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3 IMMUNITY Summarization of Immune Response The B cell finds an antigen which matches its receptors It waits until it is activated by a helper T cell Then the B cell divides to produce plasma and memory cells Plasma cells produce antibodies that attach to the current type of invader Eater...

3 IMMUNITY Summarization of Immune Response The B cell finds an antigen which matches its receptors It waits until it is activated by a helper T cell Then the B cell divides to produce plasma and memory cells Plasma cells produce antibodies that attach to the current type of invader Eater cells prefer intruders marked with antibodies and eat loads of them If the same intruder invades again, memory cells helps the immune system to activate IMMUNITY Sum total of defense mechanism of the human body to resist infectious disease. it is the total processes that occur to defend the body against foreign organism and molecules. Primary Defense Mechanism against Infection 1. Natural/Innate/Non-specific this is the ability of an individual to resist infection by means of normally present body functions 2. Acquired/Adaptive/Specific this is a type of body resistance that is characterized by specificity of each type of pathogen Natural / Innate / Nonspecific Immunity Present at birth Non-specific responses Response is immediate Response is standardized Pattern-recognition molecules No memory Rarely malfunctions SYSTEMS 1. External Defense System First line of defense consists of structural barriers that prevents most infectious agents from entering the body. 2. Internal Defense System Second line of defense consists of internal components that promote inflammation and phagocytosis First Line of Defense 1. Physical factors Intact skin impervious to almost all organisms. Skin shedding has a cleansing effect Protects epithelial cells, organisms are trapped in the mucus and are removed Viscous mucus by coughing. Coughing and sneezing Beating of cilia of epithelial cells Vomiting and 1.through vomiting and diarrhea, we diarrhea can eliminate pathogenic organisms 2. Biochemical factors flush microbes; the body fluids all have protective effects Secretions saliva sweat tears Very low pH of vagina and not conducive for the growth of stomach microorganisms. 3. Miscellaneous Physiologic factors Body temperature can make it difficult for certain microorganisms to thrive inside our bodies Oxygen tension an aerobes can grow and multiply in the lungs because of high oxygen tension plays a role in immunity, it was found that patients receiving corticosteroids Hormonal balance have decreased inflammatory responses and high susceptibility to infectious agents Age it’s proven that there is sub-optimal responsiveness for extreme ages, those who are very young and very old second line of Defense 1. Cellular Components are capable of phagocytosis Phagocytic cells second main line of defense Eg: Neutrophils, Eosinophils, Monocytes cytotoxic lymphocytes which can kill tumors and virally infected cells as well as parasitic, fungal and bacterial organisms Produce Perforin – pore-forming Natural killer cells proteins that polymerize in the presence of calcium and form channels in the target cell membrane. This is an important step in cell lysis or destruction of target cell. 2. humoral Components Cytokines interferons and interleukins Complement alternative and lectin the end product of Complement activation is cell lysis or cell destruction. Cellular components: granulocytes neutrophils they have the shortest life span. The neutrophils are considered as the principal leukocytes associated with phagocytosis and localized inflammatory responses. Responds to Chemotaxins; substance released by a bacteria, injured tissue, as well as White blood cells that stimulates the movement of neutrophils and other white blood cells to the site of injury. Cellular components: granulocytes Eosinophils Eosinophils suppress inflammatory reactions. These eosinophils have some phagocytic ability, are also capable in killing some parasites and they produce major basic proteins and eosinophil cationic protein. basophils have granules that contain histamine and heparin. Basophils play a role in Hypersensitivity reactions Cellular components: agranulocytes Monocytes Monocytes are not granulocytes, they are considered as Mononuclear Plays a role in phagocytosis, they process and present antigens to Lymphocytes Also migrates to tissues, they become macrophages and they also respond to Chemotaxins Releases Interleukin-1 and other cytokines Phagocytes die as small pus cells; Phagocytes are the first to migrate to the site of infection. Monocytes do not stay in the blood circulation long they migrate to tissues within 30 (thirty) hours where they differentiate into macrophages  Macrophages tissue cells that play a role in immunity Consist of monocytes (in blood) and macrophages (in tissues) Macrophages are transformed monocytes, they are activated by contact with microorganism or by cytokines from T lymphocytes Play a role in phagocytosis; they eliminate bacteria, intracellular parasites, as well as tumor cells. They also secrete cell mediators; they also take part in the Antigen presentation. Macrophages Alveolar macrophages (lungs) Histiocytes (connective tissues) Kupffer cells (liver) Mesangial cells (kidney) Microglial cells (brain) Osteoclasts (bone) Splenic macrophages (spleen) Peritoneal macrophages (peritoneal fluid) Dendritic cells (lymph nodes) Langerhans cells (dendritic cells in the skin)  mast cells connective tissue cells that resemble basophils but they are larger and they have more granules. They play a role in hypersensitivity reactions. Dendritic cells they are the most EFFICIENT antigen presenting cells They present antigens to the Helper T Lymphocytes in blood and lymphoid organs. Initiates Acquired Immune responses; they also play a role in phagocytosis. lymphocytes that contribute to NON-SPECIFIC IMMUNITY natural killer cells Non-T, Non-B Markers: CD 16 and CD 56 Percentage: 10 to 15% of lymphocytes are natural killer cells. they are the first line of defense against tumor cells and cells infected with viruses (viral) They are considered as the bridge between the innate and acquired immunity Lymphokine-Activated Killer Cells Antibody-Dependent Cytotoxic Cells They use interleukin 2 to help lyse Tumor cells; Can lyse antibody-coated target cells Specifically kill cancer cells. Pathogen-Associated Molecular Patterns and Pattern-Recognition Receptors Pathogen-Associated Molecular Patterns (PAMPs) molecules associated with groups of pathogens that are recognized by the cells of innate immune system. Pattern-Recognition Receptors (PRRs) these are the receptors of the Innate immune system that recognize the PAMPs Pattern-Recognition Receptors (PRRs) Secreted PRRs these are molecules that circulate in the blood and the lymph; they are considered as circulating proteins that bind to PAMPs on the surface of many pathogens Phagocytosis Receptors these are cells’ surface receptors that bind the pathogen initiating a signal leading to the release of effector molecules Toll-Like Receptors these are set of transmembrane receptors that recognize different types of PAMPs; they are found on Macrophages, Dendritic cells, and Epithelial cells. CYTOKINES Cytokines are small proteins that are crucial in controlling the growth and activity of other immune system cells and blood cells. When released in the circulation, they signal the immune system to do its job. Cytokines affect the growth of all the blood cells and other cells that help the body’s immune and inflammatory responses. Other textbooks refer to cytokines as small secreted proteins released by cells that have a specific effect on the interactions and communications between cells. Cytokine is a general name other names include the following: Lymphokine made by lymphocyte Monokine made by monocytes Chemokine cytokine that has chemotactic activities cytokine made Interleukin leukocytes by one leukocyte and acting on other INTERFERON Interferon are proteins that are produced by virally infected cells to protect neighboring cells. The interferons induce the neighboring cells to produce antiviral proteins that interfere with the viral messenger RNA FUNCTIONS: Inhibit viral replication in the neighboring uninfected cell Activate macrophages Enhance T-cell activity Increase cytotoxic action of Natural Killer cells TYPE 1 said to be non-immuned produced primarily in the initial innate response to viral infection. a. IFN - alpha secreted by leukocytes induced by viruses or synthetic polynucleotides major producers: Natural Killer cells or the null cells referred to as leukocyte interferon. B. IFN - beta secreted by fibroblasts induced by viruses or synthetic polynucleotides major producers: fibroblasts or epithelial cells referred to as fibroepithelial interferon TYPE 2 said to be mmuned produced primarily as a component of a specific immune response to viral organisms and other pathogens a. IFN - gamma stimulation with a specific antigen secreted by lymphocytes following a stimulation with a specific antigen major producers: T cells referred to as the immune interferon tumor-necrosis factor TNFs are cytotoxic against tumor cells and virally infected cells TNF-alpha TNF-beta Also known as Cachectin / cachexin Also known as Lymphotoxin The TNF-alpha is produced by macrophages Produced by CD4+ and CD8+ cells. INTERLEUKINS Interleukins is any of a group that is naturally occurring proteins that mediate communication between cells. Interleukins regulate cell growth, differentiation and motility. They are particularly important in stimulating immune responses such as inflammation IL-1: pro-inflammatory cytokine produced by activated phagocytes has immunoregulatory functions and endocrine effects IL-1 induces fever IL-2: T cell growth factor IL-2 activates NK cells to become lymphokine- activated killer cells formerly known as T cell factor  IL-3: hematopoiesis IL-6: induces the acute phase response of multicolony - stimulating factor inflammation IL-3 induced hematopoiesis IL-6 induces the acute phase response of inflammation formerly known as the multicolony - synthesized by several cells in response to IL-1 and TNF stimulating factor IL-6 causes hepatocytes to synthesize several plasma proteins Acute Phase Reactants These are proteins that increase due to infection, injury or trauma Examples: C-reactive Protein (CRP) Serum Amyloid A (SAA) Fibrinogen Haptoglobin Ceruloplasmin Betalysin Betalysin is a heat stable cationic substance with bactericidal activity found in the serum of many animal species including humans. An antibacterial protein that is released from the blood platelet when they rupture Active primarily against gram positive bacteria except from Streptococcus. complement Complement is a series of proteins that are normally present in serum whose overall function is the mediation of inflammation End product of the complement activation is cell lysis or destruction. Complement proteins have the following functions: Activation of the immune system Opsonization Cell lysis Lysozyme Lysozyme hydrolyzes the mucopeptide layer of the cell wall of many different bacteria It is present in tears, saliva, nasal secretions and other body fluids. PROPERDIN Properdin is a serum protein that exerts bactericidal and virucidal effects in the presence of C3 and Mg. The C3 is a complement protein. PHAGOCYTOSIS The most important function of the internal defense system Phagocytosis results in the destruction of foreign cells and organisms. Neutrophils kill ingested organisms through oxidative metabolism or respiratory burst. rapid release of reactive oxygen species such as superoxide anion and H2O2 from different type of cells STEPS IN PHAGOCYTOSIS 1. Initiation Physical contact between the phagocytic cell and the microorganism occurs Note: This is referred to as the adherence 2. CHEMOTAXIS Outflowing of the cytoplasm to surround the microorganism 3. ENGULFMENT Formation of Phagosome: happens when the cytoplasm is completely surrounded by a part of cell membrane Formation of Phagolysosome: happens when the cytoplasmic granules fused with the membrane of the phagosome, emptying the contents into this membrane bound space. 4 DIGESTION Digestion of the microorganism by Hydrolytic enzymes Excretion of contents of phagolysosome to the outside by exocytosis INITIATION phagocytosis is initiated as a result of tissue damage because of trauma or as a result of a microorganism multiplication activated phagocyte has increased surface receptors that allow for adherence RECEPTORS Complement receptor Laminin receptor Leucy!-Formyl-Methionyl-Phenylalanine Receptor CHEMOTAXIS Process by which cells tend to move in a certain direction under the stimulation of a chemical substance called chemotaxin. CHEMOTAXIN substance release by bacteria, injured tissue, and leukocytes that stimulates the movement of neutrophils and other WBC to the injured area. Diapedesis when cells emigrate from capillaries Chemokynes group of cytokines involves the activation of WBC during migration across the endothelium POSITIVE: towards the source of stimulation NEGATIVE: is away from the source of stimulation  JOB’S SYNDROME LAZY LEUKOCYTE SYNDROME the phagocyte have normal random activity but both random and chemotactic activity of abnormal chemotactic activity phagocytes are abnormal engulfment Occurs via Active amoeboid motion OPSONIZATION process of enhancing phagocytosis via the presence of opsonins; coating of particles with plasma factors to speed up phagocytosis OPSONIN interact with surfaces of bacteria rendering them acceptable in the phagocyte Examples: -Complement (C3b: most potent, C4a, C5b), antibodies, fibrinonectin, leukotrienes, and tuftsin End product of engulfment: phagosome, or phagocytic vacuoles digestion aka Cytopepsis formation of phagolysosome, minute cell particles that contain hydrolytic enzyme and peroxidase approach the phagosome, fuse with it forming the phagolysosome and there is a rupture and discharge of the contents of phagolysosome the cells become degranulated as foreign materials are digested FACTORS THAT ENHANCE PHAGOCYTOSIS Integrins enhance cell-to-cell interaction cell surface proteins, important during inflammation and immune responses Opsonins coat particles Complement proteins most potent: C3b crystallizeable fragment; enhance Fc of Ig interaction between phagocytic cells and antibody coated particles Fibronectin causes neutrophils and target cells to stick together Leukotrienes arachidonic acid Tuftsin found in the spleen it has chemotactic and phagocytic activities ANTIGEN DESTRUCTION Phagolysosome defensins, lactoferrin, and lysozyme Nitric oxide produced by activated macrophages which is toxic to microorganisms reactive oxygen intermediates (superoxide anion, hydrogen peroxide, hydroxyl NADPH oxidase radicals); present in phagosome membrane leading to the production of reactive oxygen intermediates INFLAMMATION Tissue reaction to injury that is due to physical and chemical agents including microorganisms; sequence of events following tissue damage that protects the host from foreign invaders and also attempt to minimize tissue damage It is the over-all reaction of the body to injury or invasion by an infectious agent SIGNS Rubor redness Tumor swelling Calor Heat Dolor pain Functio laesa loss of function STAGES OF INFLAMMATION Vascular Response: Mast cells: release of histamine Dilation of blood vessels Redness and heat experienced because of the blood to the affected area Endothelial cells contract that increases the permeability and allows fluids in the plasma to leak in the tissues that causes swelling and pain Swelling and pain Cellular Response Neutrophils: major cells present during infx; mobilized by chemotaxins within 30-60 mins after injury, they last for 24-48 hours, presence indicate ACUTE INFLAMMATION Monocytes/Macrophages: arrived much later peak at 16-48 hours; when phogocytic cells die they become pus cells; second to migrate and long-live: CHRONIC INFLAMMATION Cellular RESOLUTION AND REPAIR Fibroblast proliferation- replace the old and dying cells Totally repaired Abscess: with some loss of function Granuloma: due to T-cell accumulation that is typical of delayed hypersensitivity or cell-mediated immunity Fibrinogen: forms a clot; gives strength to the wound Natural Immunity CELLULAR HUMORAL Also known as innate/non-specific immunity Mast cells Complement Composed of cellular and humoral components Neutrophils Lysozyme Macrophages Interferon INherent qualities EXTERNAL DEFENSE SYSTEM skin, mucous membrane; structural barriers that prevent infectious agents from entering the body INTERNAL DEFENSE SYSTEM NK cells, inflammation; cells and soluble factors involve in immunity; phagocytosis is under internal defense system acquired/adaptive/specific Immunity relies on genetic events and cellular growth 1. Formed after exposure – to a non-self particle or to a pathogen 2. Antigen-dependent - response 3. Lag time between exposure and maximal response – the response develops over the days 4. Antigen-specific – it is very specific. Each cell is genetically programmed to respond to a single antigen 5. Uses antigen-recognition molecules 6. Immunologic memory – exposure results in the induction of memory cells, so acquired immunity has immunologic memory on repeated exposures, the response becomes faster, stronger, and qualitatively different 7. Frequently malfunctions – may lead to autoimmunity and immunodeficiency CELLULAR LYMPHOCYTES T-helper cells, cytotoxic T-cells, memory B-cells, plasma cells ANTIGEN PRESENTING CELLS (APC) Macrophages, monocytes, dendritic cells, B cells HUMORAL CYTOKINES the lymphokines are cytokines produced by T-cells. Cytokines are small proteins that stimulate or inhibit many normal cell functions ANTIBODIES are immunoglobulins produced by plasma cells in response to an antigen COMPLEMENT for acquired immunity, the pathway involved is the classical pathway ANTIGEN ELIMINATION Important process: Phagocytosis most injected antigens are removed within minutes but complete removal may take months or years Antibody Production A. Primary Response Latent phase: No antibody is produced for about 5 to 7 days so during this time the host is producing plasma cells that will secrete antibodies. First immunoglobulin to be produced: IgM is the first antibody produced although a small amount of IgG is made later the majority of immunoglobulin produced during the primary response is the immunoglobulin M or IgM so remember for the primary response antibody production starts slowly and then it peaks it levels off then it declines 1. Lag Phase - no antibody is detectable 2. Log Phase - antibody titer will increase logarithmically 3. Plateau Phase antibody tier stabilizes 4. Decline Phase - the last phase, the antibody is catabolized B. SECONDARY Response Latent phase: short latent phase. This usually ranges from three to five days Predominant immunoglobulin: IgG is the predominant immunoglobulin. There is higher antibody concentration and the circulating antibody titer is much higher and last longer than in the primary response. You can also see the presence of memory cells. So the secondary response is also known the anamnestic response TYPES OF Adaptive Immunity A. HUMORAL IMMUNITY B CELLS bursa or bone marrow derived lymphocytes produced by plasma cells ANTIBODIES antibody mediated Plasma cells are derived from the b cells PRIMARY DEFENSE AGAINST examples of humoral response is the active and passive antibody BACTERIAL INFECTION production B. CELL-MEDIATED IMMUNITY Defense against viral and fungal infections, intracellular organisms, tumor antigens, and graft rejection T CELLS T-cells are thymus derived cells CYTOKINES Occurs via cell-to-cell contact Cytokines are soluble products secreted by cells. Types of ImmunizatioN 1. ACTIVE IMMUNIZATION Involves administration of vaccines to recipients Administration of killed or attenuated microorganisms or their products to the recipients Vaccines are unable to cause disease but are still immunogenic. For attenuated vaccines, they induce both cell-mediated and humoral immunity. 2. PASSIVE IMMUNIZATION There is administration of 3 basic types of serum preparation: ANTITOXIN toxin neutralizing antibody, it is specific to a given toxin IMMUNE GLOBULIN OR used for passive immunization against various diseases and maintenance of GAMMA GLOBULIN immunodeficient individuals SPECIFIC IMMUNE obtained from people who have recently recovered form a specific GLOBULIN infectious disease or hyperimmunized human volunteers. ROUTES OF ADMINISTRATION INTRAMUSCULAR AND considered as the most common methods SUBCUTANEOUS INTRADERMAL OR used as a route for re-vaccination INTRACUTANEOUS ORAL used for polio vaccine or sabin vaccine INTRANASAL used for some influenza vaccines SPECIFIC IMMUNITY MODE OF AQCUISITION NATURAL ACTIVE this develops during convalescence from an infection or recovery from a disease like chickenpox. develops after the placental passage of antibody from mother to fetus. NATURAL PASSIVE Immunity results from utero transfer to the fetus of antibodies formed earlier by the mother. Antibodies may also be transferred through the colostrum. ARTIFICAL ACTIVE immunity is obtained after vaccination. This is acquired by injection of synthetic or biological preparations such as vaccine, toxin, and toxoid. Immunity is obtained after injection of gamma globulin for the induction of ARTIFICIAL PASSIVE an immune state. Immunity is acquired by injection of immune sera or anti- toxin originally manufactured by a human or an animal.  NATURAL ACTIVE NATURAL PASSIVE Infection Colostrum Transplacental transfer artificial ACTIVE ARTIFICIAL PASSIVE RhoGAM Vaccination HBIg - Hepatitis B immune globulin provides immediate short term protection against hepatitis B infection. Has large amounts of hepatitis B antibodies taken from donated human blood. SPECIFIC IMMUNITY MODE OF AQCUISITION BASIS OF DIFFERENTIATION ACTIVE IMMUNITY PASSIVE IMMUNITY MODE OF Induced after effective contact Transmitted by antibodies (and ACQUISITON with antigen cells) pre-formed in another host ADVANTAGES Long term resistance Prompt availability of large Cell-mediated immunity amounts of antibodies Slow onset of resistance Short life span DISADVANTAGES Requires prolonged and repeated Possibility of allergic reactions contact with antigen Convalescence Placental passage of antibody COMMON EXAMPLES Vaccination Colostrum Exposure to microbial products Injection of antiserum or gamma globulin Stages of Immune Response Differentiation of Natural and Acquired Immunity NATURAL IMMUNITY ACQUIRED IMMUNITY External and internal components Third line of defense Resistance not improved by repeated infections Resistance improved by repeated nfections Factor involved: lysozyme Factor involved: antibodies Cells involved: phagocytes, natural killer cells Cells involved: T and B lymphocytes Not specific and without memory Specific and with memory