bacterial antigenic structure
TRANSCRIPT
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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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