what are antigens? Significance and interaction with human body.

antigens are foreign substances that are unknown to body and are able to cause severe reactions and responses. they interfere with the bodily functions and react with antibodies that are formed in response to them.

1. Lucknow university ISABELLA THOBURN COLLEGE INTERNAL ASSESSMENT PAPER-2 TOPIC- ANTIGEN SUBMITTED TO – DEPARTMENT OF ZOOLOGY SUBMITTED BY – NAME- ADITI BAJPAI CLASS- M.SC SEMESTER-2 SUBJECT-DEVELOPMENTAL BIOLOGY AND IMMUNOLOGY ROLL NO- Z/22/40

2. Contents INTRODUCTION TO ANTIGENS ANTIGEN PROPERTIES ANTIGEN STRUCTURE TYPES OF ANTIGENS ANTIGEN PROCESSING AND PRESENTATION PATHWAYS OF ANTIGEN PROCESSING AND PRESENTATION BIBLIORAPHY

3. INTRODUCTION Antigen, substance that is capable of stimulating an immune response, specifically activating lymphocytes, which are body’s infection-fighting white blood cells. An antigen is any substance that causes your immune system to produce antibodies against it . An antigen may be a substance from the environment, such as chemicals, bacteria, viruses or pollen. An antigen that induces an immune response i.e.; stimulates the lymphocytes to produce antibody or to attack directly is called an immunogen and process is known as immunogenicity .

4. P roperties of antigens Antigens have different properties which determine the immunogenicity of the antigens. The following are some of the properties of antigens; 1 . Foreign Nature All antigens that induce an immune response in the host are foreign to the body of the recipient. The host body recognizes the antigen to be different from the normal body components. The immunogenicity of the antigen increases with the increase in the degree of foreignness. In the case of biological antigens, the foreignness increases with the increase in the phylogenetic gap between the two species. However, there are some exceptions in that some proteins occurring within the host might also induce an immune response, as in the case of auto antigens . Similarly, proteins and other molecules from other species might also not induce an immune response if they lack antigenic determinants or epitopes .

5. 2.CHEMICAL PROPERTIES The most potent and commonly encountered antigens are proteins followed by polysaccharides. However, other molecules like lipids and nucleic acids can also act as antigens when complex with proteins and polysaccharides. In the case of proteins, the antigen should contain immunogenic regions with at least 30% of amino acids like lysine, glutamine, arginine, glutamic acids, asparagine, and aspartic acid, along with a high number of hydrophilic or charged groups . The level of immunogenicity also increases with the heterogenicity of the molecules. Homopolymers are usually less immunogenic than heteropolymers. 3. Molecular Size The molecular size of the antigens is also crucial in the immunogenicity of the molecules. It has been established that antigens should have a minimum size of greater than 5000 Da before they can be considered immunogenic.

6. However , low molecular weight substances can demonstrate immunogenicity when coupled with large-sized carriers. The low molecular weight substances are termed haptens that are considered ‘partial antigens’ with at least one antigenic determinant . 4. Molecular Rigidity and Complexity The rigidity and complexity of molecules are essential factors that determine immunogenicity. In general, rigid molecules are good antigens as they can raise antibodies to certain structures when compared to the less rigid ones. 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.

7. Properties of antigen…. 5. Antigenic Determinants and Cross-reactivity Antigenic determinants are regions in an antigen molecule that is involved in the reaction with antibodies. Usually, antigens with two or more antigenic determinants can induce antibody production. 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. Cross-reactivity of antigens is also an essential factor where antibodies induced by a different antigen can interact with another antigen.

8. Antigen structure The molecular structure of an antigen is characterized by its ability to bind to the antigen-binding site of an antibody. Antibodies differentiate between different antigens on the basis of the specific molecular structures present on the surface of the antigen. Most antigens are proteins or polysaccharides. These can include coats, capsules, flagella, toxins, and fimbriae of bacteria, viruses, or other microorganisms. Besides, secretions and other chemicals of the same nature can also act as antigens. Lipids and nucleic acids of these microorganisms are only antigenic when these are combined with proteins or polysaccharides.

9. The structure of antigens might be different depending on the nature of the antigen, their size, and immunogenicity. All immunogenic antigens have a specific structural component called epitope antigenic determinant. The number of epitopes differs in different antigens and determines the number of antibodies a single antigen can bound to.  The structural components of interaction in antigens are different, which determines the classes of antibodies they bound to . The region on antibodies that interacts with antigens is called a paratope. It has been established that the structure of epitope and paratope can be defined with a lock and key metaphor as the structures are specific and fit with one another. 

10. Types of antigen Antigens can be grouped into different types based on different factors. Some of the common classifications are based on the origin of the antigen and its immunogenicity. 1. Types of antigen-based on their origin Antigens can be classified into two groups on the basis of their origin; a. Exogenous Antigens Exogenous antigens are the antigens that are originated outside the body of the host and, thus, are foreign to the host . These antigens might enter the body through inhalation, ingestion, or injection and then circulate throughout the body via bodily fluids. The uptake of exogenous antigens is primarily mediated by phagocytosis via Antigen Processing Cells (APCs) like macrophages, dendritic cells, etc. Many antigens like intracellular viruses might begin as exogenous antigens and later become endogenous.

11. Types of antigen b . Endogenous Antigens Endogenous antigens are antigens that originate within the body of the host during metabolism or as a result of intracellular viral or bacterial infection. Endogenous antigens are usually the cells of the body or fragments, compounds, or antigenic products of metabolism . These are usually processed in the macrophages and are later detected by cytotoxic T-cells of the immune system. Endogenous antigens include antigens that are xenogenic or heterologous, autologous, and idiotype or allogenic . Endogenous antigens might result in autoimmune diseases as the host immune system detects its own cells and particles as immunogenic.

12. Types of antigen Autoantigens Autoantigens are proteins or protein complexes of the host that are attacked by the host’s immune system, resulting in autoimmune disease. Autoantigens can be deadly to the host as the body’s own cells should not be targeted by the immune system. The immunological tolerance to such antigens is lost as a result of genetic and environmental factors. Tumor Antigens (Neoantigens) Tumor antigens or neoantigens are presented by Major Histocompatibility complex(MHC ) I and II on the surface of tumor cells. The antigens are produced as a result of a tumor-specific mutation during the malignant transformation of normal cells. These antigens usually do not induce an immune response as the tumor cells develop ways to evade antigen presentation and immune defense.

13. Types of antigens Native Antigens Native antigens are antigens that are not processed by any antigen-presenting cells (APC), and thus immune cells like T-cells cannot bind to these antigens. However, B-cells can be activated such antigens even without any processing. 2. Types of antigens on the basis of immune response Antigens can be classified into two distinct groups on the basis of immune response; a. Complete antigens/ Immunogens Complete antigens or Immunogens are antigens that elicit a specific immune response. These antigens can induce an immune response by themselves without any carrier particles.

14. Types of antigen These are usually proteins, peptides, or polysaccharides with high molecular weight (greater than 10,000 Da). b. Incomplete antigens/ Haptens Incomplete antigens or hapten are antigens that cannot generate an immune response by themselves. These are usually non-protein substances that require a carrier molecule to form a complete antigen. Haptens have a low molecular weight (usually less than 10,000 Da) and fewer antigenic determinant sites. The carrier molecule bonded to the hapten is considered a non-antigenic component and is a protein or a polysaccharide molecule.

15. Antigen processing and presentation T cells can only recognize antigens when they are displayed on cell surfaces . This is carried out by  Antigen-presenting cells   (APCs) , the most important of which are dendritic cells, B cells and macrophages . APCs can digest proteins they encounter and display peptide fragments from them on their surfaces for another immune cell to recognize.   This process of antigen presentation allows T cells to “see” what proteins are present in the body and to form an adaptive immune response against them.

16. Antigen presentation Antigens are delivered to the surface of APCs by  Major Histocompatibility Complex  (MHC) molecules. Different MHC molecules can bind different peptides. There are different classes of MHC, which have different functions: MHC class I  molecules are found on all nucleated cells (not just professional APCs) and typically present  intracellular  antigens such as viruses. MHC class II  molecules are only found on APCs and typically present  extracellular  antigens such as bacteria. This is logical because should a virus be inside a cell of any type, the immune system needs to be able to respond to it. This also explains why pathogens inside human red blood cells (which are non-nucleated) can be difficult for the immune system to find, such as in malaria . Whilst this is the general rule, in  cross-presentation  extracellular antigens can be presented by MHC class I and in  autophagy  intracellular antigens can be presented by MHC class II.

17. The antigen presented on MHCs is recognized by T cells using a  T cell receptor   (TCR) . These are  antigen-specific . T Cell Receptors Each T cell has thousands of  TCRs , each with a unique specificity that collectively allows our immune system to recognize a wide array of antigens. This diversity in TCRs is achieved through a process called V(D)J recombination during development in the thymus. TCR chains have a variable region where gene segments are randomly rearranged, using the proteins  RAG1  and  RAG2  to initiate cleavage and non-homologous end joining to rejoin the chains. The diversity of the TCRs can be further increased by inserting or deleting nucleotides at the junctions of gene segments; together forming the potential to create up to 10 15  unique TCRs. TCRs are specific not only for a particular antigen but also for a specific MHC molecule. T cells will only recognize an antigen if a specific antigen with a specific MHC molecule is present: this phenomenon is called   MHC restriction .

18. Co-Receptors As well as the TCR, another T cell molecule is required for antigen recognition and is known as a co-receptor. These are either a  CD4  or  CD8  molecule: CD4 is present on  T helper cells  and only binds to antigen-MHC II complexes. CD8 is present on  cytotoxic T cells  and only binds to antigen-MHC I complexes . Kills viruses and produces antiviral cytokines such as interferon gamma. This therefore leads to very different effects. Antigens presented with MHC II will activate T helper cells and antigens presented with MHC I activate cytotoxic T cells. Cytotoxic T cells will kill the cells that they recognize, whereas T helper cells have a broader range of effects on the presenting cell such as activation to produce antibodies (in the case of B cells) or activation of macrophages to kill their  intracellular pathogens.

19. Antigen processing Before an antigen can be presented, it must first be  processed . Processing transforms proteins into antigenic peptides. MHC Class I Molecules Intracellular  peptides for MHC class I presentation are made by proteases and the proteasome in the cytosol, then transported into the endoplasmic reticulum via TAP (Transporter associated with Antigen Processing) to be further processed. They are then assembled together with MHC I molecules and travel to the cell surface ready for presentation .

20. MHC class 1 pathway

21. Antigen processing 2.MCH Class II Molecules The route of processing for  exogenous  antigens for MHC class II presentation begins with endocytosis of the antigen . Once inside the cell, they are encased within endosomes that acidify and activate proteases, to degrade the antigen. MHC class II molecules are transported into  endocytic vesicles  where they bind peptide antigen, and then travel to the cell surface.

22. AUTOIMMUNE DISEASES It is important to note that APCs may deliver foreign antigens or self-antigens. In the case of autoimmune diseases, self-antigens are presented to T cells, which then initiates an immune response against our own tissues. For example, in  Graves’ disease , TSHR (thyroid stimulating hormone receptor) acts as a self-antigen and is presented to T cells. This then activate B cells to produce autoantibodies against TSHRs in the thyroid. This results in activation of TSHRs leading to hyperthyroidism and a possible goitre.

23. BIBLIOGRAPHY BOOKS- Modern trends in biology and economic zoology by-H.C.NIGAM, Vishal Publications co.,2011-12. WEBSITES- https:// teachmephysiology.com/immune-system/adaptive- https:// microbenotes.com/antigen