Test #4, Chapters 15, 16 & 17

7). Understand that plasmids and lysogenic bacteriophages can contribute to pathogenicity of microorganisms.

Plasmids and Pathogenicity: - Plasmids can carry virulence factors. - Produces enzyme that works to decay teeth Lysogeny and Pathogenicity: - Bacteriophage can infect bacteria and remain in a latent state inside the bacteria = lysogenic. - Can increase pathogenicity of bacteria. Example of bacteriophage genes that contribute to pathogenicity: a). Diphtheria toxin b). Botulism neurotoxin Pathogenic Properties of viruses: - Viruses depend on the ability to gain access to the host. - Viruses penetrate into host cells and grow inside the host's cells. - The immune system is unable to attack virus inside cells. Cytopathic Effects of Viruses: - Visible effects of viral infection - Infection of host cells by animal virus usually kills the host cell. Death of host cell caused by: a). Accumulation of large number of multiplying viruses in a cell. b). Effects of viral proteins on the permeability of host cell's plasma membrane causing cell to go through lysis. c). Inhibition of host cell's DNA, RNA, and protein synthesis. Types of Cytopathic effects: Cytocidal effect = cytopathic effects that result in cell death. Noncytocidal effects are the cytopathic effect that result in cell damage but not cell death. Example of cytopathic effects 1). Virus causes the macro-molecular synthesis within the host cell to stop....sometimes irreversibly stopping mitosis (example Herpes virus). 2). Virus can cause cell's lysosomes to release their enzymes resulting in destruction of intracellular contents and host cell death. d). Virus changes the function of the cell or antigenic change of surface of infected cells. 3). Formation of a granule of virus particle known as an inclusion body that is located in the cytoplasm or nucleus of some infected cells; they are important in the ID of viruses (example measles, smallpox). 4). Several adjacent infected cells fuse to form a very large multinucleated cell called syncytium (example: measles, mumps, and common cold). 5).Change in cell function with no visible signs of infection. (Example: Measles causes reduce production of IL-2, reducing host ability to fight infection. 6). Viral infection can induce antigenic changes on surface of infected cell. These antigenic changes elicit a host antibody response against the infected cell, thus targeting the cell for destruction by hosts immune system.

3). What are antigenic determinants? - What are haptens?

What are antigenic determinants? - Antigenic determinants (epitopes) are regions on the antigen where the antibody recognizes and interacts. What are haptens? - Haptens are molecules too small to stimulate an antibody formation by itself. - Haptens can interact with a carrier molecule (large serum protein) and can now function as an antigen. Example: Penicillin = hapten - Reason why some people are allergic to penicillin.

10.) - How does the classical complement pathway work? - How does the alternative pathway work? - How does the lectin pathway work?

Classical Pathway: - Initiated by an antigen-antibody reaction - Antibody molecule attaches to an antigen - Antibody-antigen complex bind to activate C1 Alternative Pathway: - Activated by contact between certain complement proteins and a pathogen. - Complement proteins (factors) are attracted to microbial cell surface material. Lectin Pathway: - When macrophages ingest bacteria, viruses and other foreign matter by phagocytosis they release a chemical (cytokines) - Chemicals stimulate the liver to produce lectins Lectins = protein that bind to carbohydrates Example: Surface of bacteria contains Mannose containing carbohydrate: Lectin produced by body binds to bacteria and activates complement proteins.

10). What are antimicrobial substances that our body makes as part of the second line of defense? - Understand the complement system - Understand how proteins of complement system destroy microbes: Cytolysis, Inflammation, Phagocytosis

What are antimicrobial substances that our body makes as part of the second line of defense? Antimicrobial substance: a). Complement System: - Defensive system - Consists of over 30 proteins produced by the liver - Found in circulating blood serum and within tissue throughout the body Proteins of complement system destroy microbes by: a). Cytolysis b). Inflammation c). Phagocytosis - Prevents excessive damage to host tissue - Complement protein act in cascade, that is one reaction triggers another, which turns on another. Complement activation occurs: a). Classical pathway b). Alternative Pathway c). Lectin Pathway Activation of complement results in: a). Cytolysis b). Inflammation c). Phagocytosis Cytolysis: -C3b can also activate cytolysis - Several complement proteins join and attach to invading cell's plasma membrane and form a cylinder membrane shaped Membrane Attack complex (MAC) (complement proteins attach to plasma membrane of invading bacteria). - MAC creates a trans-membrane hole in the membrane which then causes water to enter the cell and ions to leave the cell = cytolysis Activation of Inflammation: -C3B can also activate - Complement proteins attach to mast cells which release histamine and other chemicals that increase blood vessel permeability and attract phagocytic cells (starts inflammation system)

3). Understand action of phagocytic cells....what is the order of events that happen,

Actions of Phagocytic cells: 1). Infection occurs 2). Granulocytes, especially neutrophils, and monocytes migrate to infected area. - Neutrophils are actively phagocytic. (Leads to increase in number of white blood counts.) 3). Monocytes need to mature and leave blood and enter tissue, where they enlarge and develop into macrophages - Macrophages now dominate: scavenge and phagocytize remaining cells.

5). How can microbes evade phagocytic cells...understand 3 ways that I talk about - How can microbe avoid attachment ? - How can a microbe survive inside phagocyte? - How can microbe kill phagocyte?

Examples of way microbes evade Phagocytosis: How can microbe avoid attachment ? 1). Avoidance of attachment: a). M protein on surface of Streptococcus pyogenes inhibits/makes difficult attachment of phagocyte to surface. b). Heavily encapsulated microorganism is not easily phagocytized because can slide away easily - Need to trap organism against a rough surface such as blood vessel or clot How can a microbe survive inside phagocyte? 2). Ingested in phagocyte but not killed a). Staphylococcus can be ingested but not killed Produces leukocidins that may kill phagocyte by causing the release of the phagocyte's own lysosomal enzyme into its cytoplasm. b). Streptococcus releases Streptolysin which is similar to above. How can microbe kill phagocyte? 3). Microbe survives inside phagocyte: a). Intracellular pathogens can secrete membrane attack complexes that lyse phagocyte cell membranes. -Listeria monocytogenes produces attack complex that lyses phagolysome membrane and microbe is released into cytoplasm of phagocyte and grows. - Will release more attack complexes to get released. b). The microorganism may need low pH inside phagolysosome to grow, so actually wants to get inside a phagocyte. - Coxiella burnetti c). The microorganism can prevent fusion of phagocyte and lysosome -HIV, Mycobacterium tuberculosis & Chlamydia all can prevent fusion of phagosome with lysosome - Multiply inside phagocyte and when phagocyte dies it is released

4). Understand factors that contribute to virulence of an organism. What do the following do to help organisms invade body and cause disease: 1.) Capsule 2.) M protein 3.) Enzymes: a.) Bacterial coagulates b.) Bacteria kinases c.) Bacterial hyaluronidases d.) Bacterial collagenase e.) IgA protease f.) antigenic variation - Production of proteins called invasions: how do these microbes penetrate?

Factors that contribute to the ability of a bacteria to invade: Contributes to virulence: 1. Capsule: - Impairs phagocytosis (engulfing and destroying). - Chemical nature of the capsule prevents the phagocytic cells from adhering to bacteria. - Example of bacteria that owe virulence to capsule: Klebsiella pneumoniae - Many nonpathogenic bacteria will produce a capsule, so just because one may have a capsule does not mean it's virulent. Contributes to virulence: 2. Proteins: - Produces a heat resistant and an acid resistant protein called M-protein. - Found on cell surface and fimbriae. - Mediates attachment of bacteria to epithelial cells of the host and helps bacterium resist phagocytosis. - Can also multiple inside phagocytes Contributes to virulence: 3. Enzymes: - Bacteria produce extracellular enzymes. - Can dissolve material between cells and form or dissolve blood clots. Example of enzymes: a.) Bacterial Coagulases: - Coagulates the fibrinogen in blood and forms blood clots. - Clot protects bacteria from phagocytosis and isolates from host defenses. - Can be involved in a walling off process when bacteria produce boil (Staphylococci). Contributes to virulence: b.) Bacteria Kinases: - Breaks down fibrin and dissolves clot formed by body that is suppose to isolate infection (Clostridia). Contributes to virulence: c.) Bacterial Hyaluronidases: - Digests hyaluronic acid, a type of polysaccharide that holds the connective tissues of cells together. - Involved in tissue blackening of infected wounds and helps microbes spread from the initial site of infection. Example: Gas Gangrene caused by Clostridia. Contributes to virulence: d.) Bacterial Collagenase: - Breakdown collagen which forms connective tissue of muscles and other body organs - Facilitates spread. Contributes to virulence: e.) IgA proteases: - The human body produces a class of antibodies called IgA, which is a defense against adherence of pathogens to surfaces. - Some pathogens produce an enzyme that can destroy antibodies and allow attachment. Example: Neisseria gonorrhoeae. Contributes to virulence: f.) Antigenic Variation: - The body produces antibodies in response to being introduced to an antigen. - An antibody binds to the antigen and inactivates or destroys them. - Some pathogens alter their surface antigens by a process called antigenic variation. - When a body mounts an immune response against a pathogen, the pathogen has already altered its antigen on their surface and the antibody can no longer bind, causing the cell to be unaffected by the antibody. Example: Neisseria gonorrhaeae Contributes to virulence: Invasins: Example: Salmonella and E. coli: - Contact with host cell's plasma membrane. - Produces proteins called invasins that can rearrange actin filaments of the cytoskeleton. - Causes a cytoplasmic structure to form a basket around the bacteria cell and move it inside the cell.

9). What is the function of fever in the body. - What causes a fever? - What does higher temperatures accomplish?

Fever: Part of second defense system - Systemic or all over body response to injury - Most frequent cause of fever is infection from bacteria and toxins or viruses. - Caused by release of cytokines by phagocytic cells. Function of fever in the body: - Body normal thermostat = 37°C set by hypothalamus - When the body invaded by pathogen cytokines are produced by phagocytes: a). IL-1 b). Alpha tumor necrosis factor -IL-1 causes hypothalamus to release prostaglandins causing the thermostat to reset to higher temp - Body adjusts to new thermostat by a). Blood vessel constriction b). Increased metabolism c). Shivering - Temperature remains high until Interleukin -1 is eliminated and thermostat is reset to 37°C - Heat loss mechanism by vasodilatation and sweating to lower temperature. - Fever is a defense mechanism against disease - IL-1 helps step up the production of T lymphocytes of the immune system (part of specific immunity). High temperature: - Intensifies the effects of Interferon (protein produced by the body in response to an infection) - Interferon is believed to inhibit the growth of some microorganisms by decreasing the amount of iron available. - Speeds up the body reactions (helps body to repair tissue)

3). How do microorganisms attach to host tissues? - What are adhesions or ligand? - What are receptors on the host cell? - What is a biofilm?

How do microorganisms attach to host tissues? Adherence: - A microorganism attaches to the host's tissue. - The surface molecules on pathogens are adhesion or ligands. - Adhesion molecules binds to receptors on certain host cells. What are adhesions or ligand? Adhesions or ligand: - The attachment between pathogen and host is accomplished by means of surface molecules on the pathogen called adhesions or ligands that bind specifically to complementary surface receptors on the cells of certain host tissues. - Adhesions or ligands are a carbohydrate-specific binding protein that projects from prokaryotic cells. Location of adhesion molecules on pathogen: a). Glycocalyx b). Pili c). Fimbraie d). Flagella What are receptors on the host cell? Receptor on a host cell: - The receptor on a host cell are sugar molecules, usually mannose. What is a biofilm? Biofilms: - Microbes have the ability to come together in masses, cling to surfaces, and take in and share available nutrients. These communities, which constitute masses of microbes and their extracellular products that can attach to living and nonliving surfaces, are called biofilms.

4). What are the four steps in phagocytosis? a). chemotaxis b). Adherence c). Ingestion d). Digestion - Understand what is going on in each step and how microorganisms are destroyed. - What is a phagolysosome & phagosome? - What is opsonization? - What is residual body?

Mechanism of Phagocytosis: a). Chemotaxis: - Chemical attraction of phagocytes to a microorganism. Chemicals that attract phagocytes: - Microbial products - Components of white blood cells - Damaged tissue - Peptides of complements b). Adherence: - Attachment of the phagocyte plasma membrane to the surface of the microorganism or other foreign material. - Microbe can be more readily phagocytized if they are coated with proteins that promote attachment = opsonization (done by complement system or antibodies) c). Ingestion: - The plasma membrane of the phagocyte extends projections called pseudopods. - Pseudopods meet and fuse surrounding the microorganism with a sac called phagosome - The membrane of phagosome has enzymes that pump protons (H+) into the phagosome reducing the pH to 4 At pH 4 = activation of hydrolytic enzymes d). Digestion - Phagosome pinches off the plasma membrane and enters the cytoplasm. - Phagosome contacts with lysosome that contains digestive enzymes and bactericidal substances Upon contact: Phagosome and lysosome fuse to form a single layer structure called phagolysosome. - Phagolysosome will destroy most types of bacteria in 10-30 minutes Phagolysosome contains: a). Lipases b). Proteases c). Lysozyme d). deoxyribonucleases - Enzymes digest contents of phagolysosome - Indigestible material in phagolysosome is called residual body. - Residual body moves toward the cell boundary and discharges its waste outside the cell

5). Microbes cause damage to host cell by? - How do bacteria get iron? - How do they cause direct damage?

Microbes cause damage to host cell by? How bacterial pathogens damage host cells: - Bacteria enter the host's cell and encounter phagocyte. a). Phagocyte will destroy microbe b). Pathogen overcomes phagocyte Microbe damages host cell: a). Using host nutrients b). Cause damage where invaded c). Produce toxins that are transported by blood or lymph system and cause damage to part away from the initial site. d). Produce hypersensitive reactions a). Using Host Nutrients: - Most bacterial pathogens need Iron to grow. - Iron in a body is bound to Iron transport proteins. How do bacteria get iron? Bacteria can get iron by: 1). When a pathogen needs iron, the pathogen secretes proteins called siderophores are released into the medium where they take the iron away from iron-transport proteins by binding the iron even more tightly. Once the iron-siderophore complex is formed, it is taken up by siderophore receptors on the bacterial surface & then brought into the bacterium. - Alternative to siderophores, some pathogens have receptors that bind directly to iron-transport proteins and hemoglobin. They are then taken into the bacterium directly along with the iron. - Some bacteria even produce toxins when iron levels are low. The toxins kill the host cell causing the release of their iron and thereby making it available to the bacteria. Iron can enter cells: a). Iron alone b). Iron-siderophore complex 2). Pathogen receptor for iron transport proteins - Bacteria will bind directly to iron transport proteins and take iron into cell to get iron. 3). Cell produces toxins - Toxins cause host cells to die and release iron, which can be used by bacteria. How do they cause direct damage? Direct Damage. Microbe causes direct damage by: 1). Use host cells for nutrients 2). Produce waste products - Microbes multiply in cells causing host cells to rupture. Or - Bacteria induce host cells to engulf and enter cells. - Disrupts activity of host cell and is extruded from the cell. - The microbe can now go disrupt other cells. Or - The microbe produce toxin.

1). What are nonspecific defenses of the host: - What is the first line of defense & how does it protect us? - What are mechanical factors? a. Skin b. Lacrimal apparatus c. Saliva d. Mucus e. Cilia lined hair f. epiglottis g. Urine flow

Nonspecific Defenses of the host: - Defenses that protect against any pathogen regardless of species First line of defense: - Intact skin - Mucous membrane & their secretions - Normal microbiota Mechanical Defense Factors of skin: The skin has two portions: - Dermis - Epidermis Dermis: - The skin's inner, thicker portion that is composed of connective tissue. Epidermis: - The outer thinner portion that is in direct contact with the environment - The epidermis is composed of many layers of continual sheets of tightly packed epithelial cells. - The top layer of the epidermis are dead cells that contain a protective protein called keratin. The skin provides Barriers to Microorganisms: - Closely packed cells - Continual layering - Presence of Keratin - Dryness and shedding of skin - The healthy intact epidermis is rarely penetrated by microorganisms Infections results of: - Cuts - Burns - Stab wounds Mechanical factors: b.) Lacrimal apparatus (mechanically helps protect epithelial surfaces:): - The lacrimal apparatus makes and drains tears in the eyes. - Provides continual washing action and prevents microbes from settling on the surface of the eye. - Secretes heavily when an irritant or large number of microbes get in the eye. Mechanical factors: c). Saliva: - Produced by salivary glands. - Saliva helps dilute the number of microbes and washes them from the surface of teeth and mucous membrane of the mouth. - Helps prevent colonization of microbes. Mechanical factors: d.) Mucous membranes: - Mucous membranes line the gastrointestinal tract & respiratory tract. - They consist of epithelial layers and connective tissue. - Epithelial cells secrete mucus Mucus: - A viscous glycoprotein produced by goblet cell of the mucous membrane - Prevents tracts from drying out and traps microbes that have entered. Mechanical factors: e.) Cilia: The lower respiratory tract is lined with cilia: - Helps propel upward in a synchronized beating of cilia. Nose lined with hair: - Traps microbes Mechanical factors: f.)Epiglottis: - Prevents microbes from entering the lower respiratory tract (covers larynx during swallowing). Mechanical factors: f.) Urine flow (genitourinary tract) - Flow of urine prevents colonization. - Vaginal secretions move microorganism out of the female body.

1). Understand what pathogenicity and virulence. How can a pathogen cause a disease?

Pathogenicity is the ability of a microorganism to cause disease by overcoming the defenses of a host. Virulence is the degree of pathogenicity of a microorganism. To cause Disease pathogens must: a). Gain access to host-portal of entry b). Adhere to host tissue c). Penetrate or evade host defense d). Damage the host tissue or accumulation of microbial waste products - Microbes that cause acne or dental caries don't penetrate the skin but they do cause problems.

6). Understand exotoxins and endotoxins....understand differences between them - Know three different types of exotoxins - What is shock? - What causes fever?

Production of toxins by bacteria: - Toxins are poisonous substances that are produced by some microbes. - Toxigenicity is the capacity of a microbe to produce a toxin. - Toxins that are produced by a microbe are transported around the body by the blood and lymph system. Toxins cause: a). Fever b). Cardiovascular disturbances c). Shock d). Diarrhea e). Inhibit protein synthesis f). Destroys blood cells and blood vessels g). Disrupts nervous system by causing spasms - 40% of toxins cause damage by damaging cell membrane Exotoxins: - Produced in some bacteria as part of the growth and metabolism process. - Secreted into the surrounding medium or released following lysis of the host cell. - Toxin is a protein that catalyzes many reactions. - Even small amounts of toxins can cause damage because they can be used over and over. - Produced by both gram negative and gram positive cells. - The ability to produce can be carried by plasmids or bacteriophages. Exotoxins: - Symptoms are specific (except for superantigens) Depends on where toxin attaches and binds. - Why get different response depending on which cells they bind to. Work by: a). Destroys parts of hosts cells b). Inhibiting certain metabolic functions Exotoxins: - Are highly specific in effects only certain/specific cells or functions of host - One of the most lethal substances known Example: 1 mg botulism toxin kills 1 million guinea pigs. - When exotoxins are produced, bacterial diseases are usually caused by exotoxin, and not by presence of bacteria. Example: Botulism is from ingesting toxin and not bacteria infection. Can use Exotoxin as way to produce Vaccine: - Body produces antitoxins to provide immunity to exotoxin. 1). Can inactivate toxin with heat or formaldehyde 2). Inject inactivated toxin into body 3). Body will produce antitoxin without host getting disease. Example: Diphtheria and Tetanus vaccines 3 Types of exotoxins: different structures: a). A-B toxin b). Membrane disrupting c). Superantigens A-B toxins: - Consists of two part (A and B) A = Active enzyme component B= Binding component Example of A-B toxin = Diphtheria 1). A-B toxin is released by bacteria 2). B part binds to surface receptor of particular host cell. 3). A-B toxin is transported across the plasma membrane into the host cell's cytoplasm 4). A-B components separate -A inhibits protein synthesis and kills host cell Membrane Disrupting Toxins: - Causes lysis of a host cell by disrupting the plasma membrane. a). Forms protein channels in plasma membrane b). Disrupts phospholipid's structure of the membrane. - Contributes to virulence by killing host cells, especially phagocytes. - Aids in bacteria escaping from sacs in phagocyte Example: Staphylococcus aureus: forms protein channels Clostridium perfrigens: disrupts phospholipids structure. Superantigens: - Antigens that provoke an intense immune response. Superantigen is a bacterial protein release by the organism. What supergantigens do: - Nonspecifically stimulates proliferation of immune cells called T cell (white blood cells). - Acts against foreign organisms and tissue. - Regulate activation and proliferation of other cells of the immune response. - T cells release chemical called cytokines - Cytokines are protein hormones that stimulate or inhibit normal functions of cells. Excessive high level of cytokines enter blood stream and cause: a). Fever b). Nausea c). Vomiting d). Diarrhea e). Possible shock and death Example of an organism that produces superantigen: - Staphylococcal toxins that cause food poisoning and toxic shock. Endotoxins: - Caused by the lipid A portion of the outer membrane of a cell wall of gram-negative cells. - Lipid A is the lipopolysaccharide of the outer membrane. (Exotoxins are proteins) = Endotoxins are released when gram-negative bacteria undergo lysis and the cell wall is broken down and lipid A is released. - The reason why sometimes symptoms get worse when you take an antibiotic before they get better is that of the lysing/release of bacteria. - Stimulates macrophages to release cytokines in very high concentration. - All endotoxins produce the same signs and symptoms: Fever, Weakness, Aches, Sometimes shock and also death. - Can also activate blood clotting proteins causing the formation of small blood clots. - Obstruct capillaries, decrease blood supply and cause the death of some tissue. - Endotoxins do not promote antitoxin formation because of their carbohydrate structure. so you can't produce vaccines from endotoxins. -Antibodies are produced against the organism but do not counter the effects of the toxin. - Material that has been sterilized may still contain endotoxins even though you can't culture any living bacteria. How endotoxin cause a fever: 1). Bacteria is ingested by phagocyte. 2). Bacteria is degraded in vacuole of phagocyte - Lipid A of cell wall released (endotoxin released) 3). Endotoxin causes macrophage to produce a cytokine called interleukin 1 (IL-1). 4). IL-1 is carried via the blood to the hypothalamus (Temperature control center of blood). 5). IL-1 induces the hypothalamus to release lipids called prostaglandins. - Resets the thermostat in the hypothalamus at a higher temp causing a fever. - Aspirin and Acetaminophen reduce fever by inhibiting the synthesis of prostaglandins Effect of High temperature: (what is fever doing): - Intensifies the effects of Interferon (a protein produced by the body in response to an infection). - Interferon is believed to inhibit the growth of some microorganisms by decreasing the amount of iron available. - Speeds up the bodiy's reactions (helps body to repair tissue). Shock: - Is the life-threatening loss of blood pressure. - Related to secretions of a cytokine (protein) by macrophages in response to bacterial infection. - Phagocytosis of gram-negative bacteria cause the phagoctye to secrete the cytokine tumor necrosis factor. - Tumor necrosis factor binds to many tissues in the body and alters their metabolism and damages blood capillaries by increasing their permeability and causes loss of fluids which results in the drop in blood pressure. - If blood pressure drops too far it causes damage to kidneys, lungs, & the gastrointestinal tract.

2). What is the second line of defense? - What is phagocytosis? - What are the two types of leukocytes: granulocytes and Agranulocytes? - What are 3 types of granulocytes? What does each one do? - What are the types of Agranulocytes? What does each do? - How are phagocytes activated?

Second line of defense: - Phagocytes - Inflammation and fever - Production of antimicrobial substances - Complement system - Interferons What is phagocytosis? Phagocytosis: - The way in which the human body counters infection. - Ingestion of a microorganism or other particles by a cell. Phagocytes: cells, which are all white blood cells Leukocytes: white blood cells During infection: - Total number of white blood cells increases as a protective response to combat microbes, this response is called leukocytosis. What are the two types of leukocytes? granulocytes and Agranulocytes 2 types of Leukocytes: a). Granulocytes: - Can see large granules in cytoplasm with a light microscope. b). Agranulocytes - Can't see granules with microscope. What are 3 types of granulocytes? What does each one do? 3 Types of granulocytes: a). Neutrophils: - Neutrophils are highly phagocytic and motile. - Neutrophils are active in the initial stage of infection. - Neutrophils have the ability to leave the blood, enter infected tissue, and destroy microbes and foreign particles. b). Basophils: - Basophils release substances such as histamine - Important in inflammation and allergic reactions c). Eosinophils: - Eosinophils have some phagocytic properties and ability to leave blood - Eosinophils produce toxic proteins against certain parasites. - Eosinophil numbers increase during parasitic worm infections and allergy reactions. What are the types of Agranulocytes? What does each do? Agranulocytes: a). Monocytes: - Monocytes are not actively phagocytic until they leave circulating blood, enter body tissue, and mature into a macrophage (a large phagocytic cell found in stationary form in the tissues or as a mobile white blood cell, especially at sites of infection). - The maturation and proliferation of macrophages is one factor responsible for swelling of lymph nodes during an infection (along with lymphocytes) - Macrophages will remove microorganism and also dispose of worn-out blood cells b). Lymphocytes: (T cells and B cells) - Not phagocytic - Play a role in specific immunity Occur in lymphoid tissue of lymphatic system: - Tonsils, Spleen, Thymus, Thoracic duct, lymph nodes, respiratory, gastrointestinal, and circulate in blood. How are phagocytes activated? Phagocytes may be activated by: a). Components of bacteria - Lipid A, Lipopolysaccahride of cell wall b). Cytokines - Small protein hormones secreted by phagocytes and other cells of the immune system.

8). Understand what tissue repair is and how it works

Tissue Repair: - Final stage of inflammation - The way tissue replaces dead or damaged cells - Begins during active phase of inflammation - Cannot complete until all harmful substances have been removed or neutralized at site of injury - Ability for tissue to regenerate or repair self depends on the type of tissue. - Skin = high regeneration rate - Cardiac muscle = no regeneration Tissue is repaired when it produces new cells by: stroma= supporting connective tissue (not involved in function) or parenchyma = functional part of tissue produces new cells

7). Understand complete phagocyte migration and phagocytosis process - What is margination - What are macrophages: how are they made? - What is pus?

Understand complete phagocyte migration and phagocytosis process: Phagocyte Migration and Phagocytosis: Process: - Phagocytes appear within an hour of initiated inflammation. - Blood flow gradually decreases. - Phagocyte stick to the inner surface of the blood vessel (neutrophils and monocytes). What is margination - Sticking process = margination - Collected phagocytes begin to squeeze between blood vessels to reach damaged area - Migration process = immigration - Chemicals attract neutrophils to site of injury = chemotaxis Chemicals: - Chemical produced by microorganism - Kinins, leukotrienes, components of complement -Steady stream of neutrophils is ensured by the production and release of additional granulocytes by bone marrow. - Monocytes now follow the granulocytes to infected area - Once Monocytes are contained in the tissue they undergo a change in biological properties and become wandering macrophages - Granulocytes predominate in early stages of infection but tend to die off - Macrophages enter during later stage of infection What are macrophages: how are they made? - Macrophages are more phagocytic then granulocytes and are large enough to phagocytize: a). Tissue that has been destroyed b). Granulocytes that have been destroyed c). Invading microorganism What is pus? - Granulocytes and macrophages engulf large numbers of microorganisms and damaged tissue and eventually die = pus formation - Pus = mixture of dead cells and body fluids Pus is then: a). Pushed to surface of body or into internal cavity for disposal b). Pus remains after infection stops and gradually destroyed over time or absorbed by body

4). Understand what antibodies are and what antigen binding site is? - What is the structure of antibodies? - What are the five classes of antibodies and what do they do?

Understand what antibodies are and what antigen binding site is? - Antibodies (Immunoglobins) are proteins made in response to an antigen. - Antibodies can recognize and bind to an antigen. - Antibodies are highly specific in recognizing the antigen that stimulated their original formation. - An antigen has several antigenic determination sites which cause the production of different antibodies against the same antigen. - An antigen binding site: (On the antibody) binds to an antigenic determinant. What is the structure of antibodies? - The structure of a typical antibody: is 4 protein chains, 2 are light chains and 2 are heavy chains - The variable region reflects the nature of the antigen for which they are specific. - The constant region reflects the class of an antibody. There are 5 classes. - The Fc region is the stem, the part of the antibody that can bind to complement or binds to cells to invoke allergic reactions. What are the five classes of antibodies and what do they do? 5 Classes: -IgG -IgM -IgA -IgD -IgE IgG: - 80% of all antibodies in serum - IgG = most abundant in serum - Able to cross walls of blood vessels and enter tissue. - Protects against circulating bacteria and viruses - Neutralizes bacterial toxins - Triggers complement system (Classical activation pathway) - Enhances effect of phagocytosis when bound to an antigen. - Provides protection for fetus and newborns. - Monomer structure IgM: - 5-10% of antibodies in serum - Pentamer structure - 5 monomers held together by chains - Involved in ABO blood group antigens - IGM is the first antibody produced in response to the initial infection. - IGM enhances ingestion of target cells by phagocytic cells. IgA: - 10-15% of antibodies in serum - Most common form in mucous membrane and in body secretions (tears, breast milk) - Prevents attachment of pathogen to mucosal surfaces - IgA = most abundant in body (IgG = most abundant in serum) - There are two forms - the monomer form and the dimer form = secretory IgA. - Produced by plasma cells of mucous membrane. - Prevents attachment of pathogens to mucosal surface - Short lived. Immunity against respiratory infections is short. IgD: -.2% of antibodies in serum - Monomer structure - Found in blood and lymph and surface of B cells - Act as antigen receptor on surface of B cells IgE: - Monomer structure - .002% of total serum - Involved in allergic reactions: - Binds tightly by Fc stem region to receptors on mast cells and basophiles - If antigen reacts with IgE antibody attached to mast cell or basophile causes cell to release histamine.

- What are chemical factors of nonspecific defenses of the host? a. Sebaceous glands b. Sweat glands c. Gastric juices d.) Vaginal secretions e.) Iron binding proteins

What are chemical factors of nonspecific defenses of the host? a). Sebaceous (oil) glands of skin - Produces oily substance called sebum. - Prevents hair from drying out and becoming brittle. - Forms protective film over the surface of skin. - Inhibits the growth of some pathogenic bacteria pH of skin 3-5 - Bacteria that live commensally on skin, decompose sloughed skin cells and produce body odor as end product of metabolism. Chemical factors of nonspecific defenses of the host: b.) Sweat glands - Produce perspiration. - Helps maintain body temperature. - Eliminates certain waste products of the body. - Flushes microorganism from the surface of the skin. - Perspiration contains lysozyme which breaks down bonds of peptidoglycan. - Lysozyme is also found in tears, saliva, & nasal secretions. Chemical factors of nonspecific defenses of the host: c.) Gastric Juices produced by glands of stomach: - Mixture of hydrochloric acid, enzymes & mucus. - High acidy = pH 1.2-3.0 which can destroy most bacteria. - Pathogens can be protected by food particles and enter intestines via the gastrointestinal tract - Helicobacter pylori: causes stomach ulcers because neutralizes stomach acids Chemical factors of nonspecific defenses of the host: d). Vaginal secretions: - Slightly acidic which discourages growth. Chemical factors of nonspecific defenses of the host: e). Iron binding proteins: Transferrins: - Iron is not free in the body, it is bound to proteins so microbes can't use it easily. - Iron overload increases risk of infection

2). What are the portals of entry? - What does perenteral entry route mean? - What is a preferred entry route? - What is the ID 50?

What are the portals of entry? 1). Portals of entry: way microbes gain access to Body: A). Mucous Membrane (penetrates mucous membrane lining) 1). Respiratory tract 2). Gastrointestinal tract 3). Genitourinary Tract 4). Conjunctiva of the eye (a delicate membrane that covers the eyeballs and lines the eyelids.) Respiratory tract: - The most common place of entry. - Inhaled through the nose or throat. Example of diseases: Cold, Flu, Pneumonia, Smallpox Gastrointestinal tract: - Eat/drink contaminated food or water. - Most microbes are destroyed by stomach acid but the ones that survive cause disease. Example of diseases: Cholera, hepatitis A, Salmonella. Genitourinary Tract: - Sexual contact Example of disease: HIV, Chlamydia, Herpes. Conjunctiva of the eye: - A delicate membrane that covers the eyeballs and lines the eyelids. - Although a relatively effective barrier against infection, certain diseases such as conjunctivitis, trachoma, and ophthalmic neonatorium are acquired through the conjunctiva. What does parenteral entry route mean? - The parenteral entry route is when the skin barrier is penetrated or broken. B). Skin Unbroken skin is impenetrable by most microorganisms. - Microbes can gain access through hair follicles, sweat glands or when the skin barrier is penetrated or broken which is then considered a parenteral route of entry. Example: Bites, cuts, surgery. Microorganism has a preferred entry route: - If an organism gains access in another route it is less likely to cause disease. - The occurrence of a disease depends on many factors, only one of which is the portal of entry. Even if a microorganism enters the body, it doesn't necessarily cause disease. What is a preferred entry route? Example of preferred entry route: Rabies (skin) Salmonella enteria (gastrointestinal tract) Measles (respiratory tract) A number of pathogens increase the likelihood of disease increase. Virulence of microbe is expressed as ID 50: - If only a few microbes enter the body, they will probably be overcome by the host's defenses. However, f large numbers of microbes gain entry, the stage is probably set for disease. - THe likelyhood of disease increases as he numner of pathogens increases. - The number of microbes that cause 50% of the sample population to get the disease. - This may depend on the portal of entry.

5). What do B cells do? produce antibodies - How are B cells formed? - How are antibodies produced? - Understand that each B cell produces antibodies against 1 antigen, but you have a large population of antibodies. - What is clonal selection and how does it work? Produces antibodies and memory cells for long term immunity.

What do B cells do? (Humoral Immunity) - Production of antibodies starts when B cells are exposed to free antigens and are activated. How are B cells formed? - B cells develop from stem cells located in the red bone marrow in adults (liver in fetus). - Mature B cells migrate to lymph nodes or spleen (lymphoid organs) - B cells recognizes antigen by means of antigen receptors found on cell surface - Production of antibodies start when B cells are exposed to free antigens and are activated How are antibodies produced? - Understand that each B cell produces antibodies against 1 antigen, but you have a large population of antibodies. B cell activation and antibody production: Activation of antibody: - Each B cell produces antibodies against 1 kind of antigen. - Total population of B cells = produce assortment of antibodies. - A person can respond to as many as 100 million different antigens What is clonal selection and how does it work? Produces antibodies and memory cells for long term immunity. B cell activation and clonal selection: -Antigen binds directly to antigen receptor on B cells: B cell becomes activated -B cells proliferate into clone of B cells, which differentiate into 1). Long lived memory cells 2). Plasma cells which secrete antibodies During process: -Antigen selects the immune cell (lymphocyte) that will multiply to form a clone of cells with the same immunological specificity

6). What is apoptosis and how does it happen -why do we need apoptosis and what happen if apoptosis is not working -what is necrotic death and what does it cause to happen

What is apoptosis and how does it happen? How does the population of immune cells stays in check: Apoptosis: -programmed cell death by enzymes called caspases Human body makes ~ 100 million lymphocytes / day -Need ~ 100 million to day / die -if don't = leukemia (proliferation of lymphocytes) Process of apoptosis: 1). Cut genome into fragments 2). External membrane bulges outward in a manner called blebbing 3). Signal are displayed on cells surface that attract circulating phagocytes to digest remain of cell before leakage of contents occurs -way of getting rid of cells without inducing inflammatory response

6). What is inflammation? - What are four signs of inflammation? - What is the function of inflammation? - What are the 3 stages of inflammation? Understand what happens in each step. - What causes vasodilatation? What are chemicals that cause this?

What is inflammation? Inflammation - Inflammation is part of the second defense mechanism of the nonspecific defense mechanism - Inflammation is a local response of the body to damaged tissue (injury). What are four signs of inflammation? Signs of inflammation: a). Redness b). Pain c). Heat d). Swelling Function of Inflammation: a). Destroys the agent that caused injury and removes it. b). If destruction is not possible then inflammation limits the effect on the body by confining or walling off the injuring agent. c). Repair or replace tissue damaged by the injuring agent. What are the 3 stages of inflammation? Understand what happens in each step. 3 Stages of Inflammation: 1). Vasodilation - increase the permeability of blood vessels 2). Phagocyte migration and phagocytosis 3). Tissue repair What causes vasodilatation? What are chemicals that cause this? 1). Vasodilation - increases the permeability of blood vessels: - Vasodilation occurs after initial damage to tissue - Blood vessels dilate in the damaged area and permeability increases. - Increased blood flow to damage is the cause of redness and heat associated with inflammation. - Vasodilation allows the defense substances that are normally retained in blood to pass through the walls of the blood vessel and enter the injured area (granulocytes-Neutrophils and monocytes). - Causes fluid to also move into area = swelling - Helps deliver clotting elements into the injured area - Blood clot forms to prevent microbes from spreading Pain of inflammation can be caused by: a). Nerve damage b). Irritation by toxins of microorganisms c). Pressure from swelling Vasodilation is the result of chemicals released by damaged cells in response to injury: Chemicals: a). Histamine- released by Basophil cells-attract phagocytic cells b). Kinins - attracts phagocytic granulocytes c). Prostoglandins - intensify effect of histamine and kinins. -helps phagocytes move through capillary walls d). Leukotrienes - causes increased permeability of blood vessel and helps attack phagocyte to pathogen.

11). What is interferon and how does if protect host cells? - What is the function of interferon? - How does interferon work without harming the host? - What does alpha, beta, and gamma interferon do and why are they not good antiviral drugs ?

What is interferon and how does if protect host cells? Interferons: (the activity of these proteins increases with fever) - Counter viral and bacterial infection without affecting the host's cells. What is the function of interferon? - Function = to interfere with viral and bacterial multiplication How does interferon work without harming the host? - Plays a role in acute and short-term viruses (cold) Interferon is host and cell-specific, not virus specific. - Interferon produced by human cells only protects human cells. - Different cells produce different types of interferon What does alpha, beta, and gamma interferon do and why are they not good antiviral drugs ? Human interferon : 3 types: a). Alpha interferon b). Beta interferon c). Gamma interferon -produced by fibroblast cells in connective tissue and by lymphocytes Alpha and Beta interferon: - Produced by virus-infected host cells in small quantities - Diffuse to uninfected neighboring cells - React with plasma membrane receptors inducing the uninfected cells to manufacture mRNA for the synthesis of antiviral proteins (AVP) - Antiviral proteins disrupt various stages of viral multiplication Examples of Antiviral proteins: a). Oligoadenylate synthase: degrade viral mRNA b). Proteins kinase: inhibits viral synthesis. Gamma interferon: - Produced by lymphocytes - Induces neutrophils and macrophages to kill bacteria by phagocytosis Interferons are not a good class of antiviral drugs: 1). Only effective for short period 2). Cause side effects such as nausea, fatigue, vomiting if inject into body 3). High concentrations are toxic to liver and kidney 4). Have no effect on viral multiplication in cells already infected 5). Some viruses have a resistant mechanism that inhibit antiviral proteins 6). Some viruses don't stimulate the host cell to produce enough antiviral proteins

2). What is meant by humoral immunity and cell-mediated immunity? - What is humoral immunity effective against and how are the antibodies produced? - What are cell-mediated immunity effective against? - - What do T cells do?

What is meant by humoral immunity and cell-mediated immunity?? - Humoral immunity is effective against freely circulating pathogens. - Humoral immunity is an antibody-mediated immunity. What is humoral immunity effective against? - Production of antibodies that act against foreign organisms and substances. Antibodies are found in extracellular fluids such as blood plasma, lymph, and mucous secretions. How are the antibodies produced? - B Cells are responsible for the production of antibodies. - Antibodies take care of bacteria, toxins, and viruses circulating freely in the body. What is cell-mediated immunity effective against? - Cell-mediated immunity is effective against intracellular pathogens, foreign organisms, or tissue. - Cell-mediated immunity involves specialized lymphocytes called T cells. What do T cells do? - T cells regulate the activation and proliferation of other immune system cells. - For example: T cells activate macrophages. - T-cells are effective against bacteria and viruses located within phagocytic or infected host cells (not free living). - Cell-mediated immunity is not transferred to the fetus via placenta. - Requires the continued presence of the antigen for Effectiveness

1). What is meant by specific defenses of the host? - What is an antigen? - What is an antibody? - What is acquired immunity? - What is the difference between active and passive immunity? - What is Naturally acquired immunity vs. active? - What is artificially acquired immunity and how do you acquire it actively or passively?

What is meant by specific defenses of the host? The immune response is a specific defense of the host. What is an antigen? - An antigen is a substance that provokes a specific response. What is an antibody? - Antibodies are proteins produced by the immune response. What is acquired immunity? - Acquired immunity is protection a host develops against certain types of microbes or foreign substances. It is developed during a lifetime. What is the difference between active and passive immunity? - With active immunity, a person is exposed to a microorganism or foreign substance and the immune system responds. - With passive immunity, antibodies are transferred from one person to another. The person is only protected while the antibodies are present (weak). What is naturally-acquired active immunity vs. passive? - Naturally acquired active immunity is when a person is exposed to an antigen in the course of their lifetime. - Immunity is lifelong for some disease and shorter for other. - For example: Lifelong = chickenpox - Shorter term (years) = many intestinal diseases - Naturally-acquired passive immunity is the natural transfer of antibodies from a mother to her infant. a). In transplacental transfer, the mother transfers antibodies to the baby across the placenta. This provides temporary immunity to the baby. b). Transfer through breast milk: - The immunity will last as long as the antibodies are there. - This naturally-acquired passive immunity provides immunity until infant's own system matures. What is artificially-acquired immunity and how do you acquire it actively or passively? - Artificially-acquired immunity is provided by vaccination or immunization which introduces antigens called vaccines into the body. - These vaccines can be: a). Inactivated bacterial toxins b). Killed microorganisms c). Attenuated microorganisms d). Or part of the microbe, such as the capsule - Vaccines don't cause disease but they do stimulate the immune response. - Artificially-acquired passive immunity is the introduction of antibodies into a body. - These antibodies come from an animal or a person who is immune to the disease (antibodies found in the serum of blood). - Comes from blood fraction that is rich in antibodies. - Artificially-acquired passive immunity provides immediate immunity but it is short-lived because the antibodies become degraded by the recipient.