Basics of Immunity PDF

Basics of immunity  Topic outcomes 2-3.5. explain the terms antigen, immunogens, hapten, epitope, adjuvant, superantigen and heterophile antigen. 2-3.4. list the primary and secondary lymphoid organs and the different cells involved in immunity.  TERMINOLOGY 2-3.5. e...

Basics of immunity  Topic outcomes 2-3.5. explain the terms antigen, immunogens, hapten, epitope, adjuvant, superantigen and heterophile antigen. 2-3.4. list the primary and secondary lymphoid organs and the different cells involved in immunity.  TERMINOLOGY 2-3.5. explain the terms antigen, immunogens, hapten, epitope, adjuvant, superantigen and heterophile antigen.  A molecule or any substance (part of a molecule) recognized by the receptors of the adaptive immune system that causes the body to make an immune Antigens response against that molecule or substance (a specific target of the immune response) composed of many determinants or EPITOPES, IMMUNOGENS Include Toxins: chemicals Microorganisms: bacteria, viruses self antigens or foreign antigens  a substance that stimulates an immune response such as production of an antibody & Immunogen serves as the target of that response when introduced into an animal example of an immunogen is the surface antigen of the hepatitis B virus a single antigenic determinant-the portion Epitopes of a molecule that will combine with a particular antibody combining site. the antigen-binding site of an antibody molecule  Epitopes Immune cells do not interact with or recognize an entire immunogen instead they recognize discrete sites on the macromolecule which is called epitopes Epitopes are immunologically active regions of an immunogen that bind to antibodies (or other receptors) An epitope is part of a much larger antigen, such as a viral protein, with which an antibody can react A viral protein may contain a large number of epitopes capable of interacting with many different specific antibodies or T-cell receptors.  Haptens Haptens are incomplete antigens which could never induce an immune response when administered by themselves, but which can when coupled to a carrier molecule. Haptens though non immunogenic can react with the products of a specific immune response Haptens are compounds capable of being bound by immunologic receptors, but they do not necessarily elicit an immune response by themselves For example, a relatively simple chemical compound such as penicillin cannot by itself induce an antibody response. If the hapten is coupled to a macromolecule, such as a protein, antibodies can be generated that bind very specifically to the hapten  Superantigens The antigens which polyclonally activate a large fraction of the T cells. Examples: ✓ Staphylococcal enterotoxins (food poisoning) ✓ Staphylococcal toxic shock toxin (TSST 1) The result is that a whole 'family' of T cells respond, rather than a single clone, with excessive & potentially damaging over production of cytokines.  Common antigens that exist among humans, animals & microorganisms a variety of viruses & bacteria have similar antigenic structures with some tissues or Heterophile extracellular components of normal human antigens body immune response to these heterophilic antigens will produce cross-reactive antibodies and cause autoimmune diseases  COMPONENTS OF IMMUNE SYSTEM 2-3.4. list the primary and secondary lymphoid organs and the different cells involved in immunity.  Mechanisms of immunity Innate immunity (natural, or native, immunity) react immediately, constitute the first line of defense Adaptive immunity (acquired, or specific, immunity) develops more slowly than innate immunity, more powerful in combating infections, consists of mechanisms that are stimulated by (“adapt to”) exposure to microbes and other foreign substances COMPONENTS OF THE INNATE IMMUNE RESPONSE epithelial barriers that block entry of microbes phagocytic cells (neutrophils & macrophages) dendritic cells natural killer cells innate lymphoid cells several plasma proteins, including the proteins of the complement system  COMPONENTS OF THE INNATE IMMUNE RESPONSE The first cells to appear at the site of damage Neutrophils or infection Phagocytose bacteria promote inflammation through the secretion of cytokines secrete cytokines signaling often initiates the innate immune response, as they are Macrophages resident in many tissues phagocytose pathogens & antigens  COMPONENTS OF THE INNATE IMMUNE RESPONSE tissue-resident lymphocytes that lack T-cell antigen receptors cannot respond to antigens, activated by Innate lymphoid cytokines & other mediators produced at sites cells (ILCs) of tissue damage sources of inflammatory cytokines during early phases of immune reactions  COMPONENTS OF THE INNATE IMMUNE RESPONSE provide early protection against many viruses & intracellular bacteria Natural killer (NK) cells recognize mutated or damaged cells Takes part in both Innate & Adaptive immune response One type of innate lymphoid NK cells contain special proteins perforin & proteases cells known as granzymes Upon release in close proximity to a cell slated for killing, perforin forms pores in the cell membrane of the target cell through which the granzymes & associated molecules can enter, inducing apoptosis  COMPONENTS Basics OF THE of Immunity INNATE IMMUNE RESPONSE specialized cells present in epithelia, lymphoid organs, & most tissue Dendritic cells phagocytose antigens secrete cytokines , which recruit activate other immune cells promote inflammation Cellular Receptors for Microbes, Products of Damaged Cells, & Foreign Substances Cells that participate in innate immunity are capable of recognizing certain components that are shared among related microbes & that are often essential for infectivity (cannot be mutated to allow the microbes to evade the defense mechanisms). These microbial structures are called pathogen-associated molecular patterns Pattern recognition receptors are located in all cellular compartments plasma membrane receptors detect extracellular microbes endosomal receptors detect ingested microbes cytosolic receptors detect microbes in the cytoplasm Five major families of cellular receptors in innate immunity: ✓ TLRs (Toll-like receptors) ✓ CLRs (C-type lectin receptors) ✓ NLRs (NOD-like receptors) ✓ RLRs (RIG-like receptors) ✓ CDSs (cytosolic DNA sensors)  Adaptive Immunity Adaptive immune system consists of lymphocytes & their products, including antibodies Two types of adaptive immunity humoral immunity cell-mediated immunity protects against extracellular microbes responsible for defense against & their toxins intracellular microbes & against cancers Humoral immunity is mediated by B (bone Cellular immunity is mediated by T (thymus- marrow–derived) lymphocytes & their derived) lymphocytes secreted products, antibodies Both classes of lymphocytes express highly specific receptors for a wide variety of substances, which are called antigens  Cells of the Adaptive Immune System-T lymphocyte ▪ Mature lymphocytes that have not encountered the antigen for which they are specific are said to be naïve (immunologically inexperienced) ▪ After they are activated by recognition of antigens & other signals, lymphocytes differentiate into effector cells  Cells of the Adaptive Immune System-T lymphocyte Helper T lymphocytes stimulate B lymphocytes to make antibodies & activate other leukocytes to destroy microbes Cytotoxic (killer) T lymphocytes (CTLs) kill infected cells Regulatory T lymphocytes limit immune responses & prevent reactions against self-antigens T cell recognizes a specific cell-bound antigen by means of an antigen-specific TCR TCR recognizes peptide antigens that are bound to & presented by major histocompatibility complex (MHC) molecules on the surfaces of antigen-presenting cells (APCs)  The principal classes of lymphocytes & their functions. B and T lymphocytes are the cells of adaptive immunity Cells of the Adaptive Immune System  B Lymphocytes B lymphocytes are the only cells in the body capable of producing antibodies, the mediators of humoral immunity. B lymphocytes develop from precursors in the bone marrow B cells recognize antigen via the B-cell antigen receptor complex Membrane-bound antibodies of the IgM & IgD isotypes, present on the surface of all mature, naïve B cells, are the antigen-binding component of the B-cell receptor (BCR) complex After stimulation by antigen & other signals B cells develop into plasma cells (protein factories for producing antibodies as well as long-lived memory cella)  Antigen-presenting cells Dendritic cells are the most important antigen-presenting cells for initiating T-cell responses against protein antigens Macrophages are a part of the mononuclear phagocyte system:important functions in the induction & effector phases of adaptive immune responses are discussed. Macrophages function as antigen-presenting cells in T-cell activation (macrophages that have phagocytosed microbes & protein antigens process the antigens & present peptide fragments to T cells) Macrophages are key effector cells in certain forms of cell-mediated immunity, the reaction that serves to eliminate intracellular microbes In this type of response, T cells activate macrophages & enhance their ability to kill ingested microbes  Tissues of the Immune System consist of Thymus, where T cells develop Primary (central ) lymphoid organs Bone marrow: site of production of all blood cells, including naïve B cells in which T & B lymphocytes mature & become competent to respond to antigens Lymph nodes Secondary (peripheral) Spleen lymphoid organs Mucosal & cutaneous lymphoid tissues in which adaptive immune responses to microbes are initiated  Thymus ▪ Located in the anterior mediastinum ▪ Immature T cell precursors that migrate from the bone marrow undergo maturation & selection to become mature, naïve T cells that are capable of responding to antigen ▪ The thymus is critical to the development of a normal T cell Homes of Acquired Immunity Both, T and B cells proliferate, Immunologically competent B and get education and become T cells migrate here and wait for immunologically competent. fight with pathogens. Tonsils (T(Tcells) cells) (B cells) MALT (mucosa associated lymphoid tissue) in GIT (Peyer Patches); Tracheobronchial tree & Genitourinary tract. Origin of Immune Cells  Secondary lymphoid organs Secondary lymphoid organs are the residence for a variety of lymphoid cells (mainly T and B lymphocytes, dendritic cells) Lymph nodes are nodular aggregates of lymphoid tissues located along lymphatic channels throughout the body As lymph slowly suffuses through lymph nodes, antigen-presenting cells are positioned to recognize antigens (e.g., derived from microbes that may enter through epithelia into tissues and are carried in the lymph). In DCs pick up & transport antigens of microbes from epithelia & tissues via lymphatic vessels to the lymph nodes. The location of B cells ( stained green, using the immunofluorescence technique) and T cells (stained red) in a lymph node. Normal lymph node, microscopic well-defined connective tissue capsule subcapsular sinus where afferent lymphatics drain lymph fluid from tissues peripheral to the node germinal centers- red arrows The lymph may contain macrophages & dendritic cells, both forms of antigen- presenting cells, carrying antigens to the node. Beneath the subcapsular sinus is the paracortical zone (▲) with lymphoid follicles having pale germinal centers with a predominance of B lymphocytes. In the germinal centers (∗), immune responses to antigens are generated, assisted by a darker mantle zone of mainly T lymphocytes. Central to the follicles are sinusoids extending to the hilum of the node. The efferent lymphatics drain out the hilum  Normal lymph node, microscopic at high magnification Sub-capsular sinus A lymph node follicle with a germinal center contains larger lymphocytes undergoing cytokine activation. At the lower right is the subcapsular sinus (+). The center of the lymphoid follicle—the germinal center—is where CD4 helper lymphocytes and antigen- presenting cells (macrophages and follicular dendritic cells) interact with B lymphocytes, leading to an antibody-mediated adaptive immune response. The spleen is an abdominal organ that serves the same role in immune responses to blood- borne antigens as the lymph nodes do in responses to lymph-borne antigens  Spleen The spleen is an abdominal organ that serves the same role in immune responses to blood-borne antigens as the lymph nodes do in responses to lymph-borne antigens Blood entering the spleen flows through a network of sinusoids lined by macrophages and DCs. Blood-borne antigens are trapped in the spleen by these cells, which can then initiate adaptive immune responses to these antigens Individuals without a functioning spleen are more susceptible to encapsulated bacteria. The spleen also sequesters roughly one third of the body’s platelets The spleen contains white pulp & red pulp, surrounded by a fibrous capsule Red pulp contains large numbers of red blood cells & macrophages and other antigen presenting cells (APCs) phagocytose antigens White pulp contains large numbers of white blood cells The cutaneous and mucosal lymphoid systems ▪ located under the epithelia of the skin & the gastrointestinal & respiratory tracts, respectively ▪ They respond to antigens that enter through breaches in the epithelium ▪ Pharyngeal tonsils & Peyer patches of the intestine are two anatomically defined mucosal lymphoid tissues ▪ At any time, a large fraction of the body's lymphocytes are in the mucosal tissues (reflecting the large size of these tissues), and many of these are memory cells