2-The Cells and Organs of the Immune System.pdf

Lecture 2: The Cells and Organs of the Immune System IMMC  Objectives Differentiate between primary and secondary lymphoid organs. Describe the general organization found in the lymph node and spleen, and the predominant cells...

Lecture 2: The Cells and Organs of the Immune System IMMC  Objectives Differentiate between primary and secondary lymphoid organs. Describe the general organization found in the lymph node and spleen, and the predominant cells in each area. Describe the cells of the immune system and their functions. Differentiate between T and B lymphocytes in terms of site of maturation. Explain what a cluster of differentiation (CD) is. Identify the immune cells by their characteristic marker, eg. CD19 (B cell) CD3 (T cell) & CD56 (NK cell).  Introduction The immune system defends against pathogens through innate and adaptive mechanisms. These mechanisms are conducted by complex network of cells, tissues, and organs that work together to protect the body. Both innate and adaptive immune responses depend upon the activities of white blood cells which contain of immune cells. These cells originate in the bone marrow then migrate to guard peripheral tissues. Some reside in tissues and some circulate in the blood or lymph.  2º Major Immune Tissues: 2º Lymphoid Organs 1º 2º 2º Primary Lymphoid Tissues 2º Cells originate or mature 2º Secondary Lymphoid Tissues 2º Cells are maintained and 1º initiate immune responses 4  Primary Lymphoid Organs: ▪ Bone marrow and thymus are primary sites for immune cell development and maturation.​ Bone Marrow ▪ A source of all hematopoietic progenitor (stem) cell ▪ Site of Production of T lymphocyte and B lymphocyte ▪ Site of maturation of B lymphocytes 5 Kuby Immunology (8th ed)  Thymus ▪ The site of T cell development and maturation. ▪ It gradually enlarges during childhood but after puberty it undergoes a process of involution (it becomes smaller) ▪ The thymus is arranged into an outer cortex and an inner medulla. ▪ Immature T-cells in the cortex ▪ Mature T cells are in the medulla 6 Kuby Immunology (8th ed)  Secondary Lymphoid Organs ▪ Also known as the peripheral lymphoid organs or tissues. ▪ Composed of aggregations of lymphocytes in a framework of non- leukocytes stromal cells ▪ Mostly contains resident macrophages and dendritic cells. ▪ Naïve lymphocytes re-circulate between the blood and these organs until they encounter their specific antigen. ▪ The site of lymphocyte activation by an antigen. ▪ It is the cite where adaptive immune responses are initiated.  2º Major Immune Tissues: 2º Secondary Lymphoid Organs 1º ▪ Secondary Lymphoid Tissues 2º ▪ Spleen 2º ▪ Lymph nodes ▪ Mucus Associated Lymphoid Tissue (MALT) ▪ Lymph nodes 2º ▪ Tonsils 2º ▪ Adenoids ▪ Gut Associated Lymphoid Tissue (GALT) ▪ Peyer’s patches ▪ Mesenteric lymph nodes 2º ▪ Appendix 1º ▪ Skin Associated Lymphoid Tissue (SALT) ▪ Bronchus Associated Lymphoid Tissue (BALT) ▪ Function: Cells are maintained and initiate immune responses 8  Spleen ▪ Mainly regulates red blood cell flow and fate, and contain germinal centers which regulating an immune response. ▪ Germinal centers form in follicles during immune responses, as seen in lymph nodes. ▪ The marginal zone (MZ) acts as a cellular border between blood and the spleen's white pulp, housing specific immune cells. ▪ MZ is crucial for trapping blood-borne pathogens and is inhabited by unique dendritic cells, macrophages, and MZ B cells. ▪ Naïve B cells and T cells in the spleen encounter antigens, leading to immune activation. ▪ Activated CD4+ T cells helps B cells and CD8+ T cells, triggering migration back to follicles to create germinal centers. ▪ Germinal center B cells evolve into memory or plasma cells, spreading to various tissues, including bone marrow.  Lymph Nodes ▪ Unlike the spleen, which regulates red blood cell flow and fate, lymph nodes are fully committed to regulating an immune response. ▪ Encapsulated, bean-shaped structures ▪ They are networks of stromal cells (i.e., support tissue) packed with lymphocytes, macrophages, and dendritic cells. ▪ Interconnected by a system of lymphatic vessels. ▪ Organized lymphoid structure to encounter antigens that enter the tissue spaces.  Lymph Node Function and Immune Cell Activation ▪ Naïve T Lymphocyte Navigation ▪ Entry through high endothelial venules (HEVs), navigating MHC-peptide combinations presented by antigen-presenting cells (APCs) in the T-cell zone (paracortex). ▪ Immune Cell Activation ▪ T cells bind specific MHC-peptide combinations, initiating proliferation and differentiation into effector cells (CD8 + killers and CD4+ helpers). ▪ B cells activated in follicles by direct antigen recognition and helper T cell interaction, differentiating into antibody- secreting plasma cells. 11 Kuby Immunology (8th ed)  Mucus Associated Lymphoid Tissue (MALT) ▪ MALT organs are covered by epithelial layers, like the skin, guarding against pathogen entry. ▪ These layers play a key role in innate immunity. ▪ Beyond physical barriers, they include T-cell zones and lymphoid follicles, similar to the spleen and lymph nodes. ▪ They actively combat pathogens by releasing cytokines, chemokines, and antimicrobial substances. Kuby Immunology (8th ed)  Lymphatic System ▪ Site of antigen presentation. ▪ Immune cell traffic via blood and lymphatic systems. ▪ Endothelial and innate immune cells recruit white blood cells to infected tissues. ▪ White blood cells enter tissues from blood, guided by chemokines to infection sites. ▪ Exclusive access to the lymphatic system for white blood cells. ▪ Secondary lymphoid tissues located along lymphatic vessels. ▪ Lymphatic vessels return seeped fluid to the circulatory system, preventing lymphedema. ▪ Immune cell navigation through lymph, blood, and tissues is directed by chemokines, secreted by various cell types. Kuby Immunology (8th ed)  Hematopoiesis: The Origin of Immune Cells Hematopoiesis is the process of blood cell formation from hematopoietic stem cells (HSCs). HSCs differentiate into myeloid and lymphoid lineages. Critical for the continuous supply of immune cells. Kuby Immunology (8th ed) 15  Cells of the Immune System: Myeloid Lineage ▪ Neutrophils: ▪ The most abundant type of white blood cells ▪ First responders to microbial infection ▪ Capable of engulfing pathogens through phagocytosis. ▪ Monocytes/Macrophages: ▪ Monocytes circulate in the blood and differentiate into macrophages upon entering tissues. ▪ Phagocytic. ▪ Resident in most the tissues, self-renewal (long lived) ▪ They have microbiocidal activity (degradative enzymes, nitrogen and oxygen free radical) ▪ Primary antigen-presenting cells to T cells. ▪ Releasing cytokines to regulate immune responses. Kuby Immunology (8th ed)  Cells of the Immune System: Myeloid Lineage ▪ Dendritic Cells: ▪ Phagocytic ▪ They have long finger-like processes (dendrities) ▪ They migrate from the blood to the lymph nodes where they activate T lymphocytes ▪ Primary antigen-presenting cells to T cells. Kuby Immunology (8th ed)  Cells of the Immune System: Myeloid Lineage ▪ Mast Cells: ▪ Present in many tissues such as the skin. ▪ Mast cells are like basophiles, they play a major role allergic responses. ▪ They play a role in responses against parasitic worms. ▪ Their granules contain allergic substances such as histamine. ▪ Express IgE receptors (FcεRI) ▪ Eosinophils and Basophils: ▪ Eosinophils: involved in combating multicellular parasites and allergic reactions. ▪ Basophils: play roles in allergic responses by releasing histamine and other mediators. Kuby Immunology (8th ed)  Cells of the Immune System: Lymphoid Lineage ▪ Lymphoid lineage consists of B cells, T cells, and NK cells. ▪ Innate Lymphocytes Cells (NK cells) are involved in innate immunity, targeting virus-infected and tumor cells. ▪ T cells are central to cell-mediated immunity and include: ▪ T-helper, T-cytotoxic, and T-regulatory subtypes. ▪ B cells are responsible for antibody-mediated (humoral) immunity.  Natural Killer (NK)Cells ▪ NK Cells ▪ Comprise 5% to 10% of lymphocytes in human peripheral blood. ▪ Role in Immunity ▪ Provide first line of defense against pathogens. ▪ Active in skin and mucosal tissues. ▪ Targets include virus-infected or tumor cells. Kuby Immunology (8th ed)  T Cells and Their Subtypes ▪ T cells: They mature in the thymus and mediate T-cell mediated immunity. ▪ Helper T cells (CD4+): ▪ Help in activating B cells and macrophages. ▪ Target cells bearing antigenic peptides complexed with a MHC class II molecule. ▪ T helper 1 (Th1): ▪ Enhances the cytotoxic immune response against intracellular pathogens ▪ T helper 2 (Th2): ▪ Enhances B cell production of IgE and the immune response to pathogenic worms. ▪ T helper 17 (Th17): ▪ Enhances an inflammatory immune response against some fungi and bacteria ▪ Secrete IL-17 Kuby Immunology (8th ed)  T Cells and Their Subtypes ▪ T cells: They mature in the thymus and mediate T-cell mediated immunity. ▪ Cytotoxic T cells (CD8+): ▪ Destroy infected with intracellular pathogens (such as viral infections) or malignant cells. ▪ Target cells bearing antigenic peptides complexed with a MHC class I molecule. ▪ Regulatory T cells (CD25+): ▪ Modulate the immune response, suppress autoimmune activities. ▪  T cells: ▪ Present mainly in the gut Kuby Immunology (8th ed)  B Cells: Antibody Production ▪ B cells: They mature in the bone marrow and Mediate in Humoral immunity. ▪ Mostly require T cells activation. ▪ Sometimes, they can be activated independently from T cells. ▪ Activation leads to differentiation into plasma cells, which produce antibodies. ▪ They recognize specific antigens via B-cell receptors (BCRs). ▪ They are antigen presenting cells. Kuby Immunology (8th ed)  Cluster of Differentiation (CD) Cell Type Cluster of Differentiation CD3+, CD4+, (CD8-) Various depending on function T Helper Cells (e.g., Th1: CXCR3, Th2: CCR3, Th17: CCR6) Cytotoxic T Cells CD3+, CD8+, (CD4-) Regulatory T Cells CD3+, CD4+, CD25+, FoxP3+ B Cells CD19+, CD20+, CD21+, CD22+ Natural Killer Cells CD16+, CD56+ (low levels of CD3) Macrophages CD11b+, CD14+, CD68+ Eosinophils CD11b+, CD11c+, Siglec-8+ Basophils CD123+, HLA-DR-, CD11b+, CD11c- CD117+, FcεRI+ (not CD markers but characteristic Mast Cells features) Neutrophils CD11b+, CD16+, CD66b+ Dendritic Cells CD11c+, HLA-DR+, CD123+, CD207+ Conclusion 25  Clinical Relevance ▪ Diagnosis of Immune Disorders: ▪ Autoimmune Diseases: CD4/CD8 ratios important in diagnosing conditions such as HIV/AIDS and autoimmune diseases. ▪ Hematological Malignancies: Detection of select Cluster Differentiation (CD) important in diagnosis, CD19 for B-cell lymphomas and CD3 for T-cell leukemias. ▪ Immunotherapy Applications: ▪ Cancer Immunotherapy: CAR-T cell therapy targets cancers like lymphoma. ▪ Autoimmune Disorders: Therapies modulating T cells treat lupus and Crohn’s disease. ▪ Vaccine Development: ▪ Infectious Diseases: Lymphoid organ knowledge enhances vaccines for flu and COVID-19. ▪ Transplantation Medicine: ▪ Stem Cell Therapy: Hematopoietic Stem Cell Transplantation (HSCT) effective in treatments of conditions like leukemia and severe combined immunodeficiency (SCID) 26 Thank you 27