeated on every subsequent invasion by the same antigen, meaning that the infection can be destroyed and removed before any symptoms of disease develop.
Antibody Concentration
The first or primary response is slow because there are very few B cells specific to the antigen.
The secondary response is faster because there are many memory cells, which quickly divide and differentiate into plasma cells.
Immunological Memory
Memory cells last for many years, often a lifetime, explaining why someone is unlikely to catch measles twice, due to a fast secondary response.
Repeated infections of the common cold and influenza occur because of many different and new strains of the viruses that cause these diseases, each one having different antigens.
Each time a pathogen with different antigens infects us, the primary response must occur before we become immune, and during that time we often become ill.
Antibodies
Globular glycoproteins with quaternary structure, forming the group of plasma proteins called immunoglobulins.
The basic molecule consists of four polypeptide chains: two 'long' or 'heavy' chains and two 'short' or 'light' chains, held together by disulfide bonds.
Each molecule has two identical antigen-binding sites formed by both light and heavy chains.
The sequences of amino acids in these regions make the specific three-dimensional shape that binds to just one type of antigen.
The antigen-binding sites form the variable region, which is different on each type of antibody molecule produced.
The 'hinge' region gives the flexibility for the antibody molecule to bind around the antigen.
This type of antibody molecule with four polypeptides is known as immunoglobulin G, IgG for short. Larger types of antibody molecules are IgA with four antigen binding sites and IgM with ten.
Antibody Functions
Some antibodies act as labels to identify antigens as appropriate targets for phagocytes to destroy.
Antitoxins block the toxins released by bacteria such as those that cause diphtheria and tetanus.
T-Lymphocytes
Mature T cells have specific cell surface receptors called T cell receptors.
T cell receptors have a structure similar to that of antibodies and are each specific to one antigen.
T cells are activated when they encounter this antigen on another cell of the host (i.e., on the person’s own cells).
This cell may be a macrophage that has engulfed a pathogen and cut it up to expose the pathogen’s surface molecules, or it may be a body cell that has been invaded by a pathogen and is similarly displaying the antigen on its cell surface membrane.
The display of antigens on the surface of cells in this way is known as antigen presentation.
T cells that have receptors complementary to the antigen respond by dividing by mitosis to increase the number of cells.
T cells go through the same stages of clonal selection and clonal expansion as clones of B cells.
There are two main types of T cell: helper T cells and killer T cells (or cytotoxic T cells).
Helper T Cells:
When activated, they release hormone-like cytokines that stimulate appropriate B cells to divide, develop into plasma cells, and secrete antibodies.
Some T helper cells secrete cytokines that stimulate macrophages to carry out phagocytosis more vigorously.
Killer T Cells:
Search the body for cells that have become invaded by pathogens and are displaying foreign antigens from the pathogens on their cell surface membranes.
Killer T cells recognize the antigens, attach themselves to the surface of infected cells, and secrete toxic substances such as hydrogen peroxide, killing the body cells and the pathogens inside.
Memory helper T cells and memory killer T cells are produced, which remain in the body and become active very quickly during the secondary response to antigens.
The display of antigens on the surface of cells in this way is known as antigen presentation.
T cells that have receptors complementary to the antigen respond by dividing by mitosis to increase the number of cells.
T cells go through the same stages of clonal selection and clonal expansion as clones of B cells.
White Blood Cell Counts
The number of neutrophils in the blood increases during bacterial infections and whenever tissues become inflamed and die.
The number of lymphocytes in the blood increases in viral infections and in TB.
Most of the lymphocytes that circulate in the blood are T cells. In some blood tests, the numbers of T cells are recorded.
HIV and T Cells
Human immunodeficiency virus (HIV) invades helper T cells and causes their destruction, so blood tests for people who are HIV+ record the numbers of specific T cells.
The normal value is between 500 and 1500 cells mm^{-3}.
The specific T cell numbers provide useful information on the progress of the disease and the success of treatments, by monitoring decline in T cell number and therefore assessing the deleterious effect on the immune system.
Blood Tests
Blood tests are routinely carried out to help doctors diagnose diseases and to assess the success of treatments.
Blood samples are taken from patients and sent for analysis in laboratories that use automated cell counters.
The results usually include the numbers of red and white blood cells and platelets.
Platelets are small cell fragments that do not have a nucleus; they are formed from the break-up of cells in the bone marrow. They release substances that stimulate blood clotting.
The results of such blood tests are given as absolute values. The results for specific white blood cells, such as neutrophils and lymphocytes, are given as absolute numbers or as percentages of the white cell count.
There is considerable variation in these numbers between people.
Origin of White Blood Cells
All the white cells in the blood originate from stem cells in the bone marrow.
There are two groups of bone marrow stem cells:
Myeloid stem cells that give rise to neutrophils, monocytes and platelets.
Lymphoid stem cells that give rise to lymphocytes, both B and T cells.
Leukaemias
Cancers of the stem cells in the bone marrow.
The cells divide uncontrollably to give many cells which do not differentiate properly and disrupt the production of normal blood cells including red blood cells and platelets.
These malignant cells fill up the bone marrow and then flow into the blood and into the lymphatic system.
Types of Leukaemias
In myeloid leukaemias, the stem cells responsible for producing neutrophils divide uncontrollably, and the number of immature cells increases.
In lymphoblastic leukaemias, the cancerous cells are those that give rise to lymphocytes.
The immature white blood cells are produced very quickly, and they disrupt the normal balance of components in the blood.
This means that the body does not have enough red blood cells or platelets, causing anemia and increasing the risk of excessive bleeding.
Also, the numbers of mature neutrophils and lymphocytes decrease so that people with these cancers become more susceptible to infections; they are said to be immunosuppressed.
There are acute and chronic forms of both types of leukaemia.
Acute leukaemias develop very quickly, have severe effects, and need to be treated immediately after they are diagnosed.
Chronic leukaemias may take many years to develop, and changes in blood cell counts are usually monitored over time so that treatment is given when it is most likely to cure the disease.
Blood tests are used to help diagnose these diseases, monitor their progress, and assess the effectiveness of treatments.
Active and Passive Immunity
Active Immunity: * Occurs when a person makes their own antibodies during the course of an infection. * Lymphocytes are activated by antigens on the surface of pathogens that have invaded the body. * Natural Active Immunity: Activation occurs naturally during an infection. * Artificial Active Immunity: Immune response activated artificially by injecting antigens (vaccination) or taking them by mouth (e.g., polio). Results in long-term immunity. * In both natural and artificial active immunity, antibody concentrations in the blood follow similar patterns. * Takes time for sufficient numbers of B and T cells to be produced to give an effective defense.
Passive Immunity:
A person has not produced the antibodies themself; B and T cells have not been activated, and plasma cells have not produced any antibodies.
Artificial Passive Immunity:
Antitoxins: Immediate protection is needed for potentially fatal diseases like tetanus.
Injection of human antibodies against the tetanus toxin collected from blood donors who have recently been vaccinated against tetanus.
Provides immediate, but temporary, protection as the antibodies are not produced by the body’s own B cells and are therefore removed from the circulation by phagocytes.
Natural Passive Immunity:
Antibodies from the mother cross the placenta during pregnancy and remain in the infant for several months.
Colostrum, the thick yellowish fluid produced by a mother’s breasts for the first four or five days after birth, contains a type of antibody known as IgA.
Some IgA antibodies remain on the surface of the infant’s gut wall, while others pass into the blood undigested; IgA acts in the gut to prevent the growth of bacteria and viruses and also circulates in the blood.
Vaccines
A preparation containing antigens used to stimulate an immune response artificially.
Vaccines may contain a whole live microorganism, a dead one, a harmless version (attenuated organism), a harmless form of a toxin (toxoid), or a preparation of surface antigens.
Administered by injection into a vein or muscle, or are taken orally (by mouth).
Some are produced using techniques of genetic engineering.
Vaccination mimics a natural infection to provide good protection.
Vaccines containing live microorganisms reproduce, albeit rather slowly, so that the immune system is continually presented with a large dose of antigens.
Vaccines made from dead bacteria or viruses that do not replicate inside the body are less effective.
Some vaccines are highly effective, and one injection may well give a lifetime’s protection, while less effective vaccines need booster injections to stimulate secondary responses.
Problems with Vaccines
Poor response: Some people do not respond at all, or not very well, to vaccinations due to a defective immune system or malnutrition (protein-energy malnutrition).
Live virus and herd immunity: People vaccinated with a live virus may pass it out in their feces during the primary response and may infect others. Vaccinating a large number of people simultaneously gives herd immunity, interrupting transmission in a population.
Antigenic variation:
* Common cold: No vaccines because the rhinovirus has around 100 different strains.
* Influenza virus: Mutates regularly to give different antigens.
* Antigenic drift: Minor changes in the viral antigen.
* Antigenic shift: Major changes in antigen structure, making previous vaccination ineffective against the new strain.
* The WHO recommends the type of vaccine to use according to the antigens that are common at the time, and the vaccine is changed almost every year.Effective vaccines against protoctists (e.g., malaria, sleeping sickness) are lacking because these pathogens are eukaryotes with many more genes than bacteria and viruses.
Antigenic Concealment
Some pathogens evade attack by the immune system by living inside cells (e.g., Plasmodium in liver cells or red blood cells) or by covering their bodies in host proteins.
Other pathogens suppress the immune system by parasitizing cells such as macrophages and T cells.
Vibrio cholerae (cholera) remains in the intestine, beyond the reach of many antibodies. Oral vaccines provide limited protection.
Eradication of Smallpox
Smallpox was an acute, highly infectious disease caused by the variola virus and transmitted by direct contact.
The WHO started an eradication programme in 1956, intending to rid the world of the disease within ten years (in 1967).
Vaccination and surveillance were the main aspects of the programme.
In excess of 80% of populations at risk were vaccinated.
Ring vaccination: When a case of smallpox was reported, everyone in the household and the 30 surrounding households, as well as other relatives and possible contacts in the area, was vaccinated.
Success of Smallpox Eradication
The variola virus was stable; it did not mutate and change its surface antigens.
The vaccine was made from a harmless strain of a similar virus (vaccinia) and was effective because it was a ‘live’ vaccine.
The vaccine was freeze-dried and could be kept at high temperatures for as long as six 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, re-usable needle for its delivery (bifurcated 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 vaccinators and suppliers of information about cases, especially in remote areas.
Preventing Measles
Measles is a preventable disease that could be eradicated by a worldwide surveillance and vaccination programme.
However, a programme of one-dose-vaccination has not eliminated the disease in any country.
Poor response to the vaccine shown by some children who need several boosters to develop full immunity.
Measles is highly infectious, and it is estimated that herd immunity of 93–95% is required to prevent transmission in a population.
As the currently available vaccine has a success rate of 95%, this means that the whole population needs to be vaccinated and infants must be vaccinated within about eight months of birth.
Immunity: The protection against disease provided by the body’s internal defense or immune system.
Pathogens: Recognized by distinctive molecules on their surfaces, such as proteins, glycoproteins, lipids, and polysaccharides, as well as waste materials.
Antigen: Any molecule recognized as foreign by the body.
Phagocytes: Act as scavengers,
Antigen: A substance that is foreign to the body and stimulates an immune response.
Antibody: A glycoprotein (immunoglobulin) made by plasma cells derived from B-lymphocytes, secreted in response to an antigen; the variable region of the antibody molecule is complementary in shape to its specific antigen.
Immune response: The complex series of responses of the body to the entry of a foreign antigen; it involves the activity of lymphocytes and phagocytes.
Non-self: