Introductory Immunology 2024 PDF

Introductory Immunology Shemse Sebre (BSc, MSc, PhD fellow) DMIP, 2024 1/22/2025 1 Outline Introduction to Immunology Innate immunity Adaptive immunity (T-cell and B-cell) Cytokine APCs Complement system Immunopatholog...

Introductory Immunology Shemse Sebre (BSc, MSc, PhD fellow) DMIP, 2024 1/22/2025 1 Outline Introduction to Immunology Innate immunity Adaptive immunity (T-cell and B-cell) Cytokine APCs Complement system Immunopathology Conclusion 2  Introduction ❑ Immunology: study of host defense mechanisms ❑ Immunity: ability of host to protect itself against pathogenic foreign organisms ❑ Immune system comprises tissues, cells & molecules which mount immune response 3  Types of Immune System Natural (innate) immune system Immune system consist Skin, tears, saliva, mucus, acids, etc. Cellular components (APCs, T, B, NK -cell) Property of all living creatures Molecular components (Antibodies, cytokine, Adaptive (acquired) immune system complement) Specialist cells, cytokines, antibodies Specific and has ‘memory’ Specialized mucosal lymphoid tissue 4  Two Major Kinds of Defense Immune system consist Cellular components Molecular components Phagocytosis PMNs NK cell MNs 5  Immunogenicity and Antigenicity ❑ Immunogenicity: capacity to induce an immune response by foreign, complex and high molecular weight compounds, mostly proteins. ❑ Antigenicity is the ability to bind to Ig(s) or immune cells; an immune response may not arise. ❑ All immunogens are antigens but all Ag’s need not necessarily be immunogens. ❑ Haptens: carrier conjugate 6  1. Innate Immune System A reliable mean of protecting host in first instance(1st line) against many extracellular organisms Not dependent on prior exposure to a foreign invader Natural or native It is a property of every living organism. Unable to deal with all intracellular organisms (e.g., protozoa, viruses & certain bacteria are not killed). Non- specific, has no memory involved 7  Components of Innate Immune System ❑ Non-cellular ✓ Physio-chemical barriers (Skin, mucus, cilia) ✓ Molecules normally present in body fluids e.g. lysozyme, complement, antiproteases. ❑ Cellular ✓ Phagocytic & cytotoxic cells (neutrophils, macrophages, natural killer cells). 8 Table : Characteristics and function of cells involved in innate immunity Exterior defense 0.2% HCL 10 Table: Summary of non-specific host-defense MOA for barriers of innate immunity  2. Acquired Immune System ▪ Specific and has immunologic memory ✓ Dedicated immune cells - lymphoid cells (lymphocytes) ✓ Molecules that specifically counteract antigens (antibodies or immunoglobulins) ▪ Specific immune systems associated with barrier surfaces e.g. Mucosa and Gut associated Lymphoid Tissue (MALT and GALT) respectively. ▪ Lymphocyte also secrete cytokines e.g. interleukins. 13  Cont. ▪ Antigen specificity is single most important aspect of acquired immune system (mediated by lymphocytes). ▪ Each clone of a lymphoid cell responds only to a single antigen. ▪ T-cells deal with surface bound processed antigen (usually cell associated); Self-MHC restriction. ▪ B-cells deal with soluble (extracellular) native antigen. 14  Humoral and Cell-mediated Immunity Cellular Vs Non- Specific immunity is cellular (humoral) termed humoral when antibodies are involved in removing antigen. Cell mediated when T- cells & macrophages are involved in pathogen clearance 15  16 Fig: Major tissue of the immune system  Active and Passive Immunity ❑ Immunity after infection is termed active immunity (because the host has responded actively to the stimulus). ❑ Immunity may be transferred passively by antibodies or cells (breast milk, vaccination, maternal IgG ab’s, through placenta antivenom to snake venom). ❑ Vaccination may be passive (using Ig) or active (using antigen or attenuated organism, toxoid) 17 Passive vs. active immunization  Primary Immune Response Development of acquired immunity begins Afferent phase: Trapping and capture of Ag’s by DC’s (APCs). T-cell transformation from a resting (naive) to an active state. Effector phase: induction of other cells (B-cells & macrophages) by active T-cells secreting cytokines such as IL-2,IL-4,IL-5 19  Secondary Immune Response ❖ Accompanied by appearance Ag-specific T-cells (Th cells and CTL’s) & Ig-secreting B-cells ❖ Response on second (and subsequent) exposure to same Ag ❖ Ag-specific memory T & B-cells are recruited much sooner & more efficiently. ❖ Ig levels are consequently much higher 20 Abs Response After Exposure to Ags 21  T-Cells and CMI T cells develop from stem cells in BM Mature in thymus gland Migrate to lymphoid organs. Key cellular component of immunity Ag receptor that recognizes and reacts to a specific intracellular Ag via T cell receptor (TCR). TCR only recognize Ags combined with Major Histocompatibility Complex (MHC) proteins on surface of cells. MHC Class I: Found on all nucleated cells MHC Class II: Found on phagocytes, B cells and DC’s. 22 T Cells Only Recognize Ag Associated with MHC Molecules on Cell Surfaces 23  Con.. Clonal selection increases number of effector T cells and destroy invader. T cells regulate proliferation and activity of other cells of the immune system: ✓ B cells, macrophages, neutrophils, etc. Defense against: Bacteria ,Viruses, Fungi, protozoa, and helminths Cancer cells & Transplanted tissue CMI is not transferred to fetus (no passive immunity) 24  Types of T cells ❑ Helper T (CD4+ TH) Cells: central role in immune response, activate macrophages and help form CTLs. ❑ Cytotoxic T (CD8+ CTLs): destroy target cells on contact by producing perforin and granzymes that lyse an infected cells. ❑ Delayed hypersensitivity T (TD) Cells: Mostly Th and a few CTLs involved in some allergic reactions and rejection of transplanted tissue. ❑ Suppressor T (Ts) Cells: inhibit production of CTL cells to shut down immune response once they are unneeded, least they cause more damage than necessary. (Now called regulatory T cells). 25  Type of Recognition by CD4+ and CD8+ Cells CD4+ cells recognize Ags taken up by APCs which present Ag fragments on cell surface. CD4+ (Th ) cells interact directly with other cells by releasing cytokines to control development of immune response. Two types of Th cells: Th1 cells activate macrophages to destroy pathogens by phagocytosis and subsequent respiratory burst. Th2 cells help B-cells to make antibody. CD8 + cells recognize cells infected with virus, altered self cells such as tumor cells which they then kill after recognition. 26 T-cell Specific Responses 27  B-Lymphocytes ❑ Specialised cell for production of Igs after differentiation into plasma cells. ❑ Controls pyogenic bacteria (bacteria that causes pus formation). ❑ Prevents blood-borne infections ❑ Neutralize toxins produced by pathogens ❑ 12% of total lymphocytes. 28  Con. Can respond to peptide, carbohydrate & glycolipids. Usually require T-cell help to respond to Ag (interleukins) but can also recognize Ag directly through surface Ig. TD and TI antigens. B cells mature & proliferate in lymph nodes Fig. B cells activation by T-independent antigen and T-dependent Ag 29 Ag-Specific Responses of Abs Enhanced phagocytosis 30  Structural Biology of Igs ▪ 4-chain structure 2 light chains 2 heavy chains Ag Binding sites ▪ Chains linked by disulphide bonds. ▪ Chains are coiled into “domains”. ▪ 110 amino acids ▪ stabilized by intrachain disulphide bond disulphide bond ▪ Terminal domine: variable regions (Ag-Ab)-Ag specificity/Ab & Phagocyte diversity complement ▪ Constant regions: isotypes of Ig ▪ Ig fragments: Fab and Fc Activate ▪ Fc regions: isotype & so biological function (H-chain) Fig. Antibodies 31  Classes of Immunoglobulins 5 classes of Ig are: IgM IgA IgD IgG IgE 32  IgG (Immunoglobulin γ) o Neutralises toxins o Activates complement o Opsonisation o Able to cross placental barrier (only Ig that can) o Four subclasses: IgG1,IgG2,IgG3,IgG4. o Present in highest concentration in blood 33  IgA (Immunoglobulin α) o Monomeric & dimeric forms o Dimeric form is secretory IgA and is found in secretions such as tears, saliva, breast milk. o Important antiviral Ig. o signature molecule of mucosal immunity 34  IgM (Immunoglobulin μ) oPentameric oGood agglutinator oGood at activating complement oFirst class of Ab to be synthesized by B cells after exposure to an Ag. o10 Ag binding sites 35  IgE (Immunoglobulin ε) Active against parasitic infections (helminths) Fc portion binds to receptors on mast cells, basophils. Triggers mast cell degranulation Expressed in high concentrations in atopic individuals in response to allergens (pollen, animal dander). Mediate Type I hypersentivity reactions such as asthma. 36 37  Cytokines o Short-range, multifunctional, short-acting mediators of cellular activities, especially within immune system. o Released primarily by activated T-cells & other immune and non-immune cells. o Act in autocrine or paracrine manner o Classes of Cytokines (4 major): Interleukins (IL-1 to IL-12) Interferons (IF- α, IF- β & IF- γ) Colony Stimulating Factors (CSFs) Tumour Necrosis Factor(s) (TNF-α & TNF-β) 38 39  Antigen Presenting Cells (APCs) Normally, initiation of AIR does not take place at site of injury or penetration of foreign organisms. Antigen is taken up (trapped and captured) by APCs at site of inflammation and transported to regional lymph nodes and/or spleen where it is presented to T- & B- cells. MOA of APC 40  Cellular components APCs Dendritic cells: skin, lymph node and other tissues. ▪ Alveolar macrophages in lung ✓ Sentinel APCs ▪ Histiocytes in connective tissues ✓ Taking up antigen ▪ Kupffer cells in the liver ✓ Activate T-cells ▪ Mesangial cells in the kidney ▪ Microglial cells in the brain Monocytes: Circulating in Blood ▪ Osteoclasts in bone Macrophages: tissue (long-lived cells) B-cells: develop in to plasma cells, manufacture and secret antibodies  APCs… APCs examples DC Macrophage B-Cell oMacrophages & B- cells: recognize Ag through Ig oDC: process & present Ag to naive T-cells via MHC Class II. Most potent APC’s 42  Complement System o Comprises at least 9 plasma proteins & some regulatory factors, that mediate several functions of inflammatory process. o Synthesized by macrophages or hepatocytes. o usually circulate as inactive pro-enzymes o Heat labile 43  Complement Pathways Cascade of sequential activation converts each proenzyme into its active state & amplifies response. Three main pathways: Classical pathway - bound IgG, IgM Alternative pathway - certain antigens (LPS, endotoxin, etc.) Lectin pathway 44  Functions of Complement System Opsonisation: C3b Chemotaxis: C5a Acceleration of acute inflammation/ Anaphylatoxins: C3a and C5a Immune cytolysis: C5b, 6, 7, 8, 9 Virus neutralisation MAC causes killing of microbe through osmotic lysis. 45  Immunopathology Defects or malfunctions in either innate or adaptive immune response can provoke illness or disease. Such disorders are generally caused by an: Hypersensitivity reactions: overactive immune response Autoimmunity: inappropriate reaction to self or Immunodeficiency: ineffective immune responses  Deficiencies of immune response ❑ Immunodeficiency Diseases (IDD) Can be divided into two categories: I. Primary IDD Intrinsic (CGD or SCID) Identified by type, duration, and frequency of infectious diseases II. Secondary IDD External factors (viruses, malignancy, and drugs)  Int con. Conclusion Defense mechanisms Innate: Anatomic/physiologic/phagocytosis/inflammatory responses Adaptive/acquired: CMI (T-cells: Helper/cytotoxic) Vs AMI (B- cells) TCR vs BCR ▪ Type of T-cells: Conventional (CD4/CD8 αβ T cells ) vs TCR Unconventional (iNKT, MAIT cells and γδ T cells) bridge innate and adaptive immunity 48  Assignment Topics Group Types, role and recent 1 Developments in Vaccination The Role of Inflammation in 2 Infectious Diseases The Impact of Hypersensitivity 3 Reactions on Health Brief History of Immunology 4 Types of Antigens and Their Roles in 5 the Immune Response ❖ Paper submission (Via email: [email protected])- Max 10 Page ❖ Presentation (15 min each group at Seferselam campus)- Max 12 PPT ❖ Out of 20% (Write up (10), Q & A, presentation (10) ❖ Deadline submission: Dec 19, Presentation: Dec 22 (2 PM) 49 Thank You 50