Immunology PDF - A Comprehensive Overview

 Immune system The daunting role of the immune system is to afford protection. It serves as a host defense system against infectious diseases and foreign (nonself) antigens. To accomplish this goal, the immune system is equipped with a rapid response mechanism,...

 Immune system The daunting role of the immune system is to afford protection. It serves as a host defense system against infectious diseases and foreign (nonself) antigens. To accomplish this goal, the immune system is equipped with a rapid response mechanism, exquisite specificity, adaptability, an intricate regulatory network, and memory. Over the past several decades, dramatic progress has taken place in the field of immunology. As a consequence, significant advances have been realized not only in the research realm but also in the diagnostic and clinical arena. These advances have allowed us to better understand how the immune system works and have provided insight into a variety of immune disorders, such as infectious diseases, allergy, autoimmunity, immunodeficiency, cancer, and transplantation. This information has led to better diagnosis, new treatment strategies, and improved management for patients with these disorders Lymphatic system consists of a fluid called lymph (LIMF =clear fluid). vessels called lymphatic vessels that transport the lymph a number of structures and organs containing lymphatic tissue, and red bone marrow, where stem cells develop into the various types of blood cells, including lymphocytes. Functions:- 1. Drains excess interstitial fluid. Lymphatic vessels drain excess interstitial fluid from tissue spaces and return it to the blood. 2. Transports dietary lipids. Lymphatic vessels transport lipids and lipid-soluble vitamins (A, D, E, and K) absorbed by the gastrointestinal tract. 3. Carries out immune responses. Lymphatic tissue initiates highly specific responses directed against particular microbes or abnormal cells. Lymphatic capillaries Lymphatic Organs & Tissues Primary lymphatic organs:- the sites where stem cells divide and become immunocompetent, that is, capable of mounting an immune response. red bone marrow (in flat bones and the epiphyses of long bones of adults) & the thymus. Secondary lymphatic organs & tissues sites where most immune responses occur lymph nodes, the spleen, and lymphatic nodules (follicles) Thymus The cortex is composed of large numbers of T cells and scattered dendritic cells, epithelial cells, and macrophages. Immature T cells (pre-T cells) migrate from red bone marrow to the cortex of the thymus, where they proliferate and begin to mature. The medulla consists of widely scattered, more mature T cells, epithelial cells, dendritic cells, and macrophages Thymus The cortex is composed of large numbers of T cells and scattered dendritic cells, epithelial cells, and macrophages. Immature T cells (pre-T cells) migrate from red bone marrow to the cortex of the thymus, where they proliferate and begin to mature. The medulla consists of widely scattered, more mature T cells, epithelial cells, dendritic cells, and macrophages  Lymph Nodes Lymph nodes - only organs that filter lymph Capsule gives off trabeculae, divides node into compartments containing stroma (reticular CT) and parenchyma (lymphocytes and APCs) subdivided into cortex (lymphatic nodules) and medulla reticular cells, macrophages phagocytize foreign matter lymphocytes respond to antigens lymphatic nodules-germinal centers for B cell activation Spleen Functions ✓ blood production in fetus ✓ blood reservoir ✓ RBC disposal ✓ immune reactions: filters blood, quick to detect antigens The Immune Response A response generated against a potential pathogen. The first line of defence, which is nonspecific to the invading pathogen, is rapidly mobilized at the initial site of infection but lacks immunologic memory and is called innate immunity The second defence system is called adaptive immunity. It is specific for the pathogen and can confer protective immunity to reinfection with that pathogen. Adaptive immunity can specifically recognize and destroy the pathogen because of lymphocytes carrying specialized cellular receptors and specific antibodies. A protein that is produced in response to a particular pathogen is called antibody , and the substance that induces the production of antibodies is called the antigen Innate immunity 1. First line: Skin and mucous membranes 2. Second line: Internal defence First line: Skin and mucous membranes PHYSICAL FACTORS ▪ Epidermis of skin → Forms a physical barrier to the entrance of microbes. ▪ Mucous membranes → Inhibit the entrance of many microbes, but not as effective as intact skin. ▪ Mucus → Traps microbes in respiratory and gastrointestinal tracts. ▪ Hairs → Filter out microbes and dust in nose. ▪ Cilia → Together with mucus, trap and remove microbes and dust from upper respiratory tract. ▪ Lacrimal apparatus → Tears dilute and wash away irritating substances and microbes. ▪ Saliva→ Washes microbes from surfaces of teeth and mucous membranes of mouth. ▪ Urine → Washes microbes from urethra. ▪ Defecation and vomiting → Expel microbes from body. First line: Skin and mucous membranes CHEMICAL FACTORS ▪ Sebum→ Forms a protective acidic film over the skin surface that inhibits growth of many microbes. ▪ Lysozyme → Antimicrobial substance in perspiration, tears, saliva, nasal secretions, and tissue fluids. ▪ Gastric juice → Destroys bacteria and most toxins in stomach. ▪ Vaginal secretions → Slight acidity discourages bacterial growth; flush microbes out of vagina Second line: Internal defence ANTIMICROBIAL SUBSTANCES Interferons (IFNs)→ Protect uninfected host cells from viral infection. Complement system → Causes cytolysis of microbes, promotes phagocytosis, and contributes to inflammation. Iron-binding proteins → Inhibit growth of certain bacteria by reducing the amount of available iron. Antimicrobial proteins (AMPs)→e.g: dermicidin, defensins, cathelicidins & cathelicidins, have broad spectrum antimicrobial activities and attract dendritic cells and mast cells Second line: Internal defence NATURAL KILLER (NK) CELLS Kill infected target cells by releasing granules that contain perforin and granzymes. PHAGOCYTES Ingest foreign particulate matter. Inflammation Confines and destroys microbes and initiates tissue repair. Fever Intensifies the effects of interferons, inhibits growth of some microbes, and speeds up body reactions that aid repair. Interferons (IFNs) Lymphocytes, macrophages, and fibroblasts infected with viruses produce proteins called interferons. Once released by virus-infected cells, IFNs diffuse to uninfected neighbouring cells, where they induce synthesis of antiviral proteins that interfere with viral replication. Although IFNs do not prevent viruses from attaching to and penetrating host cells, they do stop replication. Viruses can cause disease only if they can replicate within body cells. IFNs are an important defense against infection by many different viruses. The three types of interferon are alpha-, beta-, and gamma-IFN. Natural Killer Cells lack the membrane molecules that identify B and T cells, but they able to kill a wide variety of infected body cells and certain tumor cells. attack any body cells that display abnormal or unusual plasma membrane proteins. release perforins and granzymes Action of NK cell Fig. 21.17 21-27 Phagocytes (1)neutrophils and macrophages (2) granulocytes, including PMNs, eosinophils, and basophils (3) dendritic cells.  Inflammation a nonspecific, defensive response of the body to tissue damage. Among the conditions that may produce inflammation are pathogens, abrasions, chemical irritations, distortion or disturbances of cells, and extreme temperatures. 4 characteristic signs and symptoms :- redness, pain, heat, and swelling. an attempt to dispose of microbes, toxins, or foreign material at the site of injury, to prevent their spread to other tissues, and to prepare the site for tissue repair to restore tissue homeostasis. Fever an abnormally high body temperature that occurs because the hypothalamic thermostat is reset. commonly occurs during infection and inflammation. Many bacterial toxins elevate body temperature, sometimes by triggering release of fever-causing cytokines such as interleukin-1 from macrophages. Elevated body temperature intensifies the effects of interferons, inhibits the growth of some microbes, and speeds up body reactions that aid repair. Neutrophils Phagocytize bacteria Create a killing zone degranulation lysosomes discharge into tissue fluid respiratory burst toxic chemicals are - created (O2. , H2O2, HClO) Eosinophils Phagocytize antigen-antibody complexes Antiparasitic effects Promote action of basophils, mast cells Enzymes block excess inflammation, limit action of histamine Basophils Aid mobility and action of WBC’s by release of histamine (vasodilator)  blood flow to infected tissue heparin (anticoagulant) prevents immobilization of phagocytes Monocytes Circulating precursors to macrophages Specialized macrophages found in specific localities dendritic cells epidermis, oral mucosa, esophagus, vagina, and lymphatic organs microglia (CNS) alveolar macrophages (lungs) hepatic macrophages (liver) Lymphocytes main type of cell found in lymph, which prompted the name "lymphocyte" Circulating blood contains 80% T cells 15% B cells 5% NK cells Dendritic cells:- Found in sites that are in contact with external antigens (skin epithelial & GI mucosa) Adaptive Immunity Also known as acquired immunity The ability of the body to defend itself against specific invading agents such as bacteria, toxins, viruses, and foreign tissues. depends on specific recognition of antigens either directly by antibodies on the surface of B cells or through presentation of processed antigens by host cells to T cells. Adaptive Immunity Has 2 forms: cells mediated & humoral Distinguish features are:- 1) specificity for particular foreign molecules (antigens), which also involves distinguishing self from nonself molecules 2) memory for most previously encountered antigens so that a second encounter prompts an even more rapid & vigorous response Cell-mediated immunity Effective against:- 1) intracellular pathogens, which include any viruses, bacteria, or fungi that are inside cells 2) some cancer cells 3) Foreign tissue transplants. Cellular Immunity T cells attack foreign cells and diseased host cells; memory of Ag Three classes of T cells 1. Cytotoxic T cells (Tc cells) carry out attack 2. Helper T cells: help promote Tc cell and B cell action and nonspecific defense mechanisms 3. Memory T cells: provide immunity from future exposure to antigen TC cell Recognition Antigen presentation MHC-I proteins found on nearly all nucleated body cells ( except RBC) display peptides produced by host cells TC cell activation 1. binding of cytotoxic T cells (CD8 cells) to abnormal peptides on MHC-I and 2. costimulation via a cytokine triggers clonal selection: clone of identical T cells against cells with same epitope T cell Activation TH cell Recognition Antigen presentation role of MHC-II proteins found only on antigen presenting cells display only foreign antigens stimulate helper T cells (CD4 cells)  TH cell Activation 1. binding of helper T cells (CD4 cells) to epitope displayed on MHC-II of APC 2. costimulation via a cytokine 3. triggers clonal selection Attack Phase: Role of Helper T Cells Secretes interleukins attract neutrophils, NK cells, macrophages stimulate phagocytosis stimulate T and B cell mitosis and maturation Coordinate humoral and cellular immunity 21-57 Attack Phase: Cytotoxic T Cells Only T cells directly attack enemy cells Lethal hit mechanism docks on cell with antigen-MHC-I protein complex 1. releases perforin, granzymes - kills target cell 2. interferons - decrease viral replication and activates macrophages 3. tumor necrosis factor: kills cancer cells Cytotoxic T Cell Function Cytotoxic T cell binding to cancer cell Destruction of Cancer Cell MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) I & II ✓ normal function is to help T cells recognize that an antigen is foreign, not self ✓ the reason that tissues may be rejected when they are transplanted from one person to another MHC-I MHC-II Foreign antigen that are present inside body cells Foreign antigens that are present in fluids outside are termed endogenous antigens. body cells are termed exogenous antigens. viral proteins produced after a virus infects the Bacteria & bacterial toxins, parasitic worms, cell and takes over the cell’s metabolic inhaled pollen and dust, and viruses that have machinery not yet infected a body cell. toxins produced from intracellular bacteria abnormal proteins synthesized by a cancerous cell. built into the membranes of all body cells except Appear on the surface of antigen-presenting cells red blood cells Memory Memory T cells following clonal selection some T cells become memory cells long-lived; in higher numbers than naive cells T cell recall response upon reexposure to same pathogen, memory cells launch a quick attack Immunological Surveillance When a normal cell transforms into a cancerous cell, it often displays novel cell surface components called tumor antigens. If the immune system recognizes a tumor antigen as nonself, it can destroy any cancer cells carrying that antigen. Such immune responses, called immunological surveillance, are carried out by cytotoxic T cells, macrophages, and natural killer cells. For this reason, transplant recipients who are taking immunosuppressive drugs to prevent transplant rejection have an increased incidence of virus-associated cancers Humoral Immunity Recognition B cell receptors bind antigen, take in and digest antigen then display epitopes on its MHC-II protein After costimulation by TH cell, divide repeatedly, differentiate into plasma cells, produce antibodies specific to that antigen Action antibodies bind to antigen, render it harmless, ‘tag it’ for destruction Memory some B cells differentiate into memory cells Humoral Immunity - Recognition B cells and Plasma cells Antibody Structure Antibody Classes By amino acid sequences of C region of antibody IgA: monomer in plasma; dimer in mucus, saliva, tears, milk, intestinal secretions, prevents adherence to epithelia IgD: monomer; B cell membrane antigen receptor IgE: monomer; on mast cells; stimulates release of histamines, attracts eosinophils; immediate hypersensitivity reactions IgG: monomer; 80% circulating, crosses placenta to fetus, 2 immune response, complement fixation IgM: pentamer, 10% in plasma, 1 immune response, agglutination, complement fixation Antibody Diversity Immune system capable of as many as 1 trillion different antibodies Somatic recombination DNA segments shuffled and form new combinations of base sequences to produce antibody genes Somatic hypermutation B cells in lymph nodules rapidly mutate creating new sequences 21-73 Humoral Immunity - Action Neutralizing antigen. The reaction of antibody with antigen blocks or neutralizes some bacterial toxins and prevents attachment of some viruses to body cells. Immobilizing bacteria. If antibodies form against antigens on the cilia or flagella of motile bacteria, the antigen– antibody reaction may cause the bacteria to lose their motility, which limits their spread into nearby tissues. Agglutinating and precipitating antigen. Because antibodies have two or more sites for binding to antigen, the antigen–antibody reaction may cross-link pathogens to one another, causing agglutination (clumping together). Phagocytic cells ingest agglutinated microbes more readily. Likewise, soluble antigens may come out of solution and form a more-easily phagocytized precipitate when crosslinked by antibodies. Activating complement. Antigen–antibody complexes initiate the classical pathway of the complement system Enhancing phagocytosis. The stem region of an antibody acts as a flag that attracts phagocytes once antigens have bound to the antibody’s variable region. Antibodies enhance the activity of phagocytes by causing agglutination and precipitation, by activating complement, and by coating microbes so that they are more susceptible to phagocytosis. Agglutination and Precipitation Humoral Immunity Responses After an initial contact with an antigen, no antibodies are present for a period of several days. Then, a slow rise in the antibody occurs, first IgM and then IgG, followed by a gradual decline in antibody. This is the primary response. Memory cells may remain for decades. Every new encounter with the same antigen results in a rapid proliferation of memory cells. After subsequent encounters, the antibody is far greater than during a primary response and consists mainly of IgG antibodies. This accelerated, more intense response is called the secondary response. Antibodies produced during a secondary response have an even higher affinity for the antigen than those produced during a primary response, and thus they are more successful in disposing of it Complement System Complement (C) proteins in blood that must be activated by pathogens Pathways of complement activation: C3 split into C3a and C3b classical pathway requires antibody; specific immunity alternate pathway nonspecific immunity lectin pathway nonspecific immunity 21-77 Complement Activation Fig. 21.15 21-78 Complement System Mechanisms of action 1. enhanced inflammation 2. phagocytosis promoted by opsonization 3. cytolysis membrane attack complex forms on target cell 4. immune clearance RBCs carry Ag-Ab complexes to macrophages in liver and spleen https://www.youtube.com/watch?v=iv0Ye-lIywQ&t=330s&ab_channel=DoctorMike https://www.youtube.com/watch?v=lXfEK8G8CUI&t=238s&ab_channel=Kurzgesagt%E2%80%93Ina Nutshell Exercise Physical barrier for first line defense Chemical barrier for first line defense What is immunological surveillance? Exercise What type of cells can kill the infected cells? What types of cells are APCs, and where in the body are they found?