bacterial antigenic structure

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    Antigens & Immunogens

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    Immunogen

    * A foreign substance, when introducedinto

    host body, stimulate formation of

    specificantibodies or sensitized lymphocytes

    Antigen

    * Antigens have the ability to combinespecifically with antibodies produced

    or

    sensitized T-lymphocytes induced

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    Haptens- Low molecular weight substances

    - These substances not immunogenic by itself

    - If couple to a larger carrier molecule (albumin,globulins), they become immunogenic

    - Examples :

    simple chemicals and drugs:

    penicillin, sulphonamid, aspirin, cosmetic,

    tranquillizers, neomycin skin ointment

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    Epitope or antigenic determinant

    Small part of an antigen that interacts with anantibody

    Any given antigen may have several epitopes.

    Each epitope is recognized by a differentantibody or TCR

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    Factors influencingImmunogenicty

    1-Foreigness :Foreign substances are immunogenic

    2- Molecular size:

    High molecular weight increaseimmunogenicty

    3- Chemical structure complexity:

    High complexity increase immunogenicty

    ` Protein - most effectivePolysaccharide simple , complex

    Lipids - poor

    Nucleic Acids - poor

    4- Route of administration:

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    Factors influencingImmunogenicty5- Method of administration:

    a- Antigen dose:

    Appropriate dose optimum

    antigenictyLow dose low- zone tolerance

    High dose high-zone tolerance

    b- Adjuvant:

    Substance when injected with an antigen

    enhance immunogenicty

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    YYY

    T dependent Ag - T cell help to B cells

    B

    Signal 1

    antigen & antigen

    receptor

    Th

    1. T cell antigen receptor

    2. Co-receptor (CD4)

    3.CD40 Ligand

    Th

    Signal 2 - T cell help IL-2 and other cytokines

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    T-independentantigenspolysaccharides and proteins with many

    identical polypeptides

    Many bacterial capsules & bacterial flagellarproteins

    This stimulates the B cell to generate antibody-secreting plasma cells without the help of IL-2.

    While this response is an important defense againstmany bacteria, it generates a weaker response thanT-dependent antigens and generates no memory

    cells.

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    Thymus independent antigens

    Principal example:

    LPS

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    Principal example(s):

    Bacterial capsules

    Bacterial flagella

    Mechanism:

    extensive cross-linking of mIg

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    T

    Dependent

    Antigens

    TI-1

    Antigens

    TI-2

    Antigens

    Induce responses in athymics No Yes Yes

    Polyclonally activate B cells No Yes No

    Require repeating epitopes No No Yes

    Affinity maturation Yes No No

    Isotype switching Yes No Limited

    Immunological memory Yes No No

    T Dependent & Independent Antigens

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    Innate Immunity

    PAMPs: Pathogen Associated Molecular PatternsPRRs: Pattern Recognition Receptors

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    Y

    Inflammatoryand effector

    cytokines

    PRR

    PAMP

    Innate Immune cells

    Direct Bactericidal ActivityPhagocytosisOxygen burstAnti-microbial peptides

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    Bacterial Structures Flagella

    Pili Capsule

    Plasma Membrane

    Cytoplasm Cell Wall

    Lipopolysaccharides

    Teichoic Acids

    Inclusions

    Spores

    Chapter 4

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    Macromolecule Primary Subunits Where found incell

    Proteins amino acids Flagella, pili, cellwalls, cytoplasmicmembranes,ribosomes,cytoplasm

    Polysaccharides sugars(carbohydrates)

    capsules, inclusions(storage), cell walls

    Phospholipids fatty acids membranes

    Nucleic Acids(DNA/RNA)

    nucleotides DNA: nucleoid(chromosome),

    plasmidsrRNA: ribosomes;mRNA, tRNA:cytoplasm

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    CytoplasmBacterial chromosome (DNA)

    Ribosomes

    various sorts ofinclusionsBacterial CpG DNA: (PuPuCpGPyPy) ISS-DNA

    unmethylated, present in expected 1/16frequency,

    CpG in vertebratesmethylated, frequency at around 1/60

    TLR 9 Potent Immune response Macrophage activation

    Cytoplasmic membrane Lipid rich

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    Cell wall & its associated

    structuresCapsule

    Pili and FimbriaeFlagella

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    Capsule

    Polysaccharide

    Except B. anthracis protein

    polymer of D-glutamic acidPhagocytosis protection

    Anticapsular antibodies

    protect animal

    K antigens

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    Fimbriae and PiliFimbriae attachment & Pili conjugationF antigens

    Short protein appendages

    smaller than flagellaAdhere bacteria to surfaces

    E. coli has numerous types K88, K99, F41, etc.

    Antibodies to will block adheranceF-pilus; used in conjugation

    Exchange of genetic information

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    Flagella

    Flagellin

    H antigen

    MotilityTLR 5

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    Chapter 4

    Cell WallPeptido-glycan Polymer (amino acids +

    sugars)

    Unique to bacteria

    Sugars; NAG & NAMN-acetylglucosamine

    N-acetymuramic acid

    D form of Amino acids used

    Hard to break down D form

    Amino acids cross link NAG & NAM

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    Teichoic AcidsGram + only

    Glycerol, Phosphates, & Ribitol

    Attachment for PhagesLiptoteichoic acid ion transport

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    E d f

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    Endotoxin ofGram-negatives

    cytopl.mem.

    peptidoglycan

    outer mem.

    Gram-negative

    cell

    Lipid A Corepolysaccharide

    O sidechain

    The toxic partHelps solubilise Lipid A Somatic antigen

    Lipopolysaccharide(LPS)

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    Lipopolysaccharide (LPS)G- bacteria onlyLipid A

    Polysaccharide

    O Antigen somatic antigenAppearance of Colonies

    Mucoid = Smooth (lots of LPS or capsule)

    Dry = Rough (little LPS or capsule)

    O Ags differ in Sugars, not Lipid A

    Configuration of Glycosidic linkage Oserotypes

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    Proteins of Outer

    membraneLipoproteinOuter membrane proteins

    Outer membrane phospholipids

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    LipopeptidesPeptidoglycan

    Lipoteichoic Acid

    Unmethylated DNA Oligomers

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    a- Antigens related to bacterial cellsSomatic antigen (O) - cell wall Gm ve bacter.Capsular antigen (K) - usually polysaccharide

    Flagellar Ag (H) - flagellinFimbrial Ag (F) Fimbrial protein

    b- Antigen secreted by bacteria: - Exotoxins

    - Enzymes

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    Other antigensPorins

    Heat shock proteins

    Mycobacteria Trehalose dimycolate (cordfactor)

    M protein ofStreptococci

    Protein A Staph. Aureus Fc portion of IgG

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