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Immunogens & Antigens

HAFIZ M WASEEM
UE LAHORE
Immunogenicity & Antigenicity
Immunogenicity
– Ability to induce humoral and/or cell-mediated
immune response
– Immunogen is substance that induces response
Antigenicity
– Ability to combine specifically with Abs or T-cell
receptor/MHC
– Not all antigens are immunogenic
– Haptens
Immunogenicity & Antigenicity
Immunogenicity & Antigenicity
Properties of an Immunogen
– Foreignness
– Molecular size
– Chemical composition and complexity
– Ability to be processed and presented on MHC
Foreignness
• Ability to tolerate self antigens arises during lymphocyte
development, during which immature lymphocytes are
exposed to self-components
• Lymphocytes that do not bind to self antigens are allowed to
further develop
• Therefore they will later only recognize non-self antigens
• Bovine serum albumin (BSA) is not immunogenic when
injected into cow but is immunogenic when injected into
chicken
• Some macromolecules are highly conserved throughout
evolution and display little immunogenicity (Cytochrome c,
collagen)
Molecular Size
– Active (good) immunogens
–> 100,000 Daltons
– Poor immunogens
–< 5,000-10,000 Daltons
Chemical composition & complexity
• Synthetic homopolymers (polymers composed of a single amino acid or
sugar) tend to lack immunogenicity regardless of their size

• Copolymers composed of different amino acids or sugars are usually more


immunogenic

• Protein organization—primary, secondary, tertiary, and quaternary all


contribute to the structural complexity of a protein and hence affect its
immunogenicity

• Lipids are haptens and need to be conjugated with carrier to produce


antibodies
– Important for assays for detection of some steroids, vitamins
Antigen processing
• Large, insoluble macromolecules generally are more immunogenic than small,
soluble ones because the larger molecules are more readily phagocytosed and
processed

• Macromolecules that cannot be degraded and presented with MHC molecules are
poor immunogens.

• Degradative enzymes within antigen-presenting cells can degrade only proteins


containing L-amino acids, polymers of D-amino acids cannot be processed and
thus are poor immunogens.
Antigen presenting cells (APC’S)
• Internalize antigens by phagocytosis or pinocytosis and
process the antigens
• Display part of the antigens on their membrane along with
MHC complex to T cells
• Types of APC’S (Dentritc cells, Macrophages and B cells)
The Biological system &
Immunogenecity
– Host Genetic make-up
– Immunogen dosage & route of administration
– Use of agents (adjuvants) to enhance
immunogenicity
Host Genotype
Genetic variability in all of these genes affects the
immunogenicity of a given macromolecule in different
animals

– Genes of MHC
– Genes coding for specific antibodies
– Genes for BCR & TCR
– Immunoregulatory genes
Immunogen dosage and route of administration
– Too low or high of dosage can induce tolerance

– Single dose is often not enough – booster is needed


– Route
• Intravenous (iv)
• Intradermal (id)
• Subcutaneous (sc)
• Intramuscular (im)
• Intraperitoneal (ip)

– Antigen administered iv would travel to spleen;


administered sc would travel to lymph nodes
Adjuvants
– Antigen persistence is prolonged
– Co-stimulatory signals are enhanced
– Local inflammation is increased
– The nonspecific proliferation of lymphocytes is stimulated
• Aluminum potassium sulfate (alum) prolongs the persistence
of antigen
Antigens
• Antigen is a substances usually protein in nature
and sometimes polysaccharide, that generates a
specific immune response and induces the
formation of a specific antibody or specially
sensitized T cells or both.
• Epitope is immunologically active regions of an
antigen that binds to antigen-specific membrane
receptors on lymphocytes or to secreted
antibodies. It is also called antigenic
determinants.
Chemical nature of Antigens
• Proteins
The vast majority of immunogens are proteins. These may be pure
proteins or they may be glycoproteins or lipoproteins. In general,
proteins are usually very good immunogens.
• Polysaccharides
Pure polysaccharides and lipopolysaccharides are good
immunogens.
• Nucleic Acids
Nucleic acids are usually poorly immunogenic. However, they may
become immunogenic when single stranded or when complexed
with proteins.
• Lipids
In general lipids are non-immunogenic, although they may be
haptens.
Types of Antigens
Exogenous antigens

• These antigens enters the body or system and start


circulating in the body fluids and trapped by the APCs
(Antigen processing cells such as macrophages,
dendritic cells, etc.)
• The uptakes of these exogenous antigens by APCs are
mainly mediated by the phagocytosis
• Examples: bacteria, viruses, fungi etc
• Some antigens start out as exogenontigens, and later
become endogenous (for example, intracellular
viruses)
Endogenous antigens
• These are body’s own cells or sub fragments or
compounds or the antigenic products that are
produced.
• The endogenous antigens are processed by the
macrophages which are later accepted by the cytotoxic
T – cells.
• Endogenous antigens include xenogenic
(heterologous), autologous and idiotypic or allogenic
(homologous) antigens.
• Examples: Blood group antigens, HLA
(Histocompatibility Leukocyte antigens), etc.
Autoantigens
• An autoantigen is usually a normal protein or complex
of proteins (and sometimes DNA or RNA) that is
recognized by the immune system of patients suffering
from a specific autoimmune disease
• These antigens should not be, under normal
conditions, the target of the immune system, but, due
mainly to genetic and environmental factors, the
normal immunological tolerance for such an antigen
has been lost in these patients.
• Examples: Nucleoproteins, Nucleic acids, etc.
Complete Antigen or Immunogen
• Posses antigenic properties denovo, i.e. these
are able to generate an immune response by
themselves.
• High molecular weight (more than 10,000)
• May be proteins or polysaccharides
Incomplete Antigen or Hapten
• These are the foreign substance, usually non-protein
substances
• Unable to induce an immune response by itself, they
require carrier molecule to act as a complete antigen.
• The carrier molecule is a non-antigenic component and
helps in provoking the immune response. Example: Serum
Protein such as Albumin or Globulin.
• Low Molecular Weight (Less than 10,000)
• Haptens can react specifically with its corresponding
antibody.
• Examples: Capsular polysaccharide of pneumococcus,
polysaccharide “C” of beta haemolytic streptococci,
cardiolipin antigens, etc.

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