6.3: Defense Against Infectious Disease

Define "antigen." Understanding: Production of antibodies by lymphocytes in response to particular pathogens gives specific immunity.

An antigen is any molecule that causes the immune system to produce antibodies against it. This means the immune system does not recognize the substance, and is trying to fight it off. An antigen may be a substance from the environment, such as chemicals, bacteria, viruses, or pollen. In the case of autoimmune diseases, an antigen may also be a natural molecule inside the body.

Compare allowable research risks of the past with those of the present.​ Nature of Science: Risks associated with scientific research- Florey and Chain’s tests on the safety of penicillin would not be compliant with current protocol on testing.

Florey tested antibiotic effects on humans even though there were ethical issues and possible risks involved in these experiments relative to today's standards: Past: Small sample sizes No established protocols or rules to follow Impure drug samples Not enough of the drug for multiple tests Rushed, fast testing Consent not required Trial patients near death Present: Large sample sizes Well established protocols and rules to follow Highly purified drug samples Significant quantities of the drug can be synthesized Testing can take many years Consent must be given Healthy people often tested before sick

Outline the relationship between HIV and AIDS. Application: Effects of HIV on the immune system and methods of transmission.

HIV attacks cells of the immune system. Without treatment, the virus will reduce the number of functional CD4+ T cells. In the advanced stages of HIV infection, loss of the T cells leads to the symptomatic stage of infection known as the acquired immunodeficiency syndrome (AIDS). Symptoms of AIDS include: Rapid weight loss Recurring fever or night sweats Extreme and unexplained tiredness Prolonged swelling of the lymph glands Diarrhea Sores of the mouth, anus, or genitals Pneumonia

List ways the HIV virus is transmitted. Application: Effects of HIV on the immune system and methods of transmission.

HIV is found in body fluids such as blood, semen, vaginal fluids and breast milk. Infection only occurs when body fluids from an infected person enter the bloodstream of another person. HIV can be transmitted by: Sex without a condom Sharing needles, syringes and other equipment for injecting drugs Unsterile body piercing or tattooing Mother-to-child during pregnancy, childbirth or breastfeeding Blood transfusion and/or blood products in some countries

Explain methods and results of Florey and Chain’s experiments.​ Application: Florey and Chain’s experiments to test penicillin on bacterial infections in mice.

Howard Florey and Ernst Chain (1940) injected eight mice with a lethal suspension of bacteria, and four of these were also given the antibiotic penicillin. The four mice which received penicillin lived and the mice that were not given penicillin died. This experiment provided evidence that antibiotics could treat serious bacterial infections.

Define "lymphocytes." Understanding: Production of antibodies by lymphocytes in response to particular pathogens gives specific immunity.

Lymphocytes are a type of white blood cell. There are B and T type lymphocytes. B lymphocytes produce antibodies. Antibodies attach to a specific antigen and make it easier for the immune cells to destroy the antigen. T lymphocytes attack antigens directly. They also release chemicals, known as cytokines, which control the entire immune response.

State the function of the coronary arteries. Application: Causes and consequences of blood clot formation in coronary arteries.

The coronary arteries branch from the aorta and carry blood to the heart muscle itself, supplying it with the oxygen and nutrients that the heart cells needs to function.

Explain how the human body defends itself against pathogens. Essential Idea: The human body has structures and processes that resist the continuous threat of invasion by pathogens.

The first time of defense against pathogens is provided by skin and mucous membranes. Skin provides a physical barrier and mucus traps pathogens. Tears and mucus contain the enzyme lysozyme which destroy bacterial cell walls. Additionally, stomach, skin and vaginal mucus produce acid which kills pathogens. For example, sebaceous glands in the skin secrete fatty acids that make the surface of the skin acidic. If there is a cut in the skin, platelets activate the clotting cascade, creating a clot so pathogens cannot enter. If a pathogen makes it through those physical and chemical defenses, then phagocytic white blood cells can ingest and digest pathogens. These phagocytes provide non-specific immunity to disease. Specific immunity is provided by lymphocytes. Lymphocytes divide to produce clones of plasma cells which produce antibodies that are specific to an antigen. The binding of an antibody to an antigen stimulates destruction of the pathogen. Memory cells provide immunity against future attacks by the same antigen.

Summarize the primary (first line) of defense against infectious disease. Understanding: The skin and mucous membranes form a primary defense against pathogens that cause infectious disease.

The primary, " first line" of defense against infection are the surface barriers that prevent the entry of pathogens into the body. There are two main types of primary defences: the skin and mucous membranes. The skin acts as a physical barrier to prevent pathogens from entering our body. Mucus traps pathogens. Additionally, both the skin and mucous membranes release chemical secretions which restrict the growth of microbes on their surfaces.

Define "pathogen." Understanding: The skin and mucous membranes form a primary defense against pathogens that cause infectious disease.

A pathogen is a bacterium, virus, fungus or other microorganism that can cause disease can produce infectious disease.

Define "antibiotic." Understanding: Antibiotic blocks processes that occur in prokaryotic cells but not in eukaryotic cells.

Antibiotics are chemicals that destroy or slow down the growth of bacteria. They include a range of powerful drugs and are used to treat diseases caused by bacteria. Antibiotics cannot treat viral infections

List factors that are correlated with an increased risk of coronary thrombosis and heart attack. Application: Causes and consequences of blood clot formation in coronary arteries.

Coronary thrombosis is caused by a blood clot within the coronary arteries of the heart. The main factors that are correlated with coronary thrombosis are: -high LDL cholesterol -smoking -sedentary lifestyle -hypertension -diabetes -heart failure -obesity

Define coronary thrombosis. Application: Causes and consequences of blood clot formation in coronary arteries.

Coronary thrombosis is the formation of a blood clot inside a blood vessel of the heart. This blood clot restricts blood flow within the heart and can lead to myocardial infarction (heart attack).

List example disease defenses that provide non-specific immunity. Understanding: Ingestion of pathogens by phagocytic white blood cells gives non-specific immunity to diseases.

Examples of non-specific, innate immunity defenses include: 1. Lysozyme enzyme in tears, digest bacterial cell wall 2. Mucus, which traps bacteria and small particles 3. Skin, a physical barrier 4. Low pH of sweat, prevents growth of bacteria 5. Stomach acid, pH denatures microbial enzymes 6. Fatty acids in sweat, inhibit the growth of bacteria 7. Fever, temperature denatures microbial enzymes 8. Cilia in trachea, keep air passages free from pathogens 9. Phagocytic white blood cells, engulf and digest pathogens 10. Normal microbiome of the skin and in the gut can prevent the colonization of pathogenic bacteria by secreting toxic substances or by competing with pathogenic bacteria for nutrients or attachment to cell surfaces

Outline the role of fibrin in the blood clotting cascade. Understanding: The cascade results in the rapid conversion of fibrinogen to fibrin by thrombin.

Fibrin is a fibrous protein involved in the clotting of blood. It is formed by the action of the enzyme thrombin on its precursor molecule, fibrinogen. Fibrinogen is soluble and circulates in the blood until activated by thrombin. This ensures that a clot doesn't form when not necessary. Fibrin forms long strands of tough insoluble protein that are bound to platelets. The fibrin strands form a mesh atop the platelet plug that completes the clot.

Outline how genes confer antibiotic resistance to bacteria. Understanding: Some strains of bacteria have evolved with genes that confer resistance to antibiotics and some strains of bacteria have multiple resistance.​

Several mechanisms have evolved in bacteria which confer them with antibiotic resistance. Most, but not all, resistance mechanisms are encoded by genes located on plasmids. These genes for code proteins that either: 1. chemically modify the antibiotic in such a way that it no longer affects the bacteria (most common). 2. transport the antibiotic out of the cell. 3. modify the target of the antibiotics action so that it is not recognized by the antibiotic.

Define “specific immunity.” Understanding: Production of antibodies by lymphocytes in response to particular pathogens gives specific immunity.

Specific immunity, also known as adaptive or acquired immunity, is specialized immunity for particular pathogens. Specific immunity develops with exposure to pathogen specific molecules called antigens. The immune system builds a defense against that specific antigen.

Outline the mechanisms by which antibiotics kill prokaryotic cells. Understanding: Antibiotic blocks processes that occur in prokaryotic cells but not in eukaryotic cells.

Different families of antibiotics have different ways of killing bacteria. For example, some antibiotics: 1. ...block bacterial cell wall synthesis. Without support from a cell wall, pressure inside the cell becomes too much and the cell bursts. 2. ...inhibit the 70s bacterial ribosomes and prevent them from building proteins. A bacterium that cannot build proteins cannot survive. 3. ...cause the DNA strands to break and then prevent the breaks from being repaired. Without intact DNA, bacteria cannot live or reproduce.

List five measures that can be taken to avoid the development of antibiotic resistance in bacteria. Understanding: Some strains of bacteria have evolved with genes that confer resistance to antibiotics and some strains of bacteria have multiple resistance.​

1. Doctors should not prescribe antibiotics inappropriately, such as for the treatment of non-serious infections. 2. Antibiotics should not be prescribed to treat diseases caused by viruses. 3. Patients should always complete the full course of antibiotics to ensure all bacteria are killed and none survive to mutate and form resistant strains. 4. The agricultural use of antibiotics should be restricted. 5. Antibiotics should be disposed of properly, to avoid the chemicals contaminating environmental bacterial populations.

State two benefits of blood clotting when skin is cut. Understanding: Cuts in the skin are sealed by blood clotting.

A blood clot is a clump of blood that has changed from a liquid to a gel-like or semisolid state. Clotting is a necessary process that can: 1) Prevent excessive bleeding when a blood vessel is injured or cut. 2) Prevent pathogens from entering the body.

Outline the role of mucous membranes in the defense against pathogens.​ Understanding: The skin and mucous membranes form a primary defense against pathogens that cause infectious disease.

A mucous membrane (mucosa) is a tissue that lines cavities in the body at openings such as the eyes, ears, inside the nose, inside the mouth, lip, vagina, the urethral opening and the anus. Mucous membranes secrete mucus, a thick protective fluid. As a sticky fluid, mucus traps pathogens and prevents them from entering the body. Additionally, mucus can be acidic (eg in the stomach) which will kill some microbes. Mucus also contains the antibacterial enzyme lysozyme, which catalyzes the destruction of the cell walls of certain bacteria.

State an example of a multidrug resistant bacteria. Understanding: Some strains of bacteria have evolved with genes that confer resistance to antibiotics and some strains of bacteria have multiple resistance.​

A notorious example of multidrug resistant bacteria is methicillin-resistant Staphylococcus aureus (MRSA), which is resistant to most antibiotics and disinfectants. MRSA can act as a major source of hospital-acquired infections and cannot be treated easily.

Outline how natural selection has lead to antibiotic resistance in bacteria. Understanding: Some strains of bacteria have evolved with genes that confer resistance to antibiotics and some strains of bacteria have multiple resistance.​

Antibiotic resistance in bacteria is an example of natural selection leading to evolution. 1. A named example of a species; //Bacteria, such as Staphylococcus aureus.// 2. An outline of the different variations of a relevant trait; //Within populations, bacteria vary in their resistance to antibiotics. Some varieties are more resistant to antibiotics than others;// 3. A statement that the variation is genetically inherited. //Antibiotic resistance arises by random DNA gene mutation. Resistance is passed through binary fission to subsequent generations or transferred to other bacteria by plasmids.// 4. A statement of the selective pressure;//Antibiotics, which are chemicals used to treat bacterial diseases. // 5. Consequence of the selective pressure;//Antibiotic-sensitive bacteria are killed. Antibiotic resistant bacteria survive.// 6. More reproduction by better adapted individuals; //Antibiotic resistant bacteria reproduce and pass on resistance gene(s) to the next generation.// 7. The change in the population that results.//A larger proportion of the bacteria population is antibiotic-resistant. It becomes difficult to treat some infections.//

Explain why antibiotics are ineffective against viruses. Understanding: Viruses lack a metabolism and cannot therefore be treated with antibiotics.

Antibiotics are effective against bacteria but not against viruses. Antibiotics block specific metabolic pathways found in prokaryotic cells. Viruses do not have their own metabolic pathways (they reproduce using the host cell’s metabolic pathways) and therefore are not affected by antibiotics.

Define "antibiotic resistance." Understanding: Some strains of bacteria have evolved with genes that confer resistance to antibiotics and some strains of bacteria have multiple resistance.​

Antibiotics are medicines used to prevent and treat bacterial infections. Antibiotic resistance is when bacteria evolve the ability to survive exposure to antibiotics.

Explain why antibiotics are ineffective against eukaryotic cells. Understanding: Antibiotic blocks processes that occur in prokaryotic cells but not in eukaryotic cells.

Antibiotics work by affecting things that prokaryotic cells have but eukaryotic cells do not. For example: - prokaryotic cells have peptidoglycan in their cell wall, eukaryotic cells do not. The antibiotic penicillin works by keeping a bacterium from building a cell wall. - prokaryotic and eukaryotic cells differ in the molecules within their cell membranes. Some antibiotics dissolve the membrane of just bacterial cells. - prokaryotic cells have 70s ribosomes and eukaryotic cells have 80s ribosomes. Some antibiotics affect protein-building machinery that is specific to bacteria.

Describe the structure of antibodies. Understanding: Production of antibodies by lymphocytes in response to particular pathogens gives specific immunity.

Antibodies are immune system proteins called immunoglobulins produced by plasma B-cells. Each antibody consists of four polypeptides joined to form a "Y" shaped molecule. The tips of the "Y" varies greatly among different antibodies. This variable region, composed of 110-130 amino acids, give the antibody its specificity for a certain antigen.

Describe the function of antibodies. Understanding: Production of antibodies by lymphocytes in response to particular pathogens gives specific immunity.

Antibody proteins bind to specific antigen molecules. Once an antibody binds to an antigen, it inactivates the antigen in several ways: 1. Tag the pathogen or an infected cell for destruction by a phagocyte (opsonization). 2. Block the harmful effects of the toxin (neutralization). 3. Cause clumping for easier capture by phagocytes (agglutination).

Describe the consequences of the HIV on the immune system. Application: Effects of HIV on the immune system and methods of transmission.

Human Immunodeficiency Virus (HIV) attacks a specific type of immune system cell known as the CD4+ T cell. This cell plays an important role in the initiation of the specific immune response. When HIV destroys this cell, it becomes harder for the body to fight off infections and other illnesses develop.

Define "infectious disease." Understanding: The skin and mucous membranes form a primary defense against pathogens that cause infectious disease.

Infectious diseases are disease caused by organisms — such as bacteria, viruses, fungi or other microorganisms. Infectious disease can be spread, directly or indirectly, from one person to another.

Explain why multiple drug antibiotic resistance is especially dangerous. Understanding: Some strains of bacteria have evolved with genes that confer resistance to antibiotics and some strains of bacteria have multiple resistance.​

Large amounts of antibiotics used for human disease treatment and in agriculture have resulted in the selection of pathogenic bacteria that are resistant to multiple drugs. These strains of bacteria are especially dangerous for human health because there are no treatments for the associated disease. Multidrug resistance in bacteria may be generated by one of two mechanisms. First, these bacteria may accumulate multiple genes, each coding for resistance to a single drug, within a single cell. Second, multidrug resistance may also occur by the increased expression of genes that code for multidrug efflux pumps, transporting a wide range of drugs out of the cell before they have effect.

State the function of memory cells.​ Understanding: Production of antibodies by lymphocytes in response to particular pathogens gives specific immunity.

Memory cells, also called memory B cells, are important in generating an accelerated and more robust antibody-mediated immune response in the case of reinfection. During an initial infection, B cells are produced that are specific to the antigen. Most of these differentiate into the plasma B cells which produce antibodies and help clear the infection. Some of the cells persist as dormant memory B cells that survive in the body on a long-term basis. This allows the immune system to respond faster and more efficiently the next time it is exposed to the same antigen.

Define "non-specific immunity." Understanding: Ingestion of pathogens by phagocytic white blood cells gives non-specific immunity to diseases.

Non-specific, innate immunity is the defense system with which humans are born. It protects generically against all pathogens. Non-specific immunity includes physical and chemical barriers that keep harmful materials from entering the body and non-specific phagocytic immune cells that respond to each pathogen using the same mechanism.

Compare nonspecific with specific immune responses. Understanding: Production of antibodies by lymphocytes in response to particular pathogens gives specific immunity.

Nonspecific Innate. Present and ready at all times to respond to a pathogen. Not antigen specific and reacts equally well to a variety of pathogens. Does not demonstrate immunological memory. Specific Acquired with exposure to pathogens. Requires some time to amp-up reaction to a pathogen. Reacts only to a specific antigen specific. Demonstrates immunological memory. It “remembers” that it has encountered an invading organism and reacts more rapidly on subsequent exposure to the same organism.

State the function of plasma cells.​ Understanding: Production of antibodies by lymphocytes in response to particular pathogens gives specific immunity.

Plasma cells, also called plasma B cells, are lymphocytes that originate in the bone marrow and secrete large quantities of proteins called antibodies in response to exposure to specific antigens.

Outline two roles of platelets in the blood clotting cascade.​ Understanding: Clotting factors are released from platelets.

Platelets are one of the main components of blood and play an important role in preventing blood loss through clotting. Platelets have two roles in the formation of a blood clot: 1. When platelets come across the injured endothelium cells, they change shape, aggregate and adhere to each other at the damaged vessel wall. As platelets accumulate at the site, they form a mesh that plugs the injury. 2. Platelets release clotting factors in the blood. When a blood vessel is injured, the clotting cascade is initiated and each clotting factor is activated in a specific order to lead to the formation of the blood clot.

Outline the role of sebaceous glands in the defense against pathogens.​ Understanding: The skin and mucous membranes form a primary defense against pathogens that cause infectious disease.

Sebaceous glands in the skin secrete an oil called sebum that is released onto the skin surface through hair follicles. This sebum provides a layer of defense by helping seal off the pore of the hair follicle, preventing bacteria on the skin’s surface from invading sweat glands and surrounding tissue. Additionally, some bacteria of the microbiome can digest sebum, using it as a food source. This produces oleic acid, which creates a mildly acidic environment on the surface of the skin that is inhospitable to many pathogenic microbes.

Summarize the steps of the blood clotting cascade. Understanding: The cascade results in the rapid conversion of fibrinogen to fibrin by thrombin.

The process by which blood clots are formed involves a complex set of reactions collectively called the clotting cascade. This cascade is stimulated by clotting factors released from platelets and/or a damaged vessel wall. Clotting factors trigger the conversion of the inactive prothrombin into the activated enzyme thrombin, which in turn catalyses the conversion of the soluble plasma protein fibrinogen into an insoluble fibrous form called fibrin. The fibrin strands form a mesh of fibres around the platelet plug and traps blood cells to form a clot.

Outline the role of clotting factors in the blood clotting cascade. Understanding: Clotting factors are released from platelets.

The process by which blood clots are formed involves a complex set of reactions collectively called the clotting cascade. This cascade is stimulated by clotting factors released from platelets and/or a damaged vessel wall. Clotting factors: 1. ...cause platelets to become sticky and adhere to the damaged region to form a solid plug. 2. ...initiate vasoconstriction to reduce blood flow through the damaged region. 3. ...trigger a series of reactions that ends with the formation of a mesh of fibers around the platelet plug that traps blood cells to form a temporary, insoluble clot.

Outline the role of skin in the defense against pathogens.​ Understanding: The skin and mucous membranes form a primary defense against pathogens that cause infectious disease.

The skin provides a primary line of defense against pathogens. The skin is a physical barrier made of several layers of cells that prevent pathogen entry into the body. In addition, the skin: ...has a slightly acidic pH which prevents some bacteria from growing. ...secretes antimicrobial fatty acids. ...is relatively dry, which inhibits some bacterial growth. ...is populated with beneficial bacteria that prevent other bacteria from growing. ...secretes sweat, which contains the antimicrobial lysozyme enzyme (catalyzes the destruction of the cell walls of certain bacteria).

Explain antibody production. Understanding: Production of antibodies by lymphocytes in response to particular pathogens gives specific immunity.

There is a huge variety in the antibodies produced by the B cell lymphocytes. Each antibody recognizes one specific antigen. If the antigen is detected by the immune system, the B cell will the complementary antibody to the antigen responds by repeatedly dividing to form many clones. The cloned B cells secrete antibodies against the specific antigen. The binding of an antibody to an antigen stimulates destruction of the pathogen. Some of the cloned B cells will be long lasting memory cells that provided continued immunity if the antigen is again detected.

Outline the role of thrombin in the blood clotting cascade. Understanding: The cascade results in the rapid conversion of fibrinogen to fibrin by thrombin.

Thrombin is an enzyme involved in the blood clotting cascade. In order to prevent blood from clotting when it shouldn't, thrombin circulates in an inactive form called prothrombin. Prothrombin is produced and secreted into the blood by hepatocytes in the liver. Prothrombin is activated by clotting factors, which are released by platelets when a blood vessel is damaged. Clotting factors trigger the conversion of prothrombin to thrombin. Platelets have thrombin receptors on their surfaces that bind thrombin molecules. In turn, the thrombin enzyme converts soluble fibrinogen into insoluble strands of fibrin, which form the blood clot.

Outline the causes of coronary thrombosis. Application: Causes and consequences of blood clot formation in coronary arteries.

Thrombosis (coronary or otherwise) is caused by atherosclerosis. Atherosclerosis is a disease in which a waxy substance called plaque builds up inside the arteries. Over time, the plaque may cause the vessel to rupture. Platelets clump together to form a clot at the site of the damage.

Explain the role of various proteins in the immune defense against pathogens. Essential Idea: The human body has structures and processes that resist the continuous threat of invasion by pathogens.

Various proteins are involved in the immune defense against pathogens. For example: Clotting Factors Clotting factors are proteins that catalyze the blood clotting process. For example, thrombin is an enzyme that converts fibrinogen to fibrin. Fibrin is a protein that forms a mesh around a platelet plug that forms a clot and prevents the entry of pathogen into the blood. Antibodies Immunoglobulins are antibodies. Antibodies are proteins made by plasma B cells that are specific to certain an antigens. Once an antibody binds to an antigen, it inactivates the antigen. Digestive Enzymes Lysozyme is an enzyme that catalyzes the destruction of the cell walls of certain bacteria. There are also enzymes in the lysosome of phagocytic white blood cells digest the pathogens that have been phagocytosed by the cell.

Outline the function of phagocytic white blood cells in defense against pathogens.​ Understanding: Ingestion of pathogens by phagocytic white blood cells gives non-specific immunity to diseases.

White blood cells called macrophages are phagocytic cells that engulf and digest pathogens. These cells participate in the non-specific immune system response and therefore do not differentiate between types of pathogens (the cells do have the ability to discern between what is self and what is non-self). Phagocytic macrophages are able to leave the blood and squeeze through pores in the capillaries. They extend pseudopods around the pathogens. The pseudopods eventually surround the pathogen and engulf it, enclosing it in a phagosome. The phagosome merges with the cell's lysosome. Enzymes within the lysosome then digest the pathogen. Waste material is expelled via exocytosis.