BIOL1030 Host Defenses and Pathogenicity PDF

BIOL1030 Biochemistry & Microbiology Host Defenses and Pathogenicity Infection Host Larger organism that supports the survival and growth of a pathogenic microorganism. Infection A microbe growing and multiplying on or within a host. May or may not result in overt disease. Infectious...

BIOL1030 Biochemistry & Microbiology Host Defenses and Pathogenicity Infection Host Larger organism that supports the survival and growth of a pathogenic microorganism. Infection A microbe growing and multiplying on or within a host. May or may not result in overt disease. Infectious disease Any change from a state of health. Part or all of the host is incapable of carrying on normal functions due to presence of a pathogen or its products. Pathogenicity Pathogen Any organism that causes disease. Opportunistic pathogen—may be part of normal microbiota and causes disease when the host is immunocompromised. Pathogenicity Ability of a pathogen to cause disease. Virulence Degree of harm (severity of disease) inflicted on its host. Course of Infectious Disease—Important Terms Signs Objective changes that can be directly observed and measured (that is, fever, rash). Symptoms Subjective changes (that is, pain, loss of appetite). Term often used in broader score in clinical signs. Disease syndrome Set of characteristic signs and symptoms for a disease. Importance of Resources The host provides the pathogen: Protection Nutrients Energy to use Infectious agents develop mechanisms to access and exploit hosts. To survive, must also devise methods to move on to a better environment or host when necessary.  Events in Infection and Disease Factors affecting the success of transmission: Virulence of organism. Number of invading organisms. Presence of adhesion and invasion factors. Organism outcompetes the resident microbiota for resources and survive host defense mechanisms. Disease ensues when organism produces molecules that directly damage host cells or stimulates host immune cells to destroy infected tissue. Recall...Pathogen Transmission Occurs either directly or indirectly. Main routes: Contact Vehicle Vector-borne Pregnant women can also pass a pathogen to their unborn child via vertical transmission. Transmission and Virulence Efficiency of transmission increases with extensive multiplication. Pathogen’s virulence may be influenced by its ability to live outside its host. Exposure alone is not enough for infection to occur. Tropism—pathogen must make contact with appropriate host tissue Determined by specific cell surface receptors. Adherence and Invasion Entry and adhesion establish colonization. Portal of entry Skin, respiratory, gastrointestinal, urogenital systems, or conjunctiva of eye. Attachment of microbe to target cell is first. Colonization—establish a site of microbial replication on or within host. Microbial Adherence Mechanisms Adhesions are how a pathogen attaches to a target and they have high degree of specificity to target tissues. Adherence structures: Pili Fimbriae Membrane and capsular materials. Specialized adhesion molecules on microbe’s cell surface. Invasion Disseminates Pathogens Infectivity—ability to create a discrete point of infection. Invasiveness—ability to spread to adjacent tissues. Penetration can be active or passive: Active occurs through production of lytic substances that alter host tissue. Attack the extracellular matrix and basement membranes of integuments and intestinal linings. Degrade carbohydrate-protein complexes between cells. Disrupt the host-cell surface. Passive—not related to the pathogen itself (that is, skin lesions, insect bites, wounds). Invasion Once under mucous membrane, a pathogen can penetrate deeper tissues. Bacteremia—presence of viable bacteria in the blood. Septicemia—bacterial or fungal toxins in the blood. Varies among pathogens. Clostridium tetani (tetanus) is noninvasive because it does not spread from one tissue to another, but toxins become blood borne. Bacillus anthracis (anthrax) and Yersinia pestis (plague) produce toxins and are highly invasive. Streptococcus span the spectrum of virulence factors and invasiveness.  Overcoming Host Defenses Most microbes are eliminated by the immune system before they can cause disease. Successful pathogens overcome competition and elude initial host responses as well as the adaptive immune system: Find shelter to avoid recognition by defense cells. Survive and replicate inside host cells. Squeeze between host cells. Make capsules to avoid phagocytosis. Burrow under mucus. Produce enzymes that inactivate innate resistance mechanisms. Excrete specialized proteins to selectively kill host cells. Biofilms Biofilm bacteria are protected from nutrient deprivation, predators, environmental shifts, antimicrobial agents, and host immune cells. Make biofilm community less sensitive to antibiotics and host defense mechanisms  Infection Control Plan Developing an infection control plan for a pathogen involves several steps: Identify the mode of transmission: Understanding the mode of transmission will help you determine the appropriate infection control measures to implement. Understand the factors that contribute to its spread: Overcrowding Poor ventilation Poor hygiene practices can increase the risk of transmission. Infection Control Based on Mode of Transmission Contact transmission: Providing gloves and gowns for healthcare workers Implementing hand hygiene protocol Cleaning and disinfecting frequently touched surfaces. Infection Control Based on Mode of Transmission Airborne transmission: Improve ventilation systems, using HEPA filters People wear appropriate respiratory protection such as N95 masks. Infection Control Based on Mode of Transmission Droplet transmission: Wearing surgical masks Maintaining physical distancing Providing hand hygiene stations. Infection Control Based on Mode of Transmission Vector-borne transmission: Eliminating breeding sites for vectors (such as mosquitos, ticks, fleas, bedbugs). Using insect repellents, insecticides. Wearing protective clothing. Infection Control Plan Train and educate staff and the public: Healthcare workers on proper hand hygiene The public on the importance of physical distancing and wearing masks Providing information on the signs and symptoms of the pathogen. Monitor and evaluate the effectiveness of the plan: This can include monitoring infection rates Conducting audits of infection control practices Making adjustments to the plan as needed. Microbiology in the news… Al Jazerra March 23, 2023. Marburg disease has very recently emerged in many countries in Africa. How would you design an infection control plan to prevent or limit the spread of Marburg disease if you were the Chief Medical Officer of Health for these countries? Info: - Marburg virus-> hemorrhagic fever - high fever, vomiting, diarrhea and, in the most severe cases, bleeding from orifices - direct contact with the blood or other bodily fluids of infected people and with surfaces and materials such as clothing contaminated with these fluid  Human Immune System Innate immunity - Everyone is born with these defense - Non-specific immunity- Includes 1st & 2nd line of defense Adaptive (acquired) immunity - Gained over a person’s lifetime based on exposure to antigens - Includes 3rd line of defense Human Immune System – Innate Immune System Innate immune response is present at birth prior to exposure to pathogens Non-specific – not specific to any pathogen Non-adaptive – not enhanced by exposure to any pathogen No memory – repeated exposure to the pathogen has the same results – no memory cells left after the infection Innate Immune System – First line of Defense First line of defense is preventing bacteria/ pathogen from entering the body or preventing a successful infection Defenses include: Physical Barriers Chemical Barriers Microbial antagonism (microbiota) Innate Immune System – Physical & Chemical Barriers Innate Immune System – Second line of Defense Nonspecific innate immune response also includes various internal defenses such as: Phagocytosis Inflammation Fever Antimicrobials Innate Immune System – Phagocytosis Phagocytosis is a non-specific process where foreign pathogens are ingested by our cells & recognized as “non-self” - then killed by lysosomes. Phagocytes are produced in the bone marrow and are the cells that carry out phagocytosis. Granulocytes Macrophages Dendritic Cells  Innate Immune System - Inflammation Inflammation is defensive response of almost all body tissues to damage (infection, burns, cuts, etc.) It is a non-specific attempt to: Dispose of microbes & foreign materials Dilute toxins Promote healing Innate Immune System Fever is an abnormally high body temperature due to resetting of hypothalamic thermostat White blood cells release pyrogens which raise body temperature – unfavorable environment for pathogens Non-specific response: Speeds up body reactions Increases the effects of antimicrobials Sequesters nutrients from microbes – e.g. iron and zinc Innate Immune System – Antimicrobial Chemicals In addition to Cellular Defenses, there are Molecular Defenses 1. Interferon – anti-viral 2. Complement – enhance phagocytosis Innate Immune System - Interferon Interferon is a group of antiviral proteins that “interferes” or blocks virus replication. Produced & released by cells with viral infections or endotoxins Stimulates adaptive immunity Innate Immune System – Complement System Complement – set of more than 20 large blood proteins that play a role in host defense Produced by liver & circulate in inactive form Enhance phagocytosis Lyse microorganisms (bacteria & viruses) Produce peptide fragments that regulate inflammation responses Adaptive Immune System Functions Three major functions: Recognize anything foreign to the body. Defend the host from this foreign material. T and B lymphocytes activated. Effector response—eliminates or renders foreign material harmless. Memory cells—remember the foreign material. Next encounter with same foreign substance, the immune system mounts a rapid and more intense response. Remember the foreign invader. Five Characteristics of Adaptive Immunity Discrimination Responds selectively to non-self. Specificity Activated T and B lymphocytes respond to specific non-self antigen. Diversity Generates enormous diversity of cellular receptors and antibodies that recognize the foreign substance. Timing Turned on after activation by innate response. Memory Response to a second exposure is so rapid that there is usually no noticeable illness. Types of Adaptive Immunity—Humoral versus Cellular Antibody-mediated (humoral) immunity B cells act and circulate antibodies that bind microorganisms, toxins, and extracellular viruses to neutralize them or destroy them. Cell-mediated (cellular) immunity Based on action of specific kinds of T lymphocytes. Cytotoxic T cells (CTL)—attack target cells infected with intracellular pathogens. T helper cells—direct CTL to target cell lysis. Acquisition of Immunity  Recognition of Foreignness Immune system must recognize foreign antigens as non-self and recognize host cells as self. This allows for selective destruction of invading pathogens without destruction of host tissues. This involves the Major Histocompatibility complex (MHC) Collection of genes encoding proteins that enable the host to distinguish between self and non-self. Three classes of MHC molecules: Class I—on all human cells with nucleus. Class II—on cells that can process and present antigens to T lymphocytes. Class III—include secreted proteins that have immune functions. Not required to discriminate self and non-self. Types of Lymphocytes T-cells or thymus dependent cells (made in bone marrow but mature in the thymus) make up ~ 80% of all circulating lymphocytes B-cells produced by the bone marrow - migrate to the spleen Lymphocytes Lymphocytes respond to: Invading pathogens (bacteria or viruses) Abnormal body cells (virus- infected cells or cancer cells) Foreign proteins (toxins released by some bacteria) Cell-Mediated Immunity 1. Foreign invader (with foreign antigens) enters body cell 2. Foreign antigen is presented on surface of infected body cell or surface of macrophage or infected cell = antigen presenting cell 3. Activation of t-cells 4. Elimination of foreign invader  Types of T-Cells 1. Helper t-cells (Th) – activate cytotoxic t-cells & b-cells (antibody- mediated response) 2. Cytotoxic t-cells (Tc) – kill infected cells 3. Memory t-cells – clones (copies) of t-cells which remain after initial infection  B-Cell Biology B cells mature in the bone marrow and must be activated by an antigen. Differentiate into plasma cells which secrete antibodies. B-cell receptors are made of membrane-bound antibodies. Mature, naïve B cells attach an antibody to their cell membrane so that the part of the antibody that binds to antigen is facing outward. Interaction with that antigen is communicated through a signal transduction pathway. Antibodies Antibody Immunoglobulin (Ig) Glycoprotein made by activated B cells. Five classes that share a basic structure. Antibody Structure Four polypeptide chains—two identical heavy chains and two identical light chains. Connected by disulfide bridges. Two different regions: Constant (C) regions—sequence does not vary between antibodies of same class. Variable (V) regions—form antigen-binding sites. Antibody Structure Four chains arranged in flexible Y form with hinge. Stalk of Y is the crystallizable fragment (Fc). Top of Y is two antigen-binding fragments (Fab)—composed of both constant and variable regions. Antibody Function Fab binds antigen specifically. Pocket is formed by folding of the VH and VL regions. Noncovalent bonds formed between amino acids of the binding site and the epitope. Fc mediates binding to: Receptors on various immune cells. Important in initiating the complement system. Immunoglobulin Classes—IgG and IgD IgG 80% of immunoglobulin. Opsonization bacteria and neutralizes toxins and viruses. Only immunoglobulin that can cross the placenta for natural immunity in utero. IgD Part of the B-cell receptor complex. Help signal B cells to start antibody production. Immunoglobulin Classes—IgM and IgA IgM Pentamer pinwheel with Fc ends in center. Made upon initial antigen stimulation. Agglutinates and activates complement. IgA Secreted across mucosal surfaces. Secretory IgA (sIgA)—MALT. Found in breast milk. Immunoglobulin Classes—IgE IgE Lowest Ig serum level. When cell-bound IgE becomes cross-linked by binding antigen, these cells degranulate. Aids in elimination of parasites. Antibody Kinetics Antibody synthesis and secretion rates change over time. Primary antibody response Relatively slow antibody response when an antigen is encountered for the first time. Secondary antibody response Occurs upon subsequent exposure to the same antigen. Rapid, efficient, and prevents illness. Demonstrates ability of the adaptive immune system to remember a pathogen and is the basis for vaccination. Primary Antibody Response Lag phase (up to several weeks) after first exposure to antigen. No antigen-specific antibody detectable in blood. After B-cell differentiation into plasma cells, antibody is secreted. Antibody titer—measure of serum antibody concentration. Antibody class switching–differentiate into a different class. IgM appears first, followed by IgG. Secondary Antibody Response Upon secondary exposure to same antigen, B cells are activated and expand population or differentiate into antibody secreting plasma cells. Characterized as having: Shorter lag. More rapid exponential phase. Longer persistence. Higher titer. High affinity and avidity. Antibody Production and Kinetics Action of Antibodies Antigen-antibody interaction is highly specific. Protect animal from microbes and their products, and cancer cells. Neutralization Binding of antibody to biologically active materials causes neutralization. Antibodies block adherence factors, preventing their attachment to host cells. Antibody binds extracellular toxin. Can prevent the toxin from attaching to host cells. Can prevent toxin from entering host cells. Can result in ingestion by phagocytes. Antitoxin–antibody capable of neutralizing a toxin. Viral neutralization—antibody binds virus and blocks binding to host. Opsonization Process by which complement and antibody attach to microorganisms or foreign particles. Makes it recognizable to phagocytic cells. Opsonizing antibodies (IgM and IgG) trigger the classical complement cascade. Antibodies bind Fc receptors on surface of dendritic cells, macrophages, and neutrophils. Immune Complex Formation Immune complexes—form when an antibody binds two different antigen molecules and cross-linking occurs. Precipitation (precipitin reaction)—when soluble antigens form large enough complex and settle out of solution. Agglutination reaction—occurs when cells or particles are cross-linked. The immune complex is more rapidly phagocytosed than free antigens.