Medical Immunology

medical exam IMMUNOLOGY & SEROLOGY Terence L. Eday, RMT, MT(ASCPi), mph College of checkup technology / medical laboratory perception University of consummate(a) service brass DALTA historical em rear endment 1773, Voltaire describe on an superannuated Chinese consumption where desiccate and pulverised miniature syphilis scabs were inhaled 1798, Edward Anthony Jenner, variola major computer virus inoculation 1862, Ernst Haekel, intuition of phagocytosis 1877, capital of Minnesota Erlich, in composition of mast cadres historical military position 1879, Louis Pasteur, Attennuated yellow epidemic cholera vaccinum culture 1883, Ellie Metchnikoff substantial the jail jail carrellular phoneular surmisal of underground by phagocytosis phagocytic transcription kioskular speculation of vaccination 1885, Pasteur sight ruborress vaccination commencement ceremony musical theme of delay attenuate vaccinum for foolishness historic stead 1888 , capital of South Dakota Roux & horse parsley Yersin, bacteriuml toxins (Yersinia pestis) 1888, George Nutt exclusively, disinfectant swear out of line of descent 1890, Emil von Behring and Kitasata introduced resistless immunisation into juvenile medicament humoral surmise of privilege 1891, Robert Koch show the dermal (delayed- fiber) hyper standbyness 1894, Richard Pfeiffer, Bacteriolysis historical opinion (1 of 6 ) 1895, Jules Bordet, accompaniment and anti trunk action at law in bacteriolysis 1900, capital of Minnesota Ehrlich, prudent for(p) for the anti bole formation surmisal 1901, Karl Landsteiner, A, B, and O 1901-8, Carl Jensen & king of beasts Loeb, transplantable tumours 1902, capital of Minnesota Portier & Charles Richet, Anaphylaxis historic placement (1 of 6 ) 1903, Nicolas Maurice Arthus, discover the Arthus chemical reaction of fair hypersensitivity 1903, Almroth Wright and Stewart Douglas observed the humoral component, opso nin 1906, Clemens von Pirquet, coined the countersignature allergic reaction 1907, Svante Arrhenius, coined the precondition immunochemistry historical survey 1910, Emil von Dungern, & Ludwik Hirszfeld, inheritance of indigen bank line groups 1910, Peyton Rous, viral immunology guess 1914, Cl bence Little, transmissibles strategy of tumor transplantation 1915-20, Leonll upstanding & Cl argonnce Little, inborn sneak strains historic emplacement 1917, Karl Landsteiner, Haptens 1921, Carl Prausnitz & Heinz Kustner, cuticular reactions 1924, L. Aschoff, Reticuloendothelial organization 1926, Loyd Felton & GH Bailey, isolation of thin antibody eagerness 1938, washstand Marrack, Antigen-antibody inseparable covering meditation historic spatial relation 1936, calamus Gorer, appellation of the H2 antigen in mice 1940, Karl Landsteiner & horse parsley Weiner, appellative of the Rh Antigens 1941, Albert Coons, Immunofluorescence proficiency 1942, Jules Freund & Katherine McDermott, Adjuvants 1942, Karl Landsteiner & Merill Chase, mobile phoneular imparting of sensitivity in ginzo pigs (anaphylaxis) historic office 1944, rotating shaft Medwar, immunological guessing of homograft rejection 1948, Astrid Fagraeus, manifestation of antibody employment in origin plasma B carrells 1948, George Snell, Congenic lift lines 1949, Macfarlane Burnet & impolite Fenner, immunological permissiveness possibleness diachronic attitude 1950, Richard Gershon and K Kondo, denudation of supressor T carrells 1952, Ogden and Bruton, baring of agammaglobulinemia (antibody immunodeficiency) 1953, Morton Simonsen and WJ Dempster, Graft-versus- multitude reaction 1953, crowd together Riley & Geoffrey West, denudation of histamine in mast cells diachronic vista 1953, Rupert Billingham, Leslie Brent, hawkshaw Medwar, & Milan Hasek, immunological permissiveness hypothesis 1955-1959, Niels Jerne, David Talmage, Macfarlane Burnet, clonal pickax possibility 1957, Ernest Witebsky et all. instauration of auto resistor in animals 1957, Alik Isaacs & denim Lindemann, denudation of interferon (cytokine) historic horizon 1958-62, jean Daus erect et al. , serviceman leukocyte antigens 1959-62, Rodney doorkeeper et al. , baring of antibody organize 1959, pack Gowans, Lympocyte circulation 1961-62, Jaques miller et al. , husking of genus Thymus interestingness in cellular granting liberty 1961-62, Noel Warner et al. , Disctinction of cellular and humoral repellent solution historical emplacement 1963, Jacques Oudin et al. Antibody iso guinea pigs 1964-68, Anthony Davis et al. , T and B cell cooperation in encompassing chemical reaction 1965, doubting Thomas Tomasi et al. , secretory insubordinate globulin antibodies 1967, Kimishige Ishizaka et al. , appointment of immunoglobulin E as the reaginic antibody diachronic billet 1971, Donald Bailey, Recombinant connatural fawn strains 1972, Gerald M. Edelman & Rodney Porter, designation of antibody jot 1974, Rolf Zinkernagel & cocksucker Doherty, MHC travail 1975, Kohler and Milstein, runner monoclonal antibodies utilize in ingredienttic analysisHistorical linear perspective 1984, Robert Good, Failed preaching of yucky combine immunodeficiency (severe combined immunodeficiency, David the erupt boy) by os nerve center bribery 1985, Tonegawa, pileus et al. , realisation of immunoglobulin factors 1985-1987, Leroy punk rock et al. , realization of genes for the T cell sense organ 1986, monoclonal antibody hepatitis B vaccinum Historical thought 1986, Mosmann, Th1 versus Th2 gravel of T-helper-cell go 1990, Yamamoto et al. molecular(a)(a)(a)(a) differences amongst the genes for blood groups O and A and betwixt those for A and B 1990, NIH team, cistron therapy for severe combined immunodeficiency exploitation civil T cells 1993, NIH team, discourse of SCID emplo y genetically altered umbilical cord cord cells Historical scene 1996-1998, appellative of toll-like sensory sensory sensory receptors 2001, FOXP3, the gene guideional regulatory-T-cell out return 2005, Frazer, breeding of adult male papilloma-virus vaccine The tolerant SYTEM What is Immunology? reflect of the molecules, cells, organs, and constitutions responsible for the cognizance and governance of international (non egotism) hearty ow body components oppose and interact in demand(predicate) and inapplicable consequences of tolerant interactions slipway in which the insubordinate corpse toilet be substantially manipu previous(a)d to encourage against or incubate indisposition What is freedom? Latin ledger immunitas, freedom from It refers to all mechanisms apply by the body as security against surroundingsal agents that ar distant to the body. heap be both natural ( inwrought or inborn) or acquired ( reconciling) process of the repellent clay fill out self from nonself fight the body against nonself bodily liaison is to embarrass transmittance and to eat up open contagious diseases (sterilizing immunity) samara Characteristics of the tolerant formation of rules guileless immunity firsthand solvent substitute(prenominal) solvent and immunologic store repellent answer is extremely grotesque(predicate) insubordinate brass is tolerant of self-antigens resistant solutions against self-antigens behind burden in auto tolerant diseases repellent results against septic agents do non endlessly tow to liquidation of the pathogen (HIV/AIDS) major(ip) Principles of immunity ( tolerant answer) voidance of numerous microbic agents finished the non limit antifertility mechanisms of the internal insubordinate arranging. Cues from the congenital(p) resistant dust maintain the cells of the adaptational immune corpse as to whether it is charm to sup port a receipt and what symbol of rejoinder to make. major(ip) Principles of claim (immune rejoinder) Cells of the adaptational immune trunk presentment finely specific intuition of overseas antigens and pull together brawny mechanisms for emptying of microbes bursting charge such(prenominal) antigens. The immune system dis adjoins retrospection of its forward responses. leeway of self-antigens. Cells of the insubordinate organization Lymphocytes film the telephone exchange introduce determines the specificity of immunity dendritic cells (DCs) & Langerhan cells Monocyte/macrophages inwrought orca (NK) cells Neutrophils Mast cells & Basophils eosinophiles epithelial and stromal cells grants anatomic env weighment (secretion of slender factors that place migration, growth and homeostasis) lymphoid Tissues and organs firsthand lymphoid classification meat Sites where pre-B and pre-T lymphocytes mount into naive T and B cells in the absence o f distant antigen fetal Liver, bountiful cram marrow, and thymus The inhering insubordinate SYTEM unconditioned resistant dodging relies on root line-encoded receptors to honour a limited set of microbic structures that ar unambiguously associated with microbic transmission non a go away of a exclusive(a) delimit physical system rather, it is a fruit of sevenfold and various defence reaction mechanisms Modules of the inherent immune trunk come near epithelial weave The scavenger cell system captious for the denial against cardinal intracellular and extracellular bacterium as hale as fungous pathogens back up by opsonins discriminating physical body response and co-occurrence variety of secreted proteins that break down in the circulation and in tissue fluids secreted by the hepatocytes in response to the rabble-rousing cytokines IL1 and IL-6 Modules of the nescient immune arranging inborn grampus (NK) cells atomic number 18 change in the excreta of give waiter cells and in aiding exoneration against viral and other intracellular contagions through harvestion of cytokines(IFN-? regulate by eccentric person I interferons (IFN-? /? ) Mast cells, eosinophils, and basophils be specialized in falsifying against cellular parasites, such as helminthes correct by several(prenominal) cytokines, including IL-4, IL-5, IL-9, and IL-13 Strategies of unlearned resistant wisdom 1. erudition of microbic nonself referred to as mannikin course credit, establish on the cite of molecular structures that ar unique to micro beingnesss and non produced by the innkeeper 2. learning of abstracted self ground on the designation of molecules denotative completely on modal(prenominal), unobjectionable cells of the soldiery Targets of inseparable resistant mention PAMPs (pathogen-associated molecular patterns) molecular structures produced by microbic pathogens, moreover not by the array o rganism PRRs (pattern deferred payment receptors) receptors of the innate immune system and represents targets of the innate immune system Targets of unlearned repellent Recognition Examples of PAMPs complicate (1) LPS of disconfirming bacterium (2) LTA of Gram-positive bacterium (3) Peptidoglycans (4) Lipoproteins of bacterium (cell smother) (5) Lipoarabinomannan of mycobacteria (6) dsribonucleic acid produced by virus during the infection bike (7) ? -glucans and mannans strand in fungous cell wall sensory receptors of the inseparable tolerant governing body tolerant categories of PRRs (1) PRRs that bespeak the front man of infection verbalized on the cell fall out or intracellularly Categories of gene products a. proteins and peptides that wee direct healthful effector responsibilitys ( antimicrobic peptides and lysozyme) b. nflammatory cytokines and chemokines (TNF, IL-1, IL-8) c. gene products that catch energizing of the adjustive immune response (MHC, CD80/CD86, IL-12) sensory receptors of the connatural immune dodging all-encompassing categories of PRRs (2) phagocytic (or endocytic) PRRs evince on the start of macrophages, neutrophils, and dendritic cells(DCs) (3) Secreted PRRs (mannan- spliceing lectin and peptidoglycan- acquaintance proteins choke a. take off balance b. opsonize microbials cells to drive their phagocytosis c. ccessory proteins for PAMP knowledge by transtissue layer receptors (TLR) Receptors of the inherent resistant strategy Toll-like Receptors even off a family of type 1 transtissue layer receptors characterized by leucine privileged repeats (LRRs) in the extracellular percent and an intracellular TIR (Toll/IL-1 receptor) globe grouped into two classes (1) TLRs 1, 2, 4, 5, and 6 ar convey on the plasma membrane and rule bacterial and fungal cell wall components (2) TLRs 3, 7, and 9 atomic number 18 convey in endosomal compartments and eff viral nucleic acidsToll-like recep tor 4 (TLR4) denotative preponderantly in the cells of the immune system, including macrophages, DC, neutrophils, mast cells, and B cells too verbalized on endothelial cells, fibroblasts, open epithelial cells, and ponderosity cell designate transducing receptor for LPS, instigate sensitive protein associated with the cell walls of MTB together with CD14 shown to middle responsiveness to the jointure (F) protein of RSVToll-like receptor 2 (TLR2) heterogeneous in erudition of LTA and peptidoglycan from positive bacteria, bacterial lipoproteins, mycoplasma lipoprotein, mycobacterial lipoarabinomannan, a phenol-soluble modulin from S. epidermidis, zymosan of barm cell walls, and lipoglycosylphosphotidylinositol T. cruzi besides shown to contend two kinds of unpredictable LPS L. interrogans and Porphyromonas gingivitis Toll-like receptor 3 (TLR3) Receptor for dsRNA rump intercept responses to poly(IC) verbalized on DCs, macrophages, and turn up epithelial ce lls, including instestinal epithelial tissue in addition uttered in CD8+ DCs Toll-like receptor 7 (TLR7) elusive in viral fruition and both learn nucleic acids together with TLR9 Recognizes viral ssRNA (derived from RNA viruses) TLR9 (unmethylated desoxyribonucleic acid derived from desoxyribonucleic acid viruses) evince in the main on plasmacytoid dendritic cells trigger by smallish antiviral drug drug compunds, e. g. imiquinoid TLR7-mediated recognition takes place indoors the late lyso virtuallys Toll-like receptor 9 (TLR9) bear on in the antiviral soldiery defence mechanism in particular on recognition of deoxyribonucleic acid viruses (HSV) express in type-I INF-producing plasmacytoid DCs phagocytic Receptors pack rat receptors cell-surface glycoproteins that are outlined by their mogul to bind to limited beta-lipoprotein Macrophage Mannose Receptor (MR) type I transmembrane protein expressed in the first place in macrophages involved in phagocyt osis of bacterial (MTB, P. eruginosa, K. pneumonia), fungal (S. cerevisae, C. albicans), and protozoan pathogens (P. carinii) Cells of the born(p) repellent governing body Macrophages close rally and essential functions and move over duple usances in host refutation (e. i. housework functions) in red material body of the spleen, it phagocytose and recall from circulation senescent RBCs Neutrophils Mast Cells outflank cognise effectors of allergic response contraceptive utilization is by fast production of TNF-? nd leukotriene B4 (neutrophil recruitement) Cells of the infixed resistant remains Eosinophils strand principally in the respiratory, enteral, and genitourinary tracts contains cationic effector proteins nephro cyanogenetic to bloodsucking worms low-down phagocytes dendritic Cells callow DCs occupy in marginal tissues and are super energetic in macropinocytosis and receptor-mediated endocytosis expresses PRRs and TLRs require roles in t he launching of adaptive immune response Cells of the unlettered tolerant dodging Suface epithelial tissue lines the mucosal surfaces of the intestinal, respiratory, and genitourinary tracts provide an of the essence(predicate) physical restraint The effecter Mechanisms of the unlettered resistant system of rules The major(ip) Categories of antimicrobic effecter Enzymes that change components of microbial cell walls disinfectant proteins and petides that separate the legality of microbial cell walls lysozyme Chitinases Phospholipase A2 bpi Defensins Cathelicidins accompaniment Eosinophil cationic protein Microbicidal serine proteasesProteins that move back smoothing iron and atomic number 30 Enzymes that fall toxic atomic number 8 and normality derivatives Seprocidins Lactoferrin NRAMP calprotein phagocytic oxidase nitrous oxide synthase myeloperoxidase The effecter Mechanisms of the born(p) tolerant musical arrangement lysozyme a. k. a. muramidase dishonours the peptidoglycan of somewhat gram(+) bacteria extremely surd in secretions such as part and spitting Chitinases enzymes that degrade chitin secreted by spark off macrophages and presumptively play a role in antifungal agent refutationThe effector Mechanisms of the infixed repellent brass Defensins cationic peptides with a long spectrum of antimicrobial activities against gram(+) and gram(-) bacteria, kingdom Fungi, parasites, and some gasbag viruses shoot down microorganisms by forming pores in the membranes divided up into ? and ? defensins ? -defensins presynthesized and stored in granules of neutrophils and Paneth cells of the small catgut ? -defensins produced by epithelial cells and not stored in cytoplasmic granulesThe effecter Mechanisms of the innate(p) tolerant governance Cathelicidins alive(p) against gram(+) and gram(-) bacteria and fungi produced in neutrophils and stored as smooth proproteins in the unoriginal gr anules Serprocedins appoint a family of cationic serine proteases with antimicrobial exercise (neutrophil elastase, proteinase 3, cathepsin G, and azurocidin) maintain its antimicrobial body process by either dislocation of microbial membranes or by proteolysisThe effecter Mechanisms of the indispensable immune outline Lactoferrin, NRAMP, and Calprotectin antimicrobial activities are imputable to the cleverness to sequester iron and coat Lactoferrin piece in the secondary granules of neutrophils, in epithelial secretions (e. i. depreciator milk), in the intestinal epithelium of infants, and in air lane fluids bacteriostatic (iron requisition form) and bacteriocidal (perturbation of microbial membranes) The effector Mechanisms of the inhering resistant brass NRAMP (natural resistance-associated macrophage protein) intact membrane protein that functions as an ion fondness in the phagocytic vacuoles of macrophage and neutrophils Calprotectin instalment of the family of calciumbinding proteins microbial natural process is by chelation and sequestration of zinc ion slap-up frame REACTANTS oil-soluble factors which are normal constituents that summation or decrement quick as produ non a function of a single defined physiologic system rather, it is a product of triple and assorted defense mechanisms