Lymphocytes and Immune System PDF

Here is the markdown conversion of the provided text: ### Leukocytes The image shows a hierarchy of leukocytes, with "Leukocytes" at the top. It then branches into "Agranulocytes" and "Granulocytes". Agranulocytes further branch into "Monocytes" and "Lymphocytes". Monocytes branch into "Macrophage...

Here is the markdown conversion of the provided text: ### Leukocytes The image shows a hierarchy of leukocytes, with "Leukocytes" at the top. It then branches into "Agranulocytes" and "Granulocytes". Agranulocytes further branch into "Monocytes" and "Lymphocytes". Monocytes branch into "Macrophages." Lymphocytes branch into "B Cells", "T Cells", and "Natural Killer Cells". Granulocytes branch into "Neutrophils", "Eosinophils", and "Basophils". ### The Immune System The Immune System is the Third Line of Defense Against Infection. | Nonspecific Defense Mechanisms | Specific Defense Mechanisms (Immune System) | | :----------------------------- | :----------------------------------------- | | **First line of defense** | **Third line of defense** | | Second line of defense | | | - Skin | | | - Mucous membranes | . Phagocytic white blood cells | | - Secretions of skin and mucous membranes| -Antimicrobial proteins| | | . The inflammatory response | | | -Lymphocytes | | | -Antibodies | ### Lymphocytes * Lymphocytes are a type of white blood cell (or leukocyte). * Most lymphocytes are small, featureless cells with few cytoplasmic organelles and much of the nuclear chromatin inactive. ### Types of Lymphocytes * Lymphocytes can be divided into three main types: * Large granular lymphocytes: these are part of the innate immune system, and are natural killer cells (NKCs). * Small lymphocytes: these lymphocytes are the main agents of the acquired immune system. * The two main types are: * T cells * B cells. The image is a flowchart that depicts the differentiation of blood cells from a multipotential hematopoietic stem cell (hemocytoblast). This stem cell differentiates into either a common myeloid progenitor or a common lymphoid progenitor. The common myeloid progenitor gives rise to erythrocytes, mast cells, myeloblasts (which further differentiate into basophils, neutrophils, eosinophils, and monocytes), megakaryocytes (which produce thrombocytes). The common lymphoid progenitor gives rise to natural killer cells (large granular lymphocytes) and small lymphocytes (T lymphocytes and B lymphocytes), which can become plasma cells. Monocytes can further differentiate into macrophages. The image is a flowchart showing blood cell development. It begins with a **pluripotent hematopoietic stem cell** in the **bone marrow**, which differentiates into either a **common lymphoid progenitor** or a **common myeloid progenitor**. Both progenitors reside in the bone marrow. The lymphoid progenitor gives rise to B cells, T cells, and NK (natural killer) cells, which then migrate to the **lymph nodes**. The myeloid progenitor gives rise to **granulocyte/macrophage progenitors**, **megakaryocyte/erythrocyte progenitors**, which then differentiate into **megakaryocytes** and **erythroblasts.** The megakaryocyte in the bone marrow gives rise to **platelets** in the blood, while the erythroblast becomes an **erythrocyte**. Granulocytes, which include **neutrophils**, **eosinophils**, and **basophils**, are found in the blood. In the **tissues**, immature dendritic cells can differentiate into mature dendritic cells, mast cells, or macrophages. **Effector cells** such as activated T cells, activated NK cells, and plasma cells are also shown. ### Lymphocyte structure * Lymphocytes are surrounded by a thin cytoplasm containing some mitochondria, free ribosomes, and a small Golgi apparatus. * Surface of lymphocytes highlighted with some labels like small golgi, mitochondrion and nucleus. ### Distribution of lymphocytes in the body * Lymphocytes are mainly found in lymphoid organs, in blood and scattered under mucosal surfaces. The Lymphocyte population Percentages are shown in the pie chart below: * Other Tissues 25% * Lymph nodes 40% * Blood 2% * Bone marrow 10% * Spleen 13% * Intestine 10% #### Distribution of lymphoid tissues in the body * Central lymphoid organs (yellow) * Secondary lymphoid organs (blue) The image shows a human with its lymphoid tissues highlighted, including: * adenoid * tonsil * right subclavian vein * lymph node * kidney * appendix * lymphatics * left subclavian vein * thymus * heart * thoracic duct * spleen * Peyer's patch in small intestine * large intestine * bone marrow ### Types of lymphocytes * There are two major types of lymphocyte: * B-cells & T-cells * B lymphocytes or B cells (sometimes called B-lymphocytes and often named on lab reports as CD19 or CD20 cells) which when activated differentiate into plasma cells that secrete antibodies. * B-cells develop in the bone marrow from hematopoietic stem cells. When mature, B-cells can be found in the bone marrow, lymph nodes, spleen, some areas of the intestine, and the bloodstream. ### B-Cells * When B-cells encounter foreign material (antigens), they respond by maturing into another cell type called plasma cells. * B-cells can also mature into memory cells, which allows a rapid response if the same infection is encountered again. Plasma cells are the mature cells that actually produce the antibodies. * Antibodies, the major product of plasma cells, find their way into the bloodstream, tissues, respiratory secretions, intestinal secretions, and even tears. ### B-Cells * For every foreign antigen, there are antibody molecules specifically designed to fit that antigen, like a lock and key. * When antibody molecules recognize a microorganism as foreign, they physically attach to it and set off a complex chain of events involving other components of the immune system that work to eventually destroy the germ. * Antibodies vary with respect to their specialized functions in the body. These variations are determined by the antibody's chemical structure, which in turn determines the class of the antibody (or immunoglobulin). The images show the structure of an antibody molecule, illustrating an antibody molecule with heavy and light chains, antigen-binding sites, and a diagram of an enlarged antigen-binding site with the epitope. ### B-Cells * There are five major classes of antibodies: (IgG, IgA, IgM, IgD and IgE). * IgG has four different subclasses (IgG1, IgG2, IgG3, IgG4). * IgA has two subclasses (IgA1 and IgA2). * Each immunoglobulin class has distinct chemical characteristics that provide it with specific functions. The image shows a detailed antibody structure, illustrating antigen-binding sites, variable and constant regions, disulfide bonds, carbohydrates, and different chains. The image is a colored, schematic representation of an antibody (immunoglobulin) molecule. The antibody is Y-shaped, composed of two identical heavy chains (green) and two identical light chains (yellow). The light and heavy chains are connected by disulfide bonds. The image shows antibodies digestion. On the left side is a schematic diagram showing proteolytic cleavage by papain into Fab and Fc fragments, on the right side is a schematic diagram showing proteolytic cleavage by pepsin. ### T-cells * T-cells (sometimes called T-lymphocytes and often named in lab reports as CD3 cells) are another type of immune cell. * T-cells directly attack cells infected with viruses, and they also act as regulators of the immune system. * T-cells develop from hematopoietic stem cells in the bone marrow but complete their development in the thymus. Mature T-cells leave the thymus and populate other organs of the immune system, such as the spleen, lymph nodes, bone marrow and blood. The image shows a flow chart of the Evolution of B-cells & T-cells . The steps are as fallows: From the **Bone Marrow** 1. Pluripotent stem cell 2. Lymphocyte stem cell 3. B cell From **Thymus** 1. T cell 2. Lymphoid tissue (lymph nodes, spleen, blood, and lymph) The image is a diagram showing the development of T and B cells from hemopoietic precursor cells in the bone marrow, their differentiation in the thymus (for T cells) or within the bone marrow (for B cells), their migration to lymph nodes and peripheral lymphoid tissues, and their roles in cell medicated and antibody mediated immune responses following an infection. It depicts development in the bone marrow of B cells and the Thymus of T cells respectively. ### T-cells * Each T-cell reacts with a specific antigen, just as each antibody molecule reacts with a specific antigen. * In fact, T-cells have molecules on their surfaces that are similar to antibodies are called TCR & BCR. * The variety of different T-cells is so extensive that the body has T-cells that can react against virtually any antigen. ### Types of T Cells * Helper T cells (Th) often denoted in lab reports as CD4 T-cells) * "Killer" or cytotoxic T-cells (Tc) (often denoted in lab reports as CD8 T-cells), * Suppressor T-cells or Regulatory T-cells (Treg). Each has a different role to play in the immune system. ### Functions of T-cells * Helper T-cells assist B-cells to produce antibodies and assist killer T-cells in their attack on foreign substances. * Killer, or cytotoxic, T-cells perform the actual destruction of infected cells. Killer T-cells protect the body from certain bacteria and viruses that have the ability to survive and even reproduce within the body's own cells. * Regulatory T-cells suppress or turn off other T-lymphocytes. Without regulatory cells, the immune system would keep working even after an infection has been cured. ### Lymphocyte populations in animals & human Table of Major Peripheral Blood Lymphocyte Populations in Domestic Animals and Humans | | T Cells | B cells | CD4+ | CD8+ | CD4/CD8 | | :------- | :------ | :------ | :---- | :---- | :------ | | Bovine | 45-53 | 16-21 | 8-31 | 10-30 | 1.53 | | Sheep | 56-64 | 11-50 | 8-22 | 4-22 | 1.55 | | Pigs | 45-57 | 13-38 | 23-43 | 17-39 | 1.4 | | Horses | 38-66 | 17-38 | 56 | 20-37 | 4.75 | | Dogs | 46-72 | 7-30 | 27-33 | 17-18 | 1.7 | | Cats | 31-89 | 6-50 | 19-49 | 6-39 | 1.9 | | Human | 70-75 | 10-15 | 43-48 | 22-24 | 1.9-2.4 | ### Natural killer cells (NK Cells) * Natural killer (NK) cells are so named because they easily kill cells infected with viruses. * They are said to be "natural killer" cells as they do not require the same thymic education that T-cells require. * NK cells are derived from the bone marrow and are present in relatively low numbers in the bloodstream and in tissues. * They are important in defending against viruses and possibly preventing cancer as well and are thought to be important in the innate immune defense against intracellular pathogens. The image shows a schematic and microscopic view of a natural killer (NK) cell releasing lytic granules to kill virus infected cells. ### Lymphocyte Mitogens * A mitogen is a chemical substance that encourages a cell to commence cell division, triggering mitosis. A mitogen is usually some form of a protein. * B cells can enter mitosis when they encounter an antigen matching their immunoglobulin. * Mitogens are often used to stimulate lymphocytes and therefore assess immune function. ### Lymphocyte Mitogens * Lectines are proteins that bind to cell surface glycoproteins and so trigger cell division. *Not all lymphocytes respond equally well to all lectines. | Species of Lectin | Acts upon T-cells | Acts upon B-cells | | :---------------------------- | :---------------- | :---------------- | | Phytohaemagglutinin n (PHA) | yes | no | | Concanavalin A (conA) | yes | no | | Pokeweed mitogen (PWM) | yes | yes | | Lipopolysaccharide (LPS) | no | yes | ### Types of adaptive immunity The image illustrate diagrammatically types of adaptive immunity, which are humoral immunity and cell-mediated immunity. **Humoral Immunity:** * **Microbe:** Extracellular microbes. * **Responding Lymphocytes:** B lymphocyte. * **Effector Mechanism:** Secreted antibody. * **Functions:** Block infections and eliminate extracellular microbes. **Cell-Mediated Immunity:** * **Microbe:** Intracellular microbes (e.g., viruses) replicating within infected cell. * **Responding Lymphocytes:** Helper T lymphocyte, Cytotoxic T lymphocyte. * **Effector Mechanism:**Helper T lymphocyte, Cytotoxic T lymphocyte * **Functions:** Activate macrophages to kill phagocytosed microbes. Kill infected cells and eliminate reservoirs of infection. ### Antigen Presentation to T Lymphocytes * In an adaptive immune response, antigen is recognized by two distinct sets of highly variable receptor molecules the immunoglobulins that serve as antigen receptors on B cells and the antigen-specific receptors of T cell. * T cells recognize only antigens that are displayed on cell surfaces and can detect the presence of intracellular pathogens because infected cells display on their surface peptide fragments derived from the pathogen's proteins. * These foreign peptides are delivered to the cell surface by specialized host-cell glycoproteins, the MHC molecules. The images show schematic diagrams which are labeled: a T-cell receptor with details of its structure, like the antigen-binding site, variable region, constant region. alpha and beta chains, transmembrane region and the disulfide bond. ### Antigen presenting cells (APC) * Major APCs are dendritic cells (DCs), macrophages, and activated B cells. * The major initiators of adaptive immunity are DCs, which actively migrate to the lymph nodes and secondary lymphoid organs and present antigens to T and B cells. * Macrophages are specialized to internalize extracellular pathogens, especially after they have been coated with antibody, and to present their antigens. * B cells have antigen-specific receptors that enable them to internalize large amounts of specific antigen, process it, and present it. The image displays microscopic images of three types of antigen-presenting cells: dendritic cell, macrophage, and B lymphocyte with cellular components shown on each of them. Diagram describing First stage of Antigen processing (disclose of epitope) * In this diagram, the Antibodies bind to epitopes displayed on the surface of antigens. * The epitopes recognised by T-cell are often buried, The antigen must first be broken down into peptide fragments * The epitope peptide binds to a self molecule, an MHC molecule, then The T-cell receptor binds to a complex of MHC molecule and epitope peptide. The first image a diagram of index of antigen, labeled with epitope and and showing how the antibody binds it. ### Immunity Response * Second stage of antigen processing: presenting of antigen by MHC to T-cells. * T-cell receptor differs from the B-cell receptor in an important way: * it does not recognize and bind antigen directly, but instead recognizes short peptide fragments of pathogen protein antigens, which are bound to MHC molecules on the surfaces of other cells. ### Types of MHC Other names of MHC in: * Human (HLA) * Cow (BOLA) * Horse (ELA) * Sheep (OLA) * Mice (H-2 Complex) Image illustrates structures of: * MHC class I * MHC class II * peptide * cell membrane Both types of MHC proteins are important to T cell activation ### MHC Proteins * Class I MHC proteins * Always recognized by CD8 T cells * Display peptides from endogenous antigens are egraded by proteases and enter the endoplasmic reticulum * Transported via TAP (transporter associated with antigen processing) * Loaded onto class I MHC molecules * Displayed on the cell surface in association with a class I MHC molecule The image shows the processes involved in cell-mediated immunity via class I MHC proteins. The schematic explains the steps involved in antigen processing and presentation by Class I MHC proteins: production of proteins in the cytosol -> proteolytic degradation of the proteins to form a set of peptide fragments -> transport of the peptides from the cytosol to the endoplasmic reticulum (ER) -> Assembly of peptide-Class I complexes in the ER -> surface expression of peptide class I complexes. ### MHC Proteins * Class II MHC proteins * Class II MHC proteins are found only on mature B cells, some T cells, and antigen-presenting cells * Always recognized by CD4 T cells * A phagosome containing pathogens (with exogenous antigens) merges with a lysosome * Invariant protein prevents class II MHC proteins from binding to peptides in the endoplasmic reticulum * CLIP removed by HLA-DM Diagram explaining Class II MHC proteins. The processes include: Uptake of extracellular proteins into vesicular compartments of APC, then the Processing of internalized proteins in endosomal/lysosomal vesicles, Synthesis and transport of class II MHC molecules to endosomes , Association of processed peptides with class II MHC molecules, ending up with the Expression of peptide-MHC complexes on cell surface The is a diagram describing Pathways of antigen processing. **Antigen uptake & processing pathway using Class I MHC:** * A cytotoxic microbe is in contact with ER where there is a unfolded proteins and proteins in cytosol * This proteins peptides with the Class | MHC protein to form the Class I MHC pathway for CD8+ CTL or T celll to become a product **Antigen uptake & processing pathway using Class II MHC:** * The external antigens like bacteria with proteins are endocytised, these antigens are brought into the cell. * Then Class II MHC protein join the invariant chains where proteins, * Thia all forms a Class II MHC pathway for CD4+ or T to become a porduct The image displays the co-receptors of MHC class I & II. * Th (T-Helper) contains specific molecule called CD4. * Tc (T-Cytotoxic) & Treg contains specific molecule called CD8. ### T Cell Activation * T Cell Activation required two independent signals: * Binding of the peptide: MHC complex by the T-cell receptor and, the CD4 co-receptor, transmits a signal to the T cell that antigen has been encountered (major signal). * Activation of naive T cells requires a second signal, the co-stimulatory signal, to be delivered by the same antigen-presenting cell. * Signals that plays in role in differentiation of T-cells. ### **T Cell Activation** The processes involve Biding of the T-cell receptor (TCR) and its co-receptor CD4 to the peptide:MHC class II complex on the antigen-presenting cell (APC) delivers a signal that can induce the clonal expansion of T cells only when the co-stimulatory signal is given by binding of CD28 to B7 molecules, which then activates T cell. The image describes what APCs deliver, namely: three kinds of signals to naive T cells: Activation, Survival and Differentiation. The cytokines involved are IL-6, IL-12, TGF-B, IL-4. It also demonstrates that CTLA-4 bind B7 more avidly than does CD28 and delivers inhibitory signals to activated T cells. The first image describes cell TH1recognizes complex of bacterial peptide with MHC class II and activates macrophage. The Second is showing how Helper T cell recognizes complex of antigenic peptide with MHC class II and activates B cellThe description continues with how Cytotoxic T cell recognizes complex of viral peptide with MHC class I and kills infected cell ### B-Cell Activation The humoral immune response is mediated by antibody molecules that are secreted by plasma cells. * First stage: * Antigen that binds to the BCR signals B cells and is, at the same time, internalized and processed into peptides that activate armed helper T cells. & Signals from the bound antigen and from the helper T cell induce the B cell to proliferate and differentiate into a plasma cell secreting specific antibody. Describing B cell binds bacterial polysaccharide epitope linked to tetanus toxoid protein, the steps continues with Antigen is internalized and processed then Peptides from protein component are presented to the T cell . in the diagram it goes on with Activated B cell produces antibody against polysaccharide antigen on the surface of the bacterium ### B-Cell Activation Armed helper T cells stimulate the proliferation and then the differentiation of antigen-binding B-cells . The diagram goes on witg Antigen recognition induces expression of effector molecules by the T cell, which activates the B cell ,leading to B-cell proliferation and finally Differentiation to resting memory cells and antibody-secreting plasma cells ### B-Cell Activation * Second stage: * These antibodies protect the host from infection in three main ways: * They can inhibit the toxic effects or infectivity of pathogens by binding to them: this is termed neutralization * By coating the pathogens, they can enable accessory cells that recognize the Fc portions of arrays of antibodies to ingest and kill the pathogen, a process called opsonization * Antibodies can also trigger activation of the complement system. Complement proteins can strongly enhance opsonization, and can directly kill some bacterial cells. Describe B-cell activation by antigen and helper T cells . These helper cells release cytokines . Antibody secretion by plasma cells leads to Neutralization, Opsonization and Complement activation ### Helper T Cells $(T_H)$ * Regulatory cells that play a central role in the adaptive immune response. * stimulate proliferation of other T cells. * Stimulate B cells that have already become bound to antigen. Without Th, there is no immune response ### Helper T Cells $(T_H)$ The processes involve cells that Class II MHC protein and CD 4 protein. The Helper T cell then interacts with Cytotoxic T cell via cell-mediated immunity (attack on infected cells). As well as B cell via Humoral immunity (secretion of antibodies by plasma cells) The image displays the immune response with labeled steps: Viruses infect the cell. Viral proteins are displayed on the cell surface. Viruses and viral proteins on infected cells stimulate macrophages. Stimulated macrophages release interleukin-1. Interleukin-1 activates helper T cells, which release interleukin-2. Interleukin-2 activates B cells and cytotoxic T cells. Cytotoxic T cells bind to infected cells and kill them. Activated B cells multiply. Some B cells become memory cells. Other B cells become antibody-producing factories. Antibodies bind to viral proteins, some displayed on the surface of infected cells. 11. Macrophages destroy viruses and cells tagged with antibodies. ### Mechanisms of helper T cell-mediated activation of B lymphocytes 1. B cell presents antigen to helper T cell . Cytokine receptor interactions 2. Helper T cell is activated expressses CD49L, secretes cytokines 3. B cells are activated by CD40 engagement and cytokines 4. the process leads to B cell proliferation and differentiation ### Roles of Helper T-Cells diagram * Initiate differentiation of new T cells * Shut down both cell-mediated and humoral immune responses * Activate Inducer T cells * Helper T Cells * Produce Interleukin-2 * Bind to B cell-antigen complexes * Cause Cytotoxic T cells to multiply * Produce cytokines and gamma interferon * Cause B cells to multiply * Cause cell-mediated immune response * Stimulate macrophages to congregate at site of infection * Cause Humoral immune response The image displays the roles of helper T cells. Helper T cells, through their secretion of lymphokines and interaction with other cells of the immune system, participate in every aspect of the immune response. **Thanks for your attention**