Properties and Overview of Immune Responses.
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Transcript of Properties and Overview of Immune Responses.
E. SalehiE. Salehi
Tel: 66419536Tel: 66419536
Email: Email: [email protected]@sina.tums.ac.ir
AntigensAntigens
با نام و ياد خدا
تعاريف -1
ويژگي هاي آنتي ژنها -2
انواع آنتي ژنها -3
اپي تپ و انواع آن -4
انواع آنتي ژنها از نظر -5منشاء
عوامل مواثر بر -6ايمونوژنسيته
الگوهاي مولكولي و -7پذيرنده هاي آن
DefinitionsDefinitions• Immunogen• Antigen (Ag)• Tolergen• Allergen• Epitope or Antigenic Determinant• Hapten• Carrier• Super-Antigen• Adjuant
• Degree of “foreignness”-Based on genetic relatedness
• Molecular Size-Usually MW >100,000; immunogenic MW <10,000 non immunogenic MW 10,000-100,000 is imunogenically variable
Characters of AntigenCharacters of Antigen
Characters of AntigenCharacters of Antigen
• Chemical composition-Proteins; Primary, secondary, tertiary and quaternary structure all contribute.
• Ability to be processed by APCs- Function of size
Chemical Nature of Chemical Nature of ImmunogensImmunogens
• Proteins• Polysaccharides• Nucleic Acids• Lipids
– Some glycolipids and phosopholipids can be immunogenic for T cells and illicit a cell mediated immune response
EpitopesEpitopes
• In protein antigens epitopes can be defined in terms of:– Amino acid composition
– Protein location
– Length (5-15 amino acids)
• epitopes:
• Immunodominant– Epitopes bound by a greater proportion of antibodies
than others in a normal in vivo immune response
– Also known as Major Antigenic Sites
• Sequestered
• Epitopes can be divided into 2 classes:– Discontinuous epitopes
– Continuous (linear) epitopes
Epitopes could be -
contiguous (when Ab binds to a contiguous sequence of amino acids)
non-contiguous (when Ab binds to non-contiguous residues, brought together by folding).
Sequential epitopes are contiguous epitopes.
Conformational epitopes are non-contiguous antigenic determinants.
Discontinuous EpitopesDiscontinuous Epitopes
• Constitutive residues are non-sequential in the primary sequence.
• Highly conformational dependant.
• Account for approx. 90% of epitopes on a given antigenic (globular) protein.
Linear (continuous) Linear (continuous) EpitopesEpitopes
• Constitutive residues are sequential in the primary sequence of the protein.
• Fewer conformational constraints on Ab recognition.
• Often contain residues that are not implicated in antibody interaction.
Types of EpitopesTypes of Epitopes
• Conformational / Discontinuous epitopes:• recognized by B cells
• non-linear discrete amino acid sequences, come together due to folding.
• Sequential / Continuous epitopes:
• recognized by T cells & B cells• linear peptide fragments
•
Types of Peptide Epitope
LinearB cell Epitope
Antibody or “B cell” EpitopeConformational
Non-Conformational
Class II MHCsProfessional Antigen
Presenting cells
Foreign proteins
8-20 amino acids
Class I MHCs
all cells
Foreign and self proteins
8-10 amino acids
T cell Epitope
Epitope
B cells can recognize linear or conformational epitopes on cell surfaces, of proteins, of carbohydrates or of lipids. The B cell antigen receptor is a form of membrane Ig.
T cells recognize linear peptide fragments bound to MHC class I or class II molecules.
T cells and B cells use Distinct Antigen ReceptorsT cells and B cells use Distinct Antigen Receptorsto Recognize Fundamentally Different Forms of Antigento Recognize Fundamentally Different Forms of Antigen
Sperm whale myoglobin (1vxg) contains five sequential epitopes (red, green,
magenta, blue, orange) and two conformational epitopes (yellow, pink).).
Properties of EpitopesProperties of Epitopes
• They occur on the surface of the protein and are more flexible than the rest of the protein.
• They have high degree of exposure to the solvent.
• The amino acids making the epitope are usually charged and hydrophilic.
Antigenic DeterminantsAntigenic Determinants Recognized by B cells and Ab Recognized by B cells and Ab
• Composition– Proteins, polysaccharides, nucleic acids– Sequence (linear) determinants– Conformational determinants
• Size– 4-8 residues
Antigenic DeterminantsAntigenic Determinants Recognized by B cells and Ab Recognized by B cells and Ab
• Composition• Size• Number
– Limited (immunodominant epitopes)
– Located on the external surfaces of the Ag
Fe
Antigenic DeterminantsAntigenic DeterminantsRecognized by T cellsRecognized by T cells
• Composition– Proteins (some lipids)– Sequestered determinants
• Processed• MHC presentation (lipid presentation by
MHC-like CD1)
• Size– 8 -15 residues
• Number– Limited to those that can bind to MHC
Types of AntigensTypes of Antigens
• T-cell independent antigens-Does not require T cell involvement;
polysaccharides
• T-cell dependent antigens-Requires T cell involvement;
proteins
Types of AntigensTypes of AntigensT-independentT-independent
• Polysaccharides
• Properties– Polymeric structure
– Polyclonal B cell activation
• Yes -Type 1 (TI-1)
• No - Type 2 (TI-2)
– Resistance to degradation
• Examples– Pneumococcal polysaccharide, lipopolysaccharide
– Flagella
Types of AntigensTypes of AntigensT-dependentT-dependent
• Proteins
• Structure
• Examples– Microbial proteins
– Non-self or Altered-self proteins
Hapten-carrier conjugatesHapten-carrier conjugates
• Definition
Native determinants
Haptenic determinants• Structure
– native determinants– haptenic determinants
SuperantigensSuperantigens
Conventional Antigen
Monoclonal/Oligoclonal T cell response
1:104 - 1:105
Superantigen
Polyclonal T cell response
1:4 - 1:10
• Definition
SuperantigensSuperantigens• Definition• Examples
– Staphylococcal enterotoxins– Staphylococcal toxic shock toxin– Staphylococcal exfoliating toxin– Streptococcal pyrogenic exotoxins
• T cell SAg: exotoxin, protein of reverse translate virus
• B cell SAg: SPA(staphylococcal protein A) HIV:gp120
Types of Antigens regading Types of Antigens regading the source of Antigenthe source of Antigen
1. Alloantigens-”same species” ---- ABO blood type, HLA, et al.2. Heteroantigens-”different
species”3. Xeno-substances ---- Various pathogens and their
products,xeno- proteins, etc.
4. Autoantigens- Self component Release of sequestered antigen- Such as lens protein,sperm etc. Change of molecular structure of auto-
tissues Degeneration of protein Forbidden clone rejuvenate5. Heterophile Ag (forssman Ag)- common Ags shared by different species- no specificity of species - significance immunopathology & Diagnosis
• Tumor specific Ag, TSA --only express on the tumor cells but
normal cells• Tumor associated Ag,TAA --Its express is high on tumor cells but
low on normal cells,eg. AFP CEA
Tumor antigen
Factors influencing immune Factors influencing immune response of Agresponse of Ag
Antigen PropertiesAntigen Properties
1.Foreigness
2.Chemical properties of Ag Chemical nature Proteins>Polysaccharides >Nucleic
Acids >Lipids
3.Molecule weight (size)reasonable large molecule( >10.0 kd)
has good immuogenecity.– more stationary– more surface structure for
lymphocyte to recognize
Factors influencing immune Factors influencing immune response of Agresponse of Ag
Antigen PropertiesAntigen Properties
4. Complexity of Ag structure ring > linear aromatic ring
Factors influencing immune Factors influencing immune response of Agresponse of Ag
Antigen PropertiesAntigen Properties
5. Conformation and accessibility 6. Physical states : Polymer > monomer
Particulate > Soluble Denatured > Native
7.Degradability– Ag processing by Ag Presenting Cells (APC)
Factors influencing immune Factors influencing immune response of Agresponse of Ag
Antigen PropertiesAntigen Properties
Genetics, Species:MHC
Individual :Age, health, etc.
Factors influencing immune Factors influencing immune response of Agresponse of Ag
Body FactorsBody Factors
Dose RouteSubcutaneous>Intravenous>Intragastric
timesAdjuvant
– Substances that enhance an immune response to an Ag
Factors influencing immune Factors influencing immune response of Agresponse of Ag
Method of AdministrationMethod of Administration
Biological Influences on Biological Influences on ImmunogenicityImmunogenicity
• Adjuvants-Enhance immunogenicity– Potential mechanism
• Ag persistence• Cell signaling or cytokine effect• Induction of inflammation• Lymphocyte stimulation• Change the chemical and physical charactes of Ag• Improves the Ag process and presentation ability of macrophages• stimulates proliferation of lymphocytes
Types • Biological adjuvant:BCG,LPS• Synthesized adjuvant Freund’s incomplete adjuvant Freund’s complete adjuvant• Chemical adjuvant Alum
Cross reactionCross reaction::
• Reaction between the same Ab and different Ag with same similar determiants.
Mechanism of cross reactionMechanism of cross reaction
• Common Ag determinant• Similar structure of Ag determinant• Significance: Because there are some common
antigen determinants between different microbes, so the antiserum against one kind of Ag can also react with another Ag and couse a cross reaction .
Determinants Recognized by the Determinants Recognized by the Innate Immune SystemInnate Immune System
• Adaptive Immune System – Discrete Determinants – Reacts with a specific pathogen
• Innate Immune System – Broad Molecular Patterns– Reacts with a variety of pathogens
Determinants Recognized by the Determinants Recognized by the Innate Immune SystemInnate Immune System
• PAMPs – Pathogen Associated Molecular Patterns
• PRRs – Pattern Recognition Receptors
PAMP PRRBiological Consequence of Interaction
Microbial cell wall components
Complement Opsonization; Complement activation
Mannose-containing carbohydrates
Mannose-binding protein
Opsonization; Complement activation
Polyanions Scavenger receptors
Phagocytosis
Lipoproteins of Gram + bacteriaYeast cell wall components
TLR-2 (Toll-like receptor 2)
Macrophage activation; Secretion of inflammatory cytokines
PAMP PRRBiological Consequence of Interaction
Double stranded RNA
TLR-3 Production of interferon (antiviral)
LPS (lipopolysaccharide of Gram – bacteria)
TLR-4 Macrophage activation; Secretion of inflammatory cytokines
Flagellin (bacterial flagella)
TLR-5 Macrophage activation; Secretion of inflammatory cytokines