immunogens, antigens, and haptens - judoctors€¦ · immunogens, antigens, and haptens. initiation...
TRANSCRIPT
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Immunogens, Antigens, and
Haptens
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Initiation of immune response
Interaction between receptor and ligand
Affinity
Avidity
strongbinding
strongbinding
weakbinding
Affinity: high low low
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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.
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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
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Special Types of Antigens
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
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
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Factors influencing immunogenicity
Factors
Contribution of immunogen
Contribution of biological
system
Method of administration
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Contribution of the immunogen
Foreignness
High Molecular Weight
- <1000 Daltons : nonimmunogenic
- 1000-6000 Daltons: may be immunogenic
- > 6000 immunogenic
Chemical Nature and Complexity
- Homopolymers Vs Heteropolymers
- Primary, secondary, tertiary, and quaternary structures
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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)
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Factors Influencing ImmunogenicityContribution of the Biological System
Genetics
Species
Individual
Responders vs. Non-responders
Age
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Factors Influencing ImmunogenicityMethod of Administration
Dose
Route
Subcutaneous > Intravenous > Intragastric
Rate of elimination
Adjuvant
Substances that enhance an immune response to an Ag
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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 )
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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
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Cross Reactivity
Modification of a molecule; toxins and toxoids
Sharing epitopes between unrelated macromolecules
Structural resemblance (molecular mimicry)
Significance in
- tolerance and autoimmunity
- Isohemagglutinins
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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
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Antigens: T-dependent
Require T help to activate B cells
Proteins
Structure
Examples
Microbial proteins
Non-self or altered-self proteins
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Hapten-carrier conjugates
Definition
Ag only if bound to carrier protein
Structure
Native determinants
Haptenic determinants
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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.
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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.
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Antigenic Determinants
Recognized by B cells and Ab
Composition
Proteins, polysaccharides, nucleic acids
Sequence (linear) determinants
Conformational determinants
Size
4-8 residues
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Antigenic Determinants
Recognized by B cells and Ab
Composition
Size
Number
Limited (immunodominant epitopes)
Located on the external surfaces of the Ag
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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
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T cell
TCR
T cell
TCR
APC
MHC
APC
MHC
Ag Super Ag
Superantigens
Definition
Polyclonal T cell
response
Examples
Staphylococcal
enterotoxins
Toxic shock toxin
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Superantigens
Conventional Antigen
Monoclonal/ Oligoclonal
T cell response
1:104 - 1:105
Superantigen
Polyclonal T cell response
1:4 - 1:10
Definition
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Most Important Human
Antigens
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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
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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
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B Lymphocytes
• 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
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Figure 3-13 part 1 of 2
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Figure 3-15The peptide-binding groove of MHC molecules
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Present Ag to
CD4 T cells
Present Ag to
CD8 T cells
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Help peptide loading
Present antigen peptides
to CD4+ T cells
Polymorphism allows the population to handle a variety of pathogens.
Polymorphism: presence of
multiple alternative forms
(alleles) of a gene.
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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
Different cell distribution of MHC class I and II
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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.
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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
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Table 2-4
CD - Cluster of Differentiation
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CDs which take part in T cell recognition,
adhesion and activation
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CDs which take part in B cell recognition,
adhesion and activation
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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.
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Ⅱ. Classification
Integrin family
Selectin family
Immunoglobulin (Ig) superfamily
Cadherin family
Mucin - like family
Other adhesion molecules
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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
Selectins consist of one peptide chain.
The three family members include: E- selectin,
L-selectin, and P-selectin.
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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
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4. Cadherin family
E- cadherin------ Epithelia cell
N- cadherin------ Nerve cell
P- cadherin-------Placenta
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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
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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
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IL-21
IL-10
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Cytokine Receptor Families
TLRs