The Immune System – Anatomy and Physiology BCCM dentistry.pptx

The Immune System – Anatomy and Physiology

1. The Immune System – Anatomy and Physiology

2. Objectives

3. The Immune Response R esponse generated against a potential pathogen P athogen, is rapidly mobilized at the initial site of infection but lacks immunologic memory and is called innate immunity The second defense system is called adaptive immunity Adaptive immunity can specifically recognize and destroy the pathogen because lymphocytes carry specialized cellular receptors and produce specific antibodies. A protein that is produced in response to a particular pathogen is called the antibody , and the substance that induces the production of antibodies is called the antigen .

4. Innate Immunity Innate immunity is an immediate response to a pathogen that does not confer long-lasting protective immunity. It is a nonspecific defense system and includes barriers to infectious agents, such as the skin (epithelium) and mucous membranes. It also includes many immune components important in the adaptive immune response, including phagocytic cells, natural killer (NK) cells, toll-like receptors (TLRs), cytokines, and complement.

5. Barrier Functions of Innate Immunity E pithelial cell layer Defensin are positively charged peptides located primarily in the GI and lower respiratory tracts that create holes in bacterial cell walls Mucus Effect of the chemical environment

6. Mechanisms of Innate Immunity Microbial Sensors There are three major groups of microbial sensors: TLRs NOD-like receptors (NLRs) RIG-1- like helicases MDA-5

7. Cellular Components and Phagocytosis Phagocytes include: monocytes and macrophages granulocytes , including neutrophils , eosinophils , and basophils ; dendritic cells

8. Cellular Components and Phagocytosis Phagocytes include: monocytes and macrophages granulocytes , including neutrophils , eosinophils , and basophils ; dendritic cells

9. Cellular Components and Phagocytosis Phagocytes include: monocytes and macrophages granulocytes , including neutrophils , eosinophils , and basophils ; dendritic cells

10. Natural Killer Cells are large, granular lymphocytes morphologically related to T cells, which make up 10–15% of blood leukocytes. NK cells contribute to innate immunity by providing protection against viruses and other intracellular pathogens. NK cells have the ability to recognize and kill virus-infected cells and tumor cells.

11. Complement System

12. Cytokines lymphokines (lymphocyte-derived), monokines (monocyte-derived), and several other polypeptides that regulate immunologic, inflammatory, and reparative host responses Short-acting Interleukins mediate communications between leukocytes

13. Cytokines Cytokines that mediate innate (natural) immunity. IL-1, TNF (tumor necrosis factor, also called TNF-α), type 1 interferons, and IL-6 Some cytokines, such as IL-12 and IFN-γ, are involved in both innate and adaptive immunity against intracellular microbes Cytokines that regulate lymphocyte growth, activation, and differentiation. IL-2, IL-4, IL-12, IL-15, and transforming growth factor-β (TGF-β). Other cytokines in this group, such as IL-10 and TGF-β, down-regulate immune responses.

14. Cytokines Cytokines that activate inflammatory cells. IFN- γ, which activates macrophages IL-5, which activates eosinophils TNF and lymphotoxin (also called TNF- β), which induce acute inflammation by acting on neutrophils and endothelial cells. Cytokines that affect leukocyte movement are also called chemokines Cytokines that stimulate hematopoiesis . colony-stimulating factors (CSFs) GM-CSF and G-CSF

15. Cytokines Properties: Many individual cytokines are produced by several different cell types. The actions of cytokines are pleiotropic , meaning that any one cytokine may act on many cell types and mediate many effects Cytokines are also often redundant, meaning that different cytokines may stimulate the same or overlapping biologic responses. Cytokines mediate their effects by binding to specific high-affinity receptors on their target cells.

16. Cytokines Cytokines induce their effects in three ways: They act on the same cell that produces them ( autocrine effect), such as occurs when IL-2 produced by antigen-stimulated T cells stimulates the growth of the same cells They affect other cells in their vicinity ( paracrine effect), as occurs when IL-7 produced by bone marrow or thymic stromal cells promotes the maturation of B-cell progenitors in the marrow or T-cell precursors in the thymus, respectively; They affect many cells systemically ( endocrine effect), the best examples in this category being IL-1 and TNF, which produce the systemic acute-phase response during inflammation.

17. Adaptive Immunity The adaptive immune response involves antibody-mediated and cell-mediated immune responses. Unlike innate immunity, adaptive immunity is highly specific, has immunologic memory, and can respond rapidly and vigorously to a second antigen exposure

18. T Lymphocytes Thymus-derived lymphocytes Mature T-cells are found in the blood, T-cell zones of peripheral lymphoid organs ( paracortical areas of lymph nodes and periarteriolar sheaths of the spleen. constitute 60% to 70% of lymphocytes

19. Source: Robbins and Cotran Pathologic Basis of Disease.

20. T Lymphocytes Each T cell is genetically programmed to recognize a specific cell-bound antigen by means of an antigen-specific T-cell receptor (TCR).

21. T Lymphocytes αβ TCR Found in 95% of T-cells recognize peptide antigens that are displayed by a major histocompatibility complex (MHC) molecules on the surfaces of antigen-presenting cells. γδ TCR recognize peptides, lipids, and small molecules, without a requirement for display by MHC proteins They tend to aggregate at epithelial surfaces, such as the mucosa of the respiratory and GI tracts, which suggest that these cells are sentinels that protect against microbes that try to enter through these epithelia their precise functions are not known. NK-T cells T-cells that express markers similarly found on NK cells express a very limited diversity of TCRs recognize glycolipids that are displayed by the MHC-like molecule CD1 functions are also not well-defined

22. T Lymphocytes CD4 Expressed in approximately 60% of T-cells Bind to Class II MHC molecules on antigen-presenting cells CD8 Expressed in approximately 30% of T-cells Bind to Class I MHC molecules

23. Source: Robbins and Cotran Pathologic Basis of Disease.

24. T Lymphocytes CD4+ T cells Master regulator Influence functions of other cells of the immune system Two subtypes: T-helper-1 (T H 1) – synthesizes and secretes IL-2 and INF γ T-helper-II (T H 2) – IL-4 which is involved in synthesis of IgE , and IL-5 involved in activation of eosinophils CD8+ T cells Function mainly as cytotoxic cells to kill other cells Can also secrete cytokines, primarily of T H 1 type.

25. B Lymphocytes Develop from immature precursors in the bone marrow Mature B-cells constitute 10-20% of the circulating peripheral lymphocyte population Also present in peripheral lymphoid tissues In lymph nodes, they are found in superficial cortex In spleen, they are found in the white pulp B-cell zones of lymphoid organs - follicles

26. B Lymphocytes Immunoglobulin M ( IgM ) and IgD , present on the surface of all naive B cells, constitute the antigen-binding component of the B-cell receptor complex Source: Robbins and Cotran Pathologic Basis of Disease 7 th ed.

27. B Lymphocytes

28. Macrophages Involved in the induction and effector phase of immune responses Macrophages that have phagocytosed microbes and proteins process the antigens and present peptide fragments to T cells. Activated by T H 1, which enhances its microbicidal properties and augments their ability to kill tumor cells. Phagocytose microbes that are opsonized by IgG or C3b.

29. Dendritic Cells 2 types: Interdigitating dendritic cells Located under the epithelia and in interstitia of tissues Immature dendritic cells- Langerhans cells express many receptors for capturing and responding to microbes (and other antigens), including TLRs and mannose receptors express the same chemokine receptor as do naive T cells and are thus recruited to the T-cell zones of lymphoid organs express high levels of MHC class II molecules as well as the costimulatory molecules B7-1 and B7-2 possess all the machinery needed for presenting antigens to and activating CD4+ T cells

30. Dendritic Cells 2 types: Follicular dendritic cells present in the germinal centers of lymphoid follicles in the spleen and lymph nodes bear Fc receptors for IgG and receptors for C3b and can trap antigen bound to antibodies or complement proteins presenting antigens to B cells and selecting the B cells that have the highest affinity for the antigen, thus improving the quality of the humoral immune response

31. Source: Robbins and Cotran Pathologic Basis of Disease.

32. Histocompatibility Molecules The principal physiologic function of the cell surface histocompatibility molecules is to bind peptide fragments of foreign proteins for presentation to antigen-specific T cells. Major Histocompatibility Complex Chromosome 6 Human Leukocyte Antigen Complex (HLA)

33. Histocompatibility Molecules Three Categories: Class I and Class II genes encode cell surface glycoproteins involved in antigen resentation Class III genes encode components of the complement system

34. HLA and Disease Association The diseases that show association with the HLA locus can be broadly grouped into the following categories: Inflammatory diseases , including ankylosing spondylitis and several postinfectious arthropathies, all associated with HLA-B27 Inherited errors of metabolism , such as 21-hydroxylase deficiency (HLA-BW47) and hereditary hemochromatosis (HLA-A) Autoimmune diseases , including autoimmune endocrinopathies, associated mainly with alleles at the DR locus.

35. HLA and Disease Association

36. References Jawetz , Melnick, & Adelberg's Medical  Microbiology . 23rd ed. New York, N.Y.: Lange Medical Books/McGraw-Hill, Medical Pub. Division, 2004. Robbins , Stanley L., eds.  Robbins  Basic  Pathology . Philadelphia, PA : Elsevier/Saunders, 2020