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ANTIGEN
Antigens are molecules or molecular structures that are foreign to the body and generally induce

an immune reaction in the form of the production of antibodies against them
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Even though antigens are usually defined by the induction of an immune response, all
antigens might not induce an immune response
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The ability of antigens to elicit an immune response depends on the presence of specific
regions on the antigens called antigenic determinants
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Antigens are indicated by the term ‘Ag’, and these can occur in different forms like pollen,
viruses, chemicals, or bacteria
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In response to these antigens, the body induces the production of antibodies that act
against the said antigens
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In addition, antigens might also be intentionally introduced into the body in the form of
vaccines in order to induce the adaptive immune system of the body against the antigen
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Since these properties
determine the immunogenicity, these are considered properties required to form a good antigen
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Foreign Nature
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All antigens that induce an immune response in the host are foreign to the body of the
recipient
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The immunogenicity of the antigen increases with the increase in the degree of
foreignness
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However, there are some exceptions in that some proteins occurring within the host might
also induce an immune response, as in the case of autoantigens
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2
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However, other molecules like lipids and nucleic acids can also act as antigens when
complex with proteins and polysaccharides
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The level of Immunogenicity also increases with the heterogenicity of the molecules
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3
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It has been established that antigens should have a minimum size of greater than 5000 Da
before they can be considered immunogenic
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The low molecular weight substances are termed haptens that are considered ‘partial
antigens’ with at least one antigenic determinant
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Molecular Rigidity and Complexity
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The rigidity and complexity of molecules are essential factors that determine
immunogenicity
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The complexity of the structure is also an essential factor as a peptide antigen with a
repeating unit of a single amino acid is less immunogenic than a molecule with two or more
repeating amino acids units
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Antigenic Determinants and Cross-reactivity

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Antigenic determinants are regions in an antigen molecule that is involved in the reaction with
antibodies
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Thus, a smaller antigen usually doesn’t induce antibody production as it is not possible for a
small molecule to have more than one antigenic determinant
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Antigen Structure

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The molecular structure of an antigen is characterized by its ability to bind to the antigenbinding site of an antibody
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Most antigens are proteins or polysaccharides
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Besides, secretions and
other chemicals of the same nature can also act as antigens
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The structure of antigens might be different depending on the nature of the antigen, their
size, and immunogenicity
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The number of epitopes differs in different antigens and determines the number of antibodies
a single antigen can bound to
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The region on antibodies that interacts with antigens is called a paratope
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Types of Antigens
Antigens can be grouped into different types based on different factors
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1
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Exogenous Antigens

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Exogenous antigens are the antigens that are originated outside the body of the host
and, thus, are foreign to the host
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The uptake of exogenous antigens is primarily mediated by phagocytosis via Antigen
Processing Cells (APCs) like macrophages, dendritic cells, etc
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b
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Endogenous antigens are usually the cells of the body or fragments, compounds, or
antigenic products of metabolism
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Endogenous antigens include antigens that are xenogenic or heterologous, autologous,
and idiotype or allogenic
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c
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Autoantigens can be deadly to the host as the body’s own cells should not be targeted by
the immune system
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d
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The antigens are produced as a result of a tumor-specific mutation during the malignant
transformation of normal cells
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e
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However, B-cells can be activated such antigens even without any processing
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Complete antigens/ Immunogens
• Complete antigens or Immunogens are antigens that elicit a specific immune response
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• These are usually proteins, peptides, or polysaccharides with high molecular weight
(greater than 10,000 Da)
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Incomplete antigens/ Haptens
• Incomplete antigens or haptens are antigens that cannot generate an immune response by
themselves
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• Haptens have a low molecular weight (usually less than 10,000 Da) and fewer antigenic
determinant sites
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Antigen Processing and Presentation
Antigen processing and presentation is the process of digestion of antigens into smaller peptide
fragments by an antigen-presenting cell (APCs) that are then displayed on the surface of the cells via
antigen-presenting molecules like MHC class I and II for recognition by lymphocytes
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Endogenous Pathway or Classical MHC class I Presentation

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The endogenous pathway of antigen processing and presentation utilizes mechanisms
similar to those involved in the normal turnover of intracellular proteins
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The proteasome Involved in the immune system is called the immunoproteasome, which
has components induced by exposure to interferon-γ or TNF-α
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The peptides formed after proteolysis are transported to the ER lumen by the Transporter
associated with Antigen Processing (TAP)
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Depending on the affinity of the loaded peptides, MHC class I molecules will either be
transported to the cell membrane or recycled by a mechanism dependent on UDP-glucose
glycoprotein transferase-1
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B
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The degradation of proteins Into peptides occurs within the compartments of the cell by
the endocytic processing pathway
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The APCs have a unique endosome in the MHC class II-containing compartment (MIIC),
where the final protein degradation and peptide loading take place
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When class II MHC molecules are synthesized, the class II αβ chains associate with a
protein called the invariant chain
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As the invariant chain moves through different compartments, it is degraded until it
forms a short fragment termed CLIP (class II-associated invariant chain peptide)
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The peptide binding is required to maintain the structure and stability of class II MHC
molecules
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c
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The phenomenon of cross-presentation, however, requires the internalized antigens to be
handled by the exogenous pathway leading to class II MHC presentation somehow are
redirected to a class I loading pathway
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The first mechanism assumes that cross-presenting cells contain special antigen-processing
machinery that enables the loading of exogenously derived peptides onto class I MHC
molecules
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Cross-presentation of antigens has an advantage as APCs can capture viruses from
extracellular environments, process them and activate cytotoxic T-cell lymphocytes that can
attack virus-infected cells, which inhibit the further spread of the virus
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The binding of antibody and antigen is determined by the epitope and paratope present in
the antigen and antibody, respectively
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The interaction between antigens and antibodies is highly specific, and it is determined by
the amino acid sequence in the epitope and paratope of the species
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The shape and size of the immune complex are determined by the ratio of antigen to
antibody
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Antigen-antibody complexes have become an important tool in understanding the antigenantibody interaction and determining the basis of molecular recognition between an
antibody and antigens
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Even though immune complexes are essential for different immune functions, the
deposition of the immune complex can lead to several autoimmune diseases like arthritis
and scleroderma
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Blood group antigens

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Blood group antigens are proteins or sugars present on the surface of different
components in the red blood cell membrane
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The type of sugar in the red blood cell is determined by the type of enzyme involved, which
in turn is determined by the person’s DNA
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The RhD gene encodes the D antigen, which occurs as a large protein on the red
blood cell
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2
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The capsule Is a well-organized layer that cannot be removed easily and thus is considered a
possible cause of bacterial pathogenicity
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Bacterial capsules are also used as antigens used in vaccines where the polysaccharide
component of the capsule is conjugated with protein carriers
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Applications of Antigens
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The detection of different antigens in different species can be used to differentiate between
bacteria species as antigens are usually very specific
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Antigens are an essential component of antigen-antibody complexes, which have forensic
application in the identification of human blood and other samples
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Autoantigens are responsible for autoimmune diseases, which in some cases can be lethal
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