Chapter: 18 Immune System The human body has structures and processes that resist the continuous threat of invasion by pathogens. Immunity is based on recognition of self and destruction of foreign material.

Vaccine: Calling the shots HIV and AIDS HIV life cycle A Summary of the effect of HIV infection HIV is a virus which Infects helper T-cells (white blood cells) With infection the HIV replicates using the metabolism of the helper T-cell This replications kills the helper T-cells and their number declines. As a consequence, B-lymphocytes are not activated during other infections B-lymphocytes do not make as many antibodies Opportunistic infections grow in the body. AIDS is defined by: HIV infection and a very low helper T cell count, or HIV infection with opportunistic infections is called AIDS

dust mites Questions on histone production and allergies. What type of symptoms does histone release in cells of the nose cause? What is the effect of histone on blood vessels? How could the release of histone help the macrophages and lymphocytes of the immune system fight a potential infection?

Immune response Hercptin

Defense against infectious disease A. Primary defense is to keep pathogens out 1. Pathogen: any living organism or virus that is capable of causing a disease a) Include viruses, bacteria, protozoa, fungi, and worms b) Exposure to majority of pathogens does not result in disease since we are well defended

2. Antibiotics: chemicals that can kill bacteria Skin and mucous membranes from a primary defense 1. Prevent pathogens from having the chance to cause disease: stay away from sources of infection a) Quarantine: isolate people who have highly transmittable diseases b) Not possible to avoid all sources of infection

Skin: first line of defense with two layers a) Dermis: underneath layer that is alive with sweat glands, capillaries, sensory receptors, and dermal cells (give structure and strength to skin) b) Epidermis: top layer made up of mainly dead cells that are constantly being replaced as the underlying dermal cells die and move upwards i) Forms a good barrier against most pathogens as long as it stays intact ii) Important to keep skin clean and cover cuts

Pathogens can enter the body that are not covered by skin a) Entry points are lined with tissue cells that form a mucous membrane that produce and secrete a lining of sticky mucus b) Mucous: traps pathogens to prevent them from reaching cells that they could infect c) Cilia: hair like extensions capable of wave- like movement that are on mucous membrane tissue that can move pathogens up and out (trachea) Skin

National Institute of Health: bacteria outnumber their human hosts by 10 to 1 cells. Bacteria account for 2% of body mass of an adult

Blood clotting minimizes the chances of infection and blood loss 1. Small blood vessels are broken, blood escapes and the damaged vessels are often in the skin, creating a way for pathogens to enter the body 2. Body has evolved a set of responses to create a clot that seals the damaged blood vessel

Blood Clotting Break in Capillary Wall Blood vessels injured. Clumping of Platelets Platelets clump at the site and release thromboplastin. Thromboplastin converts prothrombin into thrombin.. Clot Forms Thrombin converts fibrinogen into fibrin, which causes a clot. The clot prevents further loss of blood..

3. Plasma proteins: circulate in the blood plasma and some are involved in clotting a) Prothrombin and fibrinogen: remain inactive until events of bleeding 4. Platelets: form in the bone marrow and one cell breaks into fragments without a nucleus and live for 8-10 days

Blood clotting process a) Damage cells of blood vessel releases chemicals that stimulate platelets to stick to the damaged area b) Damaged tissue and platelets release clotting factors that convert prothrombin in thrombin i) Thrombin: active enzyme that catalyzes the conversion of soluble fibrinogen into insoluble fibrin

ii) Fibrin: fibrous protein that forms a mesh- ii) Fibrin: fibrous protein that forms a mesh- like network that helps to stabilize the platelet plug c) Cellular debris becomes trapped in the fibrin mesh to form a stable clot d) Clot prevents further blood loss and entry of pathogens Animation link Blood clotting Clot

Hemophilia: inherited (X chromosome)blood-clotting disorder a) Lack the ability to produce one of the chemicals needed for normal clotting b) Signs and symptoms of hemophilia: vary depending on your level of clotting factors. If your clotting-factor level is mildly reduced, you may bleed only after surgery or trauma. If your deficiency is severe, you may experience spontaneous bleeding. Unexplained and excessive bleeding from cuts or injuries, or after surgery or dental work Many large or deep bruises Unusual bleeding after vaccinations Pain, swelling or tightness in your joints Blood in your urine or stool Nosebleeds without a known cause In infants, unexplained irritability Hemophilia site video

When pathogens get past skin and mucous membranes 1. Immune response: series of events when a pathogen enters the body a) Primary immune response: first encounter with a particular pathogen i) Takes a week or more to be successful and symptoms of the disease with be experience as the immune system works to eliminate the pathogen

b) Secondary immune response: second or third encounter with a particular pathogen i) Quicker and more intense response so symptoms are rarely experienced ii) Immune to a disease: ability to accomplish a secondary immune response for a particular antigen

Role of phagocytic white blood cells a) White blood cells (leucocytes): cells in bloodstream that help us fight off pathogens and provide us with immunity for pathogens that we encounter more than once b) Macrophage: type of leucocyte that is involved in the early process of fighting off a pathogen i) Large and change shape to surround an invading cell through phagocytosis ii) Can squeeze their way in and out of small blood vessels and encounter invading cell outside the bloodstream

c) Non-specific immunity: macrophage c) Non-specific immunity: macrophage recognizes the invading cell as either “self” or “not-self” and engulfs a “not-self” cell and lysosomes inside the macrophage digests the cell inflammatory response

Antibodies produced by lymphocytes lead to specific immunity 1. Antibodies: proteins that are produced by the body in response to a specific type of pathogen a) Each antibody is different because it response to a different pathogen b) Y-shaped protein b) Pathogen: made up of cells with cell membranes or is a virus made up of a capsid (protein coat)

Antigen: proteins embedded on the outer surface of the invader (bacteria) “not-self” proteins that trigger an immune response 3. Antibody has a binding site where it attaches itself to an antigen a) Antigen is on the surface of the pathogen , so the antibody becomes attached to the pathogen

Plasma cells (lymphocytes): leucocytes that produce antibodies a) Body has many different types of antibody producing plasma cells b)Each type of plasma cell produces one type of antibody c) Each cell only produces a small number of antibodies in comparison with the large number of pathogens during an infection d) Evolution of the immune system has provided a way for producing many of the same type of plasma cells when needed

Steps of a typical primary immune response a) Specific antigen is identified (cold virus) b) Specific plasma cell is identified that can produce an antibody that will bind to the antigen (proteins of the capsid coat of the cold virus) c) Specific plasma cell type clones itself (division by mitosis) to increase rapidly the number of that type of plasma cell d) Newly formed army of plasm cells begins antibody production

Newly released antibodies circulate in the bloodstream and eventually find their antigen match (proteins of the virus capsid) Using various mechanisms the antibodies help eliminate the pathogens Memory cells: some of the cloned plasma cells remain in the bloodstream and provide immunity against a second infection by the same pathogen Secondary immune response: Memory plasma cells respond quickly if the same antigen is encountered again

6. Vaccines: weakened or non-pathogenic forms of the pathogens that cause a primary immune response within your body Vaccine TED How vaccines work Small pox a) Leads to the production of memory cells as the actual disease would do b) If you encounter the real pathogen later, then the memory cells with imitate a quick secondary response c) Quick response stops any symptoms of the disease

What is HIV and how does it affect the human immune system? 1. HIV: human immunodeficiency virus: targets the lymphocytes cell types involved in the immune response a) Infected person will experience a severe drop in lymphocytes and lose the ability to produce adequate antibodies b) Takes many years after the initial infection before the person loses specific immune responses and it is then called AIDS (acquired immune deficiency syndrome)

How is HIV transmitted? a) Person to person contact through unprotected sex with an infected person b) Using a hypodermic needle that had been used by someone that is HIV-positive (HIV+) c) Transmitted from HIV+ mother to her child during pregnancy, labor, delivery, or breastfeeding d) Blood transfusions: now tested for contamination and not a risk

Use of antibiotics to combat bacterial infections 1. Bacteria: prokaryotic cells with a cell wall 2. Antibiotics: chemicals that selectively block some of the biochemistry needed by bacteria while having no effect on eukaryotic (human cells)

Many categories of antibiotics depending on the biochemical pathway that is being targeted a) May selectively block protein synthesis in bacteria b) May inhibit the production of a new wall way which can block their ability to grow and divide

Antibiotics have no effect on viruses, since they use the host cell to make new viruses a) Any chemical used to inhibit this would hurt host cell b) Viruses don’t have a metabolism of their own Virus

Bacterial resistance to antibiotics 1. Bacteria show genetic variation, reproduce quickly, and populations can be very large 2. Genetic variants exist that are not affected by any one antibiotic 3. Variants can reproduce and repopulate a colony that are all resistant to the antibiotic and become a new strain of bacteria

Long-term use and overuse of antibiotics has now led to many species of bacteria that have strains that are resistant to nearly all of the antibiotics available 5. MRSA: type of staph infection caused by Staphylococcus aureus that have developed resistance to many types of antibiotics and is very difficult to treat Antibiotic resistance

II. Antibody Production A II. Antibody Production A. Blood type antigens: example of the differences in plasma membrane proteins on red blood cells 1. Two blood types a) ABO blood type: based on the presence or absence of A and B protein b) Rh blood type (rhesus: type of monkey where it was discovered): based on the presence or absence of Rh protein

2. ABO pattern a) Type A: only A protein b) Type B: only B protein c) Type AB: both A and B proteins d) Type O: neither A or B proteins 3. Rh patterns a) Rh positive: has Rh protein b) Rh negative: doesn’t have Rh protein

4. Immune system treats incompatible blood like a virus or bacteria 5 4. Immune system treats incompatible blood like a virus or bacteria 5. Antibodies target the antigen proteins and causes the blood to clump Blood types

Steps of mammalian immune response 1. B lymphocyte (plasma cell): synthesizing and secreting a specific antibody that binds to a specific antigen a) Represent 1% of all the cells in blood b) Cellular communication methods that lead to cloning of the appropriate B-cell type to combat a specific antigen when needed

2. Large phagocytic leucocyte (macrophage): first to encounter an antigen and it engulfs the not-self antigen on a pathogen and digests it Antigen presentation: pieces of the invader are displayed on the cell membrane of the macrophage Helper T cells: leucocytes that can chemically recognize the antigen being presented and they become activated

Helper T-cells turn the immune response from non-specific to antigen-specific and they communicate with (activate) specific B-cell type B-cell type: produce the needed antibody

7. Order of communication a) Macrophage presents antigen b) Helper T becomes activated c) B lymphocyte becomes activated 8. Cell cloning: activated B-cell begins a series of cell divisions by mitosis and all the cells produced the same antibody

9. Two types of cloned cells a) Plasma cells: secrete antibodies and fight off the first infection b) Memory cells: do no secrete antibodies during the first infection, but are long lived cells that remain in blood waiting for the secondary infection

True immunity 1. Primary infection: include the events of antigen presentation, T-and B-cell activation and B-cell cloning a) Immune system helps to eradicate the pathogen, but the steps take time b) Pathogen produces symptoms associated with the disease

2. Second infection of the same pathogen: memory cells that were produced during the primary infection are still circulating in the blood a) Large number of memory cells respond to the same pathogen very quickly b) More antibodies are produced compared to the primary infection c) Usually the symptoms are not produced

Antibodies and how they help destroy pathogens 1. Antibodies: protein molecules produced by plasma cell leucocytes in response to a specific pathogen a) Antibodies have similar molecular structures b) Y-shaped and share many of the same amino acids sequences i) Binding sites: ends of the forks of the Y have two sequences of amino acids that are unique to each type of antibody

ii) Two binding sites of each antibody are ii) Two binding sites of each antibody are identical to each other and are capable of binding to the same type of antigen

Antibodies help the immune response in several ways a) Binding to the pathogen and marking it for destruction by other cells b) Use their two binding sites on two antigens causing the antigens to stick together and clump the pathogen so macrophages can find them for destruction

Vaccinations confer immunity without resulting in symptoms 1. Fundamental principle of immunity: organisms can’t be immune to a pathogen before being exposed to it at least once 2. Vaccine: composed of chemical components of a pathogen after eliminating the disease causing abilities of the pathogen

a) In 1796, Edward Jenner administered the. first a) In 1796, Edward Jenner administered the first vaccine by using cowpox pus to prevent infection of smallpox b) Vaccines act as the first exposure to the pathogen since the leucocytes responsible for the primary immune response still recognize the chemical components from the vaccine as antigens and not- self c) On subsequent exposure to the real pathogen, the secondary immune response is quicker and results in higher antibody production and usually no obvious symptoms are presented

World Health Organization began a campaign in 1967 to vaccinate the world against smallpox and in 1977, the last case was reported in Somalia Vaccination are no longer given since there is no one left to transmit the virus

Diseases that cross from one species to another 1. HIV/AIDS, SARS, Ebola, H1N1 2. Viral diseases that are serious and potentially deadly symptoms have all originated in one species and made the transition to infect another species (humans) 3. Viral transition from one species to another does not happen often in nature

a) Conditions and opportunity must be just right b) Protein match must occur for a virus to recognize a cell as a host c) Viral mutations allows the virus to enter a new type of host 4. More common for diseases resulting from bacteria and fungi to cross species barriers a) Tuberculosis, salmonella, and ring worm

5. Billions of viruses, bacteria, and other microbes on Earth, but only a very small percentage of the total number of microbes is pathogenic to any one species

Production of monoclonal antibodies 1. Polyclonal response: primary immune response by an organism since the pathogen is being recognized as many antigens a) Virus capsid (protein coat) is made up of several different proteins and each one can cause an immune response b) Several different kinds of plasma B cells undergo clonal selection so different antibodies are produced

2. Monoclonal antibodies: pure antibodies all of the same type (made by researchers using a unique procedure) a) Infection of an antigen into a lab animal (mouse): choice of the antigen is important since the antibodies produce will only bind to a specific antigen b) Animals go through a primary immune response c) Spleen of the animal is harvested in order to obtain many blood cells

d) Some leucocytes cloned for the antigen will be present e) B cells are kept alive by fusing them with cancerous (myeloma cells) and some form a hybrid cell called hybridoma f) Hybridoma cells produce antibodies and are very long lived and are transferred to an environment where only the hybridoma cells can survive g) Surviving hybridoma cells are cultured in separate containers

h) Container is tested for presence of a particular h) Container is tested for presence of a particular antibody by doing an enzyme-linked immunosorbent assay (ELISA) i) ELISA identifies which containers hold a pure colony of B cells that are producing the desired antibody j) Cells can be cultured for a very long time because of the characteristics of the tumor cells

Use monoclonal antibodies to diagnose pregnancy 1. Monoclonal antibodies can be used for a wide variety of diagnostic purposes including pregnancy 2. Embryo produces human chorionic gonadotropin (HCG) hormone and only pregnant women have this hormone in small amounts in blood and urine

3. Hybridoma cells can be formed that produce antibodies specific for HCG 4. Anti-HCG antibodies are chemically bonded to an enzyme that catalyzes a color change when the antibody encounters HCG molecules (Pregnancy tests include a color indicator)

III. Allergies are the result of an immune response releasing histamine A. Allergic response: occurs when a non- pathogenic substance (allergen) is encountered by certain leucocytes 1. Allergens can include harmless substances like pollen, peanuts, egg whites, and bee venom 2. First exposure to allergen produces a class of antibodies called IgE

3. Ig E antibodies bind to the allergen during a second exposure and trigger a response that leads to the mast cell releasing large amounts of histamine Histamine: chemical that causes the symptoms characteristics of an allergy (congestion, sneezing, itchy skin, red skin blotches, and other more serious symptoms Allergy animation