1. Properties and Overview of Immune Responses

9. با نام و ياد خدا
Antigens
E. Salehi
Tel:

10. 1- تعاريف
2- ويژگي هاي آنتي ژنها
3- انواع آنتي ژنها
4- اپي تپ و انواع آن
5- انواع آنتي ژنها از نظر منشاء
6- عوامل مواثر بر ايمونوژنسيته
7- الگوهاي مولكولي و پذيرنده هاي آن

11. Definitions Immunogen Antigen (Ag) Tolergen Allergen
Epitope or Antigenic Determinant
Hapten
Carrier
Super-Antigen
Adjuant

12. Characters of Antigen
Degree of “foreignness”-Based on genetic relatedness
Molecular Size-Usually
MW >100,000; immunogenic
MW <10,000 non immunogenic
MW 10, ,000
is imunogenically variable

13. Characters of Antigen
Chemical composition-Proteins; Primary, secondary, tertiary and quaternary structure all contribute.
Ability to be processed by APCs- Function of size

14. Chemical Nature of Immunogens
Proteins
Polysaccharides
Nucleic Acids
Lipids
Some glycolipids and phosopholipids can be immunogenic for T cells and illicit a cell mediated immune response

15. Epitopes 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 15

16. Antigenic valence:
Total number of determinant which can be combined with Ab.

17. 17

18. Discontinuous 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. 18

19. Linear (continuous) Epitopes
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. 19

20. Epitopes
Sequential
Conformational
Ab-binding sites

21. Types 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 21

22. Types of Peptide Epitope
Conformational
Antibody or “B cell” Epitope
Epitope
LinearB cell Epitope
Non-Conformational
T cell Epitope
Class I MHCs
all cells
Foreign and self proteins
8-10 amino acids
Class II MHCs
Professional Antigen
Presenting cells
Foreign proteins
8-20 amino acids 22

23. T cells and B cells use Distinct Antigen Receptors to Recognize Fundamentally Different Forms of Antigen
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. 23

24. Sperm whale myoglobin (1vxg) contains five sequential epitopes (red, green, magenta, blue, orange) and two conformational epitopes (yellow, pink). 24

25. كاربرد شناسايي اپي تپ ها

26. Properties 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. 26

27. Antigenic Determinants Recognized by B cells and Ab
Composition
Proteins, polysaccharides, nucleic acids
Sequence (linear) determinants
Conformational determinants
Size
4-8 residues

28. Antigenic Determinants Recognized by B cells and Ab
Composition
Size
Number
Limited (immunodominant epitopes)
Located on the external surfaces of the Ag Fe

29. Antigenic Determinants Recognized 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

30. Types of Antigens
T-cell independent antigens-Does not require T cell involvement;
polysaccharides
T-cell dependent antigens-Requires T cell involvement;
proteins

31. Types of Antigens T-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

32. Types of Antigens T-dependent
Proteins
Structure
Examples
Microbial proteins
Non-self or Altered-self proteins

33. Hapten-carrier conjugates
Definition
Structure
native determinants
haptenic determinants
Native determinants
Haptenic determinants

34. Superantigens Definition Conventional Antigen Superantigen
Polyclonal T cell response
1:4 - 1:10
Monoclonal/Oligoclonal T cell response
1: :105

35. Superantigens 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

36. Types of Antigens regading the source of Antigen
Alloantigens-”same species”
---- ABO blood type, HLA, et al.
Heteroantigens-”different species”
Xeno-substances
---- Various pathogens and their products,xeno- proteins, etc.

37. - common Ags shared by different species
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 rejuvenate
5. Heterophile Ag (forssman Ag)
- common Ags shared by different species
- no specificity of species
significance
immunopathology & Diagnosis

38. Tumor antigen
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

39. Factors influencing immune response of Ag Antigen Properties
1.Foreigness
2.Chemical properties of Ag
Chemical nature
Proteins>Polysaccharides >Nucleic Acids >Lipids

40. Factors influencing immune response of Ag Antigen Properties
3.Molecule weight (size)
reasonable large molecule( >10.0 kd) has good immuogenecity.
more stationary
more surface structure for lymphocyte to recognize

41. Factors influencing immune response of Ag Antigen Properties
4. Complexity of Ag structure
ring > linear
aromatic ring

42. Factors influencing immune response of Ag Antigen Properties
5. Conformation and accessibility
6. Physical states :
Polymer > monomer
Particulate > Soluble
Denatured > Native
7.Degradability
Ag processing by Ag Presenting Cells (APC)

43. Factors influencing immune response of Ag Body Factors
Genetics, Species:MHC
Individual :Age, health, etc.

44. Factors influencing immune response of Ag Method of Administration
Dose
Route
Subcutaneous>Intravenous>Intragastric times
Adjuvant
Substances that enhance an immune response to an Ag

45. Biological Influences on Immunogenicity
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 45

46. Cross reaction:
Reaction between the same Ab and different Ag with same similar determiants.

47. Mechanism 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 .

48. Determinants Recognized by the Innate Immune System
Adaptive Immune System – Discrete Determinants
Reacts with a specific pathogen
Innate Immune System – Broad Molecular Patterns
Reacts with a variety of pathogens

49. Determinants Recognized by the Innate Immune System
PAMPs – Pathogen Associated Molecular Patterns
PRRs – Pattern Recognition Receptors

50. PAMP
PRR
Biological Consequence of Interaction
Microbial cell wall components
Complement
Opsonization; Complement activation
Mannose-containing carbohydrates
Mannose-binding protein
Polyanions
Scavenger receptors
Phagocytosis
Lipoproteins of Gram + bacteria
Yeast cell wall components
TLR-2 (Toll-like receptor 2)
Macrophage activation; Secretion of inflammatory cytokines

51. PAMP
PRR
Biological 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

52. PAMP
PRR
Biological Consequence of Interaction
U-rich single stranded viral RNA
TLR-7
Production of interferon (antiviral)
CpG containing DNA
TLR-9
Macrophage activation; Secretion of inflammatory cytokines