Immune System (2).pptx
- 1. IMMUNE SYSTEM Dr. Saket Kumar
- 5. Innate immunity Introductio n Components • Epithelia • Neutrophils and monocytes • Dendritic cells • NK cells • Mast cells • Complement system Receptors of innate immunity (Pattern recognition receptors) • Toll like receptors • NOD like receptors • C lectin type receptors • RIG like receptors • G protein coupled receptors • Mannose receptors Reactions of innate immunity • Inflammation • Anti viral defense • Stimulate adaptive immunity
- 7. Introduction • Innate immunity is always present, ready to provide defence against microbes and to eliminate damaged cells • Does not have memory or fine antigen specificity • Innate immunity uses about 100 different receptors to recognize 1,000 molecular patterns • In contrast, adaptive immunity uses two types of receptors (antibodies and T-cell receptors, described later), each with millions of variations, to recognize millions of antigens.
- 9. Components • Epithelia • Neutrophils and monocytes • Dendritic cells • NK cells • Mast cells • Complement system
- 10. Epithelia • Provide mechanical barriers to the entry of microbes • Also produce antimicrobial molecules such as defensins
- 11. Neutrophils and monocytes • Monocytes and neutrophils are phagocytes in the blood • All tissues contain resident macrophages, the professional phagocytes of the body
- 12. Dendritic cells • Dendritic cells are involved in the initiation of innate immune responses, but, unlike macrophages, they are not key participants in the destruction of microbes • Present in epithelia, lymphoid organs • They capture protein antigens and display peptides for recognition by T lymphocytes
- 13. Natural Killer cells • Early protection against many viruses and intracellular bacteria
- 14. Mast cells • Capable of producing many mediators of inflammation
- 17. Tolllike receptors • All these receptors signal by a common pathway that culminates in the activation of two sets of transcription factors: • NF-κB – critical for the recruitment and activation of leukocytes through • synthesis and secretion of cytokines • expression of adhesion molecules • Interferon regulatory factors (IRFs) - antiviral cytokines
- 19. Reactionsof innate immunity The innate immune system provides host defence by • Inflammation • Vascular and cellular components of inflammation • Stimulate adaptive immunity
- 20. ADAPTIVEIMMUNITY
- 21. Adaptive immunity • Introductio n • Type s • Humoral • Cell mediated • Cells of adaptive immunity • Lymphocytes • T lymphocytes • B lymphocytes • Dendritic cells • Macrophage s • NK cells • Tissues of adaptive immunity • Generative lymphoid organs • Thymus • Bone marrow • Peripheral lymphoid organs • Lymphnode s • Spleen • MALT
- 23. INTRODUCTION – TYPESOFADAPTIVE IMMUNITY Humoral immunity Mediated by Blymphocytes by secreting antibodies Protect against extracellular microbes and their toxins Cell mediated immunity Mediated by Tlymphocytes Protect against intracellular pathogens
- 26. T Lymphocytes Type s Helper T cells (CD4) -stimulate B lymphocytes to make antibodies and activate other leukocytes (e.g., phagocytes) to destroy microbes -60% of all T cells Cytotoxic T cells (CD8) - kill infected cells - 30% of all T cells Regulator T cells - limit immune responses and prevent reactions against self antigens Mature T cells are found in the blood, where they constitute 60% to 70% of lymphocytes, and in T- cell zones of peripheral lymphoid organs
- 28. Introduction • Also called Human leukocyte antigens (HLA) because they were initially detected on leukocytes • Clustered on a small segment of chromosome 6 • MHC molecules are • Fundamental to the recognition of antigens by T cells; display peptide fragments of protein antigens
- 29. T ypes • Class I MHC • Display peptides from viral and tumour antigens; that are located in the cytoplasm; recognized by CD8+ T lymphocytes • Class II MHC • Present antigens that are internalized into vesicles, typically derived from extracellular microbes and soluble proteins; recognized by CD4+ T cells
- 30. Roleof MHC antigens • Organ transplantation • MHC system is highly polymorphic, meaning that there are many alleles of MHC genes (in the thousands) in humans and each individual’s alleles differ from those inherited by most other individuals in the population. • This constitutes a formidable barrier in organ transplantation and graft rejection • Autoimmune diseases • Number of autoimmune diseases are associated with the inheritance of particular HLA alleles • Immune response • Individual mounts an immune response against a protein antigen only if he or she inherits the genes for those MHC molecules that can bind peptides derived from the antigen and present it to T cells • By segregating cytoplasmic and internalized antigens, MHC molecules ensure that the correct immune response is mounted against different microbes • Allergic reactions • If the antigen is a peptide from ragweed pollen, the individual who expresses class II molecules capable of binding the antigen would be genetically prone to allergic reactions against pollen
- 32. Introduction • All adaptive immune responses develop in steps, consisting of: • Antigen recognition, activation of specific lymphocytes • Differentiation into effector and memory cells • Elimination of the antigen • Decline of the response, with memory cells being the long-lived survivors
- 36. Humoral immunity • Each plasma cell is derived from an antigen- stimulated B cell and secretes antibodies that recognize the same antigen that was bound to the BCR and initiated the response • T cell dependent response – • B cells ingest protein antigens into vesicles, degrade them, and display peptides bound to class II MHC molecules for recognition by helper T cells • T-dependent responses show features such as immunoglobulin isotype switching and affinity maturation • T cell independent response – • Many polysaccharide and lipid antigens are able to engage receptor molecules on B cell and initiate the process of B-
- 37. Wayshumoral response works an important goal of vaccination
- 38. HYPERSENSITIVITY
- 39. Hypersensitivity General features And Classification Type I • Localised reaction • Immediate reaction • Activation of TH2 Cells and Production of IgE Antibody • Sensitization and Activation of Mast Cells • Mediators of Immediate Hypersensitivit y • Late-Phase Reaction • Allergy • Systemic Anaphylaxis • CLINICAL MANIFESTATIO NS Type II • Introduction • Mechanisms • Opsonization and Phagocytosis • Inflammation • Cellular dysfunction • Examples Type III • Introduction • Immune complex diseases • Systemic Immune Complex Disease • Acute • Chronic • Morphology • Local Immune Complex Disease (Arthus Reaction) Type IV • Introduction • CD4+ T Cell–Mediated Inflammation • Responses of Differentiated Effector T Cells • Clinical Examples of CD4+ T Cell– Mediated Inflammatory Reactions • CD8+ T Cell–Mediated Cytotoxicity
- 41. General features • Hypersensitivity implies an excessive or harmful reaction to antigen • Can be elicited by • Exogenous environmental antigens – Allergy • Dust, pollens, foods, drugs, microbes, and various chemicals • Immune responses to such antigens range from itching of the skin, to potentially fatal diseases, such as bronchial asthma and anaphylaxis • Endogenous self antigens – Autoimmune diseases • Results from an imbalance between the effector mechanisms of immune responses and the control mechanisms that serve to normally limit such responses • Often associated with the inheritance of particular susceptibility genes Hypersensitivit y
- 42. Classification • TYPE I – Immediate hypersensitivity • Caused by TH2 cells, IgE antibodies, and mast cells and other leukocytes • TYPE II – Antibody mediated disorders • Secreted IgG and IgM antibodies injure cells by promoting their phagocytosis or lysis • TYPE III – Immune complex mediated diseases • IgG and IgM antibodies bind antigens usually in the circulation, and the antigen- antibody complexes deposit in tissues and induce inflammation • TYPE IV – Cell mediated immune Hypersensitivit y
- 44. Steps in Type I HS reaction
- 45. Immediate reaction • Vasodilation, vascular leakage, and depending on the location, smooth muscle spasm or glandular secretions • Within minutes after exposure to an allergen • Subside in a few hours
- 46. Late-phase reaction • Sets in 2 to 24 hours later • Without additional exposure to antigen • May last for several days • Characterized by infiltration of tissues with eosinophils, neutrophils, basophils, monocytes, and CD4+ T cells, as well as tissue destruction, typically in the form of mucosal epithelial cell damage
- 47. IMMEDIATE REACTION 1. Activation of TH2 Cells and Production of IgE Antibody
- 48. 1.Activation of TH2 Cellsand Production of IgEAntibody • Presentation of the antigen to naive CD4+ helper T cells by dendritic cells • T cells differentiate into TH2 cells • TH2 cells produce IL4 acts on B cells to stimulate class switching to IgE
- 49. IMMEDIATE REACTION 2. Sensitization and Activation of Mast Cells
- 50. 2. Sensitization andActivation of MastCells • Mast cells • They are bone marrow derived counterparts of basophils in tissues • Various mediators secreted - Vasoactive amines (Histamine) - Intense smooth muscle contraction - increased vascular permeability Lipid mediators - Leukotrienes - Increase vascular permeability - bronchial smooth muscle contraction - Prostaglandins – intense bronchospasm - Increased mucus secretion - Cytokines - TNF, IL-1, and chemokines - promote leukocyte recruitment
- 52. LATE PHASE REACTION • In the late-phase reaction, eosinophils that are recruited amplify and sustain the inflammatory response without additional exposure to the triggering antigen • TH2 cytokine IL-5 is the most potent eosinophil-activating cytokine known • Late-phase reaction is a major cause of symptoms allergic asthma • Treatment of these diseases requires the use of steroids, rather than anti-histamine drugs, which are of benefit in the immediate reaction
- 54. GENERAL FEATURES
- 55. General features • Caused by antibodies that react with antigens present on cell surfaces or in the extracellular matrix • Cause disease by destroying these cells, triggering inflammation, or interfering with normal functions • The antibodies may be • Specific for normal cell or tissue antigens (autoantibodies) • Specific to exogenous antigens, such as chemical or microbial proteins, that bind to a cell surface or tissue matrix
- 56. MECHANISMS 1. Opsonization and phagocytosis
- 57. 1. Opsonization and Phagocytosis IgG and C3b
- 58. 1. Opsonization and Phagocytosis Antibody dependent cellular cytotoxicity - ADCC • Contribution of ADCC to common hypersensitivity diseases is uncertain • Occur in the following situations • Transfusion reactions, in which cells from an incompatible donor react with and are opsonized by preformed antibody in the host • Hemolytic disease of the newborn (erythroblastosis fetalis), in which there is an antigenic difference between the mother and the fetus, and IgG antierythrocyte antibodies from the mother cross the placenta and cause destruction of fetal red cells • Autoimmune hemolytic anemia, agranulocytosis, and thrombocytopenia, in which individuals produce antibodies to their own blood cells, which are then destroyed • Drug reactions, in which adrug acts asa“hapten” by attaching to plasma membrane proteins of red cells and antibodies are produced against the
- 60. 2. Inflammation • When antibodies deposit in fixed tissues, such as basement membranes and extracellular matrix, the resultant injury is due to inflammation
- 62. 3.Cellulardysfunction • Antibodies directed against cell surface receptors impair or dysregulate function without causing cell injury or inflammation
- 63. EXAMPLES
- 66. INTRODUCTION
- 67. INTRODUCTION Immune complexes may be formed when • Antigen combines with antibody in the circulation and deposits in vessel walls • Complexes may be formed at sites where antigen hasbeen “planted” previously (called in situ immune complexes) Antigens that form immune complexes may be • exogenous, such as a foreign protein that is injected or produced by an infectious microbe • endogenous, if the individual produces antibody against self antigens (autoimmunity)
- 68. Systemicimmune complex disorders (Acute) Pathogenesis • Complement protein C3 plays an active role in Type III reaction • Serum C3 levels can be used to monitor disease activity • Protein antigen triggers an immune response that results in the formation of antibodies, typically about a week after the injection of the protein. • These antibodies are secreted into the blood, where they react with the antigen still present in the circulation and form antigen-antibody complexes • The circulating antigen- antibody complexes are deposited in various tissues • Organs where blood is filtered at high pressure to form other fluids, like urine and synovial fluid, are sites where immune complexes become concentrated and tend to deposit; hence, immune complex disease often affects glomeruli and joints. • Once immune complexes are deposited in the tissues, they initiate an acute inflammatory reaction • During this phase (approximately 10 days after antigen administration), clinical features such as fever, urticaria, joint pains (arthralgias), lymph node enlargement, and proteinuria appear • Resultant inflammatory lesion is termed vasculitis if it occurs in blood vessels, glomerulonephritis • if it occurs in renal glomeruli, arthritis if it occurs in the joints
- 69. Acute vasculitis • Necrosis of the vessel wall and intense neutrophilic infiltration • The necrotic tissue and deposits of immune complexes, complement, and plasma protein appear as a smudgy eosinophilic area of tissue destruction, termed fibrinoid necrosis
- 71. INTRODUCTION
- 72. INTR ODUC TION • The cell-mediated type of hypersensitivity is caused by inflammation resulting from cytokines produced by CD4 and CD8 T cells
- 73. CD4+ T Cell–Mediated Inflammation
- 74. CD4+T Cell–Mediated Inflammation (Delayed type Hypersensitivity -DTH) • DTH is a tissue reaction to in immune individuals • In this reaction, an antigen administered into the skin of a previously immunized individual results in a detectable cutaneous reaction within 24 to 48 hours (hence the term delayed, in contrast to immediate hypersensitivity) • Both TH1 and TH17 cells contribute to organ- specific diseases • The inflammatory reaction associated with TH1 cells is dominated by activated macrophages, and that triggered by TH17 cells has a greater neutrophil component
- 75. Stagesof CD4+TCell–MediatedInflammation APCs produce 1. IL6 – TH1 cells 2. IL1/6/23 – TH17 cells TH1 cells Secrete IFN-γ, augments the ability of macrophages to kill microorganisms TH17 cells secrete IL-17, IL-22 - recruit neutrophils and monocytes to the reaction
- 77. Tuberculin reaction (Mantoux test) • Used to check whether the individual has been previously exposed to tuberculous antigen • Intracutaneous injection of purified protein derivative (PPD, also called tuberculin), is given • In a previously sensitized individual, reddening and induration of the site appear in 8 to 12 hours, reach a peak in 24 to 72 hours, and thereafter slowly subside • Morphologically, characterized by the accumulation of mononuclear cells, mainly CD4+ T cells and macrophages, around venules, producing perivascular