Custom Study Session 11-13

#separator:tab #html:true interplay between microbe, its virulence factors, and function of the immune system to determine if infection is possible, mild, or severe Outcome of infection functions to recognize and destroy foreign molecules, invading microbes and their products, and mutant or damaged cellsImmune system provides a broader response to a variety of pathogens but not sufficiently equiped to handle foreign pathogens nonspecific, inherent, present at birth and acts before the infection does not require any previous exposure to microbesInnate Immune System exactly equipped to fight off certain pathogens; takes longer to respond Specific and develops over time as a response to infectionsAdaptive Immune System allergic reaction when immune system goes into overdrive (immune system becomes very sensitive)Hypersensitivity reaction adverse immune response to protein molecules associated with allergensAllergies failure of immune system to distinguish self from non-selfAutoimmune disease components that microbes have but human cells do not innate immune cells rely on PAMPs to identify and respond to an infection ex. cell wall components, flagella, certain carbohydrate structures used by the innate immune system*Pathogen-associated molecular patterns (PAMPs) innate immune cells (most notably white blood cells/leukocytes) have these receptors to recognize PAMPs used by the innate immune system*Pattern Recognition Receptors (PRRs) Immune system that relies on lymphocytes, specifically T cells and B cells, as well as their receptorsAdaptive Immune System* red blood cellserythrocytes  white blood cells; responsible for most immune functionleukocytes Platelets Thrombocytes  neutrophils, eosinophils, basophils deal with innate immune systemGranulocytes make up 60-70% of leukocytes in the human body; deal with phagocytosis primarily deals with innate immune systemneutrophils  make up 2-4% of leukocytes; deal with inflammatory response had has limited phagocytosis ability; some are infectious primarily deals with innate immune systemEosinophils Make up .5-1%; not clear what they deal with, contain histamine primarily for innate immune systemBasophils lymphocytes monocytes B and T lmyphocytes (B and T cells) Natural killer (NK) cells primarily deals with adaptive immune systemAgranulocytes lymphocytes that produce an antibody response mostly adaptive immune systemB lymphocytes (B cells) lymphocytes that are neccessary for adaptive immunity mostly deals with adaptive immune systemT lymphocytes (T cells) lymphocytes that give an innate response to viral infection deals with innate immune systemNatural Killre (NK) cells cells responsible for the process of phagocytosis make up 3-8% of total blood leukocytes primarily deals with innate immune systemmonocytes cells responsible for antibody-formation cell mediated immunity make up 25-35% of total blood leukocytes  primarily deals with adaptive immune systemlymphocytes produced by cells function as the voices of cell; induces growth, differentiation, movement, and cell deathCytokines  located on the surface of cells functions for cell to cell adhesion (grabbing of other cells)Adhesion molecules located on the span membrane and connects outside to inside Functions as the eyes and ears of the cell; bind to specific ligant to induce responseSurface receptors largest component of the immune system that helps to regulate immune response and mount antiviral responses if infected with virus, it helps detect and destroy virus infected cells trigger the production of virus blocking enzymesinterferons reflects ratio of the type of white blood cells present and is important for diagonosing types of infectionsDifferential count  noncellular fluid part of blood consisting of water and proteins (80-90% water)blood plasma promotes T-cell activation, macrophage activation, T-cell proliferation, T- and B-cell growth; inflammatory response, and inducing feverinterlukins (ILs) series of proteins that act as a significant defense mechanism and amplifies the immune systemComplement proteins globulin fraction that contains the most antibodiesGamma globulin responsible for recognizing and binding to specific foreign antigens (an adaptive response) type of protein produced by B cells antibodies contain phagocytic cells and mature T and B cells; site of antibody production almost all antigens are carried to this location part of the secondary immune structure; contributes to innate and adaptive immunity Lymph Nodes located in the armpits, groin, or neck can indicate an active immune response to an infectionswollen lymph nodes situated along the path of the lymphatic veins also contains phagocytic cellslymph nodes destroy microbes and stimulate adaptive immune responsephagocytic cells contains most lymphocytes located in specialized tissues known as lymphoid tissues of lymphoid organs is anatomically connected to blood circulatory systemLymphatic system where lymphocytes develop and mature to be able to respond to specific pathogens Primary lymphoid tissues Bone marrow ThymusPrimary immune structures major site of hematopoiesis in adults found in the skull, ribs, sternum, vertebrae, femur, and pelvis location of metaopoietic stem cells contains two pathways of blood cell maturation a primary immune structureBone Marrow Myeloid pathway Lymphoid pathwayPathways of blood cell maturation contains platelets, red blood cells, and leukocytes for blood cell production and maturation Myeloid pathway where B lymphocytes mature in bone marrow; capable of detecting a foreign invader and mounting a response in bone marrow;  Where T lymphocytes are created but not maturedLymphoid pathway process by which all blood cells are formedhematopoiesis organ located behind the sterun and just above the heart Where T lmyphocytes go to mature and learn self primary immune stuctureThymus  Lymph nodes Spleen Tonsils and Adenoids Peyer's patches all contain B cells, T cells, and phagocytic cells; all assist with T cell communicationSecondary Immune Structures where all important parts of the immune system come together with lymphocytes to initiate adaptive immunity Secondary/peripheral lymphoid tissues spongy, fist-sized organ contains phagocytic cells and matured T and B cells secondary immune structureSpleen located at the back of the throat protect against microbes from entering the nose and throat  secondary immune structureTonsils and Adenoids located in lining of the gastrointestinal, respiratory, and urinary tracts Protect against microbes from entering through mucosal surfaces Secondary immune structurePeyer's patches macrophages and neutrophils are the biggest players in this system characterized by physiological defenses that 1. operate to prevent microbes from the external environment from gaining access into the body 2. Quickly eliminate microbes that gain access less effective than adaptive immunityInnate immunity Skin Mucous Membranes Antimicrobial substances Normal macrobiota Immune system Mechanical and Chemical barriers  first line of defense against microbial infection; physical barrier that blocks entry of microbes into the body  outer layer continues to shed along with any microbes attached contains many layers to breach repels water and is a dry environment (unfavorable towards microbes)Skin include digestive, respiratory, and genitourinary tracts; constantly bathed in secretions that move contains Peristalsis of intestine contains mucociliary escaltor of respiratory tract to remove microbes into the pharynx and killed in stomach acidMucous Membranes helps to protect the skin and mucous membranes ex. Salt, lysozyme, peroxidase, lactoferrin, Antimicrobial Peptides (AMPs)Antimicrobial substances accumulates from respiration and located on skinSalt (Antimicrobial) degrades peptidoglycan and located in tears, saliva, mucous, phagocytic cells, and bloodLysozyme (Antimicrobial) capable of breaking down Hydrogen peroxide located in saliva, milk, body tissues, and phagocytesPeroxidase (Antimicrobial) Iron-binding protein located in saliva, mucous, milk, and some phagocytesLactoferrin (Antimicrobial) short chains of AA's that have antimicrobial activity  promote and direct immune responses; located in epithelial cells and phagocytesAntimicrobial Peptides (AMPs) part of skin and mucous membranes; contributes to innate immunity competes with pathogens for space and nutrients, immune stimulation, and nutritional support uses potential secretion of toxins to ward off pathogens helps with recognizing self from non-selfNormal microbiota movement of phagocytic cells to invaded site recruited by chemoattractant to invader 1st step of phagocytosis chemotaxis significant innate defense mechanism by which monocytes, macrophages, and neutrophils engulf and destroy foreign substances including microbesPhagocytosis 1. Chemotaxis 2. Recognition/Attachment 3. Engulfment 4. Phagosome Maturation/Phagolysosome Formation 5. Destruction/Digestion 6. ExocytosisSteps of Phagocytosis  phagocytes recognize and bind to invader 2nd step of phagocytosis Recognition/Attachment pseudopods surround invader and form phagosome 3rd step of phagocytosis Engulfment lysosomes fuse with phagosome forming phagolysosome 4th step of phagocytosis Phagosome Mautration/Phagolysosome formation Within phagolysosome, invader is killed and digested via enzymes and product of toxic products 5th step of phagocytosis Destruction/Digestion release of degraded products last step of phagocytosis Exocytosis always present in tissues and live for weeks and monthsMacrophages are the first to be recruited from the bloodstream to the site of infection more powerful than Macrophages but have a shorter life span (1-2 days; rapid response mechanism)Neutrophils  prevents the spread of infection but damages the cells tissue damage results in thisInflammatory Response/inflammation purpose is to contain site of damage, localize response, eliminate invader, and restore tissue function can result in redness, heat, swelling, and pain due to local blood vessels caused by tissue damage, cytokines, histamines, and microbesinflammation redness, heat, swelling, and painFour cardinal signs of inflammation "<ol> <li>dilation of small blood vessels</li> <li>migration of leukocytes from bloodstream to tissues</li> <li>clotting factors to wall of site of infection</li> <li>Dead neutrophils, tissue debris, accumulate as pus</li></ol>"Inflammatory process important host defense mechanism; acts as a strong indicator of infectious diseases body temperature raises during this stage, increasing the rate of enzymes and slowing down bacterial growth Enhances: inflammatory response, phagocytosis, multiplication of lymphocytes, production of interferons, and antibodies, release of leukocytes from bone marrowFever optimal temperature for bacterial growth37 C Diversity specificity Memory Differentiation Principles of Adaptive Immunity  able to respond to almost an infinite number of antigensDiversity (adaptive immunity) specific to a target antigenSpecificity (adaptive immunity) recognizes antigens if they enter againMemory (adaptive immunity) self from non-selfDifferentiation (adaptive immunity) responds to foreign microbes that have breached the external and internal innate defense mechanisms Divided into humoral and cell mediated immunityAdaptive immune system large protein molecules that are associated with microbes, tumor cells, damaged cells, allergens, and some foods engage and sensitize lymphocytes so an effective immune response can be developed. Can trigger immune response to eliminate that antigenantigens  work together to eliminate foreign antigens  parts of the adaptive immune systemHumoral and cell-mediated immunity  antibody-mediated immunity works to eliminate extracellular antigens (will not target those inside the cell) triggers production of proteins called antibodies  Includes B cells and Helper T cells (Th cells specifically) Humoral immunity  bacteria, toxins, or viruses found in the bloodstream or tissuesextracellular antigens critical in activating B lymphocytes Helper T cells present endogenous proteins produced by all nucleated cellsMajor Histocompatibility Complex 1 (MHC 1) present exogenous antigens, presenting them on their molecules to signal a present invader  produced by antigen-presenting cellsMajor Histocompatibility Complex 2 (MHC 2) dendritic cells, B cells, and macrophages antigen-presenting cells proteins that signal health cellsendogenous antigens external antigens that antigen-presenting cells have digested exogenous antigens how antigens select the appropriate B cells for activation and expansion as plasma cellsClonal Selection Theory  first class of antibodies produced during primary immune response has primary role in bloodstream infectionsIgM first and most abudant class of antibodies produced during secondary immune response provides longest-term protection against antigens can be transported across placenta to fetus to give immune protection to the fetus and newborn for the first 6 monthsIgG most abudant class of antibodies produced primary responsible for  mucosal immunity IgA antibodies involved in development and maturation of antibody responseIgD antibodies responsible for allergic reactions invovled in the immune responseIgE another name for antibodies Y-shaped proteins with two parts named light chain and heavy chain types of proteins produced by B cellsimmunoglobulins (IgGs) contains antigen binding sight; a highly specific process and the more important chain of antibodies IgG light chain less important chain of antibodiesHeavy chain of IgGs Viral inhibition agglutination precipitation neutralization opsonization complement activation each facilitates inactivation or destruction of antigensAntibody-Antigen binding outcomes antibodies that bind to a virus preventing attachment to host cells by taking up spike proteinsViral inhibition antibodes combine with antigens on the cell surface and bind the whole cell together, restricting the movement of the foreign invading cell can help with recognition by phagocytic cellsAgglutination antibodies cause soluble antigens to precipitate, dissolving the antigen itselfPrecipitation antitoxins bind to toxin molecules and neutralize themneutralization uses opsonins: enhance phagocytosis helps anchor the phagocytic cells to the antibodyOpsonization antibodies bound to bacteria activate complement system resulting in bacterial lysisComplement activation immune response during the first encounter with a new antigen takes 10-14 days for substantial antibody accumulation person may be sick during this response main players in this response include IgG and IgMPrimary Immune Response immune response during re-exposure to an antigen significantly faster and more effective than primary memory B cells are primarily responsible for the response pathogen is usually eliminated before causing harm vaccines exploit this natural phenomenon  IgG's are more prevalent in this response than primary Secondary Immune response Includes Cytotoxic T cells and T helper Cells deals with antigens residing within a host cell causes the production of T cells directed against an antigenCell-Mediated Immunity  marked by CD4 function to activate B cells that produce antibodies recognizes antigens presented on MHC 2 molecules Helps to activate macrophages also activates cytotoxic T cells and inflammatory cellsT-Helper cell (Th) marked by CD8 killer cell that targets cells with foreign intracellular antigens, including viruses, bacteria, and cancer cellsCytotoxic T cell (Tc/CTL)  antigens residing in host cells ex. tumor cells, virally infected cells, protozoans, and bacteria that live within a host cellintracellular antigens activate T cells by presenting foreign antigens they have come acrossDendritic cells initial method of trying to control spread of small pox; powdered scabs from smallpox lesions were inhaled or placed in skin occasionally fatal person was contagious became popular in Europe due to dangers and cost, many people remained unprotected Variolation process of inducing immunity (relies on memory B cells) one of the ten great health achievements in the U.S can be acquired naturally or artificially immunization stimulates a person's immune system to reproduce antibodies and memory B cellsActive immunity achieved by the natural process of recovering from a particular diseaseNatural active immunity uses a vaccine to provoke a humoral immune response as a future protective measureArtificial active immunity involves acquiring antibodies from another sourcePassive immunity igG antibodies cross the placenta; breast milk that contains secretory IgANatural passive immunity patients receives performed antibodies from immune serum or immunoglobulin (human or animal source) antitoxis or anti-venom immunity is short-lived and no memory B cells are created Used when immediated protection is required (usually against tetanus toxins or spider-venom) Can cause serum sicknessArtificial passive immunity Dose of an organism or a fraction of it to induce adaptive immunityVaccine to produce memory B cells to produce high antibody titers to protect the individual and population from diseases (increase herd immunity)Goals of Vaccines when a critical portion of the population is immune to disease due to vaccination efforts infectious agent is unable to spread due to insufficient susceptible hostsHerd immunity 80-90% of the population is immune to a diseasecritical herd immunity safety, effectiveness, and stabilityGeneral vaccine requirements Safety, Effectiveness, Stability, Affordability adminstrated as a nasal spray or edible no need for refrigerators; stable at ordinary tropical temps one dose or one shot long shelf lifeIdeal vaccine requirements elicit stronger immune response but can sometimes cause the disease you are trying to vaccinate against composed of a live, weakened version of organism/virus you are trying to vaccinate against (active version)Attenuated Vaccines elicits weaker immune response but cannot cause disease composed of whole organism/virus that is deadInactivated Vaccine composed of toxins treated to destroy toxic parts but retain antigen ex. diphtheria, tetanusToxoids Composed of key protein antigens or antigenic fragments from pathogens ex. bacterial meningitis, acellular pertussisSubunit vaccines Composed of empty capsids reproduced by genetically engineered organisms ex. HPVVirus-like Particle Vaccines composed of capsules ex. pneumococcal vaccine for adultsPolysaccharide Vaccines manufactured piece of mRNA that codes for antigen of pathogen fragile, falls apart easily, and uses freezing to keep it stable a new vaccine technologymRNA vaccines one of the cornerstones of microbial infection prevention and control killing or inactivating microbes that cause diseaseDisinfection destroying all live microbes, spores, and viruses a step further than disinfectionsterilization  reduces the number of pathogenic microbes; a heating methodPasteurization takes very few molecules of a heavy metal to kill or be toxic to microbesOligodynamic effect can be used on inanimate objects and surfaces but is too toxic to the bodyDisinfectant can be used on the living body and tissues like woundsantiseptics Heat Low temperature control Radiation Physical RemovalPhysical methods of disinfection heavy metals alcohol aldehydes halogens quaternary ammonium compounds (QUATS) Salt Hydrogen peroxide ethylene oxide gasChemical methods of disinfection considered the single most important discovery for the treatment of infectious diseases in the history of medicine compounds produced by microbes, bacteria, or fungi meant to combat other microbesAntibiotics became the first antibiotic used  didn't become prescription until 1950sPenicillin first wonder drugs considered antimicrobials, not antibiotics since they are synthetic saved millions in WWIISulfonamide (sulfa drugs) original penicillinPenicillin G the idea of antimicrobials causing greater harm to microbes than their host interfere with essential structures or properties common in microbes but not in human cells toxicity is relative and expressed by an indexSelective Toxicity inhibit growth of bacterial cellsBacteriostatic directly kill the bacteria cellsBactericidal antibiotics that kill a wide variety of bacteria; also targets and wipe out the human normal flora often used if bacterial causative agent is unknown or there is little time to identify agentBroad-spectrum antibiotics used to target a specific species/group of bacteria less detrimental effect on normal floranarrow spectrum antibiotics interfere with each otherAntagonistic one medication enhances anothersynergistic medications neither antagonistic or synergisticadditive antagonistic synergistic additiveAntimicrobial Effects of Combination broad spectrum or narrow spectrumAntimicrobial Spectrum of Activity bacteriostatic vs bactericidalantimicrobial action antimicrobials differ in behavior in the body Can it cross Blood-brain barrier pH of antimicrobial half-life Tissue distribution, metabolsim, and excretion of antimicrobials how long an antibiotic can be present in the bodyhalf-life allergic reactions toxic effects dybiosisAdverse effects of antimicrobials interference with cell wall synthesis interference with protein synthesis interference with cell membrane interference with nucleic acid synthesis metabolic pathway interferenceMechanisms of action of antibiotics Common Beta-lactam ring target the petidoglycan portion inside bacterial cell walls (narrow spectrum); inhibits enzyems that catalyze formation of peptide bridges between strands of PG layer, disrupting cell wall synthesis, weakening cell wall, and leading to cell lysis only effective against actively growing cell and usually more effective against Gram positive bacteria ex. Penicillin, Cephalosporins, Vancomycin, BacitracinInterference with cell wall syntthesis exploit difference between prokaryotic (70s) and eukaryotic (80s) ribosomes and their subunits; blocks translation broad spectrum (works against Gram positive and gram negative bacteria) some are toxic due to huamn mitochondria also have 70s ribosomes classes include: tetracylines, macrolides, streptogramins, and aminoglycosidesinterference with protein synthesis  damages bacterial membranes, causing cells to leak and lead to cell death restricted to tropical applications (skin appliance) because of toxicity narrow spectrum classes include Daptomycin and Polymyxin interference with cell membrane Block DNA replication only by interfering with the enzyme gyrase Blocks RNA polymerase (transcription) Bactericidal and broad spectrum bacteria can develop resistance rapidly Classes include Fluoroquinolones and Rifamycins Interference with nucleic acid synthesis antimetabolites competitively bind with enzymes called molecular mimicry rendering them inactive interfere with folic acid synthesis by interfering with the 1st enzyme using sulfa drugs and the 3rd enzyme in the process using Trimethoprims  Bacteriostatic and broad spectrum classes: sulfa drugs and TrimethoprimMetabolic pathway interference when germs (bacteria/fungi) develop the ability to defeate the antibiotics designed to kill them does not mean your body is resistant to antibiotics naturally occurs over timeAntibiotic resistance bacteria is resistant to all types of antibioticspan resistant cause of antibiotic resistance crisisOveruse of antibiotics, inappropriate prescribing, Extensive Agricultural use antibiotic of last resort; very toxiccarbapenem an alternative to antibiotics difficult to target bacterial infection but can be used as indirect method to prevent secondary bacterial infections by preventing primary infectionVaccines alternative vaccines antibodies bacteriophages fecal microbiota transplant (FMT) other small molecule agentsAlternatives to antibiotics Prevent Viral Entry Interfere with Viral uncoating interfere with viral nucleic acid synthesis prevent genome integration prevent assembly and release of viral particlesMechanisms of Action for Antivirals

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