University:
Franklin University
Course:
SCIE-254 | Health & Human Disease
Academic year:

2021
Views:

438

Pages:

43
Author:

LunarLullaby

Antigen-Antibody Antigen versus Immunogen     A pathogen is recognized by its foreignness. This foreignness is equal to antigenicity. Antigen: A molecule which is able to specifically bind to antibody or T cell receptor Immunogen: A molecule which is able to induce an immune response Antigen versus Immunogen  All molecules that have the property of immunogenicity also have the property of antigenicity, but the reverse is not true.  Allergen is an antigen which is involved in allergic immune responses. Hapten  Haptens are small antigens, not capable to induce a specific immune response, by themselves. They might be immunogenic if bond to a larger immunogen (carrier). Thyroid hormone as hapten Antigen types based on source Autoantigen Isoantigen Alloantigen Hetroantigen or Xenoantigen Superantigen Conventional antigens versus supe-rantigens Conventional antigens activate 1/10000 to 1/100000 of lymphocytes  Super-antigens activate 1-2% of lymphocytes (Polyclonal activation)  T cell TCR T cell TCR SuperAg MHC Ag MHC APC Examples: Staphlycoccal enterotoxins Toxic shock toxin APC Based on thymus dependence Thymus independent such as polysacharids Thymus dependent such as proteins (class switch) Antigen Biochemistry  For B cell responses:    Proteins (most potent immunogens) Polysaccharides (the highest amount of antigens in nature but has lower immunogenicity) Lipids and nucleic acids usually do not serve as immunogens unless complexed with proteins or polysaccharides.  For T cell responses:  Only proteins and some lipids (glycolipids and phospholipids) serve as immunogens. 13 Epitope  Antibodies do not interact with entire immunogen. They recognize distinct sites called epitopes, or antigenic determinants.  Epitope is an immunologically active region of a molecule, that binds to BCR or TCR.  B cells recognize accessible epitopes on surface of the immunogen.  T-cells recognize peptides bound on MHC molecules. Sequential and non-sequential epitops of B cells Factors That Influence Immunogenicity  Intrinsic properties of an immunogen:      Foreignness to recipient Molecular size Chemical composition and heterogeneity Susceptibility to processing and presentation The biological system:    Genotype of the recipient human/animal Immunogen dosage and route of administration Adjuvants Foreignness Phylogenetic distance between two species  Some macromolecules (e.g., collagen and cytochrome c) are highly conserved and has little immunogenicity.  Some self-components (e.g., corneal tissue and sperm/semen componenets) are effectively sequestered from the immune system.  Fetus is semi-allogenic but the mother do not respond it  Molecular size  The best immunogens tend to have a high molecular mass >100 kDa.  Generally, substances with a molecular mass < 5-10 kDa are poor immunogens. Chemical composition and complexity  Synthetic homopolymers lack immunogenicity.  Structural complexity of its immunogenicity. a protein affect Susceptibility to processing and presentation  Development of both B cell & T-cell-mediated immune responses requires T cells activation through recognition of the presented antigen on MHC molecules  Large and insoluble macromolecules are more immunogenic than small and soluble ones, due to better phagocytosis and processing.  Molecules which cannot be digested, cannot be presented on MHC molecules and are poor immunogens. The biological system contributes to immunogenicity, too  Genotype of the recipient human or animal  Immunogen dosage and route of administration  Application of adjuvants Immunogen dosage and route of administration  Doses: Too low  no response, too high  tolerance  Exposure: Repeated administration (booster) over a period of time is usually more effective  Routes:  Oral: ingestion  Nasal: inhalation Intravenous (iv): into a vein Intradermal (id): into the skin (derm) Subcutaneous (sc): beneath the skin (hypoderm) Intramuscular (im): into a muscle Intraperitoneal (ip): into the peritoneal cavity      Review of previous class  Cells of adaptive immune system B cells – T cells –  The main question is that how they sense or recognize a pathogen? 23 Some questions raise about Ag receptors How do lymphocyte receptors recognize diverse Ags?  How detection signals transmit to the cell and activates them?  What is the difference of BCR an TCR?  How so many diverse receptors are generated?  Antibodies An antibody molecule is composed of four polypeptide chains:  Two identical heavy (H) chains and two identical light (L) chains  Each chain contain a variable region and a constant region  Antibodies or immunoglobulins (Igs) Antibody forms Secreted antibodies are present in the blood and mucosal secretions and defend against microbes as the effector molecules of humoral immunity.  Antibodies exist in two forms—as membranebound antigen receptors on B cells or as secreted proteins and recognize microbial antigens and toxins by their variable regions.  TCRs exist only as membrane receptors on T cells.  Antibodies The constant regions of some secreted antibodies have the ability to bind to other molecules that participate in the elimination of antigens.  These molecules include receptors on phagocytes and proteins of the complement system  FC receptor Antibodies Antibodies serve different functions at different stages of humoral immune responses:  Membrane-bound antibodies on B cells recognize antigens to initiate the responses.  Secreted antibodies neutralize and eliminate microbes and their toxins in the effector phase of humoral immunity.  Antibodies 32 Production of Monoclonal Abs 35 Production of Monoclonal Abs BCR and TCR  B and T lymphocytes express special receptors that recognize antigens: B cells express membrane-bound B cell receptors (BCR) or antibodies or Immunoglobulins – T cells express membrane-bound T cell receptors (TCRs) – BCR versus TCR  BCR can recognize many types of chemical structures (including proteins, lipids, carbohydrates, and nucleic acids), while most TCRs recognize only peptides bound to major histocompatibility complex (MHC) molecules. BCR versus TCR    BCR or antibodies can recognize diverse microbes and toxins in their native form. In contrast, most T cells recognize only peptides (part of protein) displayed on antigen presenting cells (APCs) bound to MHC molecules. This specificity of T cells restricts their recognition to only cell-associated microbes (MHC restriction) Variable and Constant regions Different regions of antigen receptors are involved in:  Antigen recognition; therefore varying between clones of lymphocytes  Effector functions; thus relatively conserved among all clones. They are required for structural integrity, too.  Variable and Constant regions The antigen-recognizing domains of BCR and TCR are called variable (V) regions, and their conserved portions are the constant (C) regions.  Even within each V region, the variability is due to short parts, which are called hypervariable regions, or complementarity-determining regions (CDRs), because they are complementary to the shapes of antigens (as a key and lock).  Domain structure of antibody How this diversity is produced Special mechanisms (somatic recombination) exist in developing lymphocytes to create genes that encode different variable regions of BCR and TCR.  We will talk about them latter.  Signal transduction Antigen receptor chains are associated with membrane proteins whose function is to deliver signals following antigen recognition.  These signals, which are transmitted to the cytosol and the nucleus, may cause a lymphocyte to divide, to differentiate, or in certain circumstances to die.  BCR complex and TCR complex Thus, lymphocyte receptors have two functions: specific antigen recognition and signal transduction  These functions are mediated by different polypeptides.  So, we have BCR complex and TCR complex. 

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