PBS 803 - Class #2 Introduction to the Immune System part II Suggested reading: Abbas, pgs. 15-25, 27-30 Learning Objectives Compare and contrast the maturation of B and T lymphocytes Compare and contrast the function of primary and secondary lymphoid tissues Describe the role of the lymphatic system in the transport of antigen and immune cells in the body. Discuss the location and function of secondary lymphoid tissues such as the lymph nodes, the spleen and mucosal-associated-lymphoid tissues Explain the function of the secondary lymphoid organs in trapping and processing of antigens. List the phases of the adaptive immune response recognition, activation, antigen elimination, contraction and memory. Compare and contrast humoral and cell-mediated immunity with respect to the cells involved, and the benefits of each with regarding to maintaining health. Describe the concept of innate pattern recognition of microbes by cells of the innate immune system
Abbas Figure 1-10. Maturation of lymphocytes. Lymphocytes develop from precursors in the generative lymphoid organs (bone marrow and thymus). Mature lymphocytes enter the peripheral lymphoid organs, where they respond to foreign antigens and recirculate in the blood and lymph. Some immature B cells leave the bone marrow and complete their maturation in the spleen (not shown). Abbas Fig. 1-13 Distribution of lymphocytes in lymphoid organs and other tissues. Approximate numbers of lymphocytes in different organs of healthy adults are shown.
The sites of lymphoid tissues in the body are shown in the figure below. The bone marrow and the thymus are the primary lymphoid tissues (denoted in red within the figure below), while other secondary lymphoid tissues include the spleen and lymph nodes (denoted in yellow within the figure below). There are also other discrete collections of lymphoid cells in the body such as the tonsils, adenoids (pharyngeal tonsils) and Peyer s patches in the small intestine. Pathogens can enter the blood directly, as occurs when blood-feeding insects transmit disease. Also, if lymph nodes draining infected tissue have failed to remove all microorganisms from the lymph, then pathogens can return to the blood. The spleen is the lymphoid organ that serves as a filter for the blood. One purpose of the filtration is to remove damaged or senescent red cells; the second function of the spleen is that of a secondary lymphoid organ that defends the body against blood-borne pathogens. Of note, blood borne pathogens are captured by antigen presenting cells (APC s) located in the spleen. The thin branching lines in the figure on page 4 are the lymphatic system. Lymphatic vessels collect interstitial fluid and carry it (lymph) via a system of afferent vessels into regional lymph nodes. As the lymph passes through these nodes, APC s located there are exposed to antigens that may have originally entered into tissues. Lymph leaves the nodes via efferent vessels, which eventually drain back into the blood by way of the thoracic duct and the left subclavian vein. Parham Fig. 1.19 The sites of the principal lymphoid tissues within the human body. Lymphocytes arise from stem cells in the bone marrow. B cells complete their maturation in the bone marrow, whereas T cells leave at an immature stage and complete their development in the thymus. The bone marrow and the thymus are the primary lymphoid tissues and are shown in red. The secondary lymphoid tissues are shown in yellow, and the thin black branching lines are the lymphatics. Plasma that has leaked from the blood is collected by the lymphatics as lymph and is returned to the blood via the thoracic duct, which empties into the left subclavian vein.
Abbas Figure 01-14. Morphology of lymph nodes. A, Schematic diagram shows the structural organization of a lymph node. B, Light micrograph shows a cross section of a lymph node with numerous follicles in the cortex, some of which contain lightly stained central areas (germinal centers). Abbas Figure 01-15. Morphology of the spleen. A, Schematic diagram shows a splenic arteriole surrounded by the periarteriolar lymphoid sheath (PALS) and attached follicle containing a prominent germinal center. The PALS and lymphoid follicles together constitute the white pulp. B, Light micrograph of a section of spleen shows an arteriole with the PALS and a follicle with a germinal center. These are surrounded by the red pulp, where old or damaged erythrocytes (red blood cells) are removed from circulation. which is rich in vascular sinusoids.
Abbas Fig. 01-16. Mucosal immune system. Schematic diagram of the mucosal immune system uses the small bowel as an example. Many commensal bacteria are present in the lumen. The mucus-secreting epithelium provides an innate barrier to microbial invasion (discussed in Chapter 2). Specialized epithelial cells, such as M cells, promote the transport of antigens from the lumen into underlying tissues. Cells in the lamina propria, including dendritic cells, T lymphocytes, and macrophages, provide innate and adaptive immune defense against invading microbes; some of these cells are organized into specialized structures, such as Peyer s patches in the small intestine.
Abbas Figure 01-17A. Segregation of T and B lymphocytes in different regions of peripheral lymphoid organs. A, Schematic diagram illustrates the path by which naive T and B lymphocytes migrate to different areas of a lymph node. Naive B and T lymphocytes enter through a high endothelial venule (HEV), shown in cross section, and are drawn to different areas of the node by chemokines that are produced in these areas and bind selectively to either cell type. Also shown is the migration of dendritic cells, which pick up antigens from epithelia, enter through afferent lymphatic vessels, and migrate to the T cell rich areas of the node. B, In this histologic section of a lymph node, the B lymphocytes, located in the follicles, are stained green, and the T cells, in the parafollicular cortex, are stained red using immunofluorescence. The anatomic segregation of T and B cells also occurs in the spleen (not shown). Abbas Figure 01-18. Migration of T lymphocytes. Naive T lymphocytes migrate from the blood through high endothelial venules into the T cell zones of lymph nodes, where the cells are activated by antigens. Activated T cells exit the nodes, enter the bloodstream, and migrate preferentially to peripheral tissues at sites of infection and inflammation. The adhesion molecules involved in the attachment of T cells to endothelial cells are described in Chapters 5 and 6.
Parham Fig. 1.20. Lymphocyte recirculation. Small lymphocytes are unique among blood cells in traveling through the body in the lymph as well as the blood. That is why they were named lymphocytes. Lymphocytes leave the blood through the walls of fine capillaries in secondary lymphoid organs. A lymph node is illustrated here. After spending some time in the lymph node, lymphocytes leave in the efferent lymph and return to the blood at the left subclavian vein. If a lymphocyte in a lymph node encounters a pathogen to which its cell-surface receptor binds, it stops recirculating. Parham Fig. 1.21 Circulating lymphocytes meet lymphborne pathogens in draining lymph nodes. Lymphocytes leave the blood and enter lymph nodes, where they can be activated by pathogens in the afferent lymph draining from a site of infection. The circulation pertaining to a site of infection in the left foot is shown here. When activated by pathogens, lymphocytes stay in the node to divide and differentiate into effector cells. If lymphocytes are not activated, they leave the node in the efferent lymph and are carried by the lymphatics to the thoracic duct (see Figure 1.19), which empties into the blood at the left subclavian vein. Lymphocytes recirculate all the time, irrespective of infection. Every minute, 5 10 6 lymphocytes leave the blood and enter secondary lymphoid tissues.
Abbas Fig. 1-19 Phases of adaptive immune response. An adaptive immune response consists of distinct phases; the first three are recognition of antigen, activation of lymphocytes, and elimination of antigen (effector phase). The response declines as antigenstimulated lymphocytes die by apoptosis, restoring the baseline steady state called homeostasis, and the antigen-specific cells that survive are responsible for memory. The duration of each phase may vary in different immune responses. These principles apply to both humoral immunity (mediated by B lymphocytes) and cell-mediated immunity (mediated by T lymphocytes). humoral immunity - the adaptive immune response mediated by antibodies produced by plasma cells, is principle mechanism of defense against extracellular microbes and toxins cell mediated immunity the adaptive immune response mediated by T lymphocytes, serves as a defense mechanism against intracellular microbes in addition to unhealthy host cells.
Introduction to Innate Immunity As described in Abbas Fig. 1-3, the innate immune system provides an initial defense against microbes, as adaptive (or acquired) immunity typically requires up to 4-5 days to be effective. Cells of the innate immune system are essential for the initial protective inflammatory responses against invading organisms, and for the communication to the adaptive immune system regarding the presence of infection. Receptors used in innate immunity are confined to molecules typically associated with pathogens, and are neither strain nor pathogen specific. Recognition of microbial pathogens is mediated by pattern recognition receptors. These receptors recognize specific pathogen-associated molecular motifs/patterns (PAMPs). For example, lipopolysaccharide (LPS) is a PAMP characteristic of Gram-negative bacteria. Upon binding of the pathogen associated ligands, these receptors of innate immune cells activate a cascade of intracellular events resulting in the production of a large array of effectors molecules, including pro-inflammatory mediators. Among these mediators, the cytokines play an essential role in orchestrating the responses designed to eradicate the pathogens. One innate immune cell typically contains many pattern recognition receptors. In contrast to cells of innate immunity, cells of adaptive immunity (e.g. B-cells and T-cells) recognize pathogens by very specific receptors. Each B- or T-cell can only recognize one specific structure on the pathogen. The generation of these B-cell and T-cell receptors will be discussed later in the course, yet it involves a unique mechanism for recombining DNA, the genes for these B-cell and T-cell receptors are not inherited in the germline. Abbas Figure 02-01. Specificity and receptors of innate immunity and adaptive immunity. This figure summarizes the important features of the specificity and receptors of innate and adaptive immunity, with select examples illustrated. Ig, Immunoglobulin (antibody); TCR, T cell receptor.