Host-Pathogen Interactions PDF

Microbial Pathogenesis and Host-Pathogen Interactions ECOLOGICAL RELATIONSHIPS Microbial Interactions Host-Parasite Interactions Environment  HOST io site ns ra ra te Pa ct...

Microbial Pathogenesis and Host-Pathogen Interactions ECOLOGICAL RELATIONSHIPS Microbial Interactions Host-Parasite Interactions Environment  HOST io site ns ra ra te Pa ct DISEASE In st- Ho TRIAD PATHOGEN ENVIRONMENT Microbial Interactions OTHER MICROBES  ECOLOGICAL RELATIONSHIPS SYMBIOSIS: neutral, antagonistic or synergistic relationship between two dissimilar organisms (SYMBIOTES, SYMBIONTS) living in close association with each other; MUTUALISM (+/+): mutually beneficial relationship between two species COMMENSALISM (+/0): relationship between two species in which one is benefited and the other is not affected, neither negatively nor positively PARASITISM (+/-): relationship between two species in which one benefits (parasite) from the other (host); usually involves detriment to the host BASIC ECOLOGICAL DEFINITIONS FLORA; MICROBIOTA (Microbiology Definition): microorganisms present in or characteristic of a special location (FLORA generically refers to plants; FAUNA generically refers to animals) INDIGENOUS (Resident) MICROBIOTA: microbial flora typically occupying a particular niche; given diversity of environmental conditions, organisms tend to segregate TRANSIENT FLORA: microbial flora only temporarily occupying a given niche NICHE (ecological niche): the place of an organism within its community (ecosystem); unique position occupied by a particular species, perceived in terms of actual physical space occupied & function performed within ecosystem NATURAL MICROBIAL HABITATS Soil Water Air Animals and Animal Products  MICROBIAL FLORA OF THE NORMAL HUMAN BODY (a.k.a., normal flora) SKIN RESPIRATORY TRACT Nose and Nasopharynx; Mouth and Oropharynx EYE (Conjunctivae) and OUTER EAR INTESTINAL TRACT Stomach and Small Intestine; Large Intestine; Intestinal Tract of Newborn Antibiotic Alteration of Flora Significance of Intestinal Flora GENITOURINARY TRACT External Genitalia & Anterior Urethra Vagina BLOOD and TISSUES  NORMALLY STERILE SITES IN THE HUMAN BODY Colonization of one of these sites generally involves a defect or breach in the natural defenses that creates a portal of entry ¨Brain; Central nervous system ¨Blood; Tissues; Organ systems ¨Sinuses; Inner and Middle Ear ¨Lower Respiratory Tract: Larynx; Trachea; Bronchioles (bronchi); Lungs; Alveoli ¨Kidneys; Ureters; Urinary Bladder; Posterior Urethra ¨Uterus; Endometrium (Inner mucous membrane of uterus ); Fallopian Tubes; Cervix and Endocervix FACTORS CONTROLLING GROWTH OF MICROORGANISMS 1. NUTRIENT AVAILABILITY: the accessibility of a necessary resource, substance or compound providing nourishment to maintain life, i.e. capable of conversion to energy and structural building blocks Fastidious: an organism that has complex nutritional or cultural requirements, making isolation and culture more difficult MAJOR ESSENTIAL ELEMENTS: C, O, H, N, S, P, K, Mg, Ca, Fe, Na, Cl MINOR ESSENTIAL ELEMENTS: Zn, Mn, Mo, Se, Co, Cu, Ni, W 2. PHYSICO/ENVIRONMENTAL PARAMETERS: WATER ACTIVITY/OSMOTIC PRESSURE: OXYGEN: metabolic oxygen requirements; OBLIGATE or FACULTATIVE, ANAEROBIC or AEROBIC, or in between, (MICROAEROPHILIC) pH: power of hydrogen; a measurement of the amount of hydrogen ion in solution; the logarithm of the reciprocal of the hydrogen ion concentration in an aqueous solution used to express its acidity or alkalinity (0-14) TEMPERATURE: Psycrophile (psychrophilic): liking cold temperatures; Optimal growth at 15o to 20oC Mesophile (mesophilic): liking moderate temperatures; Optimal growth at 20o to 45oC Thermophile (thermophilic): liking elevated temperatures; Optimal growth at 50o to 70oC  FACTORS CONTROLLING GROWTH OF ORGANISMS: 3. COMPETITION: the simultaneous demand by two or more organisms or species for a necessary, common resource or physical space that is in limited or potentially limited supply, resulting in a struggle for survival 4. HOST IMMUNE SYSTEM: the cells and tissues involved in recognizing and attacking foreign substances in the body ACQUIRING INFECTIOUS AGENTS PORTAL OF ENTRY/EXIT INGESTION INHALATION DIRECT PENETRATION Trauma or Surgical Procedure Needlestick Arthropod Bite Sexual Transmission Transplacental ACQUIRING INFECTIOUS AGENTS (cont.) COLONIZATION: the successful occupation of a new habitat by a species not normally found in this niche Adherence (attachment): close association of bacterial cells and host cells generally characterized by receptors on target sites Adhesin: structure or macromolecule located on the surface of a cell or extracellularly that facilitates adherence of a cell to a surface or to another cell; site of attachment is often a specific receptor and host cell receptors are often sugar moieties (lectin), but the adherence may also be nonspecific ACQUIRING INFECTIOUS AGENTS (cont.) INVASION: the entry and spread throughout the cells and/or tissues of the host; specific recognition of receptor sites on target cells enhances pathogenic advantage Invasins (invasive factors): structures or macromolecules that facilitate invasion by a pathogenic microorganism MULTIPLICATION: the ability of a microorganism to reproduce during an infection; influenced by underlying disease, immunologic status, antibiotic treatment, nutrient availability  TRANSMISSION OF DISEASE ENTRANCE, COLONIZATION, PENETRATION: Dependent upon Age, Sex, Nutrition, Immunologic State and General Health of Host, and Bacterial Virulence Factors VECTOR: a carrier, especially the animal that transfers an infectious agent from one host to another, usually an ARTHROPOD CARRIER (Carrier State): symptomless individual who is host to a pathogenic microorganim with the potential to pass the pathogen to others NOSOCOMIAL INFECTIONS: an infection acquired in a hospital setting that was not present in the host prior to admission, generally occurring within 72 hours of admission  NOSOCOMIAL INFECTIONS in ACUTE CARE INSTITUTIONS Percentage of All Infection Nosocomial Most Common Agents Site Infections Urinary Escherichia coli, Enterococcus, 40% Proteus, Klebsiella, Tract Pseudomonas aeruginosa Surgical Staphylococcus aureus, 20% Wound Staphylococcus epidermidis, E. coli Pulmonary 10% Klebsiella, Pseudomonas, E. coli, S. aureus Primary S. aureus, S. epidermidis, 5% - 10% Bacteremia Gram-negative rods Others 20% - 25% S. aureus, E. coli EPIDEMIOLOGY EPIDEMIC: disease occuring suddenly in numbers clearly in access of normal expectancy ENDEMIC: disease present or usually prevalent in a population or geographic area at all times PANDEMIC: a widespread epidemic distributed or occuring widely throughout a region, country, continent, or globally  Emerging Infectious Diseases ¨ New diseases and diseases with increasing incidences are called emerging infectious diseases (EIDs). ¨ EIDs can result from the use of antibiotics and pesticides, climatic changes, travel, the lack of vaccination, and insufficient case reporting. ¨ The CDC, NIH, and WHO are responsible for surveillance and responses to emerging infectious diseases. Tuberculosis SARS* Venezuelan Equine Encephalitis Hepatitis C AIDS Enterohemorrhagic E. Coli Malaria Lassa Fever S.American Hemorrhagic Fevers Influenza Hantavirus Pulmonary Syndrome Lyme Disease West Nile Fever/Encephalitis*  PATHOGENICITY vs. VIRULENCE PATHOGENICITY: the quality of producing disease or the ability to produce pathologic changes or disease VIRULENCE: a measure of pathogenicity; a measurement of the degree of disease-producing ability of a microorganism as indicated by the severity of the disease produced; commonly ascertained by measuring the dosage required to caused a specific degree of pathogenicity; one general standard is the LD50 (lethal dose 50%)  PATHOGENICITY vs. VIRULENCE DOSAGE: the number of pathogenic microorganisms entering the host LD50 = the number of microorganisms required to cause lethality (death) in 50% of the test host TRUE PATHOGEN: any microorganism capable of causing disease; an infecting agent OPPORTUNISTIC PATHOGEN: a usually harmless microorganism that becomes pathogenic under favorable conditions causing an opportunistic infection  INFECTION vs. DISEASE INFECTION: the colonization and/or invasion and multiplication of pathogenic microrganisms in the host with or without the manifestation of disease DISEASE: an abnormal condition of body function(s) or structure that is considered to be harmful to the affected individual (host); any deviation from or interruption of the normal structure or function of any part, organ, or system of the body  INFECTION vs. DISEASE BENIGN: a non-life or non-health threating condition MALIGNANT: a disease tending to become progressively worse (MORBIDITY = illness) and potentially result in death (MORTALITY = death) CONTAGIOUS: capable of being transmitted from one host to another; communicable; infectious INFECTIOUS DOSE: number of pathogenic organisms required to cause disease in a given host  KOCH'S POSTULATES Four criteria that were established by Robert Koch to identify the causative agent of a particular disease, these include: 1. the microorganism (pathogen) must be present in all cases of the disease 2. the pathogen can be isolated from the diseased host and grown in pure culture 3. the pathogen from the pure culture must cause the same disease when inoculated into a healthy, susceptible laboratory animal 4. the pathogen must be reisolated from the new host and shown to be the same as the originally inoculated pathogen Bacterial Virulence Mechanisms Adherence (Colonization) Invasion Degradative enzymes Exotoxins Endotoxin Induction of excess inflammation Evasion of phagocytic & immune clearance Byproducts of growth (gas, acid) Superantigen Resistance to antibiotics  MICROBIAL PATHOGENICITY VIRULENCE FACTORS COLONIZATION FACTORS: specific recognition of receptor sites on target cells enhances pathogenic advantage 1. CAPSULE: nonspecific attachment 2. SURFACE RECEPTORS/TARGET SITES: Receptors on both bacteria (adhesins) and host (target) Examples include: i) fimbriae (formerly known as pili) of Enterobacteriaceae ii) Chlamydia binds host N-acetyl-D-glucosamine which is a cell surface lectin (polysaccharide target receptor) iii) Protein adhesin of Mycoplasma located in specialized tip structure; adheres to sialic acid-containing cell receptors  MICROBIAL PATHOGEN ADHESIN RECEPTOR Staphylococcus aureus Lipoteichoic acid Unknown Staphylococcus spp. Slime layer Unknown Group A Streptococcus LTA-M protein complex Fibronectin Streptococcus pneumoniae Protein N-acetylhexosamine-gal Escherichia coli Type 1 fimbriae D-Mannose CFA 1 fimbriae GM ganglioside P fimbriae P blood grp glycolipid Other Enterobacteriaceae Type 1 fimbriae D-Mannose Neisseria gonorrhoeae Fimbriae GD1 ganglioside Treponema pallidum P1, P2, P3 Fibronectin Chlamydia spp. Cell surface lectin N-acetylglucosamine Mycoplasma pneumoniae Protein P1 Sialic acid Vibrio cholerae Type 4 pili Fucose and mannose  VIRULENCE FACTORS (cont.) INVASIVE FACTORS (invasins): enable a pathogenic microorganism to enter and spread throughout the tissues of the host body; specific recognition of receptor sites on target cells enhances pathogenic advantage DEGRADATIVE ENZYMES: a class of protein capable of catalytic reactions; bacterial and host enzymes both play roles in the disease process  VIRULENCE FACTORS (cont.) TOXIGENICITY: the ability of a microorganism to cause disease as determined by the toxin it produces which partly determines its virulence 1. ENDOTOXIN: a complex bacterial toxin that is composed of protein, lipid, and polysaccharide (LPS) which is released only upon lysis of the cell 2. EXOTOXINS: a potent toxic substance formed and secreted by species of certain bacteria  BASIC EFFECTS of ENDOTOXIN FEVER: any elevation of body temperature above normal LEUKOPENIA/LEUKOCYTOSIS: abnormal reduction in number of leukocytes in blood, (12,000mm3) METABOLIC EFFECTS : pathogenic organisms can affect any of the body systems with disruptions in metabolic processes, e.g.,hypotension, hypoglycemia, etc. RELEASE OF LYMPHOCYTE FACTORS: agranular leukocyte concentrated in lymphoid tissue; active in immunological responses, including production of antibodies  BASIC EFFECTS of ENDOTOXIN CELLULAR DEATH: SEPTIC SHOCK: associated with overwhelming infection resulting in vascular system failure with sequestration of large volumes of blood in capillaries and veins; activation of the complement and kinin systems and the release of histamines, prostaglandins, and other mediators may be involved DISSEMINATED INTRAVASCULAR COAGULATION (DIC): disorder characterized by a reduction in the elements involved in blood coagulation due to their utilization in widespread blood clotting within the vessels; late stages marked by profuse hemorrhaging ORGAN NECROSIS: the sum of morphological changes indicative of cell death and caused by the progressive degradative action of enzymes  EXOTOXINS TWO-COMPONENT (BIPARTITE) A-B TOXINS with INTRACELLULAR TARGETS: conform to general structural model; usually one component is a binding domain (B subunit) associated with absorption to target cell surface and transfer of active component across cell membrane, the second component is an enzymatic or active domain (A subunit) that enzymatically disrupts cell function BACTERIAL CYTOLYSINS (a.k.a. Cytotoxins) with CELL MEMBRANE TARGETS: hemolysis, tissue necrosis, may be lethal when administered intravenously  EXAMPLES of BIPARTITE A-B TOXINS with INTRACELLULAR TARGETS ¨ Diphtheria toxin - ADP-ribosylation inhibits cell protein synthesis by catalyzing transfer of ADP- ribose from NAD (nicotinimamide adenine nucleotide) to EF-2 (elongation factor- 2) ¨ Pseudomonas aeruginosa toxin - similar action as DT ¨ Cholera toxin - A-subunit catalyzes ADP-ribosylation of the B-subunit of the stimulatory guanine nucleotide protein Gs; profound life-threatening diarrhea with profuse outpouring of fluids and electrolytes ¨ Enterotoxigenic Escherichia coli (ETEC) heat-labile enterotoxin - similar or identical to cholera toxin ¨ Tetanus neurotoxin - less well understood; binding domain binds to neuroreceptor gangliosides, releases inhibitory impulses with trismus ¨ Botulinum neurotoxin - among most potent of all biological toxins; binding domain binds to neuroreceptor gangliosides, inhibits release of acetylcholine at myoneural junction resulting in fatal paralysis  BACTERIAL CYTOLYSINS with CELL MEMBRANE TARGETS Three Major Types: 1. Hydrolyze membrane phospholipids (phospholipases); e.g., Clostridium, Staphylococcus 2. Thiol-activated cytolysins (oxygen-labile) alter membrane permeability by binding to cholesterol; e.g., Streptococcus, Clostridium 3. Detergent-like activity on cell membranes; e.g., Staphylococcus, rapid rate of lysis  ENDOTOXINS EXOTOXINS 1.Integral part of cell wall 1.Released from the cell before or after lysis 2.Endotoxin is LPS; 2.Protein lipid A is toxic 3.Heat stable 3.Heat labile 4.Antigenic; questionable 4.Antigenic and immunogenic immunogenicity 5.Toxoids not be produced 5.Toxoids can be produced 6.Many effects on host 6.Specific in effect on host 7.Produced only by gram- 7.Produced by gram-positive negative organisms & gram-negative organisms  MICROBIAL PATHOGENICITY (cont.) RESISTANCE TO HOST DEFENSES ENCAPSULATION and ANTIGENIC MIMICRY, MASKING or SHIFT CAPSULE, GLYCOCALYX or SLIME LAYER Polysachharide capsules Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, etc. Polypeptide capsule of Bacillus anthracis EVASION or INCAPACITATION of PHAGOCYTOSIS and/or IMMUNE CLEARANCE PHAGOCYTOSIS INHIBITORS: mechanisms enabling an invading microorganism to resist being engulfed, ingested, and or lysed by phagocytes/ phagolysosomes RESISTANCE to HUMORAL FACTORS RESISTANCE to CELLULAR FACTORS  MICROBIAL PATHOGENICITY (cont.) DAMAGE TO HOST DIRECT DAMAGE (Tissue Damage from Disease Process): Toxins Enzymes INDIRECT DAMAGE (Tissue Reactions from Immunopathological Response): Damage Resulting from Vigorous Host Immune Response (a.k.a, immunopathogenesis; autoimmune hypersensitivy) Hypersensitivity Reactions (Types I - IV) HOST RESISTANCE  HOST RESISTANCE The degree to which a host can limit the effects of an infection, ranging from: ¨ TOLERANCE in which symptoms are suppressed or unusually large doses of a drug, toxin, or protein are able to be endured ¨ HYPERSENSITIVITY in which only a few cells surrounding the infected cell(s) are affected or an increased susceptibility to an antigen, such as an allergic reaction to a previous exposure to an antigen, the extreme case being anaphylactic shock ¨ IMMUNITY in which the microorganisms do not multiply due to any one or a combination of host immune factors or the biological condition by which a body is capable of resisting or overcoming an infection or disease  HYPERSENSITIVITY REACTIONS TYPE I: ANAPHYLACTIC REACTION (ANAPHYLAXIS, ANAPHYLACTIC SHOCK): a life- threatening immediate hypersensitivity reaction to a previously encountered antigen, characterized by respiratory distress, vascular collapse, and shock; allergy or atopic diseases TYPE II: CYTOTOXIC REACTION: a specific destructive action against certain cells by an invading agent; humorally mediated, autoimmune diseases, cytotoxic diseases, antibody diseases TYPE III: IMMUNE COMPLEX REACTION: serum sickness diseases TYPE IV: CELL-MEDIATED IMMUNE RESPONSE: delayed-type hypersensitivity, cell- mediated cytotoxic diseases, granulomatous diseases IMMUNOPATHOLOGICAL RESPONSE with TISSUE REACTIONS ¨Type I Hypersensitivity Reactions: Anaphylactic Reaction (Anaphylaxis; Anaphylactic shock) · IgE-mediated: Cross-linking of cell-bound IgE antibodies by antigen with degranulation of mast cells or basophils · Life-threatening immediate hypersensitivity reaction to a previously encountered antigen, characterized by respiratory distress, vascular collapse, and shock Allergy or atopic diseases  Atopy: hereditary hypersensitivity to common environmental antigens IMMUNOPATHOLOGICAL RESPONSE with TISSUE REACTIONS ¨Type II Hypersensitivity Reactions: Humorally-Mediated Autoimmune Diseases  Interaction of cross-reactive antibody with host cell surface antigen; Autoantibodies and immune complexes  Cytotoxic reaction (antibody-mediated) (ADCC): Specific destructive action against certain cells presenting antigens from an invading agent  IMMUNOPATHOLOGICAL RESPONSE with TISSUE REACTIONS ¨Type III Hypersensitivity Reactions: Immune Complex Reaction  Antibody-mediated  Deposition of circulating immune complexes in small vessels with complement activation causing damage to vessels  Serum sickness diseases IMMUNOPATHOLOGICAL RESPONSE with TISSUE REACTIONS ¨Type IV Hypersensitivity Reactions: Cell-Mediated Immune Response  T cells sensitized to “self” antigens secrete lymphokines that either do direct damage to host cells (e.g., TNF) or indirect damage enhancing the inflammatory response  Delayed-type hypersensitivity (TB test) (CD4+ mediated)  Cell-mediated cytotoxic diseases (CD8+ mediated)  Granulomatous disease  HOST DEFENSE MECHANISMS EXTERNAL (PRIMARY): Physical barrier of gross surface area; e.g., skin, respiratory tract, gastrointestinal tract, genitourinary tract Mechanical and Physical Factors: sweat, fatty acids, pH, indigenous competitive flora (microbial antagonism), peristalsis, hair, cilia, urinary flushing, mucus, [tears, nasal secretions, saliva (lysozyme)], semen (spermine), mucosal secretory antibody (IgA predominant)  HOST DEFENSE MECHANISMS (cont.) INTERNAL (SECONDARY): When an infecting parasite succeeds in penetrating the skin or mucuos membranes, cellular defense mechanisms include local macrophages and blood-borne phagocytic cells. Mononuclear phagocytes (monocytes and macrophages) and polymorphonuclear leukocytes (PMNs) are the most important phagocytic cells targeting bacterial infections. MONONUCLEAR PHAGOCYTE SYSTEM (formerly Reticular Endothelial System): total pool of monocytes and cells derived from monocytes; predominantly macrophages (phagocytic cells) HOST DEFENSE MECHANISMS (cont.) OTHER: NON-SPECIFIC: oxygen metabolites (superoxide anion radical, hydrogen peroxide, hydroxyl radicals, halide radicals), kinin forming system related to clotting HOST-GENERATED PROTEINS: complex array of humoral and cellular mediators; e.g., lysosomal enzymes, lipid mediators, prostaglandins, histamine, heat-shock proteins (stress proteins)  HOST DEFENSE MECHANISMS (cont.) CELLULAR IMMUNE RESPONSE: any immune response directed at the cellular level; includes INFLAMMATION and PHAGOCYTOSIS processes INFLAMMATORY RESPONSE: a protective response of tissues affected by disease or injury characterized by redness, localized heat, swelling, pain, and possibly impaired function of the infected part PHAGOCYTOSIS: the process by which certain phagocytes can ingest extracellular particles by engulfing them; particles OPSONIZED with antibody are more rapidly and efficiently ingested T-LYMPHOCYTES and CYTOKINES  HOST DEFENSE MECHANISMS (cont.) HUMORAL IMMUNE RESPONSE: the sum total of components of the immune response circulating in the blood or body fluids ; includes ANTIBODY and COMPLEMENT systems COMPLEMENT PROTECTIVE SYSTEM: a protein system in serum that combines with antibodies to form a defense against cellular antigens B-LYMPHOCYTES and ANTIBODY PRODUCTION: a class of proteins produced as a result of the introduction of an antigen that has the ability to combine with the antigen that caused its production