Immune System Presentation PDF

1. Phagocytes ▪ Phagocytes are specialized “eating” cells and there are two main types, neutrophils and macrophages. ▪ Neutrophils, often called polymorphonuclear cells (PMNs) because of the multilobed nature of their nuclei, are mobile phagocytes that comprise the majority of blood leukoc...

1. Phagocytes ▪ Phagocytes are specialized “eating” cells and there are two main types, neutrophils and macrophages. ▪ Neutrophils, often called polymorphonuclear cells (PMNs) because of the multilobed nature of their nuclei, are mobile phagocytes that comprise the majority of blood leukocytes. ▪ They have granules that contain peroxidase, alkaline and acid phosphatases, and defensins, which are involved in microbial killing. ▪ PMNs have receptors for chemotactic factors released from microbes, for example muramyl dipeptide (MDP), and for complement components activated by microbes. Macrophages ▪ Phagocytic cells distributed throughout the body. ▪ Monocytes are blood-borne precursors of the major tissue phagocytes, macrophages. ▪ Different organs/tissues each have their versions of monocyte-derived phagocytic cells. Mouse alveolar macrophages with ingested bacteria Phagocytosis ▪ Opsonization is the process of making a microbe easier to phagocytose. A number of molecules called “opsonins” do this by coating the microbe. ▪ They aid attachment of the microbe to the phagocyte and also trigger activation of phagocytosis. ▪ Opsonins include the complement component C3b and antibodies produced by activated B cells. ▪ Mononuclear phagocytes use their surface receptors, which bind to C3b or to the Fc region of IgG antibody. Mast cells and Basophils ▪ Mast cells are tissue resident cells and uniquely required for immediate hypersensitivity. Basophils are circulating cells, but home to areas of allergic inflammation during the late phase response. ▪ Both have large characteristic electron- dense granules in their cytoplasm. ▪ Stimulation results in the fusion of the intracellular granules with the surface membrane and the release of their contents by the process of exocytosis. ▪ This release is almost instantaneous and is essential in the development of the acute inflammatory response NK cells ▪ NK cells are found throughout the tissues of the body but cells mainly in the circulation and are important for protection against viruses and cancer cells. ▪ Changes in the surface molecules of cells as the result of virus infection allow NK cells to bind to and kill infected cells by releasing perforins and inducing apoptosis. ▪ In addition, on binding to virus infected cells, NK cells secrete interferon gamma (IFNγ), which protects adjacent cells from infection by viruses and helps to activate T-cell- mediated immunity. Dendritic cells ▪ Link the innate and adaptive immune systems. ▪ These cells have membrane folds that are similar in appearance to dendrites of the nervous system. ▪ These folds allow maximum interaction with other cells of the immune system. ▪ DCs represent a primary interface between the innate and adaptive immune systems in that they recognize microbial antigens through PRRs, and through cytokine production and antigen processing and presentation they are able to initiate adaptive immune responses by presenting peptide antigens to T-helper (CD4+) cells. ▪ Although macrophages can process and present antigen to T cells, the conventional DCs are much more efficient in carrying out this function. Adaptive Immune cells ▪ The two main types of lymphocytes, T cells and B cells, mature in the thymus and bone marrow, respectively. ▪ There are three main functional classes of T lymphocytes: T helper (Th) cells, T cytotoxic (Tc) cells, and T regulatory cells (Tregs). ▪ All T lymphocytes have antigen receptors (TCR) that determine their specificity and CD3, which is essential for their activation. ▪ These molecules also serve as “markers” to identify T cells. Cell surface markers of T cells: CD3+CD4+: Th cell CD3+CD8+: Tc cell CD3+CD4+CD25+Foxp3+: Treg T helper cell Activation  Helper T cells are arguably the most important cells in adaptive immunity, as they are required for almost all adaptive immune responses. They not only help activate B cells to secrete antibodies and macrophages to destroy ingested microbes, but they also help activate cytotoxic T cells to kill infected target cells. Cytotoxic T cell NK cells have cytotoxic granules already formed and are ready to kill target cells. CD8+ T cells don’t have cytotoxic granules until they have been activated by their cognate antigen. B cells B cells are responsible for humoral immunity. On encountering a foreign substance (antigen), the B cell differentiates into a plasma cell, which secretes antibodies. Lymphoid organs produce large numbers of B cells, each with unique antigen receptors (antibodies) such that, overall, there is sufficient B-cell diversity to recognize all of the antigens in our environment (generate diversity). The B-cell receptor (BCR) is a transmembrane protein on the surface of a B cell. A B-cell receptor includes both CD79 and the immunoglobulin.  B cell activation be T-cell independent or dependent. B cell activation occurs in the secondary lymphoid organs (eg, human lymph nodes and spleen). T-cell independent B-cell activation This type of activation produces plasma cells and IgM. B cells are activated by conserved repeat epitopes on the surface of bacteria or virus, including lipopolysaccharides (LPS), or DNA fragments. BCRs will cluster and cross-link with T- independent antigens. A secondary response is provided through engaging the toll-like receptor (TLR). Activated B cells will deliver a potent antibody response and do not generate memory B cells  This type of activation produces memory and plasma B cells. Naïve B cells bind to soluble or membrane bound antigens and internalize the antigen. The B cell presents this antigen on a MHCII and is recognized by a helper T cell (Th). Cytokines are secreted by the Th cell and this activates the B cell into differentiating into mature B cells capable of IgG, IgA, or IgE production Difference between B cells and Plasma cells Why do you think plasma cells have a high RER content? Clonal selection: From a large pool of B and T cells, antigen selects those which have receptors for it and stimulates their expansion and differentiation into memory and effector cells. Although B cells can recognize and bind native antigen, T cells only see antigen associated with MHC molecules on antigen-presenting cells (APC). APCs present antigens for recognition by certain lymphocytes such as T cells. Classical APCs include dendritic cells, macrophages, and B cells. Interactions between innate and adaptive immunity Interaction between innate and adaptive immunity ▪ Innate and Adaptive immune system do not work in isolation, but in a highly dependent and coordinated manner. ▪ Macrophages are phagocytic but produce important cytokines that help to induce the adaptive immune response. ▪ Cytotoxic T cells kill virus-infected body cells. These have to be cleared from the body by phagocytic cells. ▪ Complement components of the innate immune system can be activated directly by microbes, but can also be activated by antibodies (molecules of the adaptive system). ▪ The various cells of both systems work together through direct contact with each other, and through interactions cytokines and chemokines. ▪ The lymphocytes selected for clonal expansion are of two major types, B cells and T cells, each giving rise to different kinds of immunity. ▪ T lymphocytes mature under the influence of the thymus and, on stimulation by antigen, give rise to cellular immunity. ▪ B lymphocytes mature mainly under the influence of bone marrow and give rise to lymphoid populations which, on contact with antigen, proliferate and differentiate into plasma cells. ▪ These plasma cells make antibody (immunoglobulin) which is specific for the antigen and able to neutralize and/or eliminate it (humoral immunity).