Transcript Immunogens, Antigens, and Haptens Initiation of immune response

Immunogens, Antigens, and
Haptens
Initiation of immune response
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Interaction between receptor and ligand
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Affinity
Avidity
Affinity: high
low
strong
binding
low
strong
binding
weak
binding
Introduction
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Immune responses arise as a result of exposure to
foreign stimuli
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The compound that evokes an immune response is
referred to as “antigen” or “immunogen.”
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The distinction between the two is functional but
they are commonly used as synonyms.
Definitions
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An immunogen is any substance capable of
inducing an immune response
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An antigen is any substance capable of binding
specifically to the products of the immune response
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All immunogens are antigens but not all antigens
need be immunogens
Special Types of Antigens
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Allergen
Mitogen
Super antigen
Tolerogen
According to source of antigen:
- Xenoantigen
- Heteroantigen
- Alloantigen
- Autoantigen
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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
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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
Factors influencing immunogenicity
Factors
Contribution
of immunogen
Contribution
of biological
system
Method of
administration
Contribution of the immunogen
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Foreignness
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High Molecular Weight
- <1000 Daltons : nonimmunogenic
- 1000-6000 Daltons: may be immunogenic
- > 6000 immunogenic
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Chemical Nature and Complexity
- Homopolymers Vs Heteropolymers
- Primary, secondary, tertiary, and quaternary structures
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
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Particulate > Soluble
Denatured > Native
Degradability
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Ag processing by Ag Presenting Cells (APC)
Factors Influencing Immunogenicity
Contribution of the Biological System
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Genetics
 Species
 Individual
 Responders vs. Non-responders
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Age
Factors Influencing Immunogenicity
Method of Administration
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Dose
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Route
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Subcutaneous > Intravenous > Intragastric
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Rate of elimination
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Adjuvant
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Substances that enhance an immune response to an Ag
Adjuvants
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Substances which when mixed with an immunogen enhance
the immune response against the immunogen
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They differ from carriers as they do not enhance immunity
to haptens
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Release immunogens slowly but continuously
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Types: Freund’s incomplete or complete adjuvants, BCG,
Corynebacterium parvum, Bordetella pertussis, LPS, and
Alum precipitate (most widely used )
Major Classes of Immunogens
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Proteins: Best immunogens
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Carbohydrates: Usually but not always good
immunogens
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Nucleic Acids: Poor immunogens by themselves
unless coupled to carriers
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Lipids: Non immunogens unless coupled to carriers
Cross Reactivity
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Modification of a molecule; toxins and toxoids
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Sharing epitopes between unrelated macromolecules
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Structural resemblance (molecular mimicry)
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Significance in
- tolerance and autoimmunity
- Isohemagglutinins
Antigens: T-independent
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Activate B cells without MHC class II T help
Polysaccharides
Properties
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Polymeric structure
Polyclonal B cell activation, but poor memory
Resistance to degradation
Examples
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Pneumococcal polysaccharide, LPS
Flagella
Antigens: T-dependent
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Require T help to activate B cells
Proteins
Structure
Examples
 Microbial proteins
 Non-self or altered-self proteins
Hapten-carrier conjugates
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Definition
 Ag only if bound to carrier protein
Structure
 Native determinants
 Haptenic determinants
Sequential (or linear) determinants
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Epitopes formed by several adjacent amino acid
residues are called linear determinants.
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They exist on the surface of antigen molecules or
inside of antigen molecules.
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They are mainly recognized by T cells, but some can
also be recognized by B cells.
Conformational determinants
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Conformational determinants are formed by amino
acid residues that are not in a sequence but become
spatially juxtaposed in the folded protein.
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They normally exist on the surface of antigen
molecules.
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They are recognized by B cells or antibody.
Antigenic Determinants
Recognized by B cells and Ab
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Composition
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Proteins, polysaccharides, nucleic acids
Sequence (linear) determinants
Conformational determinants
Size
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4-8 residues
Antigenic Determinants
Recognized by B cells and Ab
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Composition
Size
Number
 Limited (immunodominant epitopes)
 Located on the external surfaces of the Ag
Antigenic Determinants
Recognized by T cells
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Composition
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Proteins (some lipids)
Sequence determinants
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Size
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Processed
MHC presentation (lipid presentation by MHC-like CD1)
8 -15 residues
Number
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Limited to those that can bind to MHC
Superantigens
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T cell
T cell
TCR
TCR
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Super Ag
Ag
MHC
MHC
APC
APC
Definition
Polyclonal T cell
response
Examples
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Staphylococcal
enterotoxins
Toxic shock toxin
Superantigens
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Definition
Conventional Antigen
Monoclonal/ Oligoclonal
T cell response
1:104 - 1:105
Superantigen
Polyclonal T cell response
1:4 - 1:10
Most Important Human
Antigens
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
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Pathogen recognition by adaptive immunity: great
variety, selectivity
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
B Lymphocytes
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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
Figure 3-13 part 1 of 2
The peptide-binding groove of MHC molecules
Figure 3-15
Present Ag to
CD8 T cells
Present Ag 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.
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 antigenpresenting cells (APC).
• IFN-g increases the expression
of MHC II in APC and induces
the expression in non-APC
cells at sites of infection
Leukocyte Differentiation Antigens and CD
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Leukocyte differentiation antigen: Cell
surface molecules expressed (or disappeared)
during different developmental and differential
phases, activation or inactivation process of
blood cells.
Identifying Cell Using the CD
Nomenclature
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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
CD - Cluster of Differentiation
Table 2-4
CDs which take part in T cell recognition,
adhesion and activation
CDs which take part in B cell recognition,
adhesion and activation
Adhesion Molecules
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Cell adhesion molecules (CAMs) are cell surface
proteins involved in the interaction of cell-cell or
cell-extracellular matrix.
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CAMs take effect by the binding of receptor and
ligand.
Ⅱ. Classification
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Integrin family
Selectin family
Immunoglobulin (Ig) superfamily
Cadherin family
Mucin - like family
Other adhesion molecules
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)
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2. Selectin family
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Selectins consist of one peptide chain.
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The three family members include: E- selectin,
L-selectin, and P-selectin.
3. Ig superfamily(IgSF)
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The structure of these adhesion molecules resemble
that of Ig.
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CD4, CD8, CD2(LFA-2), CD58(LFA-3), VCAM-1,
ICAM-1,2,3
4. Cadherin family
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E- cadherin------ Epithelia cell
N- cadherin------ Nerve cell
P- cadherin-------Placenta
5. Mucin -like family
CD34, GlyCAM-1(glycosylation dependent cell
adhesion molecule-1)
PSGL-1(P-selectin glycoprotein ligand-1)
6. Other adhesion molecules
CD44
Ⅲ. Functions
1. 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
IL-21
IL-10
Cytokine Receptor Families
TLRs