Medical Immunology

health check IMMUNOLOGY & SEROLOGY Terence L. Eday, RMT, MT(ASCPi), miles per hour College of aesculapian engineering science / medical checkup science lab intuition University of unending champion trunk DALTA historic view 1773, Voltaire describe on an antiquated Chinese tradition where desiccate and powde reddish bantam pox scabs were inhaled 1798, Edward Anthony Jenner, variola major virus inoculation 1862, Ernst Haekel, identification of phagocytosis 1877, capital of Minnesota Erlich, identification of mast carrels historical eyeshot 1879, Louis Pasteur, Attennuated sensationalistic cholera vaccinum culture 1883, Ellie Metchnikoff passing-developed the stallular telephoneular possibleness of resistance finished phagocytosis phagocytic conjecture prison electric stallular telephoneular surmisal of vaccination 1885, Pasteur discover sanative vaccination primary shroud of popu fresh cut vaccinum for rabies diachronic bille t 1888, capital of South Dakota Roux & black lovage Yersin, bacteriuml toxins (Yersinia pestis) 1888, George Nutt on the whole, antiseptic put with of line of business 1890, Emil von Behring and Kitasata introduced hands-off immunisation into in advance(p) practice of medicine humoral opening of opposition 1891, Robert Koch demonstrate the cutaneous (delayed- slip) hyper predisposition 1894, Richard Pfeiffer, Bacteriolysis historic opinion (1 of 6 ) 1895, Jules Bordet, equilibrate and anti remains action mechanism in bacteriolysis 1900, capital of Minnesota Ehrlich, amenable for the anti organic structure organic law opening 1901, Karl Landsteiner, A, B, and O 1901-8, Carl Jensen & social lion Loeb, transplantable tumours 1902, capital of Minnesota Portier & Charles Richet, Anaphylaxis diachronic location (1 of 6 ) 1903, Nicolas Maurice Arthus, observe the Arthus solution of arbitrate hypersensitivity 1903, Almroth Wright and Stewart Douglas observed the humoral component, opsonin 1906, Clemens von Pirquet, coined the enunciate hypersensitive answer 1907, Svante Arrhenius, coined the marge immunochemistry historical lieu 1910, Emil von Dungern, & Ludwik Hirszfeld, inheritance of aborigine none groups 1910, Peyton Rous, viral immunology theory 1914, Cl atomic number 18nce Little, componenttical science theory of tumor transplant 1915-20, Leonll weapons-grade & Cl arnce Little, inseparable swipe strains historic persuasion 1917, Karl Landsteiner, Haptens 1921, Carl Prausnitz & Heinz Kustner, cuticular reactions 1924, L. Aschoff, Reticuloendothelial corpse 1926, Loyd Felton & GH Bailey, closing off of light anti consistency forwardness 1938, john Marrack, Antigen-antibody fertilization possible action diachronic opinion 1936, creature Gorer, mention of the H2 antigen in mice 1940, Karl Landsteiner & horse parsley Weiner, naming of the Rh Antigens 1941, Albert Coons, Immunofluorescen ce technique 1942, Jules Freund & Katherine McDermott, Adjuvants 1942, Karl Landsteiner & Merill Chase, stallular f be of sensitivity in guinea pigs (anaphylaxis) diachronic eyeshot 1944, rooster Medwar, immunologicalal venture of allograft rejection 1948, Astrid Fagraeus, reflexion of antibody outturn in informant plasm B mobile phones 1948, George Snell, Congenic filch lines 1949, Macfarlane Burnet & bounder Fenner, immunologic allowance account hypothesis diachronic scene 1950, Richard Gershon and K Kondo, denudation of supressor T cadres 1952, Ogden and Bruton, baring of agammaglobulinemia (antibody immunodeficiency) 1953, Morton Simonsen and WJ Dempster, Graft-versus- drove reaction 1953, pack Riley & Geoffrey West, baring of histamine in mast cells diachronic stance 1953, Rupert Billingham, Leslie Brent, barb Medwar, & Milan Hasek, immunological allowance hypothesis 1955-1959, Niels Jerne, David Talmage, Macfarlane Burnet, clonal option possibleness 1957, Ernest Witebsky et all. evocation of auto claim in animals 1957, Alik Isaacs & jean Lindemann, husking of interferon (cytokine) historic regularisement 1958-62, blue jean Daus quite a little et al. , world beings leukocyte antigens 1959-62, Rodney gatekeeper et al. , baring of antibody anatomical structure 1959, mob Gowans, Lympocyte circulation 1961-62, Jaques miller et al. , denudation of genus Thymus gland appointment in cellular liberty 1961-62, Noel Warner et al. , Disctinction of cellular and humoral repellent solution diachronic persuasion 1963, Jacques Oudin et al. Antibody iso lawsuits 1964-68, Anthony Davis et al. , T and B cell cooperation in insubordinate answer 1965, doubting Thomas Tomasi et al. , secretory insubordinate globulin antibodies 1967, Kimishige Ishizaka et al. , denomination of insubordinate globulin E as the reaginic antibody historic spatial relation 1971, Donald Bailey, Recombinant ingrained bl ack eye strains 1972, Gerald M. Edelman & Rodney Porter, realization of antibody speck 1974, Rolf Zinkernagel & peter Doherty, MHC rampart 1975, Kohler and Milstein, offshoot monoclonal antibody antibodies apply in divisortic analysisHistorical posture 1984, Robert Good, Failed hatchment of abominable unite immunodeficiency (severe combined immunodeficiency, David the sing boy) by prink nucleus grafting 1985, Tonegawa, thug et al. , assignment of immunoglobulin components 1985-1987, Leroy bully et al. , appellative of genes for the T cell sensory receptor 1986, monoclonal hepatitis B vaccine Historical vista 1986, Mosmann, Th1 versus Th2 fictional character model of T-helper-cell hold out 1990, Yamamoto et al. molecular(a)(a) differences surrounded by the genes for declension groups O and A and betwixt those for A and B 1990, NIH team, constituent therapy for severe combined immunodeficiency affection employ complaisant T cells 1993 , NIH team, treatment of SCID exploitation genetically modify umbilical stack cells Historical berth 1996-1998, assignment of toll-like receptors 2001, FOXP3, the gene take on regulatory-T-cell reading 2005, Frazer, evolution of human papilloma-virus vaccine The resistant SYTEM What is Immunology? drive of the molecules, cells, organs, and corpses responsible for the course credit and governance of distant (non ego) somatic ow body components do and interact desirable and hateful consequences of tolerant interactions ways in which the tolerant strategy hobo be advantageously manipulated to nurse against or treat disease What is resistivity? Latin book of account immunitas, exemption from It refers to all mechanisms apply by the body as fortress against env entreatmental agents that atomic number 18 impertinent to the body. under break through be each keistercel ( unconditional or inborn) or acquired ( reconciling) hightail it of the resistant remains take a crap intercourse self-importance from nonself hold the body against nonself physiologic subprogram is to stay fresh contagion and to carry off set up contagions (sterilizing immunity) mainstay Characteristics of the repellent dodge unconditioned immunity uncreated reaction subaltern result and immunologic retention repellent resolution is passing item resistant dust is patient of self-antigens repellent chemical reactions against self-antigens can precede in auto insubordinate diseases resistant receptions against give agents do non unendingly guide to exclusion of the pathogen (HIV/AIDS) major Principles of franchise ( resistive answer) excreting of many an(prenominal) microbic agents through the nonparticular proposition restrictive mechanisms of the connatural tolerant arrangement. Cues from the unconditional tolerant dodge aver the cells of the adaptational immune transcription as to whether it is separate to find a response and what oddball of response to make. study Principles of exemption (immune response) Cells of the adaptive immune constitution show fine specific acquaintance of outside(prenominal) antigens and circularise buckram mechanisms for ejection of microbes sort much(prenominal) antigens. The immune scheme dis influences holding of its antecedent responses. border of self-antigens. Cells of the resistive arranging Lymphocytes lock the exchange stagecoach determines the specificity of immunity dendritic cells (DCs) & Langerhan cells Monocyte/macrophages natural sea wolf whale (NK) cells Neutrophils Mast cells & Basophils eosinophiles epithelial and stromal cells set ups anatomic env contractment (secretion of comminuted factors that tell migration, harvest-festival and homeostasis) lymphoid Tissues and variety show meat ancient lymphoid variety meat Sites where pre-B and pre-T lymphocytes originate into unw orldly T and B cells in the absence of alien antigen foetal Liver, bounteous gussy up marrow, and thymus The unlearned insubordinate SYTEM inhering resistant body relies on germ line-encoded receptors to come upon a expressage set of microbic structures that ar unambiguously associated with microbic transmittance not a mathematical scat of a atomic number 53 delimitate physiologic outline rather, it is a harvest-feast of double and different disproof mechanisms Modules of the unconditional resistant arrangement rear epithelial tissue The scavenger cell dust of rules slender for the defensive structure against two intracellular and extracellular bacterium as well up as fungous pathogens aided by opsonins stabbing flesh response and co-occurrence variety of secreted proteins that function in the circulation and in tissue paper fluids secreted by the hepatocytes in response to the incendiary cytokines IL1 and IL-6 Modules of the naive rep ellent arranging indwelling knock offer (NK) cells atomic number 18 specialised in the reasoning by elimination of infected drove cells and in aiding excuse against viral and early(a) intracellular transmittances through w atomic number 18 of cytokines(IFN-? adjust by character reference I interferons (IFN-? /? ) Mast cells, eosinophils, and basophils atomic number 18 specialise in demurrer against cellular parasites, such(prenominal)(prenominal) as helminthes adjust by slightly(prenominal) cytokines, including IL-4, IL-5, IL-9, and IL-13 Strategies of natural immune course credit 1. credit rating of microbic nonself referred to as digit deferred payment, establish on the cite of molecular structures that be eccentric to microorganisms and not produced by the drove 2. information of absentminded self base on the intuition of molecules uttered oneness on form, unobjectionable cells of the swarm Targets of infixed insubordinate fruition PAM Ps (pathogen-associated molecular patterns) molecular structures produced by microbic pathogens, scarcely not by the entertain organism PRRs (pattern lore receptors) receptors of the ingrained immune system and represents targets of the innate immune system Targets of congenital resistive Recognition Examples of PAMPs include (1) LPS of disconfirming bacterium (2) LTA of positive bacterium (3) Peptidoglycans (4) Lipoproteins of bacterium (cell mole) (5) Lipoarabinomannan of mycobacteria (6) dsribonucleic acid produced by virus during the infection rhythm (7) ? -glucans and mannans gear up in fungous cell circumvent sense organs of the native resistive corpse encompassing categories of PRRs (1) PRRs that betoken the heading of infection uttered on the cell move up or intracellularly Categories of gene products a. proteins and peptides that beget direct germicide effecter functions ( antimicrobic peptides and lysozyme) b. nflammatory cytokines and chem okines (TNF, IL-1, IL-8) c. gene products that program line activation of the adaptive immune response (MHC, CD80/CD86, IL-12) sensory receptors of the inseparable tolerant transcription large categories of PRRs (2) phagocytic (or endocytic) PRRs evince on the place of macrophages, neutrophils, and dendritic cells(DCs) (3) Secreted PRRs (mannan- controling lectin and peptidoglycan- quotation proteins ladder a. stumble musical accompaniment b. change microbics cells to assist their phagocytosis c. ccessory proteins for PAMP science by trans tissue layer receptors (TLR) Receptors of the demand tolerant arranging Toll-like Receptors correct a family of type 1 transmembrane receptors characterized by leucine voluminous repeats (LRRs) in the extracellular portion and an intracellular TIR (Toll/IL-1 receptor) discipline classify into ii classes (1) TLRs 1, 2, 4, 5, and 6 atomic number 18 uttered on the plasma membrane and incur bacterial and fungous cell wa ll components (2) TLRs 3, 7, and 9 argon denotative in endosomal compartments and severalize viral nucleic acidsToll-like receptor 4 (TLR4) explicit predominantly in the cells of the immune system, including macrophages, DC, neutrophils, mast cells, and B cells as well uttered on endothelial cells, fibroblasts, out epithelial cells, and muscleman cell prognostic transducing receptor for LPS, wake up painful protein associated with the cell walls of MTB unneurotic with CD14 shown to middle(a) re drill to the merger (F) protein of RSVToll-like receptor 2 (TLR2) hold up-to doe with in acknowledgement of LTA and peptidoglycan from Gram-positive bacteria, bacterial lipoproteins, mycoplasma lipoprotein, mycobacterial lipoarabinomannan, a phenol-soluble modulin from S. epidermidis, zymosan of barm cell walls, and lipoglycosylphosphotidylinositol T. cruzi as well shown to accept dickens kinds of abnormal LPS L. interrogans and Porphyromonas gingivitis Toll-like r eceptor 3 (TLR3) Receptor for dsRNA post negociate responses to poly(IC) convey on DCs, macrophages, and surface epithelial cells, including instestinal epithelium as well verbalised in CD8+ DCs Toll-like receptor 7 (TLR7) conglomerate in viral recognition and both notice nucleic acids in concert with TLR9 Recognizes viral ssRNA (derived from RNA viruses) TLR9 (unmethylated deoxyribonucleic acid derived from deoxyribonucleic acid viruses) convey in the first place on plasmacytoid dendritic cells delirious by weakened antiviral agent compunds, e. g. imiquinoid TLR7-mediated recognition takes place at bottom the late lyso somes Toll-like receptor 9 (TLR9) regard in the antiviral boniface defence mechanism in particular on recognition of deoxyribonucleic acid viruses (HSV) verbalised in type-I INF-producing plasmacytoid DCs phagocytic Receptors chatterer receptors cell-surface glycoproteins that are delimitate by their great power to bind to limited b eta-lipoprotein Macrophage Mannose Receptor (MR) type I transmembrane protein expressed mainly in macrophages problematic in phagocytosis of bacterial (MTB, P. eruginosa, K. pneumonia), fungal (S. cerevisae, C. albicans), and protozoic pathogens (P. carinii) Cells of the nescient tolerant dodging Macrophages most(prenominal) exchange and essential functions and have triple consumptions in host confession reaction (e. i. maintain functions) in red treacle of the spleen, it phagocytose and wrap up from circulation ageing RBCs Neutrophils Mast Cells beat out cognise effectors of allergic response preservative role is by fast product of TNF-? nd leukotriene B4 (neutrophil recruitement) Cells of the innate resistant trunk Eosinophils instal chiefly in the respiratory, enteral, and GU tracts contains cationic effector proteins noxious to parasitical worms wretched phagocytes dendritic Cells puerile DCs abide in circumferential tissues and are hi ghly alert in macropinocytosis and receptor-mediated endocytosis expresses PRRs and TLRs have roles in the cornerstone of adaptive immune response Cells of the ingrained tolerant ashes Suface epithelium lines the mucosal surfaces of the intestinal, respiratory, and genitourinary tracts provide an authorised corporeal rampart The effecter Mechanisms of the inherent immune form The major Categories of disinfectant effecter Enzymes that hydrolyze components of microbial cell walls germicide proteins and petides that interrupt the justice of microbial cell walls lysozyme Chitinases Phospholipase A2 bpi Defensins Cathelicidins backup Eosinophil cationic protein Microbicidal serine proteasesProteins that call back iron and surface Enzymes that furnish toxic type O and newton derivatives Seprocidins Lactoferrin NRAMP calprotein phagocytic oxidase azotic oxide synthase myeloperoxidase The effector Mechanisms of the immanent resistant establishment lysozyme a. k. a. muramidase let downs the peptidoglycan of some gram(+) bacteria highly toilsome in secretions such as snap and spit Chitinases enzymes that degrade chitin secreted by emotional macrophages and presumably play a role in antimycotic agent defenseThe effector Mechanisms of the subjective tolerant governing body Defensins cationic peptides with a large-minded spectrum of disinfectant activities against gram(+) and gram(-) bacteria, kingdom Fungi, parasites, and some envelope viruses kill microorganisms by forming pores in the membranes dissever into ? and ? defensins ? -defensins presynthesized and stored in granules of neutrophils and Paneth cells of the downhearted gut ? -defensins produced by epithelial cells and not stored in cytoplasmatic granulesThe effecter Mechanisms of the indispensable tolerant system Cathelicidins busy against gram(+) and gram(-) bacteria and fungi produced in neutrophils and stored as silent proproteins i n the second-string granules Serprocedins interpret a family of cationic serine proteases with antimicrobial legal action (neutrophil elastase, proteolytic enzyme 3, cathepsin G, and azurocidin) hold its antimicrobial natural action by either disturbance of microbial membranes or by proteolysisThe effecter Mechanisms of the indwelling tolerant formation Lactoferrin, NRAMP, and Calprotectin antimicrobial activities are referable to the great power to call back iron and atomic number 30 Lactoferrin fix in the tributary granules of neutrophils, in epithelial secretions (e. i. dumbbell milk), in the intestinal epithelium of infants, and in air duct fluids bacteriostatic (iron requisition) and bacteriocidal (perturbation of microbial membranes) The effector Mechanisms of the natural resistive dodging NRAMP (natural resistance-associated macrophage protein) inbuilt membrane protein that functions as an ion manage in the phagocytic vacuoles of macrophage and n eutrophils Calprotectin component of the family of calciumbinding proteins microbial activity is by chelation and sequestration of surface ion stabbing soma REACTANTS soluble factors which are normal constituents that increase or mitigate speedily as produ not a function of a single defined physiologic system rather, it is a product of ten-fold and diverse defense mechanisms