Immunogens, Antigens, and Haptens

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Immunogens, Antigens, and Haptens
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Initiation of immune response

• Interaction between receptor and ligand
• Affinity
• Avidity

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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
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Contribution of the immunogen

• Foreignness
• High Molecular Weight
• - lt1000 Daltons nonimmunogenic
• - 1000-6000 Daltons may be immunogenic
• - gt 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 gt Soluble
• Denatured gt 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 gt Intravenous gt 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 Freunds 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 DeterminantsRecognized 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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Superantigens

• Definition
• Polyclonal T cell response
• Examples
• Staphylococcal enterotoxins
• Toxic shock toxin

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Superantigens

• Definition

Monoclonal/ Oligoclonal T cell response 1104 -
1105
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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 ? MHC molecules
• CD molecules CD1339
• 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
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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.

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Figure 3-13 part 1 of 2
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Figure 3-15
The peptide-binding groove of MHC molecules
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Present Ag to CD8 T cells
Present Ag to CD4 T cells
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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.
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Figure 3-22
Different cell distribution of MHC class I and II

• 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

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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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CD - Cluster of Differentiation
Table 2-4
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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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?. 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 a and ß chains.
• According to ß subunits, Integrins are divided
  into eight groups ß1- ß8
• 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?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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?. 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

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IL-21 IL-10
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Cytokine Receptor Families
TLRs