Immunopathology Lecture Notes 2024-2025 PDF

Nineveh university - College of medicine Immunopathology 2024-2025 Dr. Hadeel. T. Ali. AL-Obaidy College of medicine, Nineveh university M.B.Ch.B, MS...

Nineveh university - College of medicine Immunopathology 2024-2025 Dr. Hadeel. T. Ali. AL-Obaidy College of medicine, Nineveh university M.B.Ch.B, MSc., (Path.) C.A.B. (Path.) Immunopathology Immunity means protection against diseases. Immune system is the collection of cells & molecules that are responsible for defending the body against countless pathogenic microbes in the environment. Immune response is the coordinated reaction of the cells and molecules to infectious agents. Immune System Functions The major functions of immune system are : I Recognition of self from non-self Ag II Mounting a specific response against non-self Ag III Memory of what was earlier recognized as non-self Ag IV Antibody formation V Cell-mediated reactions  While normal function of immunity is for body defense, its failure or derangement in any way results in diseases of the immune system which are broadly classified into the following Types of immunity IMMUNITY INNATE ADAPTIVE IMMUNITY IMMUNITY NATURAL ARTIFICIAL PASSIVE ACTIVE PASSIVE ACTIVE (antibody (infection ) (maternal) (immunization) transfer)  Innate (Natural/Native) Immunity General Features ❖ First line of defense ❖present by birth. ❖Provides immediate initial protection against an invading pathogen. ❖ Does not depend on the prior contact with foreign antigen or microbes. ❖ Lacks specificity, but highly effective. ❖ Triggers the adaptive immune response. ❖ No memory is seen. Major components of innate immunity ❖Epithelial Barriers : Epithelia of the skin and gastrointestinal and respiratory tracts act as mechanical barriers to the entry of microbes from the external environment, Epithelial cells also produce antimicrobial molecules such as defensins. ❖Humoral: comprised by complement. ❖Cellular: consists of neutrophils, macrophages, and natural killer (NK) cells.  Specific or adaptive immunity If the innate immune system fails to provide effective protection against invading microbes, the adaptive immune system is activated. General Features Acquired in nature Second line of defense. Takes more time to develop and is more powerful than innate immunity. Prior exposure to antigen is present. Capable of recognizing both microbial and non microbial substances. Long-lasting protection (Memory) specific  adaptive immunity has 2 main components: Humoral immunity ✓ it protects against extracellular microbes and their toxins. ✓ it is mediated by B (bone marrow–derived) lymphocytes and their secreted products, antibodies (also called immunoglobulins, Ig). Cell-mediated (or cellular) immunity it is responsible for defense against intracellular microbes and against cancers. It is mediated by T (thymus-derived) lymphocytes. ❖Both classes of lymphocytes express highly specific receptors for a wide variety of substances, which are called antigens.  ORGANS OF IMMUNE SYSTEM a) Primary lymphoid organs: The principal primary lymphoid organs are the thymus, where T cells develop, and the bone marrow, the site of production of all other blood cells, including naïve B cells. b) Secondary lymphoid organs: lymph nodes, spleen, and the mucosal and Cutaneous lymphoid tissues—are the tissues where adaptive immune responses occur. Several features of these organs promote the generation of adaptive immunity—antigens are concentrated in these organs, naïve lymphocytes circulate through them searching for the antigens, IMMUNE SYSTEM CELLS I) Lymphocytes II) Monocytes, macrophages and dendritic cells. III) Mast cells and basophils IV) Neutrophils and Eosinophils Lymphocytes ❖ CD8+ T cell: These subset of T cells have CD8 molecule and are called as cytotoxic/killer T cells. They constitute about 30% of T cells. CD8+ T cells function as cytotoxic (killer) T lymphocytes (CTLs) to destroy host cells harboring microbes and tumor cells. ❖ Regulatory T lymphocytes: suppress the immune response II. B Lymphocytes ❑ Development: ❑ Distribution: – Peripheral blood: Mature B cells constitute 10% to 20% of the circulating peripheral lymphocyte population – Peripheral lymphoid tissues: Lymph nodes (cortex), spleen (white pulp), and mucosa associated lymphoid tissues. ❑ B-cell Receptor (BCR): B cells have receptors composed of IgM and IgD on their surface and has unique antigen specificity. ❑ Functions of B cells: – Production of antibodies: The primary function of B cells is to produce antibodies. After stimulation by antigen and other signals, B cells develop into plasma cells. These cells secrete antibodies like IgG, IgM, IgD, IgA and IgE. Initially, the first antibody produced by the plasma cell is IgM and later, other antibodies like IgG, IgA etc – Antigen presenting cell: B cells also serve as APCs and are very efficient at antigen processing. Structure of Ig III. Natural Killer Cells ❑ Non-phagocytic lymphocytes also called ‘Large granular lymphocytes’ as they are morphologically larger than both T and B lymphocytes and contain azurophillic granules (which are absent in both T and B lymphocytes) ❑ Markers: They do not bear the markers for T or B cells. Two cell surface molecules, CD16 and CD56, are commonly used to identify them. ❑Comprise about 5% to 15% of human peripheral lymphoid cells. ❑ Function: kills a variety of virus-infected cells and tumor cells, without prior exposure to or activation by these microbes or tumors. They recognize abnormal cells in two ways: 1- Antibody-dependent cellular cytotoxicity (ADCC): NK cells bear (CD16) is an Fc receptor for IgG, and it confers on NK cells the ability to lyse IgG-coated target cells. 2- Perforin-granzymes system : NK cells have a variety of surface receptors for MHC (major histocompatibility complex) class I. These are activating and inhibitory receptors. ◆ Inhibitory receptors: MHC class I molecules are normally expressed on healthy/ normal host cells. NK cell inhibitory receptors recognize self–class I MHC molecules. They prevent NK cells from killing normal host cells by inhibiting the death pathway (apoptosis). ◆ Activating receptors: If the target cell with which NK cells interact, do not have MHC molecules on their surface. These activating receptors makes holes in the target cell membrane by secreting perforins and cause apoptosis of target cell. surface receptors of natural killer (NK) cells. MONOCYTES AND MACROPHAGES Circulating monocytes are immature macrophages and constitute about 5% of peripheral leukocytes. Functions of macrophages are as follows: 1. Antigen recognition 2. Phagocytosis 3. Secretory function : (i) Cytokines (ii) Secretion of proteins involved in wound healing e.g. collagenase, elastase, fibroblast growth factor, angiogenesis factor (iii) Acute phase reactants e.g. fibronectin, microglobulin, complement components. 4. Antigen presentation Soluble Mediators of Immunity Development of innate immunity and regulation of the behavior of effector immune cells all depend on the secretion of soluble molecules 1. Opsonins 2. Cytokines 3. proteins of the complement system.  1. Opsonins There are many mechanisms in which our immune system fights pathogens. One is opsonization. Opsonization: The process of recognizing and targeting invading particles for phagocytosis, by coating of pathogens, such as microbes. Opsonins: The coating materials like immunoglobulins and complements to enhance phagocytosis. 2. CYTOKINES Short-acting soluble proteins. secreted by haematopoietic and non-haematoopoietic cells in response to various stimuli. These cytokines represent the messenger molecules of the immune system and mediate communications between various cells of the immune system. Classification Most of the cytokines have a many effects and can be classified depending on their functions. I.Cytokines of Innate Immunity ❑ These cytokines are produced rapidly in response to microbes and other stimuli ❑ Mainly secreted by macrophages, dendritic cells, and NK cells ❑ Mediate inflammation and anti-viral defense ❑ These cytokines include TNF, IL-1, IL-12 and chemokines. II.Cytokines of Adaptive Immunity ❑ These cytokines are produced mainly by CD4+ T lymphocytes in response to antigen and other signals ❑ They promote lymphocyte proliferation and differentiation and activate effector cells ❑ This category include IL-2, IL-4, IL-5, IL-17, and IFN-. III.Colony-Stimulating Factors ❑ These cytokines stimulate hematopoiesis and are assayed by their ability to stimulate formation of blood cell colonies from bone marrow progenitors. ❑ They increase leukocyte numbers during immune and inflammatory responses. Function Cytokines are involved in following actions: 1. Activation of immune system 2. Inflammatory mediators 3. Regulation of cell growth Major histocompatibility complex (MHC) ❑Membrane bound proteins on the cell membrane encoded by a MHC gene. ❑They serve as peptide display molecules for recognition by T lymphocytes. ❑ histocompatibility molecules are critical to the induction of T-cell immunity. ❑In humans, the genes encoding MHC molecules are located on a short arm of chromosome 6. ❖The human major histocompatibility complex (MHC) are commonly called the human leukocyte antigen (HLA) complex is the name of cluster of genes located on short arm of chromosome 6 (6p) ❖They were named HLA because in humans MHC-encoded proteins were initially detected on leukocytes by the binding of antibodies Importance of MHC: 1) in organ/tissue transplantation 2) HLA is linked to many autoimmune diseases. Classification of MHC Molecules Class I MHC Molecules ❑ They are the products of MHC class I genes and are expressed on all nucleated cells and platelets (except erythrocytes and trophoblasts). ❑They are encoded by three closely linked loci, designated HLA-A, HLA- B, and HLA-C. ❑ Functions: Products of MHC class I gene are integral participants in the immune response to intracellular infections, tumors, and allografts. ❑Class I molecules interact with CD8+ T lymphocytes during antigen presentation and are involved in cytotoxic reactions. CD8+ T lymphocytes recognize antigens only in he context of self- class I molecules. Class II MHC Molecules ❑They are encoded in a region called HLA-D, which has three sub-regions: HLA- DP, HLADQ, and HLA-DR. ❑Class II antigens are expressed only on professional antigen presenting cells (B lymphocytes, monocytes/macrophages, Langerhans’ cells, dendritic cells) and activated T cells. ❑Function: This locus contains genes that encode many proteins involved in antigen processing and presentation. The class II–peptide complex is recognized by CD4+ T cells (function as helper cells) and these CD4 molecule acts as the co-receptor. ❑ CD4+ T cells can recognize antigens only in the context of self–class II molecules. Class III MHC Molecules ❑Their gene encode components of the complement system, cytokines, and some proteins without apparent role in the immune system.  HLA and Disease Association Some diseases are associated with the inheritance of certain HLA alleles and these diseases can be broadly grouped into: ✓Inflammatory diseases: e.g. ankylosing spondylitis most striking associated with HLA-B27. ✓ Autoimmune diseases: e.g. autoimmune endocrinopathies associated with alleles at the DR locus. ✓Inherited errors of metabolism: e.g. hereditary hemochromatosis (HLA-A).