Some antigens and toxins Prepared by :

Mohammed A Qazzaz

Staphylococcus aureus :

Protein A :Protein A is a 40-60 kDa MSCRAMM surface protein originally found in the cell wall of the bacteria Staphylococcus aureus. It is encoded by the spa gene and its regulation is controlled by DNA topology, cellular osmolarity, and a two-component system called ArlS-ArlR. It has found use in biochemical research because of its ability to bind immunoglobulin. It binds proteins from many of mammalian species, most notably IgGs. It binds with the Fc region of immunoglobulins through interaction with the heavy chain. The result of this type of interaction is that, in serum, the bacteria will bind IgG molecules in the wrong orientation (in relation to normal antibody function) on their surface which disrupts opsonization and phagocytosis.

Techoic acid: skin-colonizing gram-positive bacteria produce Wall teichoic acids (WTAs) or related glycopolymers for unclear reasons. Using a WTA-deficient Staphylococcus aureus mutant, we demonstrated that WTA confers resistance toantimicrobial fatty acids from human sebaceous glands by preventing fatty 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 six hours after ingestion of the toxin .

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), which

occurs most commonly in infants and young children. It also may occur as epidemics in hospital nurseries. The protease activity of the exfoliative toxins causes peeling of the skin observed with SSSS.

P-V leukoidin :

The bicomponent toxin Panton-Valentine leukoidin (PVL) is associated with severe necrotizing

pneumonia in children. The genes encoding the components of PVL are encodedon a bacteriophage found in community-associated methicillin-resistant S. aureus (MRSA) strains.

Streptococcus :

C carbohydrate :Determine the group of β hemolytic streptococcus and its located in the cell wall

M Protein :M protein is a virulence factor that can be produced by certain species of Streptococcus. M protein 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 can generate antibodies against M protein which will help in opsonization and further off destruction of the microorganism by the macrophages and neutrophilis. Cross-reactivity of anti-M protein antibodies with heart muscle is the basis for rheumatic fever.

It was originally identified by Rebecca Lancefield, who also formulated the Lancefield classification system for Streptococcal bacteria. Bacteria like S. pyogenes which possess M protein are classified in group A of the Lancefield system.

Erythrogenic toxin :An Erythrogenic toxin is a toxin produced by strains of Streptococcus pyogenes, the primary cause of Scarlet fever. Past studies have shown that multiple variants of erythrogenic toxins may be produced, depending on the strain of S. pyogenes present in the host. A small percentage 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 is oxygen-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 S which is stable in the presence of oxygen. Another difference is that that SLO is antigenic while SLS is non-antigenic due to its small size.

Neisseria meningitides :

Lipopolysaccharides (LPS), also known as lipoglycans, are large molecules consisting of a lipid and a 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 is the major component of the outer membrane of Gram-negative bacteria, contributing greatly to the structural integrity of the bacteria, and protecting the membrane from certain kinds of chemical attack. LPS also increases the negative charge of the cell membrane and helps stabilize the overall membrane structure. It is of crucial importance to gram-negative bacteria, whose death results if it is mutated or removed. LPS is an endotoxin, and induces a strong response from normal animal immune systems. It has also been implicated in non-pathogenic aspects of bacterial ecology, including surface adhesion, bacteriophage sensitivity, and interactions with predators such as amoebae.

Lipooligosaccharides are naturally occurring variants of the more common glycolipid, lipopolysaccharide. While lipopolysaccharides are common in the enteric bacteria, LOS is present in bacteria that colonize those mucosal surfaces that are not bathed in bile. LOS is a highly phase variable molecule.

LOS is clinically relevant in Neisseria meningitidis infections, where it has been shown to correlate with the severity of disease, as well as cause the complications listed above which are hallmarks of meningococcal meningitis.

IgA protease :

 Many bacteria which colonize the mucous membranes produce an IgA protease

which degrades  secretory IgA.

Neisseria gonorrhoeae :

IgA protease .

Lipooligosaccharides.

Pili .

Bacillus anthracis :

D-glutamate capsule: It is the only bacterium known to synthesize a protein capsule (D-glutamate) capsular polypeptide 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, and efforts at exploiting the polymer for vaccine development have focused on increasing its inherent immunogenicity through chemical coupling to immune-stimulating protein carriers .

Anthrax toxin :each individual anthrax toxin protein is, in fact, nontoxic. Toxic symptoms are not observed when these proteins are injected individually into laboratory animals. 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 edema toxin, and the latter combination is called lethal toxin. Thus the manifestation of physiological symptoms requires, in either case, the presence of the PA component.

The PA requirement observed in animal-model experiments demonstrates a common paradigm for bacterial toxins, called the A / B paradigm. The A component(s) are enzymatically active, and the B component is the cell

binding component. Anthrax toxin, in fact, is of the form A2B, where the

two enzymes, EF and LF, are the A components and PA is the B component. Thus PA acts as a Trojan Horse, which carries EF and LF through the plasma membrane into the cytosol, where they may then catalyze reactions that disrupt normal cellular physiology.

Clostridium tetani :

Tetanus toxin : Tetanus toxin is an extremely potent neurotoxin , causing tetanus. It has no known function for clostridia in the soil environment where they are normally encountered. It is also called spasmogenic toxin, tetanospasmin or abbreviated to TeTx or TeNT. C. tetani also produces the exotoxin tetanolysin, the effects of which are as yet unclear.

Clostridium botulinum :

Botulinum toxin :Botulinum toxin  is extremely neurotoxic. When introduced intravenously in

monkeys, type A (Botox Cosmetic) of the toxin exhibits an LD50 of 40-56 ng, type

C1 around 32 ng, type D 3200 ng, and type E 88 ng, rendering the above types some of the most powerful neurotoxins known. Popularly known by one of its trade names, Botox or Dysport, it is used for various cosmetic and medical procedures.

Clostridium Perfringns :

Alpha toxin lecithinase :Lecithinase is a type of phospholipase that acts upon lecithin. C. perfringens alpha toxin (lecithinase) causes my necrosis and hemolysis.

Enterotoxin .

Clostridium Difficile :

Exotoxin A & B .

Cyanobacteria diphtheria :

Diphtheria toxin :causes diphtheria. Unusually, the toxin gene is encoded by bacteriophage (a virus that infects bacteria). The toxin causes the disease diphtheria in humans by gaining entry into the cell cytoplasm and inhibiting protein synthesis. Diphtheria toxin is a single polypeptide chain of 535 amino acids consisting of two subunits linked by disulfide bridges. Binding to the cell surface of the less stable of these two subunits allows the more stable part of the protein to penetrate the host cell.

Listeria monocytogenes :

internalin :Listeria monocytogenes can use two different surface proteins, internalin (InlA) and InlB, to invade mammalian cells. The exact role of these invasiveness factors in vivo remains to be determined. In cultured cells, InlA is necessary to promote Listeria entry into human epithelial cells, such as Caco-2 cells, whereas InlB is necessary to promote Listeria internalization in several other cell types, including hepatocytes, 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 cell adhesion molecule E-cadherin and demonstrated that nonpermissive fibroblasts become permissive for internalin-mediated entry when transfected with the gene coding 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 to promote internalization into cells expressing its receptor

. Indeed, internalin confers invasiveness toboth Enterococcus faecalis and internalin-coated latex beads. As shown bytransmission electron microscopy, these beads were phagocytosed via a"zipper" mechanism similar to that observed during the internalin-E-cadherin- mediated entry of Listeria. Moreover, a functional analysis of internalin demonstrates that its amino-terminal region, encompassing the leucine-rich repeat (LRR) region and the inter-repeat (IR) region, is necessary and sufficient to promote bacterial entry into cells expressing its receptor. Several lines of evidence suggest that the LRR region would interact directly with E-cadherin, whereas the IR region would be required for a proper folding of the LRR region. 

Listeriolysin :Seeligeriolysin O (LSO), one of the cholesterol-dependent cytolysins produced by Listeria seeligeri, shows 80% homology to listeriolysin O (LLO) produced byListeria monocytogenes at the amino acid sequence level. In addition to cytolytic activity, LLO has been shown to exhibit cytokine-inducing activity. In order to determine whether LSO is also capable of exhibiting these two different activities, we constructed a recombinant full-length LSO (rLSO530)and a noncytolytic truncated derivative with a C-terminal deletion (rLSO483) and compared these molecules with recombinant LLO. The cytolytic rLSO530 molecule could induce gamma interferon (IFN- ) production in spleen cells when the 

cytolytic activity was blocked by treatment with cholesterol. The noncytolytic truncated rLSO483 molecule also induced IFN-  production. Anti-LLO polyclonal antibody inhibited not only LLO-induced IFN-  production but also LSO-induced IFN-  production. Both NK cells and CD11b+ cells were required for LSO-induced IFN-  production. Among the various cytokines expressed in CD11b+ cells, interleukin-12 (IL-12) and IL-18 appeared to be essential. We concluded that LSO exhibits the same biological activity as LLO.

Gram negative rods :

Cell wall antigen O

Flagellar protein H

Capsular K

E coli :Shiga toxin and LT toxin which is adeylate cyclase and heat labile and the other toxin is ST which is the heat staple low molecular weight toxin and its guanylate cyclase .

Salmonella :It has the O and H and Vi antigens and the type of typhoid salmonella has a typhoid 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 react with the rickettsia antigen and they are OX-1 OX-2 OX-K

Pseudomonas aeruginosa :

Pyocyanin :is an antibiotic pigment produced by the Gram negative bacterium Pseudomonas aeruginosa. It is a redox-active virulence factor which allows 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 that

induce oxidative stress in bacterial and mammalian cells.

Pyoverdin :  is a fluorescent siderophore secreted by e.g. Pseudomonas aeruginosa. It's used to help the microbe leech iron out of its surroundings and is produced mostly in iron deficient environments.

Bortetella :

Pertussis toxin :is a protein-based AB5-type exotoxin which causes whooping cough. PT is involved

in the colonization of the respiratory tract and the establishment of infection. Research suggests PT may have a therapeutic role in treating a number of common human ailments including hypertension, viral inhibition, and

autoimmune inhibition.

Filamentous haemagglutinin : is a large, filamentous protein that serves as a dominant attachment factor for adherence to host colliery epithelia cells of the respiratory tract. It is associated with biofilm formation and possesses at least four binding domains which can bind to different cell receptors on the epithelial cell surface.

Yersinia :

Polysaccharide protein complex capsule

Envelope capsular antigen F1Y. pestis has typical cell wall and whole-cell lipid compositions and an enterobacterial antigen. Its lipopolysaccharide is characterized as rough, possessing core components but lacking extended O-group side chains; while there is no true capsule, a carbohydrate-protein envelope, termed capsular antigen or fraction 1 (F1), forms during growth above 33 C (14, 32, 215). This facultative anaerobe possesses a constitutive glyoxylate bypass and unregulated L-serine deaminase expression but lacks detectable adenine deaminase, aspartase, glucose 6-phosphate dehydrogenase, ornithine decarboxylase, and urease activities, as well as a possible lesion in -ketoglutarate dehydrogenase

Exotoxin W and V antigens .

Yop " Yersinia outer protein " :Yersinia outer protein E (YopE) are delivered directly into the cytosol of target cells in a TTSS-dependent fashion. This unique translocation mechanism can be used by attenuated Salmonella carrier vaccines for the delivery of heterologous antigens fused to YopE into the MHC class I-restricted antigen processing pathway. In orally immunized mice, this novel vaccination strategy results in the induction of pronounced peptide-specific cytotoxic CD8 T cell responses.

Epstein - Barr virus :

Viral capsid antigen "VCA" :

Early antigen "EA":

Nuclear antigen "EBNA":

Membran antigen "MA" :

Epstein - Barr virus :

Fibers protruding hemoglutinin :

Papilloma virus :

Genes E6 and E7:

 Cervical cancer is the second most common cancer in women worldwide and is

caused by human papillomavirus (HPV). Silencing of HPV E6 and E7 gene expression was achieved using siRNAs to target the respective viral mRNAs. E6 silencing induced accumulation of cellular p53 protein, trans activation of the cell cycle control p21gene, and reduced cell growth. By contrast, E7 silencing induced apoptotic cell death. HPV-negative cells appeared to be unaffected by the antiviral siRNAs. Thus siRNA can induce selective silencing of exogenous viral genes in mammalian cells, and the process does not interfere with the recovery of cellular regulatory systems previously inhibited by viral gene expression.

Influenza virus :

Hemoglutinin :Influenza hemagglutinin (HA) or haemagglutinin (British English) is a type of hemoglutinin found on the surface of the influenza viruses. It is an antigenic glycoprotein. It is responsible for binding the virus to the cell that is being infected.

The name "hemoglutinin" comes from the protein's ability to cause red blood cells (erythrocytes) to clump together ("agglutinate") in vitro

Neuraminidase :viral neuraminidase is a type of neuraminidase found on the surface of influenza viruses that enables the virus to be released from the host cell. Neuraminidases are enzymes that cleave 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 molecule found on the surface of the virus that binds to sialic acid groups. Sialic acids are found on various glycoproteins at the host cell surface, and the virus exploits these groups to bind the host cell. In order for the virus to be released from the cell, neuraminidase must enzymatically cleave 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 treat influenza.

In some viruses including Mumps virus and Human Para influenza virus, a hemagglutinin-neuraminidase protein combines the neuraminidase and hemoglutinin functions in a single protein.

NS1 Protein : Inhibit the interferon

Measles virus :Hemoglutinin

Fusin:

Mumps virus :Hemoglutinin

Neuraminidase

Respiratory syncytial virus :Fusin

Para Influenza virus :Fusin

Hemoglutinin

Neuraminidase

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 the CREB/ATF-, SRF- and NF-κB-associated pathways. In addition, Tax employs the CBP/p300 and p/CAF co-activators for implementing the full transcriptional activation competence of each of these pathways. Tax also affects the function of various other regulatory proteins by direct protein-protein interaction. Through these activities Tax sets the infected T-cells into continuous uncontrolled replication and destabilizes their genome by interfering with the function of telomerase and topoisomerase-I and by inhibiting DNA repair. Furthermore, Tax prevents cell cycle arrest and apoptosis that would otherwise be induced by the unrepaired DNA damage and enables, thereby, accumulation of mutations that can contribute to the leukemogenic process

Hepatitis B:

Surface antigen HBsAg:Surface antigen HBsAg The first marker to appear after HBV infection, preceding clinical disease by weeks, peaking with the onset of symptoms and disappearing six months post-infection; as long as HBsAg is positive, the Pt is considered infectious and must follow prescribed sanitary procedures to avoid infecting others; if the hepatitis does not resolve, HBsAg persists and can be detected for many years or life.

Antibody to surface antigen HBsAb, anti-HBs, antibody to surface antigen HBsAb begins to rise as the HBsAg falls; it is detectable 8-10 weeks post infection, is regarded as being protective against re-infection, and persists for life; HBsAb is formed after using the HBV vaccine, and is not present in the chronic phase of the disease.   

Core antigen HBcAg:Core antigen The HBc particle that contains double-stranded DNA and DNA polymerase, and is associated with the HBe antigen; HBc is not directly detected by currently-used assays; its presence indicates persistently replicating hepatitis B virus

Core 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 of HBV infection and slowly disappears; ↓ levels of IgM HBcAb indicate resolving infection; 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 liver disease; partially protective anti-HBc antibody levels can be induced by recombinant vaccination, but are short-lived

e antigen HBeAGe antigen An antigen that rises and falls parallel to HBsAg, and derives from the proteolytic cleavage of the nucleocapsid; its presence implies a carrier state

e antibody Anti-HBe An antibody that rises as HBe falls, appearing in convalescent Pts, persisting for up to several years after resolution of hepatitis

human immunodeficiency virus :p24 p7gp 120gp 41tat Rev

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