Antigens and toxins


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Antigens and toxins

  1. 1. Staphylococcus aureus :Protein A :Protein A is a 40-60 kDa MSCRAMM surface protein originally found in the cellwall of the bacteria Staphylococcus aureus. It is encoded by the spa gene and itsregulation is controlled by DNA topology, cellular osmolarity, and a two-component system called ArlS-ArlR. It has found use in biochemical researchbecause of its ability to bind immunoglobulin. It binds proteins from many ofmammalian species, most notably IgGs. It binds with the Fc region ofimmunoglobulins through interaction with the heavy chain. The result of this typeof interaction is that, in serum, the bacteria will bind IgG molecules in the wrongorientation (in relation to normal antibody function) on their surface whichdisrupts opsonization and phagocytosis.
  2. 2. Techoic acid:skin-colonizing gram-positive bacteria produce Wall teichoic acids (WTAs) or relatedglycopolymers for unclear reasons. Using a WTA-deficient Staphylococcus aureus mutant, we demonstrated that WTA confersresistance toantimicrobial fatty acids from human sebaceous glands by preventingfatty acid binding. Thus, WTA is probably important for bacterial skin colonization.Polysaccharide capsule :It gives 11 serotype based on its antigenicity .Enterotoxin :which cause a form of food poisoning characterized by vomiting and diarrhea one to sixhours after ingestion of the toxin .
  3. 3. Toxic shock syndrome toxin :This is characterized by fever, erythematous rash, hypotension, shock, multiple organ failure,and skin desquamation .Exfoliatin : EF toxins are implicated in the disease staphylococcal scalded-skin syndrome (SSSS), whichoccurs most commonly in infants and young children. It also may occur as epidemics in hospitalnurseries. The protease activity of the exfoliative toxins causes peeling of the skin observed withSSSS.P-V leukoidin : The bicomponent toxin Panton-Valentine leukoidin (PVL) is associated with severe necrotizingpneumonia in children. The genes encoding the components of PVL are encodedona bacteriophage found in community-associated methicillin-resistant S. aureus (MRSA) strains.
  4. 4. Streptococcus :C carbohydrate :Determine the group of β hemolytic streptococcus and its located in the cell wallM Protein :M protein is a virulence factor that can be produced by certain species of Streptococcus. Mprotein is strongly anti-phagocytic and is a major virulence factor. It binds to serum factor H,destroying C3 convertase and preventing opsonization by C3b. However plasma B cells cangenerate antibodies against M protein which will help in opsonization and further off destructionof the microorganism by the macrophages and neutrophilis. Cross-reactivity of anti-M proteinantibodies with heart muscle is the basis for rheumatic fever.It was originally identified by Rebecca Lancefield, who also formulated the Lancefieldclassification system for Streptococcal bacteria. Bacteria like S. pyogenes which possess Mprotein are classified in group A of the Lancefield system.
  5. 5. Erythrogenic toxin :An Erythrogenic toxin is a toxin produced by strains of Streptococcus pyogenes, the primarycause of Scarlet fever. Past studies have shown that multiple variants of erythrogenic toxinsmay be produced, depending on the strain of S. pyogenes present in the host. A smallpercentage of strains may not produce a detectable toxin at all.Streptolysin :Streptolysin is a streptococcal hemolytic exotoxin.Types include Streptolysin O (SLO), which is oxygen-labile, and Streptolysin S (SLS), which isoxygen-stable.An antibody, anti-Streptolysin O, can be detected in an antistreptolysin O titer.Streptolysin O is hemolytically active only in a reversibly reduced state unlike Streptolysin Swhich is stable in the presence of oxygen. Another difference is that that SLO is antigenic whileSLS is non-antigenic due to its small size.
  6. 6. Neisseria meningitides :Lipopolysaccharides (LPS), also known as lipoglycans, are large molecules consisting of a lipid anda polysaccharide joined by a covalent bond; they are found in the outer membrane of Gram-negative bacteria, act as endotoxins and elicit strong immune responses in animals. LPS isthe major component of the outer membrane of Gram-negative bacteria, contributing greatlyto the structural integrity of the bacteria, and protecting the membrane from certain kinds ofchemical attack. LPS also increases the negative charge of the cell membrane and helpsstabilize the overall membrane structure. It is of crucial importance to gram-negativebacteria, whose death results if it is mutated or removed. LPS is an endotoxin, and inducesa strong response from normal animal immune systems. It has also been implicated in non-pathogenic aspects of bacterial ecology, including surfaceadhesion, bacteriophage sensitivity, and interactions with predators such as amoebae.
  7. 7. Lipooligosaccharidesare naturally occurring variants of the more common glycolipid, lipopolysaccharide.While lipopolysaccharides are common in the enteric bacteria, LOS is present inbacteria that colonize those mucosal surfaces that are not bathed in bile. LOS is ahighly phase variable molecule.LOS is clinically relevant in Neisseria meningitidis infections, where it has beenshown to correlate with the severity of disease, as well as cause the complicationslisted above which are hallmarks of meningococcal meningitis.IgA protease : Many bacteria which colonize the mucous membranes produce an IgA proteasewhich degrades secretory IgA.
  8. 8. Neisseria gonorrhoeae :IgA protease .Lipooligosaccharides.Pili .Bacillus anthracis :D-glutamate capsule:It is the only bacterium known to synthesize a protein capsule (D-glutamate) capsularpolypeptide of Bacillus anthracis is composed of a unique polyglutamic acid polymer in which D-glutamate monomers are joined by gamma-peptidyl bonds. The capsule is poorly immunogenic, andefforts at exploiting the polymer for vaccine development have focused on increasing its inherentimmunogenicity through chemical coupling to immune-stimulating protein carriers .
  9. 9. Anthrax toxin :each individual anthrax toxin protein is, in fact, nontoxic. Toxic symptoms arenot observed when these proteins are injected individually into laboratoryanimals. However, the co-injection of PA and EF causes edema, and the co-injection of PA and LF is lethal. The former combination is called edematoxin, and the latter combination is called lethal toxin. Thus the manifestationof physiological symptoms requires, in either case, the presence of the PAcomponent.
  10. 10. The PA requirement observed in animal-model experiments demonstrates acommon paradigm for bacterial toxins, called the A / B paradigm.The A component(s) are enzymatically active, and the B component is the cellbinding component. Anthrax toxin, in fact, is of the form A2B, where thetwo enzymes, EF and LF, are the A components and PA is the B component. ThusPA acts as a Trojan Horse, which carries EF and LF through the plasmamembrane into the cytosol, where they may then catalyze reactions that disruptnormal cellular physiology.
  11. 11. Clostridium tetani :Tetanus toxin :Tetanus toxin is an extremely potent neurotoxin , causing tetanus. It has noknown function for clostridia in the soil environment where they are normallyencountered. It is also called spasmogenic toxin, tetanospasmin orabbreviated to TeTx or TeNT. C. tetani also producesthe exotoxin tetanolysin, the effects of which are as yet unclear.
  12. 12. Clostridium botulinum :Botulinum toxin :Botulinum toxin is extremely neurotoxic. When introduced intravenously inmonkeys, type A (Botox Cosmetic) of the toxin exhibits an LD50 of 40-56 ng, typeC1 around 32 ng, type D 3200 ng, and type E 88 ng, rendering the above typessome of the most powerful neurotoxins known. Popularly known by one of itstrade names, Botox or Dysport, it is used for various cosmetic and medicalprocedures.
  13. 13. Clostridium Perfringns :Alpha toxin lecithinase :Lecithinase is a type of phospholipase that acts upon lecithin. C. perfringensalpha toxin (lecithinase) causes my necrosis and hemolysis.Enterotoxin .Clostridium Difficile :Exotoxin A & B .
  14. 14. Cyanobacteria diphtheria :Diphtheria toxin :causes diphtheria. Unusually, the toxin gene is encoded bybacteriophage (a virus that infects bacteria). The toxin causes the diseasediphtheria in humans by gaining entry into the cell cytoplasm and inhibiting proteinsynthesis. Diphtheria toxin is a single polypeptide chain of 535 amino acidsconsisting of two subunits linked by disulfide bridges. Binding to the cell surface ofthe less stable of these two subunits allows the more stable part of the protein topenetrate the host cell.
  15. 15. Listeria monocytogenes :internalin :Listeria monocytogenes can use two different surface proteins, internalin (InlA) andInlB, to invade mammalian cells. The exact role of these invasiveness factors in vivoremains to be determined. In cultured cells, InlA is necessary to promote Listeriaentry into human epithelial cells, such as Caco-2 cells, whereas InlB is necessary topromote Listeria internalization in several other cell types, includinghepatocytes, fibroblasts, and epithelioid cells, such as Vero, HeLa, CHO, or Hep-2 cells. We have recently reported that the InlA receptor on Caco-2 cells is the celladhesion molecule E-cadherin and demonstrated that nonpermissive fibroblastsbecome permissive for internalin-mediated entry when transfected with the genecoding for LCAM, the chicken homolog of the human E-cadherin gene. In this study,we demonstrate for the first time that the internalin protein alone is sufficient topromote internalization into cells expressing its receptor
  16. 16. . Indeed, internalin confers invasiveness toboth Enterococcus faecalis andinternalin-coated latex beads. As shown bytransmission electronmicroscopy, these beads were phagocytosed via a"zipper" mechanism similar tothat observed during the internalin-E-cadherin- mediated entry of Listeria.Moreover, a functional analysis of internalin demonstrates that its amino-terminalregion, encompassing the leucine-rich repeat (LRR) region and the inter-repeat(IR) region, is necessary and sufficient to promote bacterial entry intocells expressing its receptor. Several lines of evidence suggest that theLRR region would interact directly with E-cadherin, whereas the IR regionwould be required for a proper folding of the LRR region.
  17. 17. Listeriolysin :Seeligeriolysin O (LSO), one of the cholesterol-dependentcytolysins produced by Listeria seeligeri, shows 80% homology tolisteriolysin O (LLO) produced byListeria monocytogenes at theamino acid sequence level. In addition to cytolytic activity, LLO hasbeen shown to exhibit cytokine-inducing activity. In order todetermine whether LSO is also capable of exhibiting these twodifferent activities, we constructed a recombinant full-length LSO(rLSO530)and a noncytolytic truncated derivative with a C-terminaldeletion (rLSO483) and compared these molecules withrecombinant LLO. The cytolytic rLSO530 molecule could inducegamma interferon (IFN- ) production in spleen cells when the
  18. 18. cytolytic activity was blocked by treatment with cholesterol.The noncytolytic truncated rLSO483 molecule also inducedIFN- production. Anti-LLO polyclonal antibody inhibited notonly LLO-induced IFN- production but also LSO-induced IFN-production. Both NK cells and CD11b+ cells were required forLSO-induced IFN- production. Among the various cytokinesexpressed in CD11b+ cells, interleukin-12 (IL-12) and IL-18appeared to be essential. We concluded that LSO exhibits thesame biological activity as LLO.
  19. 19. Gram negative rods :Cell wall antigen OFlagellar protein HCapsular KE coli :Shiga toxin and LT toxin which is adeylate cyclase and heat labile and the othertoxin is ST which is the heat staple low molecular weight toxin and its guanylatecyclase .
  20. 20. Salmonella :It has the O and H and Vi antigens and the type of typhoid salmonella has atyphoid toxin .Shegilla :Shiga toxin and O antigen give 4 types of shegilla A B C D .Proteus :It has an O antigen and some of them are famous because they cross reactwith the rickettsia antigen and they are OX-1 OX-2 OX-K
  21. 21. Pseudomonas aeruginosa :Pyocyanin :is an antibiotic pigment produced by the Gram negativebacterium Pseudomonas aeruginosa. It is a redox-active virulence factor whichallows P. aeruginosa to kill cells, disrupts cilia actions,inhibit lymphocyte proliferation, and alter phagocytic function. Due to its redox-active properties, pyocyanin generates reactive oxygen species thatinduce oxidative stress in bacterial and mammalian cells.
  22. 22. Pyoverdin : is a fluorescent siderophore secreted by e.g. Pseudomonas aeruginosa. Its usedto help the microbe leech iron out of its surroundings and is produced mostly in irondeficient environments.Bortetella :Pertussis toxin :is a protein-based AB5-type exotoxin which causes whooping cough. PT is involvedin the colonization of the respiratory tract and the establishment ofinfection. Research suggests PT may have a therapeutic role in treating a numberof common human ailments including hypertension, viral inhibition, andautoimmune inhibition.
  23. 23. Filamentous haemagglutinin :is a large, filamentous protein that serves as a dominant attachment factor foradherence to host colliery epithelia cells of the respiratory tract. It is associatedwith biofilm formation and possesses at least four binding domains which canbind to different cell receptors on the epithelial cell surface.
  24. 24. Yersinia :Polysaccharide protein complexcapsuleEnvelope capsular antigen F1Y. pestis has typical cell wall and whole-cell lipid compositions and an enterobacterialantigen. Its lipopolysaccharide is characterized as rough, possessing corecomponents but lacking extended O-group side chains; while there is no truecapsule, a carbohydrate-protein envelope, termed capsular antigen or fraction 1(F1), forms during growth above 33 C (14, 32, 215). This facultative anaerobepossesses a constitutive glyoxylate bypass and unregulated L-serine deaminaseexpression but lacks detectable adenine deaminase, aspartase, glucose 6-phosphate dehydrogenase, ornithine decarboxylase, and urease activities, as well asa possible lesion in -ketoglutarate dehydrogenase
  25. 25. Exotoxin W and V antigens .Yop " Yersinia outer protein " :Yersinia outer protein E (YopE) are delivered directly into the cytosol of target cellsin a TTSS-dependent fashion. This unique translocation mechanism can be usedby attenuated Salmonella carrier vaccines for the delivery of heterologous antigensfused to YopE into the MHC class I-restricted antigen processing pathway. In orallyimmunized mice, this novel vaccination strategy results in the induction ofpronounced peptide-specific cytotoxic CD8 T cell responses.
  26. 26. Epstein - Barr virus :Viral capsid antigen "VCA" :Early antigen "EA":Nuclear antigen "EBNA":Membran antigen "MA" :Epstein - Barr virus :Fibers protruding hemoglutinin :
  27. 27. Papilloma virus :Genes E6 and E7: Cervical cancer is the second most common cancer in women worldwide and iscaused by human papillomavirus (HPV). Silencing of HPV E6 and E7 geneexpression was achieved using siRNAs to target the respective viral mRNAs. E6silencing induced accumulation of cellular p53 protein, trans activation of the cellcycle control p21gene, and reduced cell growth. By contrast, E7 silencing inducedapoptotic cell death. HPV-negative cells appeared to be unaffected by the antiviralsiRNAs. Thus siRNA can induce selective silencing of exogenous viral genes inmammalian cells, and the process does not interfere with the recovery of cellularregulatory systems previously inhibited by viral gene expression.
  28. 28. Influenza virus :Hemoglutinin :Influenza hemagglutinin (HA) or haemagglutinin (British English) is a typeof hemoglutinin found on the surface of the influenza viruses. It isan antigenic glycoprotein. It is responsible for binding the virus tothe cell that is being infected.The name "hemoglutinin" comes from the proteins ability to cause redblood cells (erythrocytes) to clump together ("agglutinate") in vitro
  29. 29. Neuraminidase :viral neuraminidase is a type of neuraminidase found on the surface of influenza viruses thatenables the virus to be released from the host cell. Neuraminidases are enzymes thatcleave sialic acid groups from glycoproteins and are required for influenza virus replication.When influenza virus replicates, it attaches to the cell surface using hemoglutinin, a moleculefound on the surface of the virus that binds to sialic acid groups. Sialic acids are found onvarious glycoproteins at the host cell surface, and the virus exploits these groups to bind thehost cell. In order for the virus to be released from the cell, neuraminidase must enzymaticallycleave the sialic acid groups from host glycoproteins. As an integral part of influenza replication,blocking the function of neuraminidase with neuraminidase inhibitors is an effective way to treatinfluenza.In some viruses including Mumps virus and Human Para influenza virus, a hemagglutinin-neuraminidase protein combines the neuraminidase and hemoglutinin functions in a singleprotein.NS1 Protein :Inhibit the interferon
  30. 30. Measles virus :HemoglutininFusin:Mumps virus :HemoglutininNeuraminidaseRespiratory syncytial virus :FusinPara Influenza virus :FusinHemoglutininNeuraminidase
  31. 31. Human t cell lymphotropic :Tax protein:The viral Tax protein is considered to play a central role in the process leading to ATL.Tax modulates the expression of many viral and cellular genes through theCREB/ATF-, SRF- and NF-κB-associated pathways. In addition, Tax employs theCBP/p300 and p/CAF co-activators for implementing the full transcriptional activationcompetence of each of these pathways. Tax also affects the function of various otherregulatory proteins by direct protein-protein interaction. Through these activities Taxsets the infected T-cells into continuous uncontrolled replication and destabilizes theirgenome by interfering with the function of telomerase and topoisomerase-I and byinhibiting DNA repair. Furthermore, Tax prevents cell cycle arrest and apoptosis thatwould otherwise be induced by the unrepaired DNA damage andenables, thereby, accumulation of mutations that can contribute to the leukemogenicprocess
  32. 32. Hepatitis B:Surface antigen HBsAg:Surface antigen HBsAg The first marker to appear after HBV infection, precedingclinical disease by weeks, peaking with the onset of symptoms and disappearing sixmonths post-infection; as long as HBsAg is positive, the Pt is considered infectiousand must follow prescribed sanitary procedures to avoid infecting others; if thehepatitis does not resolve, HBsAg persists and can be detected for many years orlife.Antibody to surface antigen HBsAb, anti-HBs, antibody to surface antigen HBsAbbegins to rise as the HBsAg falls; it is detectable 8-10 weeks post infection, isregarded as being protective against re-infection, and persists for life; HBsAb isformed after using the HBV vaccine, and is not present in the chronic phase of thedisease.
  33. 33. Core antigen HBcAg:Core antigen The HBc particle that contains double-stranded DNA and DNApolymerase, and is associated with the HBe antigen; HBc is not directly detected bycurrently-used assays; its presence indicates persistently replicating hepatitis BvirusCore antibody A long-term serologic marker for HBV, with 2 antibodies• IgM HBcAb A marker of acute infection, which rises early–within 2-4 weeks ofHBV infection and slowly disappears; ↓ levels of IgM HBcAb indicate resolvinginfection; IgM HBcAb is the best serologic marker for acute HBV infection• IgG HBcAb A convalescent antibody that indicates prior HBV infection; it rises 4-6 months after infection and persists for life, especially in those with active liverdisease; partially protective anti-HBc antibody levels can be induced byrecombinant vaccination, but are short-lived
  34. 34. e antigen HBeAGe antigen An antigen that rises and falls parallel to HBsAg, and derives from theproteolytic cleavage of the nucleocapsid; its presence implies a carrier statee antibody Anti-HBe An antibody that rises as HBe falls, appearing in convalescentPts, persisting for up to several years after resolution of hepatitis
  35. 35. human immunodeficiency virus :p24 p7gp 120gp 41tatRev