The Cardiovascular System Part IV: Body Defenses and Immune Responses PDF

1 The Cardiovascular System Part IV: Body Defenses and Immune Responses Anatomy & Physiology II BIOL2220 Version 03  2 Immuni...

1 The Cardiovascular System Part IV: Body Defenses and Immune Responses Anatomy & Physiology II BIOL2220 Version 03  2 Immunity and Body Defenses Immunity (From the Latin; immunis. It means “exempt”) Introduction The Immune System is a functional Immunity is body's ability to resist or system – NOT an organ system: eliminate potentially harmful foreign materials or abnormal cells. Complex system – includes It consists of following activities: Defense against invading Skin – physical barrier pathogens (viruses & bacteria) Lining of mucus membranes – Removal of 'worn-out' cells (e.g., physical barrier old RBCs) & tissue debris (e.g., Secretions – tears, mucus, sweat from injury or disease) – antimicrobials such as lysozyme Identification & destruction of & dermcidin abnormal or mutant cells (primary Blood cells and vasculature – defense against cancer) WBCs Rejection of 'foreign' cells (e.g., Bone marrow organ transplant) Inappropriate responses: Liver – makes complement Allergies - response to proteins normally harmless substances Lymphatic system and lymphoid Autoimmune diseases organs Most tissues – have resident immune cells  3 Immunity and Body Defenses Introduction Overview: Innate Immunity vs Adaptive (Acquired) Immunity Immune System Adaptive/Acquired Innate (Specific) (Nonspecific) 2nd line of defense 1st line of defense A lag period No time lag Antigen specific Not antigen specific Development No memory of memory  4 Immunity and Body Defenses Introduction Overview: Innate Immunity vs Adaptive (Acquired) Immunity ADAPTIVE/ACQUIRED INNATE IMMUNITY IMMUNITY Rapid responses to a Slower responses to broad range of microbes specific microbes External defenses Internal defenses Skin Phagocytic cells Humoral response (antibodies) Mucous membranes Antimicrobial proteins Secretions Inflammatory response Invading Cell-mediated response Natural killer cells microbes (cytotoxic (pathogens) Complement lymphocytes)  5 Immunity and Body Defenses External Defenses Innate Immunity Anatomical Barriers - Mechanical Factors Skin (epithelia) Anatomical Barriers – Biological Factors Mucociliary escalator Flushing action of saliva, tears, urine Normal Microbiota– “Good “ microbes compete with Anatomical Barriers – Chemical Factors pathogenic microbes for Antimicrobial Peptides in sweat such as Dermcidin nutrients and HCl in stomach space Lysozyme in tears /saliva  6 Immunity and Body Defenses Internal Defenses Innate Immunity Cellular Extracellular Neutrophils Cytokines Monocytes Complement /macrophages Coagulation Cytotoxic or Killer cells Toll-Like Receptors  7 Immunity and Body Defenses Internal Defenses-Cellular Innate Immunity WBCs (leukocytes) fight infection Macrophages Lymphocytes: 20-50% of total, T and B cells, deal with specific immunity Monocytes: 2-8% of total in circulation, “grow up” to become macrophages, (“big eaters”) enter the tissues Granulocytes: Granulocytes named according to microscopic appearance, presence of granules, type of stain, B-lymphocytes etc. T-lymphocytes Neutrophils: 50-70%, numerous short-lived Natural killer(NK) cells phagocytes Eosinophils: 1-5%, stain red, attack parasites Mast cells Basophils: 0.1%, stain blue, release histamine  8 Immunity and Body Defenses Internal Defenses-Cellular Innate Immunity-Phagocytosis Associated with Neutrophils, Monocytes, Macrophages… Bacterium Enzymes in Lysosome digest Lysosome bacterium. This will Trigger an inflammatory response. Phagocyte Immunity and Body Defenses Internal Defenses-Cellular Innate Immunity-Cell Mediated Immunity Cytotoxic or Killer Cells Infected Cell CD8 T cells (cytotoxic or killer Viruses cells) are activated by the release of Il-2 from T helper cells. CD8 cells recognize antigens on the surface of infected cells, attach to these cells and secrete perforins Perforins punch holes into the T-Killer (CD8 Cell) infected cells, killing them.  10 Immunity and Body Defenses Internal Defenses-Cellular Innate Immunity-TLRs The Toll-Like Receptors (TLRs) TLRs trigger a cascade of events to TLRs ARE INNATE IMMUNE SENSORS They exist as transmembrane proteins kill or protect against pathogens They are present on macrophages / few other cells They are conserved across vertebrates Very important part of innate immune system They are sensitized to microbes (or their components) They bind to the microbes (or their components) Many microbial components are recognized by TLRs Bacterial Lipopeptides Lipoteichoic acid (from G+ bacteria) LPS (from G- bacteria) Flagellin Bacterial and Viral DNA & RNA  11 Immunity and Body Defenses Internal Defenses-Extracellular Innate Immunity-Cytokines Cytokines Inducing Stimulus Cytokines are small proteins – secreted by cells of the immune system Examples include: Interferons, Cytokine Producing Interleukins, and Tumour necrosis Cell factor (TNF) They affect the behaviour of other cells They are signalling molecules They are key players in both innate and Cytokine acquired immunity Cytokines are released by many cells of the immune system: Neutrophils – when they encounter a pathogen Macrophages – when they encounter a Target Cell pathogen Cytotoxic/Killer cells – on encountering a microbe infected cell /tumor cell Lymphocytes – when they are activated Biological Effects  12 Immunity and Body Defenses Internal Defenses-Extracellular Innate Immunity-Cytokines Interferon (IFN) Signalling proteins produced by virus infected monocytes and lymphocytes Secreted proteins – Key anti-viral proteins because they inhibit protein synthesis “Interfere” with virus replication Warn the neighbouring cells that a virus is around... If we did not have IFNs – most of us would probably die of influenza virus infection antiviral state antiviral state antiviral state  13 Immunity and Body Defenses Internal Defenses-Extracellular Innate Immunity-Cytokines Interleukins Interleukins are numbered, 1-37 They are not stored inside cells They are quickly synthesized and secreted in response to infection They are key modulators of behavior of immune cells Mostly secreted by T-lymphocytes & Macrophages What do Interleukins do? Proliferation & Activation of Immune Cells Interleukins Increase Antibody Production Inflammation  14 Immunity and Body Defenses Internal Defenses-Extracellular Innate Immunity-Cytokines Tumor Necrosis Factor (TNF) The main role of TNF is in the regulation of immune cells. It is an endogenous pyrogen (able to induce fever) Also can induce apoptotic cell death, cachexia, inflammation, and inhibit tumorigenesis and viral replication, and more! What does TNF do? LOTS! Fever Cell Death Increase Antibody Production TNF Loss of Appetite Increase T-cell Proliferation Inflammation Inhibit Tumors Inhibit Viral Replication  15 Immunity and Body Defenses Internal Defenses-Extracellular Innate Immunity-Cytokines Complement Is a large number of distinct plasma proteins that react with one another (C1-C9) Complement can bind to microbes and coat the microbes It is an essential part of innate immune response It enhances the adaptive immune response (taught later) What does Complement do? Facilitates phagocytosis (acts as an Opsonin) Complement Cause lysis of pathogens (activated complement creates holes in bacterial cell walls) Inflammation  16 Immunity and Body Defenses Key player in innate immune response Innate Immunity-Inflammation Inflammation is a complex biological process by which the body responds to injury. Many things contribute to inflammation: Neutrophils Coagulation proteins Monocytes/Macrophages Inflammation Complement proteins Cytotoxic/Killer cells Cytokines /IFN TLRs Cellular Extracellular  17 Immunity and Body Defenses Key player in innate immune response Innate Immunity-Inflammation Summary: Role of Inflammation in innate immunity Heat – increases Initiation of phagocytosis – killing of pathogen metabolic rate – leads to Limiting the spread of infection fever Stimulate the adaptive immune response Compression of nerve Initiate tissue repair endings due to swelling can lead to pain Vascular changes Capillary Vasodilatation permeability 1&2 Heat / 3 4 Redness Swelling Pain 5 Temporary loss of Fever function  18 Immunity and Body Defenses The Danger of Chronic Inflammation Innate Immunity-Inflammation Chronic inflammation - macrophages in the injured tissue. Macrophages release toxins (including reactive oxygen species or ROS) that injure tissues Chronic inflammation is almost always accompanied by tissue damage. Chronic Reduced inflammation tissue function Release of ROS Tissue damage Activation of immune Killing of host cells cells  19 Immunity and Body Defenses Adaptive (Acquired) Immunity General Overview Immunity: not being susceptible to disease Types of immunity Innate: you have it from birth. Active Active Species: as humans, immune to diseases of many other creatures Artificial Natural Genetic: presence/absence of receptors Non-specific host defenses: Previously covered. Immunization Disease Adaptive/Acquired: after exposure, your followed by body remembers specific invader. It relies Recovery quite heavily on the production of antibodies. Passive Passive 2 x 2 Matrix: Immunity is either active or passive; Artificial natural either natural or artificial. Active means that host is making his own antibodies Breastfeeding Passive means the antibodies came from Intravenous someone else. antibodies Natural means the antibodies were acquired by (IgG) the host thru natural means Artificial means they were injected.  20 Immunity and Body Defenses Antigens Antigens are also known as Immunogens Antigens An antigen is a substance that confers identity. The immune system recognizes, responds to, and remembers molecules that are antigens. A molecule that is too small to be an antigen without piggy-backing onto another is called a hapten The specific part of an antigen recognized by an antibody or receptor is called an epitope. Immunogencity: is the ability to induce a humoral (antibody) and/or cell-mediated immune response. What determines immunogenicity? Foreignness: essential for immunogenicity (self-responsive immune cells are eliminated during lymphocyte development) Size: Bigger>Smaller Chemical composition: Proteins > nucleic acids / polysaccharides / lipids Structure: Primary/secondary/tertiary structures play a role Physical form: Particulate> Soluble  21 Immunity and Body Defenses Antibodies Antibodies are also known as Immunoglobulins Antibodies Protein molecules produced by activated B cells (Plasma Cells). Y-shaped molecule with hinges Ends include variable regions where antigen binding occurs. Antibodies made by a single B cell are all the same, differ from those made by another in the “variable region” of the antibody. Antibodies occur in 2 forms: Soluble: secreted in blood and body fluids; Membrane-bound: found on surface of B-cell; B-cell receptor (BCR) The Antibodies IgG: Single Y shaped unit, and most abundant in blood and body fluids; remains in circulation for long time. IgM: 5 Y-shaped units linked together, first type of antibody made in an immune response. IgA: Present in large quantities in body secretions; a dimer (2 Y- shaped units, tail to tail), helps protect mucous membranes. IgE: Single Y shaped unit, in small quantities, found bound to mast cells attached by Fc end, involved in allergies (mast cells release histamine). IgD: Single Y shaped unit, and a bit of a puzzle... In B cells, the function of IgD is to signal the B cells to be activated. It also binds to basophils and activates them to produce various antimicrobial factors.  22 Immunity and Body Defenses The Antibodies Antibodies attach to antigens…however, because there are at least 2 binding sites, cross-bridges can form, linking antigens together in clumps. Important vocabulary: Agglutination: Antibodies links cells, viruses together to make clumps that attract macrophages. Also… Opsonization: an opsonin is something that promotes phagocytosis. Complement fixation Antibody binds to antigen, antibody changes shape Shape change activates complement Activated complement leads to increased inflammation, opsonization, and cell lysis. Precipitation: toxin molecules come out of solution, which is good…but what if the precipitates stick to the host tissues? Neutralization: toxins, viruses inactivated.  23 Immunity and Body Defenses Humoral Vs Cell Mediated Duel Nature of the Immune System Humoral refers to body fluids, specifically that this branch of the immune system uses antibodies which are protein molecules dissolved in blood, body fluids, and secretions. B lymphocytes are the source of antibodies Cell mediated (previously covered) refers to the direct involvement of cells to attack an infection T lymphocytes either kill cells directly or recruit macrophages to kill cells directly  24 Immunity and Body Defenses What is a Humoral Immune Response? An immune response is what the immune system does when confronted by an antigen. A humoral immune response is an elaborate interplay between antigen, non-specific defenses, and B and T lymphocytes. The process involves direct contact (cells, molecules bind to receptors on cell surfaces) and cytokines (messenger molecules) that also bind to receptors on cell surfaces. Certain cells, such as macrophages, encounter and process the antigen (chopping it up) and display it on the cell surface for other cells to interact with: Antigen Presenting cells (APC). Display is attached to MHC (major histocompatibility complex). Stimulation of cells by binding usually results in release of cytokines which tell a cell 2 things: Get activated; multiply. Immunity and Body Defenses Humoral Activation Macrophage Bacterium B-Cell Plasma Cell Macrophage which has encountered antigen processes it, display it with MHC II protein on surface. Via T cell receptor and CD4, T helper cell binds to this. APC T-Helper (CD4 Cell) secretes Il-1 which activates the T helper cell. T-helper cells bind to B cells and release Il-4 which activates B cell. The B cell then becomes a plasma cell and releases antibodies.  26 Immunity and Body Defenses Specificity & Memory In all cases, the response to an antigen is carried out only by those T cells and B cells which are programmed to react to that antigen, that is, have a surface receptor with the proper fit to react with that antigen. Both B cells and T cells, when stimulated to multiply, produce memory cells which are long lived. These are the Upon first exposure to cells that allow the quick antigen, accumulation of response when the antigen antibody is slow. Memory is encountered at a later cells make for a quicker, time. larger response afterwards.  27 Immunity and Body Defenses Vaccines From “vaccus” (Latin for cow) First was Jenner using cowpox to immunize against smallpox. Different Types: Live attenuated vaccine Pathogen grown to make it weak, used alive. Killed/inactivated vaccine Destroyed with formalin, weaker immune response Subunit/conjugate/engineered A portion of pathogen used, often combined with another molecule for effectiveness; antigen may be produced through genetic engineering.