Host Pathogen Interaction Lecture - Microbiology PDF

HOST PATHOGEN INTERACTION Dr P Ramjathan Department of Medical Microbiology  HOST tio gen ac ho ns ter at In st-P DISEASE Ho TRIAD PATHOGEN ENVIRONMENT...

HOST PATHOGEN INTERACTION Dr P Ramjathan Department of Medical Microbiology  HOST tio gen ac ho ns ter at In st-P DISEASE Ho TRIAD PATHOGEN ENVIRONMENT Microbial Interactions OTHER MICROBES  Overview Common definitions Normal Flora Acquiring infectious agents Bacterial Virulence Host defence mechanisms  ECOLOGICAL RELATIONSHIPS 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 Saphrophyte – microbe that lives off dead or decaying plant matter eg fungi living on dead tree trunk. BASIC ECOLOGICAL DEFINITIONS FLORA; MICROBIOTA (Microbiology Definition): microorganisms present in or characteristic of a special location INDIGENOUS (Resident) MICROBIOTA: microbial flora typically occupying a particular niche; given diversity of environmental conditions TRANSIENT FLORA: microbial flora only temporarily occupying a given niche 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, Small Intestine; Large Intestine; GENITOURINARY TRACT External Genitalia & Anterior Urethra Vagina  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; Lungs; Alveoli ¨Kidneys; Ureters; Urinary Bladder ¨Uterus; Endometrium (Inner mucous membrane of uterus ); Fallopian Tubes 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  FACTORS CONTROLLING GROWTH OF ORGANISMS (cont.): 3. COMPETITION: the simultaneous demand by two or more organisms or species for a common resource that is in 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 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 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, 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): molecules 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, 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.  NOSOCOMIAL INFECTIONS in ACUTE CARE INSTITUTIONS Infection Most Common Agents Site Urinary Escherichia coli, Enterococcus, Proteus, Klebsiella, Tract Pseudomonas aeruginosa Surgical Staphylococcus aureus, Wound Staphylococcus epidermidis, E. coli Pulmonary Klebsiella, Pseudomonas, E. coli, S. aureus Primary S. aureus, S. epidermidis, Bacteremia Gram-negative rods Others S. aureus, E. coli  EPIDEMIOLOGY EPIDEMIC: disease occuring suddenly in numbers clearly in excess 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  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 In crude terms you look at how many microbes are required to kill an animal. Few highly virulent microbes will kill you versus an microbe with low virulence (many microbes required before death) PATHOGENICITY vs. VIRULENCE (Definitons) TRUE PATHOGEN: any microorganism capable of causing diseasein most cases; an infecting agent OPPORTUNISTIC PATHOGEN: a usually harmless microorganism that becomes pathogenic under favorable conditions causing an opportunistic infection Bacterial Virulence Mechanisms Adherence (Colonization) Invasion Degradative enzymes Exotoxins Endotoxin Induction of excess inflammation Evasion of phagocytic & immune clearance 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) Example: i) fimbriae (formerly known as pili) of Enterobacteriaceae  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 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 and prostaglandins 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; ORGAN NECROSIS: host cell death that results in organ failure.  EXOTOXINS TWO-COMPONENT (BIPARTITE) A-B TOXINS with INTRACELLULAR TARGETS: usually one component is a binding domain (B subunit) 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 - inhibits cell protein synthesis, host cells die and cause a Pseudomembrane in throat. ¨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 ¨Tetanus neurotoxin - less well understood; binding domain binds to neuroreceptor gangliosides, Patient gets spasms and 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  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. 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 Hypersensitivity Reactions (Types I - IV)  HOST DEFENSE MECHANISMS EXTERNAL (PRIMARY): Physical barrier e.g., skin and endothelial lining 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.  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