The document details the definitions and properties of antigens, haptens, and epitopes, explaining their roles in stimulating immune responses from B and T cells. It distinguishes between various types of antigens, such as alloantigens, T-cell dependent and independent antigens, and outlines factors influencing their immunogenicity, including molecular structure and body genetics. Additionally, the document discusses antigen presenting cells (APCs), processing pathways for exogenous and endogenous antigens, and the significance of superantigens in immune response.

1. Antigens

2.  The ‘traditional’ definition of antigen is a substance that
may stimulate B and/or T cells and react with the products
of that response, including immunoglobulin antibodies,
and/or specific receptors on T cells.
 Immunogenicity
Is the ability to induce a humoral and/or cell mediated
(specific) immune response.
All immunogens are antigens, but not all Antigens are
immunogens.

3.  Alloantigen is an antigen present in some members or
strains of a species, but not in others.
 Alloantigen include blood group substances on erythrocytes
and histocompatibility antigens present in grafted tissues

4. Haptens
 Haptens, small organic molecules that are antigenic but not
immunogenic.
 Carrier: is Chemical coupling of a hapten to a large protein
yield an immunogenic hapten-carrier conjugate.
 It is the basis of allergic responses to drugs such as penicillin.

5. Antigenic determinant
 Epitopes are the immunologically active regions of an
immunogens that bind to antigen-specific membrane
receptors on lymphocytes or to secreted antibodies.

6. ANTIGENIC DETERMINANTS:
A. Determinants recognized by B cells
are small and are limited to approximately 4-8 residues.
(amino acids and or sugars).
are either:
primary sequence residues))Linear
Conformational(secondary, tertiary or quaternary)
B. Determinants recognized by T cells:
 are limited to approximately 8-15 residues
 Only primary sequence residues

7. Ab1
Ab2
hidden/revealed
determinant
denaturation
new/neoantigen
determinant
conformational
determinant
cleveage
conformational/linear
determinant
TYPES (STRUCTURE) OF ANTIGEN DETERMINANTS
surface/accessible
determinants
linear determinant conformational determinant
(TCR, BCR, Ig) (BCR, Ig)

8. 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

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

10. Types of Peptide Epitope
LinearB cell Epitope
Antibody or “B cell” Epitope
Conformational
Non-Conformational
Class II MHCs
Professional 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

11. 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 Receptors
to Recognize Fundamentally Different Forms of Antigen

12. 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.

13. Antigen-specific membrane receptors
 Membrane molecules or receptors that responsible for
antigen recognition by the immune system are:
1. Membrane-bound antibodies on B cells
2. T-cell receptors
3. Class I MHC molecules
4. Class II MHC molecules

14. T cell vs. B cell Epitopes

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

16. 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

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

18. Chemical nature o Antigens
 Lipids
Proteins
Carbohydrates
Nucleic Acids

19. Substances that act as antigens:
 Microbial structures:
Such as bacterial and fungal cell walls, protozoan cell
membranes, bacterial and fungal capsules, microbial
flagella, bacterial pili, viral capsids, viral envelope-
associated glycoproteins , etc.
 microbial toxins.
 Allergens
 The body's own cells that the body fails to recognize as
"normal self” such as cancer cells, infected cells, cells
involved in autoimmune diseases.

20. Factors influencing immune response of Ag
Antigen Properties
1.Foreigness:
The immune system normally discriminates between self and non-self
such that only foreign molecules are immunogenic.
2.Chemical properties of Ag
Chemical nature
Proteins>Polysaccharides >Nucleic Acids >Lipids
0

21. 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

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

23. 5. Conformation and accessibility
6. Physical states :
Polymer > monomer
Particulate > Soluble
Denatured > Native
7.Degradability
Antigens that are easily phagocytosed are
generally more immunogenic.
Factors influencing immune response
of Ag
Antigen Properties

24. Factors influencing immune response of Ag
Body Factors
Genetics, Species: Some substances are
immunogenic in one species but not in another.
Similarly, some substances are immunogenic in
one individual but not in others (i.e. responders
and non responders).
MHC
Individual :Age, health, etc.
Age can also influence immunogenicity, usually the very young
and the very old have a diminished ability to mount and
immune response in response to an immunogen.

25. Factors influencing immune response of Ag
Method of Administration
1. Genotype
Influences, MHC, T and B cell
receptors, etc…
2.Immunogen dosage
– Too small – no response
– Too large – tolerance
– Boosters – repeated
dosages
•
3. Routes of dministration

26. 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

27. 1. Binding and uptake of antigen
– depends on the physical state of the antigen
and the cell type involved.
2. Antigen processing
– MHC class I processing pathway
– MHC class II processing pathway
3. Antigen presentation
Susceptibility to Antigen
Processing & Presentation

28. Cross reaction
• Reaction between the same Ab and different Ag
with same similar determinants.
• 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 .

29. Antigen Presenting Cells (APCs)
 A group of immune cells, whose role is to take
up, process and present antigenic peptides to T
cells.
 First internalize antigen, either by Phagocytosis
or by endocytosis, and then display a part of that
antigen on their membrane bound to a class II
MHC molecule.
Except for the B cell, APCs are non specific

30. • Professional APC
– Macrophages, dendritic cells, and B cells, which
can express MHC class II molecules.
• Non-professional APC
– Other cell type capable of expressing MHC class II
molecules
eg. Endothelial cells, EC
Fibroblasts
Activated T cell

31. Dendritic cell，DC
• highly branched
morphology
• can active naive T
cells
• markers

32. 1) Markers
– CD1a, CD11c, CD83
– Pathogen receptor, FcR
– MHC II
– co-stimulating factors (CD80,CD86)
– Adhesion molecular CD40
– CD54 (ICAM-1), etc.
• secreting cytokines
– IL1, IL-6, IL-12, TNF-a, IFN-a, chemokines

33. 2) Source, distribution and classification
• Source
DC are bone marrow-derived
– Myeloid DC
– Lymphoid DC

34. • Distribution and classification
DCs are found in many organs throughout the
body
– DC in lymphoid tissue
• Interdigitating cell, IDC
• Follicular DC, FDC
• thymic dendritic cell, TDC
– DC not in lymphoid tissue
• Langerhans cells
• Interstitial DC
– DC in body fluid
• Veiled cells
• Peripheral blood DC

35. Markers of B cells

36. Antigen-presenting cells
APC
Macrophage T cell via MHC antigen
Dendritic cells T cell via MHC antigen
B cells T cell via antigen captrue by
surface antibody and MHC
antigen
Activated T cells T cell via MHC antigen

37. EXOGENOUS ANTIGENS
 Antigen that enters the body of the organism from the
outside, e.g. through inhalation, ingestion, or injection.
The immune system's response to exogenous antigens
is often subclinical. By endocytosis or phagocytosis,
 Endocytosis is a process by which cells absorb
molecules (such as proteins) by engulfing them.

38. Exogenous antigen presentation
1
2
3
4

41. Two antigen-processing pathways
MHC class I MHC class II
Major antigen
sources
endogenous
antigen
exogenous antigen
Processing
machinery
proteasome lysosomal
enzymes
Cell type where
active
all nucleated cells professional APCs
Site of antigen-
MHC binding
endoplasmic
reticulum
lysosome and
endosome
MHC utilized MHC class I MHC class II
Presents to CD8+ T cell (Tc) CD4+ T cells (Th)

42. Endogenous Antigen
• Antigen that is produced from within the cell
as part of normal cell metabolism or when the
cell is infected by bacteria or viruses.
• Endogenous antigens include xenogenic
(heterologous), autologous and idiotypic or
allogenic (homologous) antigens.

43. Endogenous antigen presentation
1
2
3

44. Autoantigen
 An autoantigen is usually a normal protein or complex of
proteins (and sometimes DNA or RNA) .
 Is an endogenous antigen that stimulates the production
of autoantibodies.

45. Tumor antigens
 Tumor antigen is an antigenic substance produced in
tumor cells.
Classification of tumor antigens:
 Tumor-Specific Antigens (TSA), which are present only
on tumor cells and not on any other cell .
 Tumor-Associated Antigens (TAA), which are present on
some tumor cells and also some normal cells.

46. Superantigens
 Superantigens (SAgs) are a substance (as an enterotoxin) that
acts as an antigen capable of stimulating much larger numbers
of T cells than an ordinary antigen.
 SAgs are produced by some pathogenic viruses and bacteria
most likely as a defense mechanism against the immune syste
 Example: Staphylococcal enterotoxins (food poisoning),
Staphylococcal toxic shock toxin (toxic shock syndrome),
Staphylococcal exfoliating toxins (scalded skin syndrome) and
Streptococcal pyrogenic exotoxins (shock).

47. Superantigens
Conventional Antigen
Monoclonal/ Oligoclonal T
cell response
1:104 - 1:105
Superantigen
Polyclonal T cell response
1:4 - 1:10
 Definition