Immunology 24 Part 2 PDF

# Types of Adaptive Immunity - **Active** - reaction of your own system - **Passive** - borrow immune agents from another person - **Natural** - occurs accidentally, on its own - **Active** - you are exposed to the flu, then develop immunity to that flu strain - **Passive** - a fetus receive...

# Types of Adaptive Immunity - **Active** - reaction of your own system - **Passive** - borrow immune agents from another person - **Natural** - occurs accidentally, on its own - **Active** - you are exposed to the flu, then develop immunity to that flu strain - **Passive** - a fetus receives antibodies from mom - **Artificial** - stimulated on purpose - **Active** - vaccination with a killed virus triggers immunity to the live virus - **Passive** - Injection of antibodies provides immunity ## Examples of Active and Passive Immunity | Type of Immunity | How Acquired by Host | Examples | | ------------------ | ---------------------------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------- | | Active Immunity | As a result of exposure to an infectious agent or one of its products (antigens) | Natural: Antibodies are produced by the host in response to the infectious agent itself (e.g. recovery from the disease). | | | | Artificial: immunization (vaccination) with some product derived from the infectious agent (e.g. toxoid, killed cells, structural components of cells, inactivated or attenuated viruses, etc.). | | Passive Immunity | As a result of the acquisition of antibodies which have been produced in another animal (by active means) or derived from cells grown in tissue culture (e.g. monoclonal antibodies) | Natural: Transplacental transfer of antibodies from mother to fetus; transfer of antibodies from mother to infant in milk by nursing. | | | | Artificial: Injection of immune serum from an individual previously immunized or recovered from disease, e.g. hepatitis; injection of serum from an animal hyperimmunized with tetanus toxoid. | ## The Immunological System - The immunological system is comprised of the lymphoid tissues and organs of the body. - Lymphoid tissues are widely distributed, they are concentrated in bone marrow, lymph nodes, spleen, liver, thymus, and Peyer's patches scattered in linings of the Gl tract. - The lymphoid system is encompassed by the system of mononuclear phagocytes. - **Lymphocytes** are the predominant cells, but macrophages, dendritic cells, and plasma cells are also present. Lymphocytes are cells which circulate, alternating between the circulatory blood stream and the lymphatic channels. - The distribution of lymphatic tissues that make up the immunological system in humans. ## The Lymphatic System - Diagram of the lymphatic system with the following labels: - Cervical lymph nodes - Right lymphatic duct - Thoracic lymph nodes - Axillary lymph nodes - Mesenteric lymph nodes - Iliac lymph nodes - Inguinal lymph nodes - Left lymphatic duct - Thoracic duct - Lumbar lymph nodes - Popliteal lymph nodes - Tonsils & adenoids - Thymus - Lymph nodes - Appendix - Bone marrow - Spleen - Peyer's patches - Lymph nodes - Lymphatic vessels ## The lymph node - Diagram of the lymph node with the following labels: - Entire region is a nodule - Afferent lymphatic vessel - Area containing mostly T cells - Outer region of nodule (mostly B cells) - Germinal center (mostly B cells) - Medulla (macrophages and lymphocytes) - Artery - Vein - Hilum - Efferent lymphatic vessel - Capsule ## Anatomy of the Immunological System - (A) The major components of the immunological system are lymph nodes connected by lymph ducts, Peyer's patches (masses of lymphocytes in the lower gastrointestinal tract), thymus, spleen, and bone marrow. - (B): A lymph node. Afferent lymph ducts bring lymph-containing antigens into the lymph node. - **Macrophages, dendritic cells and B-cells** in the cortical region make contact with the antigen and process it for presentation to immunocompetent B-cells and T-cells, thereby initiating an immune response. ## Organs comprising the immune system - **Bone Marrow** - All cells of the immune system are initially derived from the bone marrow. During hematopoiesis, bone marrow stem cells develop into either mature cells or precursors of cells that migrate out of the bone marrow to continue their maturation elsewhere. The bone marrow produces lymphocytes (B-cells, immature T-cells, and natural killer cells), granulocytes (including neutrophils, monocytes and dendritic cells), in addition to red blood cells and platelets. - **Thymus** - T-cells mature in the thymus. Immature T-cells, also known as pre-T cells), leave the bone marrow and migrate into the thymus. The mature T cells are then released into the bloodstream. - **Spleen** - The spleen is made up of B cells, T cells, macrophages, dendritic cells, natural killer cells and red blood cells. - The spleen filters antigens directly from the blood that passes through it, and migratory macrophages and dendritic cells bring antigens to the spleen via the bloodstream. - An immune response is initiated when a macrophage or dendritic cell "presents antigen" to appropriate B or T cells. In the spleen, B cells become activated and produce large amounts of antibody. ## Cells of the Immune System - Diagram of the Cells of the Immune System with the following labels: - Stem Cell - Lymphoid Stem Cell - B Cell Progenitor - Lymphocytes - T Cell Progenitor - Natural Killer Cell - Myeloid Progenitor - Granulocytes - Neutrophil - Eosinophil - Basophil - Mast Cell - Monocyte - Plasma Cell - Th Cell - Memory Cell - Tc Cell - Dendritic Cell - Macrophage ## Cells of the immune system - **B-cells** - The major function of B lymphocytes is to develop into antibody-secreting plasma cells following stimulation by foreign antigens of bacteria, viruses and tumor cells. Antibodies are specialized proteins that specifically recognize and bind to specific antigens that caused their stimulation. - Antibody production and binding to foreign antigens is often critical as a means of signaling other cells to engulf, kill or remove that substance from the body. - **Lymph Nodes** - The lymphatic system parallels the circulatory blood system. Composed mostly of T cells, B cells, dendritic cells and macrophages, the nodes drain fluid from most tissues. Antigens are filtered out of the lymph in the lymph node before returning the lymph to the circulation. In a similar fashion as the spleen, macrophages and dendritic cells capture antigens and present them T and B cells, consequently initiating an immune response. ## B-cell activation - Diagram of the B-cell activation with the following labels: - 1. Binding to antigen - B-cell receptor - B-cell - 2. Chemical signal - Helper T-cell - 3. Becomes plasma cell - 4. Releases antibodies - Can't bind ## T-cells - T lymphocytes are usually divided into two major subsets that are functionally and phenotypically different. - **T helper (TH) cells**, also called CD4+ T cells, are involved in coordination and regulation of immunological responses. They function to mediate responses by the secretion of lymphokines that stimulate or otherwise affect other cells involved in the immune responses. - The second subset type of T lymphocytes are cytotoxic T lymphocytes (Tc cells or CTLs) or CD8+ T cells - These cells are involved in: - 1- Directly killing certain tumor cells - 2- Virus-infected cells, transplant cells, and sometimes eukaryotic parasites. - CD8+ T cells are also important in down-regulation of immune responses. ## T-cell Subtypes - Diagram of the T-cell Subtypes with following labels: - Physical triggers of immune response: - Infections: - Bacterial, viral - Fungal, parasitic - Toxins: - Exogenous - Endogenous - Food peptides - Allergens - Medications - Auto antigens - Th17: - Extracellular bacteria (skin, lining of intestine) - Fungi - Autoimmunity - Antigen Presenting Cells - Th17 - Naïve T cell - Th0 - TGF-B, IL-12 - IL-12, IFN-y - IL-4, IL-2 - IL-17 - IL-21 - IL-22 - Th1: - Cell-mediated immunity and inflammation - Intracellular pathogens (Viruses, bacteria) -Autoimmunity -Inflammation - TGF-B, IL-4 - IL-17, IL-21 - IL-4, IL-2 - IL-2, IFN-y - TNF-a - Th1: - Naïve T cells - Helper T cells - Th2: - IL-35 - IL-10 - Treg: - IL-4 - IL-5 - IL-6 - IL-10 - IL-13 - Treg: - Regulatory T cells - Interleukin - Tumor necrosis factor-alpha - Interferon-gamma - Transforming growth factor-beta - Treg: - Immune tolerance - Lymphocyte homeostasis - Regulation of immune responses - T2: - Antibody-mediated immunity - Extracellular parasites - Asthma, allergy ## Cytotoxic T cell - Diagram of a cytotoxic T cell with following labels: - Infected cell - Antigen fragment - Class I MHC molecule - T cell receptor - (a) Cytotoxic T cell - 1: A fragment of foreign protein (antigen) inside the cell associates with an MHC molecule and is transported to the cell surface. - 2: The combination of MHC molecule and antigen is recognized by a T cell, alerting it to the infection. ## Natural Killer cells - Natural killer cells, known as NK cells, are similar to CTLs (CD8+ T cells). - They function as effector cells that directly kill certain tumors such as melanomas, lymphomas and virus-infected cells, most notably herpes and cytomegalovirus-infected cells. - However, NK cells, unlike the CD8+ (Tc) cells, kill their target cells without need for recognition of antigen in association with MHC molecules. ## Macrophages - Macrophages are important in the regulation of immune responses. - Besides their role in phagocytosis, they may function as antigen-presenting cells (APCs) because they ingest foreign materials and present these antigens to other cells of the immune system such as T-cells and B-cells. - This is one of the important first steps in the initiation of an immunological response. Macrophages, stimulated by certain lymphocytes, exhibit increased levels of phagocytosis and are also secrete cytokines that modulate immune responses. ## Natural Killer (NK) Cells - Why Are NK Cells so important? - They target: - TUMOR CELLS - CANCER CELLS - INFECTED CELLS - The protect against a wide variety of INFECTIOUS MICROBES (viruses, bacteria, parasites & fungil ## Dendritic cells - Dendritic cells also originate in the bone marrow and function as antigen presenting cells (APCs). - In fact, the dendritic cells are more efficient APCs than macrophages. - These cells are usually found in structural compartments of the lymphoid organs such as the thymus, lymph nodes and spleen. - However, they are also found in the bloodstream and other tissues of the body. It is believed that they capture and process antigens in lymphoid organs where an immunological response is initiated. ## Dendritic cell activation - Diagram of a dendritic cell activation with the following labels: - Non-lymphoid tissues - Draining lymph nodes - Danger signal A - Th1 - Th1 bias * - Activated DC - Foreign antigens - Danger signal B - Th2 - Th2 bias - Deletion Regulatory cells - CD4 T cell - Immunity - Tolerance - MHC II presentation - Danger * - Immature dendritic cell - Steady-state migration - Quiescent DC - Self-antigens - MHC I - CD8 T cell - Deletion Regulatory cells - Nature Reviews | Immunology ## The Immunological Response - Immunological responses are associated with macrophages or dendritic cells and two subpopulations of lymphocytes, B-cells and T-cells. - Under antigenic stimulus, B-lymphocytes become transformed into antibody-secreting plasma cells. - The plasma cells synthesize large amounts of Immunoglobulins (antibodies) which will react with the stimulating antigen. - Under antigenic stimulus, pre T-lymphocytes differentiate into several classes of effector T cells which are committed to various activities upon recognition of the specific antigen that induced their formation. - T cells have many activities relevant to immunity including: - (1) Mediation of the B-cell response to antigen - (2) Ability to recognize and destroy cells bearing foreign Ag on their surface. - (3) Production of a variety of diffusible compounds called cytokines and/or lymphokines, which include substances that are activators of macrophages, mediators of inflammation, chemotactic attractants, and interferon. - Cytokines and lymphokines are molecules (peptides, proteins) produced by cells as a means of intercellular communication. Generally, they are secreted by a cell to stimulate the activity of another cell. ## Cell diagram - Diagram of an animal cell with the following labels: - Nucleus - Nucleolus - Endoplasmic reticulum ## Immune cell interactions - Diagram of immune cell interactions. - Stem cell - Tissues - Monocyte - Macrophage (presents Ag) - Blood - Monoblast - Bone marrow - Ag - Effector T-cells: - Tc - Th1 - Th2 - PT-cells - Induction - Bone marrow - Thymus - Lymphoblast - Memory T-cells - Ag - Plasma cells - B-cells - Induction - Memory B-cells ## Three important features of an immunological response - 1. **Specificity**. An antibody or reactive T-cell will react specifically with the antigen that induced its formation; it will not react with other antigens. Generally, this specificity is of the same order as that of enzyme-substrate specificity or a receptor-ligand interaction. However, cross-reactivity is possible. The specificity of the immunological response is explained on the basis of the clonal selection hypothesis: during the primary immune response, a specific antigen selects a pre-existing clone of specific lymphocytes and stimulates exclusively its activation, proliferation and differentiation. - 2. **Memory**. The immunological system has a "memory". Once the immunological response has reacted to produce a specific type of antibody or reactive T-cell, it is capable of producing more of the antibody or activated T-cells rapidly and in larger amounts. This is referred to as a secondary or memory response. - 3. **Tolerance**. This ensures that under normal conditions, an immune response to "self" antigens (called an autoimmune response) does not occur. Autoimmune responses are potentially harmful to the host. ## The CMI response - The CMI response involves several subpopulations of T lymphocytes that recognize antigens on the surfaces of cells. TH cells (CD4+) respond to antigen with the production of lymphokines. - A distinction between TH1 cells and TH2 is based on their lymphokine profiles. - TH2 cells have previously been referred to as T-helper cells because they provide lymphokines (e.g. IL-2 and IL-4) which activate T cells and B cells at the start of the immune response. - Tc cells (CD8+) or cytotoxic T lymphocytes (CTLs) are able to kill cells that are showing a new or foreign antigen on their surface (as virus-infected cells, or tumor cells, or transplanted tissue cells). ## Membrane receptors on B-cells and T-cells - Each T cell has about 105 molecules of a specific antigen-binding T cell receptor (TCR) exposed on its surface. The TCR is similar, but not identical, to antibody. - In addition, T cell subsets bear some distinguishing surface markers, notably CD4 or CD8. - T cells bearing CD4 always recognize antigens in association with class II major histocompatability complex (class II MHC) proteins on the surfaces of other cells. - T cells bearing CD8 (CD8+) always recognize antigen in association with class I MHC proteins and typically function as cytotoxic T cells. - The important markers, actions and interactions of T cells, B cells and Antigen Presenting Cells (APC). ## TH2 Activation - Diagram of the TH2 activation with the following labels: - TH2 - Activation - AP - TH2 - IL-1 - IL-2 - IL-2 - IL - 2 - Killing by Tc - S - Tc - Killing - TH2/B cell help - IL-4 - B - IL-4 - IL-4 - TH2 ## Antigen Processing - Diagram of antigen processing with the following labels: - Antigen Processing - Macrophage - T cell - B cell - Bacteria - James A. Sullivan - www.cellsalive.com ## Induction of primary immunological responses - Induction of a primary immunological response begins when an antigen penetrates epithelial surfaces. It will eventually come into contact with macrophages or certain other classes of Antigen Presenting cells (APCs), which include B cells, monocytes, dendritic cells, Langerhans cells and endothelial cells. - Antigens, such as bacterial cells, are internalized by endocytosis and "processed" by the APC, then "presented" to immunocompetent lymphocytes to initiate the early steps of the immunological response. - Processing by a macrophage (for example) results in attaching antigenic materials to the surface of the membrane in association with MHC II molecules on the surface of the cell. ## Secondary immune response - The antigen-MHC II complex is presented to a T-helper (TH2) cell which is able to recognize processed antigen associated with a class II MHC molecule on the membrane of the macrophage. - This interaction, together with stimulation by Interleukin 1 (IL-1), produced by the macrophage, will activate the TH2 cell. - Activation of the TH2 cell causes it to begin to produce Interleukin 2 (IL-2), and to express a membrane receptor for IL-2. - The secreted IL-2 auto stimulates proliferation of the TH2 cells. Stimulated Antigen stimulated TH2 cells produce a variety of lymphokines including IL-2, IL-4, IL-6, and gamma Interferon, which mediate various aspects of the immune response. For example, IL-4 causes B cells to proliferate and differentiate into antibody-secreting plasma cells and memory B cells. - The antibodies produced and secreted by the plasma cells react specifically with the homologous antigen that induced their formation. - Many of these reactions lead to host defense and to prevention of re-infection by pathogens. - Memory cells a role in secondary immune responses. - Plasma cells are relatively short-lived (about one week) but produce large amounts of antibody during this period. - Memory cells, on the other hand, are relatively long-lived and upon subsequent exposure to Ag they become quickly transformed into antibody-producing plasma cells. ## Generation of cell mediated immunity - Generation of cell mediated immunity (CMI) begins when (for example) a Tc cell recognizes a processed antigen associated with MHC I on the membrane of a cell (usually an altered self cell, but possibly a transplanted tissue cell or a eucaryotic parasite). - Under stimulation by IL-2 produced by TH2 cells the Tc cell becomes activated to become a cytotoxic T lymphocyte (CTL) capable of lysing the cell which is showing the new (foreign) antigen on its surface, a primary manifestation of CMI. ## Interleukin-1 - The interaction between an antigen-presenting macrophage and a TH cell stimulates the macrophage to produce and secrete a cytokine called Interleukin-1 (IL-1) that acts locally on the TH cell. - The IL-1 stimulates the TH cell to differentiate and produce its own cytokines (which in this case might be called lymphokines because they arise from a lymphocyte). These lymphokines have various functions. Interleukin-4 has an immediate effect on nearby B-cells. ## Primary immunological response - Time is required before a primary immunological response to be effective as a host defense. - Antigens have to be recognized, taken up, digested, processed and presented by APCs; a few select TH cells must react with Ag and respond; preexisting B or T lymphocytes must encounter the Ag and proliferate and differentiate into effector cells (plasma cells or CTLs). - In the case of AMI, antibody level has to build up to an effective physiological concentration to render its host resistant. - It may take several days or weeks to reach a level of effective immunity, even though this immunity may persist for many months, or years, or even a lifetime due to the presence of the antibodies ## Secondary immunological response - On re-exposure to microbial antigens (secondary exposure to antigen), there is an accelerated immunological response, the secondary or memory response. - Larger amounts of antibodies are formed in only 1-2 days. This is due to the activities of specific memory B cells and memory T cells which were formed during the primary immune response. - These memory cells, when stimulated by homologous Ag, "remember" having previously seen the Ag, and are able to rapidly divide and differentiate into effector cells ## Antibody response - Diagram of antibody response with the following labels: - Antibody titer - Primary response - Secondary response - First exposure to antigen - Second exposure to antigen - Relative time ## Antibodies - They are proteins produced by lymphocytes that can specifically bind a wide variety of protein and polysaccharide antigens and elicit a response that is significant in antimicrobial defense. - In conjunction with the complement system, antibodies are the mediators of humoral (circulating) immunity, and their presence on mucosal surfaces provides resistance to many infectious agents. - Antibodies are essential for the prevention and/or cure of many types of bacterial and viral infections. - The term gamma globulin was coined for serum containing antibodies. Antibodies themselves, were called immunoglobulins. ## Clonal selection theory - The most important conceptual advance towards our understanding of the cellular basis of the antibody response was provided by the clonal selection theory proposed by MacFarlane Burnet in 1957, which improved and extended an earlier theory put forward by Niels Jerne in 1955. - According to MacFarlane Burnet's theory there is a repertoire of antibody specificities in the body that equals the number of B lymphocytes, i.e. each different B lymphocyte expresses a single antibody specificity.