Immune system-large, complex, and diffuse network of cells and fluids that penetrate into every organ and tissue4 major subdivisions of immune system-reticuloendothelial system (RES) -extracellular fluid (ECF) -blood stream -lymphatic systemWhite blood cells-(leukocytes) innate capacity to recognize and differentiate any foreign materialNonself-foreign materialSelf-normal cells of the bodyPathogen-associated patterns (PAMPs)-molecules shared by microorganismsPathogen recognition receptors (PRRs)-receptors on WBCs for PAMPsOrigin, Composition, and Functions of the blood-whole blood consists of plasma and formed elements (blood clots)Serum-the liquid portion of the blood after a clot has formed-minus clotting factorsPlasma-92% water, metabolic proteins, globulins, clotting factors, hormones, and all other chemicals and gases to support normal physiological functionsHemopoiesis-production of blood cellsStem cells-undifferentiated cells, precursor of new blood cellsLeukocytes-WBCGranulocytes-lobed nucleus, cytoplasmic granules visible with stainingAgranulocytes-unlobed, rounded nucleusPlatelets-involved in blood clotting and inflammation -formed elements in circulating blood that are not whole cells, form from megakaryocytes in bone marrowNeutrophils-phagocytes; active engulfers and killers of bacteria -55-90% of WBC, lobed nuclei with lavender granules; phagocytes -life span of 2 days, with only 4-10 hours spent in the circulationBasophils-function in inflammatory events and allergies -0.5% of WBCs, constricted nuclei, dark blue granules; release potent chemical mediators -respond to large eukaryotic pathogens and recruit other leukocytes -cytoplasmic granules contain histamines, prostaglandins, and other chemical mediators of the allergic responseEosinophils-active in worm and fungal infections, allergy, and inflammation -1-3% of WBCs, reddish granules and bilobed nucleus; destroys eukaryotic pathogens -found in much higher numbers in the spleen and bone marrowMonocytes-blood phagocytes that readily leave the circulation; mature into macrophages and dendritic cells -3-7% of WBCs -phagocytosis, followed by final differentiation into macrophages and dendritic cells -secrete several chemicals that moderate the functions of the immune system -largest WBC; nuclei large, ovoid, and often intended - no cytoplasmic granules visible using a light microscopeMacrophages-largest phagocytes; ingest and kill foreign cells; required for certain specific immune reactions -final differentiated of monocytesDendritic cells-relatives of macrophages; reside throughout the tissues and reticuloendothelial system; involved in early immune reactions with foreign matter -trap pathogens and participate in immune reactionsLymphocytes-primary cells involved in specific immune reactions of foreign matter -20-35%, specific immune response -2 types of lymphocytes exist. T cells are responsible for cell-mediated immunity, where as B cells are responsible for humoral immunityT-cells-perform a number of specific immune responses such as assisting B cells and cell-mediated immunityB-cells-differentiate into plasma cells and form antibodies (humoral immunity)Natural Killer (NK) cells-related to T cells but displaying no specificity; active against cancerous and virally infected cellsMast cells-tissue cells similar to basophils that trigger local inflammatory reactions and allergic symptoms -nonmotile elements bound to connective tissueB (humoral immunity)-activated B cells produce antibodiesT cells (cell-mediated immunity)-activated T cells modulate immune functions and kill foreign cellsMonocytes, Macrophytes-3-7%, largest of WBCs, kidney-shaped nucleus; phagocyticErythrocytes-develop from bone marrow stem cells, lose nucleus, simple biconcave sacs of hemoglobinLymphatic System-provides an auxiliary route for return of extracellular fluids to the circulatory system -acts as a drain-off system for the inflammatory response -renders surveillance recognition and protection against foreign materialLymphatic fluid-lymph -formed when blood components move out of blood vessels into extracellular spaces -made up of water, dissolved salts, 2-5% proteins -transports white blood cells, fats, cellular debris, and infectious agentsLymph-a plasma-like liquid carried by lymphatic circulationLymphatic vessels-lymphatic capillaries permeate all parts of the body except the CNS, bone, placenta, and thymus -thin walls easily permeated by extracellular fluid which is then moved through contraction of skeletal muscles -functions to return lymph to circulation; flow is one-direction, toward the heart, and eventually returning to blood streamCirculation in the lymphatic vessels and lymph nodes-the finest level of lymphatic circulation begins with blind capillaries (green) that pick up foreign matter from the surrounding tissues and transport it in lymph away from the extremities via a system of small ducts -the ducts carry lymph into a circuit of larger ducts that ultimately flow into clusters of filtering organs, the lymph nodes -a section through a lymph node reveals the afferent ducts draining lymph into sinuses that house several types of white blood cells. here, foreign materials is filtered out and processed by lymphocytes, macrophages, and dendritic cells -lymph continues to trickle from the lymph nodes via efferent ducts into a system of larger drainage vessels, which ultimately connect with large veins near the heart. in this way, cells and products of immunity continually enter the regular circulationLymphoid organs and tissues-classified as primary and secondaryPrimary Lymphoid organs-sites of lymphocytic origin and maturation - thymus and bone marrowSecondary Lymphoid organs and tissues-circulatory based locations, such as spleen and lymph nodes; collection of cells distributed throughout body tissues - skin, mucous membranes - SALT, GALT, MALTActions of the 2nd line of defense-recognition -inflammation -phagocytosis -interferon -complementRedness-increased circulation and vasodilation in injured tissues in response to chemical mediatorsWarmth-heat given off by the increased blood flowSwelling-increased fluid escaping into the tissue as blood vessels dilate - edema; WBCs, microbes, debris, and fluid collect to form pus; prevents spread of infectionPain-stimulation of nerve endingsDiapedesis-migration of cells out of blood vessels into the tissuesChemotaxis-migration in response to specific chemicals at the site of injury of infectionFever-initiated by circulating pyrogens which reset the hypothalamus to increase body temp; signals muscles to increase heat production and vasoconstrictionExogenous pyrogens-products of infectious agentsEndogenous pryogens-liberated by monocytes, neutrophils, and macrophages during phagocytosis; interleukin-1 (IL-1) and tumor necrosis factor (TNF)Benefits of fever-inhibits multiplication of temp - sensitive microorganisms -impedes nutrition of bacteria by reducing the available iron -increases metabolism and stimulates immune reactions and protective physiological processesPhagocytosis-to survey tissue compartments and discover microbes, particular matter, and dead or injured cells -to ingest and eliminate these materials -to extract immunogenic information from foreign matterWhat is neutrophil general purpose?-react early to bacteria and other foreign materials, and to damaged tissueWhat is macrophages general purpose?-derived from monocytes; scavenge and process foreign substances to prepare them for reactions w/ B and T lymphocytesWhat do dendritic cells recognize?-foreign cellsToll-like receptors-protein receptors within cell membrane of macrophages -detect foreign molecules and signal the macrophage to produce chemicals to stimulate an immune responseChemotaxis and Ingestion-phagocytes migrate and recognize PAMPs -phagosomesPhagolysosome-lysosome fused with phagosome (death ~ 30 min)Destruction and Elimination-oxygen-dependent system (respiratory burst) -liberation of lactic acid, lysozyme, and nitric oxidePhagocytosis-chemotaxis by phagoctye -adhesion of bacteria -engulfment into phagocytic vacuole -phagosome -phagolysosome formation -killing and destruction of bacterial cells -release of residual debrisInterferon-small protein produced by certain WBCs and tissue cells -produces in response to viruses, RNA, immune products, and various antigens, they bind to cell surfaces and induce expression of antiviral proteins and inhibit expression of cancer genesInterferon alpha-lymphocytes and macrophagesInterferon beta-fibroblasts and epithelial cellsInterferon gamma-T cellsComplement-consists of 26 blood proteins that work in concert to destroy bacteria and virusesHow are complement proteins activated?-by cleavage, cascade reactionClassical Pathway-activated by the presence of antibody bound to microorganismLectin Pathway-nonspecific reaction of a host serum protein that binds mannanAlternative Pathway-begins when complement proteins bind to normal cell wall and surface components of microorganismsWhat are the 4 stages of the complement cascade?-initiation -amplification -polymerization -membrane attackWhat is the 1st line of defense?-a surface protection composed of anatomical and physiological barriers that keep microbes from penetrating sterile body compartmentsWhat is the 2nd line of defense?-a cellular and chemical system that comes immediately into play if infectious agents make it past the surface defenses -ex: phagocytes that destroys foreign matter, and inflammation which holds infections in checkWhat is the 3rd line of defense?-specific host defenses that must be developed uniquely for each microbe through the action of specialized white blood cells -marked by its activity toward specific pathogens and development of memoryChapter 15...Antigen-molecules that bind the T cell receptor or B cell receptorImmunogen-molecules that bind the T cell receptor of B cell receptor and stimulate an immune responseSpecificity-function only against the antigen that they were produced in response toMemory-lymphocytes are programmed to "recall" their first encounter w/ an antigen and respond rapidly to subsequent encountersMajor Histocompatibility Complex (MHC)-class I MHC found on all cells except RBCs -also know as human leukocyte antigen (HLA) -plays a role in recognition of self by the immune system and in rejection of foreign tissueLymphocyte Receptors-lymphocytes role in surveillance and recognition is a function of their receptorsB-cell receptors-bind free antigensT-cell receptors-bind processed antigens together w/ the MHC molecules on the cells that present antigens to themClonal Selection Theory-lymphocytes use 500 genes to produce a tremendous variety of specific receptors -undifferentiated lymphocytes undergo a continous series of divisions of genetic changes that generate millions of different cell types -each cell has a particular/unique receptor specificityThe Development of Lymphocytes-in the bone marrow, lymphocytic stem cells differentiate into either T or B cells -B cells stay in the bone marrow while T cells migrate to the thymus -Both T and B cells migrate to secondary lymphoid tissue -lymphocyte specificity is preprogrammed, existing in the genetic makeup before an antigen has ever entered the system -each genetically different type of lymphocyte (clone) expresses a single specificityClonal Selection-1st introduction of each type of antigen into the immune system selects a genetically distinct lymphocyte -causes it to expand into a clone of cells that can react to that antigenSpecific B-cell receptor: immunoglobulin-composed of 4 polypeptide chains -2 identical heavy chains (H) -2 identical light chains (L)Y-shaped arrangement-ends of the forks formed by light and heavy chains contain a wide range of variable antigen binding sites -variable regions and constant regionsT-cell receptors for Antigen-formed by genetic recombination, with variable and constant regions -2 parallel polypeptide chains -small, not secretedB-cells-bone marrow -immunoglobulin, MHC I and MHC II -low number of blood circulation -receptors for antigens: immunoglobulins D and M -cortex (in follicles) -production of antibodies to inactivate, neutralize, target antigensDo B-cells require antigens presented w/ MHC?-noWhat is B-cells product of antigenic stimulation?-plasma cells and memory cellsT-cells-thymus -T-cell receptors; CD molecules, MHC I -high numbers -> circulation in blood -T-cell receptor (TCR) -> receptors for antigens -paracortical sites (interior to the follicles) -Helper and cytotoxic T cells and memory cells -regulate immune functions, kill foreign and infected cells, synthesize cytokinesDo T-cells require antigen presented w/ MHC?-yesCharacteristics of Antigens-perceived as foreign, not a normal constituent of the body -foreign cells and large complex molecules over 10,000 MW are most antigenicAntigenic Determinant (epitope)-small molecular group that is recognized by lymphocytes -antigen has many antigenic determinantsAlloantigens-cell surface markers and molecules that occur in some members of the same species but not in othersSuperantigens-potent T-cells stimulators; provoke an overwhelming responseAllergen-antigen that evokes allergic reactionsAutoantigens-molecules on self tissues for which tolerance is inadequateCooperation in immune reactions to antigens-the basis for most immune responses is the encounter b/w antigens and WBCs -lymph nodes and spleen concentrate the antigens and circulate them so they will come into contact w/ lymphocytesAntigen processing and presentation to lymphocytes-T-cell dependent antigens must be processed by phagocytes called antigen presenting cells (APC) -APCs modify the antigen; then the Ag is moved to the APC surface and bound to MHC receptor -antigen presentation involves a direct collaboration among an APC, and a T helper cellWhat does interleukin-1 secrete?-by APC to activate Th cellsWhat does interleukin-2 secrete?-by Th to activate B and other T cellsT Helper Activation-APCs (here a dendritic cell) are found in large numbers in lymphatic tissues, where they frequently encounter complex antigens such as microbes. APCs engulf the microbes, take them into intracellular vesicles, and degrades them into smaller, simpler peptides -the antigen peptides complexed w/ MHC-II receptors are transported to the APC membrane, from this surface, location the antigens are readily presented to a T helper cell, which is specific for the antigen being presented -the APC and T helper cell cooperate in the formation of a receptor complex that triggers T-cell activationWhats the 1st step of T-helper activation?-the MHC-II antigen on the APC binds to the T cell receptorWhats the 2nd step of T-helper activation?-a coreceptor on the T cell (CD4) hooks itself to a position on the MHC-II receptor. this combination ensures the simultaneous recognition of the antigen (nonself) and the MHC receptor (self)What activates the T helper cell?-the stimuli provides a signal that is relayed to the T-cell genetic materialWhat does the activated T cell release?-releases interleukins and to assist other white blood cells such as B cells in their functionsB-cell activation and antibody production-once B cells process the Ag, interact w/Th cells, and are stimulated by growth and differentiation factors, they enter the cell cycle in preparation for mitosis and clonal expansion -divisions give rise to plasma cells that secrete antibodies and memory cells that can react to the same antigen laterClonal selection and antigen binding-B cells can independently recognize microbes and their foreign antigens, and can bind them with their Ig receptors. This is now the initial selection of the antigen-specific B-cell clone occursAntigen processing and presentation-once the microbe is attached, the B-cell endocytoses it, processes it into smaller protein units, and display these on the MHC-II complex (similar to the APCs). This event readies the antigen for presentation to a specific Th cellB cell/Th cell cooperation recognition-for most B cells to become functional, they must interact w/ a T helper cell that bears receptors for antigen from the same microbe. this T cell may have been activated by APC. the 2 cells engage in linked recognition, in which the MHC-II receptor bearing antigen on the B cell binds to both the T-cell antigen receptor and the CD4 molecule on the T cellB-cell activation-the T cell gives off additional signals in the form of interleukins and B-cell growth factors, the linked receptors and the chemical stimuli serve to activate the B cell, such activation signals an increase in cell metabolism, leading to cell enlargement, proliferation, and differentiateClonal expansion/ memory cell-the activated B cell undergoes numerous mitotic divisions, which expand the clone of cells bearing this specificity produce memory cells and plasma cells, the memory cells are persistent, long-term cells that react w/ the same antigen on future exposuresPlasma cells/antibody synthesis-the plasma cells are short-lived, active secretory cells that synthesize and release antibodies, these antibodies (here IgM) have the same specificity as the Ig receptor and circulate in the fluid compartments of the body, where they react w/ the same antigens on future exposuresAntibody structure and functions-immunoglobulins -large Y-shaped proteins -consists of 4 polypeptide chains -contain 2 identical fragments (Fab) w/ ends that bind to a specific antigen -Fc binds to various cells and molecules of the immune systemOpsonization-process of coating microorganisms or other particles w/ specific antibodies so they are more readily recognized by phagocytesNeutralization-Abs fill the surface receptors on a virus or the active site on a microbial enzyme to prevent it from attachingAgglutination-Ab aggregation; cross linking cells or particles into large clumpsComplement fixation-activation of the classical complement pathway can result in the specific rupturing of cells and some virusesPrecipitation-aggregation of particulate antigenIgG-monomer, produced by plasma cells (primary response) and memory cells (secondary), most prevalentIgA-monomer circulates in blood, dimer in mucous and serous secretionsIgM-5 monomers, serves as receptor for antigen on B cells, first class synthesized following Ag encounterIgD-monomer, serves as a receptor for antigen on B cellsIgE-involved in allergic responses and parasitic worm infectionsPrimary Response-after 1st exposure to an Ag immune system produces IgM and a gradual increase in Ab titer (concentration of antibodies) with the production of IgGSecondary Response-after second contact with the same Ag, immune system produces a more rapid, stronger response due to memory cells -anamnestic responseT cells and cell-mediated immunity-cell-mediated immunity requires the direct involvement of T lymphocytes -T cells act directly against Ag and foreign cells when presented in association w/ an MHC carrier -T cells secrete cytokines that act on other cells -sensitized T cells proliferate into long-lasting memory T cellsT helper cell 1-CD4 -activates other CD4 and CD8 cells; secretes IL-2, tumor necrosis factor, and interferon gamma; responsible for delayed hypersensitivity -interacts w/ MHC-II receptorT helper cell 2-CD4 -drives B-cell proliferation -secretes IL-4, IL-5, IL-10 -can dampen Th1 activityT regulatory cell-CD4, CD25 -involved in development of immune tolerance -suppression of pathological immune responses -inflammation, autoimmunityT cytotoxic cell-CD8 -destroys a target foreign cell by lysis -important in destruction of cancer cells -virus-infected cells; graft rejection; requires MHC I for functionT helper Cells (CD4 or Th)-most prevalent type of T cell -regulate immune reaction to antigens, including other T and B cells -also involved in activating macrophages and increasing phagocytosis -differentiate into T helper I (Th1) cells or T helper 2 (Th2) cellsCytotoxic T cells (CD8 or Tc)-destroy foreign or abnormal cells by secreting perforins that lyse cellsNatural Killer Cells-lack specificity -circulate through the spleen, blood, and lungsCytotoxic T cell activity-NK cell release perforins, which polymerize and form a hole in the foreign cell membrane -granzymes from NK cell enter perforin hole and decade foreign cell proteins -foreign cell dies by apoptosis -macrophages engulfs and digests dying cellsActive Immunity-results when a person is challenged w/ antigen that stimulates production of antibodies -creates memory, takes time, and is lastingPassive Immunity-preformed antibodies are donated to an individual -does not create memory, acts immediately, and is short termNatural Immunity-acquired as part of normal life experiencesArtificial Immunity-acquired through a medical procedure such as a vaccineNatural Active Immunity-results when a person develops his own immune response to a microbe through infectionNatural Passive Immunity-results when a person receives preformed immunity through the placenta or nursingArtificial Active Immunity-results when a person develops his own immune response to a prepared microbial antigenArtificial Passive Immunity-results when a person is given selected immune substances made by another individualArtificial Passive Immunity-immune serum globuline (ISG), gamma globulin, contains immunoglobulin extracted from pooled blood; immunotherapy -treatment of choice in preventing measles and hep A and in replacing antibodies in immunodeficient patient -sera produced in horses are available for diphtheria, botulism, and spider and snake bites -acts immediately; protection lasts 2-3 monthsArtificial Active Immunity-deliberately exposing a person to material that is antigenic but not pathogenic -principle is to stimulate a primary and secondary anamnestic response to prepare the immune system for future exposure will be immediate, powerful, and sustainedVaccine Preparation-killed whole cells or inactivated viruses -live, attenuated cells or viruses -antigenic molecules derived from bacterial cells or viruses -genetically engineered microbes or microbial agentsChecklist for requirements for an effective vaccine-it should have a low level of adverse side effects or toxicity and not cause serious harm -it should protect against exposure to natural, wild forms of pathogens -should stimulate both antibody (B-cell) response and cell-mediated (T-cell) response -it should not require numerous doses or boosters -it should be inexpensive, have a relatively long shelf life, and be easy to administerKilled or Inactivated vaccines-cultivate the desired strain, treat it with formalin or some other agent that kills the agent but does not destroy its antigenicity -often require a larger dose and more boosters to be effectiveLive attenuated cells or viruses-process that substantially lessens or negates the virulence or viruses or bacteria -eliminates virulence factorsAdvantages of Attenuated vs. killed vaccines-organisms can multiply and produce infection (but not disease) like the natural organism -they confer long-lasting protection -usually require fewer doses and boostersDisadvantages of attenuated vs. killed vaccines-require special storage, can be transmitted to other people, can conceivably mutate back to virulent strainAntigenic molecules-acellular or subcellular vaccines (subunit --> if a virus) -exact antigenic determinants can be used when known: capsules - pneumococcus, meningococcus surface protein - anthrax, hep B exotoxins - diphtheria, tetanus -antigen can be taken from cultures, produced by genetic engineering, or synthesizedGenetically Engineered Vaccines-insert genes for pathogen's antigen into plasmid vector, and clone them in an appropriate host -stimulated the clone host to synthesize and secrete a protein product (antigen), harvest and purify the protein - hepatitisHerd Immunity-immune individuals will not harbor it, reducing the occurrence of pathogens -less likely that a non-immunized person will encounter the pathogenChapter 13...What is the difference between infection and disease?-is that infection refers to the presence of infectious agents getting past host defenses where they invade tissues and multiplyWhat do disease refer to?-any infection that causes damage or disruption to tissues and organs because of the presence of the microbes in the tissueCan normal resident flora "infect" us without causing disease?yesNormal Flora-include transient which are microbes that occupy the body for only short periods and are influenced by daily hygiene and residents which are microbes that become established in the bodyAre there more microbes in and on our body than there are human cells?yesWhere are the most frequent places where resident microbes exist in our bodies?-include areas of the body in contact with the outside environment like our skinWhere is the highest number of bacteria found?-mucosal surfaceWhat are microbe-free?-organs and tissues and most bodily fluidsTrue pathogens-primary pathogens -are capable of causing disease in healthy person with normal immune defensesOpportunistic pathogens-cause disease when the host's defenses are compromised or when they become established in a part of the body that is not natural to them5 steps in the development of an infection-potral of entry (skin) -attaching firmly (fimbriae) -surviving host defenses (avoiding phagocytosis) -causes of damage and disease (direct damage -> toxins, enzymes, lysis) -existing host (portal of entry)Portal of Entry for pathogens-skin -GI tract -Respiratory tract -Urogenital tract -endogenous biotaSkin-StaphylococcusGI tract-ShigellaRespiratory tract-Streptococcus pneumoniaUrogenital tract-Candida albicansInfectious dose-infection will proceed only if a minimum number is presentWhat happens if you drink water with 100 Vibrio cholera organisms in it?-nothingCommon mechanisms of adhesions that organisms can use to attach to the host-bacterial, fungal, and protozoal pathogens attach most often by appendages and surface structures such as fimbriae (pili), flagella, and adhesive slimes or capsules -viruses attach by means of specialized receptorsLeukocidins-produced by Streptococcus and Staphylococcus -substances that are toxic to white blood cellsCapsules-Exoenzymes-disrupt the structure of tissuesToxigenicity-the power to produce toxinsEndotoxin-a toxin that is not secreted but is released only after the cell is damaged or lysedExotoxin-a toxin molecule secreted by a living bacterial cell into the infected tissuesLocalized infection-the microbe enters the body and remains confined to a specific tissueSystemic infection-when a infection spreads to several sites and tissue fluids, usually in bloodstreamFocal infection-said to exist when the infectious agent breaks loose from a local infection and is seeded or disseminated into other tissuesMixed infection-several agents establish themselves simultaneously at the infection sitePrimary infection-an initial infection in a previously healthy individual that is later complicated by an additional (secondary) infectionSecondary infection-an infection that compounds a preexisting oneSequelae-to followAcute infection-infections that come on rapidly, with severe but short-lived effectsChronic infection-infections that progress and persist over a long period of time4 distinct stages of clinical infections-incubation period - the time from initial contact with the infectious agents (at the portal of entry) to the appearance of the first symptoms -prodromal stage - short period (1-2 days) -period of invasion -during which it multiplies at high levels, exhibits its greatest toxicity and becomes well established in its target tissue -convalescent period -the patient's strength and health gradually return as the immune response begins to clear the infectious agent and restore normal function to damaged tissuesSigns-any objective evidence of disease as noted by an observerSymptoms-the subjective evidence of disease as sensed by the patientThe ways that an infection can spread out of portals of entry-respiratory and salivary portals -epithelial cells -fecal exit -urogenital tract -removal of blood or bleedingReservoir of infection-the primary habitat in the natural world from which a pathogen originates -a human or animal carrier, although soil, water, and plants are also reservoirVector-indicate a live animal that transmits an infectious agent from one host to another2 types of vectors-biological vector -mechanical vectorBiological vector-actively participates in a pathogen's life cycle, serving as a site in which it can multiply or complete its life cycleMechanical vector-not necessary to the life cycle of an infectious agent and merely transport it without being infected2 patterns of disease transmissions-communicable -noncommunicableCommunicable transmission-when an infected host can transmit the infectious agent to another host and establish infection in that hostNoncommunicable transmission-infectious disease does not arise through transmission of the infectious agent from host to hostFomite-an inanimate object that harbors and transmits pathogensSTORCH-syphilis, toxoplasmosis, other diseases (hep B, AIDS, and chlamydia), rubella, cytomegalovirus, and herpes simplex virus -the most serious complications of STORCH infections are spontaneous abortion, congenital abnormalities, brain damage, prematurity, and stillbirthsNosocomial infections-infectious diseases that are acquired or develop during a hospital stayWhat are the three most common infections encountered in nosocomial infections?-UTI, surgical wounds, lower respiratoryHow can nosocomial infections be prevented?-good hand hygiene and being aware of situationsKoch's Postulate-find evidence of a particular microbe in every case of a disease -isolate that microbe from an infected subject and cultivate it artificially in the lab -inoculate a susceptible healthy subject with the laboratory isolate and observe the resultant disease -re-isolate the agent from this subjectChapter 16...Immunopathology-the study of disease statesAllergy/hypersensitivity-an exaggerated, misdirected expression of immune responses to an allergenAllergen-antigenAutoimmunity-abnormal responses to self AgImmunodeficiency-deficiency or loss of immunityCancer-both a cause and effect of immune dysfunctionType I Immune System disorder-immediate -hay fever, anaphlyaxisType II Immune System disorder-antibody-mediated -blood type incompatibilitiesType III Immune system disorder-immune complex -rheumatoid arthritis, serum sicknessType IV Immune system disorder-cell-mediated, cytotoxic -contact dermatitis, graft rejectionUnderreactions and loss of immune function-lack of T cell surveillance leads to cancer cell surival -loss of lack of T cells, B cells, or both compromises the immune systemHypersensitivity I-immediate allergies -IgE-mediated: involves mast cells, basophils, and allergic mediators -ex: anaphylaxis, allergies such as hay fever and asthmaHypersensitivity II-antibody-mediated incompatibilities -IgG, IgM antibodes act upon cells with complement and cause cell lysis; includes some autoimmune diseases -ex: blood group incompatibility, pernicious anemia; myasthenia gravisHypersensitivity III-immune complex diseases -antibody-mediated inflammation; circulating IgG complexes deposited in basement membranes of target organs; includes some autoimmune diseases -ex: systemic lupus erythematous; rheumatic feverHypersensitivity IV-T-cell mediated hypersensitivities -delayed hypersensitivity and cytotoxic reactions in tissues -ex: infection reactions; contact dermatitis; graft refection; some types of autoimmunityAtopy-any chronic local allergy such as hay fever or asthmaAnaphylaxis-a systemic, often explosive reaction that involves airway obstruction and circulatory collapseContact with allergens-generalized predisposition to allergies is familial - not to a specific allergyCan allergies be affected by age, infection, and geographic area?-yesAtopic allergies-may be lifelong or may be "outgrown"; may also develop later in lifeWhat kind of characteristics are allergens?-immunogenicWhere do allergens typically enter through epithelial portals?-respiratory, gastrointestinal, skinNature of allergens-organ of allergic expression may or may not be the same as the portal of entropySensitizing dose-on first contact with allergen, specific B cells form IgE which attaches to mast cells and basophils; generally no signs or symptomsProvocative dose-subsequent exposure with the same allergen binds to the IgE-mast cell complexDegranulation-releases mediators with physiological effects such as vasodilation and bronchoconstrictionMast cells-located in the connective tissue of virtually all organs; high concentration in lungs, skin, GI, and genital tractBasophils-circulate in blood and migrate into tissuesDo each cell bind to 10,000-40,000 IgE?-yesWhat do cytoplasmic granules contain?-physiologically active cytokines, histamine, etc.When do cells degranulate?-when stimulated by allergenType I Mechanisms-Sensitization/IgE Production -allergens enter through mucous membrane and are picked up by a dendritic cell -dendritic cell processes allergen and presents it to a T helper cell in lymph node -B cell divides to form numerous plasma cell -synthesis of IgE specific to allergen -IgEs bind with their Fc fragments to mast cell receptors; IgE-primed mast cells remain in tissues for extended periods -Subsequent exposure to allergen and provocation -allergen is encountered again and goes directly to primed mast cells -allergen attaches to IgE on mast cells and triggers degranulation and release of allergic mediators -systemic distribution of mediators in bloodstream -end result: symptoms in various organsHistamine-most profuse and fastest acting; stimulator of smooth muscle, glands, and eosinophils -response to chemical depends on the muscle location; constricts smooth muscles of small bronchi, intestines; relaxes vascular smooth musclesWhat are additional allergic mediators?-serotonin, leukotrienes, prostaglandins, and bradykininAtopic disease-hay fever, rhinitis; seasonal, inhaled plant pollen or moldAsthma-severe bronchoconstriction; inhaled allergenEczema-dermatitis; ingestion, inhalation, skin contactFood allergy-intestinal portal can affect skin and respiratory tract -vomiting, diarrhea, abdominal pain; possibly severe -eczema, hives, rhinitis, asthma, occasionally anaphylaxisDrug allergy-common side effect of treatment; any tissue can be affected; reaction from mild atopy to fatal anaphylaxisAnaphylaxis-a reaction of animals injected with a foreign proteinSystemic anaphylaxis-sudden respiratory and circulatory disruption that can be fatal in a few minutes -allergen and route are variable -bee stings, antibiotics, or serum injectionGeneral methods treatment and prevention:-avoiding allergen -use drugs that block the action of the lymphocytes, mast cells, or chemical mediators (antihistamines)Desensitization therapy-injected allergens may stimulate the formation of high-levels of allergen-specific IgG that act to block IgE; mast cells don't degranulateType II hypersensitivity-reactions that lyse foreign cells -involve antibodies, complement, leading to lysis of foreign cells -transfusion reaction -ABO blood groups -Rh factor -hemolytic disease of the newbornHuman ABO antigens-genetically determined RBC glycoproteins -inherited as 2 alleles of A, B, or O4 blood types-A, B, AB, O -named for dominant antigen(s) -type O persons lack both A and B antigens -tissues other than RBCs also carry A and B antigens -table 16.3Antibodies against A and B antigens-serum contains pre-formed antibodies that react with blood of another antigenic type-agglutination; potential transfusion complicationWhat does type A contain?-Abs that react against B antigensWhat does type B contain?-Abs that react against A antigensWhat does type O contain?-Abs that react against A and B antigensWhat does type AB contain?-no Abs that react against A or B antigensHemolytic disease of the newborn (HDN)-an Rh- mother forms antibodies to her Rh+ fetus; usually requires subsequent exposure to the antigen to be hemolytic -prevention requires the use of passive immunization with antibodies against the Rh antigen; prevents sensitization of motherType III hypersensitivity-reaction of soluble antigen with antibody and the deposition of the resulting complexes in basement membranes of epithelial tissues -immune complexes become trapped in tissues and incite a damaging inflammatory responseArthus reaction-localized dermal injury due to inflamed blood vesselsSerum sickness-systemic injury initiated by antigen-antibody complexes that circulate in the bloodPathogenesis of immune complex disease-antibody combines with excess soluble antigen, forming large quantities of Ag-Ab complexes -circulating immune complexes become lodge din the basement membranes of epithelia in blood vessels, kidney, skin, and other sites -complement factors trigger release of histamine and other inflammatory mediators -neutrophils migrate to sites of Ag-Ab complexes and release enzymes and chemokines that severely damage the target tissues and organsType IV hypersensitivity-T cell-mediated -delayed response to Ag involving activation of and damage by T cells -delayed allergic response -tuberculin skin test, contact dermatitis, from plants, metals, cosmeticsMechanisms for type IV reactions-lipid-soluable catechols are absorbed by the skin -dendritic cells close to the epithelium pick up the allergen, process it, and display it on MHC receptors -previously sensitized Th1 cells are activated and secrete cytokines (IFN, TNF) -these cytokines attract macrophages and cytotoxic T cells to the site -macrophages release mediators that stimulate a strong, local inflammatory reaction. Cytotoxic T cells directly kill cells and damage the skin -fluid-filled blisters resultsAutoimmunity-in certain type II and II hypersensitivities, the immune system has lost tolerance to autoantigens and forms autoantibodies and sensitized T cells against themDisruption of function can be systemic or organ specific-systemic lupus erythematosus -rheumatoid arthritis -endocrine autoimmunities -myasthenia gravis -multiple sclerosisSequestered antigen theory-during embryonic growth some tissues are immunologically privilegedForbidden clones-some clones were not subjected to the tolerance process, and they attack tissues carrying self moleculesTheory of immune deficiency-mutations in the receptor genes of some lymphocytes render them reactive to selfThe origins of autoimmunity disease-molecular mimicry, viral infection, microbial etiologySystemic lupus erythematous-systemic -II and III -inflammation of many organs, antibodies against red and white blood cells, platelets, clotting factors, nucleus DNARheumatoid arthritis and ankylosing spondylitis-systemic -III and IV -vasculitis; frequent target is joint lining; antibodies against other antibodies (rheumatoid factor)Scleroderma-systemic -II -excess collagen deposition in organs; antibodies formed against many intracellular organellesHashimoto's thyroiditis-thyroid -II -destruction of the thyroid folliclesGraves' disease-thyroid -II -antibodies against thyroid-stimulating hormone receptorsPernicious anemia-stomach lining -II -antibodies against receptors prevent transport of v. B12Myasthenia gravis-muscle -II -antibodies against the acetylcholine receptors on the nerve-muscle junction alter functionType I diabetes-pancreas -II -antibodies stimulate destruction of insulin-secreting cellsMultiple sclerosis-myelin -II and IV -T cells and antibodies sensitized to myelin sheath destroy neuronsGoodpasture syndrome (glomerulonephritis)-kidney -II -antibodies to basement membrane of the glomerulus damage kidneysRheumatic fever-heart -II -antibodies to group A streptococci cross-react with heart tissueDiabetes mellitus-a dysfunction in insulin production by cells in the pancreas -reduction in insulin productionMyasthenia gravis-autoantibodies bind to receptors for acetylcholine -pronounced muscle weaknessMultiple sclerosis-myelin sheath of nerve cells is damaged by both T cells and autoantibodies -paralyzing neuromuscular diseaseImmunodeficiency disease-components of the immune response system are absent -deficiencies involve B and T cells, phagocytes, and complementPrimary immunodeficiency-congenital; usually genetic errorsSecondary diseases-acquired after birth; caused by natural or artificial agentsB cell defect-agammaglobulinemia -patient lacks antibodiesT cell defect-thymus is missing or abnormal (DiGeorge syndrome)Severe combined immunodeficiency (SCID)-both limbs of lymphocyte system are missing or defective; no adaptive immune responseSecondary Immunodeficiencies-due to damage after birth -caused by; infection, organic disease, chemotherapy, or radiationWhat is the most common type of secondary immunodeficiencies?-AIDS -T helper cells are targeted; numerous opportunistic infections and cancersBenign tumors-nonspreading -self-containedMalignant tumors-that spreads from tissue of origin to other sitesAre there genetic alterations that disrupt the normal cell division cycle?-yesPossible causes of new growth of abnormal cells are:-errors in mitosis, genetic damage, activation of oncogenes, or retrovirusesImmune surveillance-immune system keeps cancer "in check"

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