1. Immunogens, Antigens, and Haptens

2. Initiation of immune response
Interaction between receptor and ligand
Affinity
Avidity
strong
binding
weak
Affinity: high
low

3. Introduction
Immune responses arise as a result of exposure to foreign stimuli
The compound that evokes an immune response is referred to as “antigen” or “immunogen.”
The distinction between the two is functional but they are commonly used as synonyms.

4. Definitions
An immunogen is any substance capable of inducing an immune response
An antigen is any substance capable of binding specifically to the products of the immune response
All immunogens are antigens but not all antigens need be immunogens

5. Special Types of Antigens
Allergen
Mitogen
Super antigen
Tolerogen
According to source of antigen:
- Xenoantigen
- Heteroantigen
- Alloantigen
- Autoantigen

6. Haptens are low molecular weight compounds (antibiotics and drugs) that by themselves are incapable of inducing an immune response, but they can react with its products
When haptens are coupled with large molecules such as proteins (carriers), the resultant conjugate induces an immune response directed against the hapten and the carrier

8. Factors influencing immunogenicity
Contribution of immunogen
Contribution of biological system
Method of administration

9. Contribution of the immunogen
Foreignness
High Molecular Weight
- <1000 Daltons : nonimmunogenic
Daltons: may be immunogenic
- > 6000 immunogenic
Chemical Nature and Complexity
- Homopolymers Vs Heteropolymers
- Primary, secondary, tertiary, and quaternary structures

10. Antigenic Determinants or Epitopes - Linear - Discontinuous
Paratope: “The site in the variable (V) domain of an antibody or T-cell receptor that binds to an epitope on an antigen
Physical Form
Particulate > Soluble
Denatured > Native
Degradability
Ag processing by Ag Presenting Cells (APC)

11. Factors Influencing Immunogenicity Contribution of the Biological System
Genetics
Species
Individual
Responders vs. Non-responders
Age

12. Factors Influencing Immunogenicity Method of Administration
Dose
Route
Subcutaneous > Intravenous > Intragastric
Rate of elimination
Adjuvant
Substances that enhance an immune response to an Ag

13. Adjuvants
Substances which when mixed with an immunogen enhance the immune response against the immunogen
They differ from carriers as they do not enhance immunity to haptens
Release immunogens slowly but continuously
Types: Freund’s incomplete or complete adjuvants, BCG, Corynebacterium parvum, Bordetella pertussis, LPS, and Alum precipitate (most widely used )

14. Major Classes of Immunogens
Proteins: Best immunogens
Carbohydrates: Usually but not always good immunogens
Nucleic Acids: Poor immunogens by themselves unless coupled to carriers
Lipids: Non immunogens unless coupled to carriers

15. Cross Reactivity Modification of a molecule; toxins and toxoids
Sharing epitopes between unrelated macromolecules
Structural resemblance (molecular mimicry)
Significance in
- tolerance and autoimmunity
- Isohemagglutinins

16. Antigens: T-independent
Activate B cells without MHC class II T help
Polysaccharides
Properties
Polymeric structure
Polyclonal B cell activation, but poor memory
Resistance to degradation
Examples
Pneumococcal polysaccharide, LPS
Flagella

17. Antigens: T-dependent
Require T help to activate B cells
Proteins
Structure
Examples
Microbial proteins
Non-self or altered-self proteins

18. Hapten-carrier conjugates
Definition
Ag only if bound to carrier protein
Structure
Native determinants
Haptenic determinants

19. Sequential (or linear) determinants
Epitopes formed by several adjacent amino acid residues are called linear determinants.
They exist on the surface of antigen molecules or inside of antigen molecules.
They are mainly recognized by T cells, but some can also be recognized by B cells.

20. Conformational determinants
Conformational determinants are formed by amino acid residues that are not in a sequence but become spatially juxtaposed in the folded protein.
They normally exist on the surface of antigen molecules.
They are recognized by B cells or antibody.

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

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

24. Antigenic Determinants Recognized by T cells
Composition
Proteins (some lipids)
Sequence determinants
Processed
MHC presentation (lipid presentation by MHC-like CD1)
Size
8 -15 residues
Number
Limited to those that can bind to MHC

25. Superantigens Definition Examples Polyclonal T cell response
Staphylococcal enterotoxins
Toxic shock toxin
T cell
TCR
APC
MHC Ag
Super Ag

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

27. Most Important Human Antigens

28. Membrane molecules of immune cells
Receptors: TCR, BCR, CR, CKR, FcR
Class I and class Ⅱ MHC molecules
CD molecules: CD1~339
Cell Adhesion Molecules
Cytokine Receptors
Blood Group Antigens

29. Pathogen recognition by adaptive immunity: great variety, selectivity

30. T Lymphocytes
Distinguishing cell-surface markers include TCR, CD3, CD2, CD4 or CD8, CD28, and CD45
Similarities between T and B cells:
Antigen receptor on surface
(TCR)
Recognize single, specific antigen
Expand through clonal selection
Some T cells exist as long-lived memory cells

31. B Lymphocytes means of surface-expressed antigen receptor
Recognize antigen by
means of surface-expressed
antigen receptor
Distinguishing cell-surface
markers include: B220 (CD45),
MHC Class II, CD80 (B7-1) and
CD86 (B7-2), CD40, CD19,
CD21, etc.
Bursa of
fabricius

32. Figure 3-13 part 1 of 2

33. The peptide-binding groove of MHC molecules
Figure 3-15

34. Present Ag to
CD8 T cells
Present Ag to
CD4 T cells

35. Present antigen peptides to CD4+ T cells
Polymorphism: presence of multiple alternative forms (alleles) of a gene.
Help peptide loading
Present antigen peptides
to CD4+ T cells
Polymorphism allows the population to handle a variety of pathogens.

36. Different cell distribution of MHC class I and II
Figure 3-22
Almost all cells express MHC I for comprehensive surveillance by CD8 T cells
Only some cells express high levels of MHC II and MHC I
These are B cells, macrophages, dendritic cells and thymic epithelial cells.
B cells, macrophages and dendritic cells are called professional antigen- presenting cells (APC).
IFN-g increases the expression of MHC II in APC and induces the expression in non-APC cells at sites of infection

37. Leukocyte Differentiation Antigens and CD
Leukocyte differentiation antigen: Cell surface molecules expressed (or disappeared) during different developmental and differential phases, activation or inactivation process of blood cells.

38. Identifying Cell Using the CD Nomenclature
CD Cluster Of Differentiation
Over 300 CD Markers
T cells, CD4 or CD8 and CD3
B cells, CD19
NK cells, CD56
Monocytes /Macrophages CD14
Dendritic Cells, CD1c

39. CD - Cluster of Differentiation
Table 2-4

40. CDs which take part in T cell recognition, adhesion and activation

41. CDs which take part in B cell recognition, adhesion and activation

42. Adhesion Molecules
Cell adhesion molecules (CAMs) are cell surface proteins involved in the interaction of cell-cell or cell-extracellular matrix.
CAMs take effect by the binding of receptor and ligand.

43. Ⅱ. Classification Integrin family Selectin family
Immunoglobulin (Ig) superfamily
Cadherin family
Mucin - like family
Other adhesion molecules

44. 1. Integrin family Integrins consist of α and β chains.
According to β subunits, Integrins are divided into eight groups: β1- β8
VLA-4(Very Late Antigen-4)------VCAM-1
LFA-1(Lymphocyte Function-associated Antigen-1) ICAM-1,2,3
MAdCAM-1 (Mucosal Addressin Cell Adhesion Molecule-1)
TSP-1 ((Thrombospondin一1)

45. 2. Selectin family Selectins consist of one peptide chain.
The three family members include: E- selectin,
L-selectin, and P-selectin.

46. 3. Ig superfamily(IgSF)
The structure of these adhesion molecules resemble that of Ig.
CD4, CD8, CD2(LFA-2), CD58(LFA-3), VCAM-1, ICAM-1,2,3

48. 4. Cadherin family E- cadherin------ Epithelia cell
N- cadherin Nerve cell
P- cadherin Placenta

49. 5. Mucin -like family CD34, GlyCAM-1(glycosylation dependent cell adhesion molecule-1) PSGL-1(P-selectin glycoprotein ligand-1) Other adhesion molecules CD44

50. Ⅲ. Functions
Participate in development and differentiation of immune cells
CD2----LFA-3
LFA-1----ICAM-1
Participate in development and maturation of thymocytes.
2. Participate in immune response and regulation

51. IL-21
IL-10

52. Cytokine Receptor Families
TLRs