Microbial Pathogenesis Quiz

Microbial Pathogenesis and Host-Pathogen Interactions

• Microbial pathogenesis involves the ways microorganisms cause disease.
• Host-pathogen interactions encompass the interplay between the host and the pathogen.

Ecological Relationships

• Microbial interactions encompass various relationships among microorganisms.

• Host-parasite interactions include symbiosis, mutualism, commensalism, and parasitism.

• The environment also plays a key role in microbial pathogenesis.

• Symbiosis: includes neutral, antagonistic, or synergistic relationships between microorganisms

• Mutualism: mutually beneficial relationship between two species

• Commensalism: one species benefits while the other is unaffected.

• Parasitism: one species benefits while the other is harmed.

Basic Ecological Definitions

• Flora/Microbiota: microorganisms present in a location. Flora usually refers to plants, while fauna refers to animals.
• Indigenous microbiota (resident flora): microorganisms that permanently occupy a niche
• Transient flora: microorganisms that temporarily occupy a niche.
• Niche: the role and position of an organism in its environment or ecosystem
• Natural Microbial Habitats: Soil, Water, Air, Animals and Animal Products

Microbial Flora of the Normal Human Body

• Skin: Respiratory Tract, Nose and Nasopharynx; Mouth and Oropharynx
• Eye (Conjunctivae) and Outer Ear
• Intestinal Tract: Stomach and Small Intestine, Large Intestine, Newborn Intestinal Tract, Antibiotic Alteration of Flora and Significance of Intestinal Flora
• Genitourinary Tract: External Genitalia & Anterior Urethra, Vagina
• Blood and Tissues

Normally Sterile Sites in the Human Body

• 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, Posterior Urethra
• Uterus, Endometrium, Fallopian Tubes, Cervix, Endocervix

Factors Controlling Growth of Microorganisms

• Nutrient Availability: accessibility of necessary resources for nourishment and structural building blocks.
• Fastidious organisms: require complex nutritional requirements, making isolation and culture difficult.
• Essential Elements: Major (C, O, H, N, S, P, K, Mg, Ca, Fe, Na, Cl) and Minor (Zn, Mn, Mo, Se, Co, Cu, Ni, W)
• Physico/Environmental Parameters: (i) Water activity/osmotic pressure, (ii) Oxygen metabolic requirements (obligate or facultative, anaerobic or aerobic, or in between [microaerophilic]), (iii) pH (power of hydrogen; measurement of hydrogen ion concentration in a solution—0 to 14), and (iv) Temperature (psychrophiles [15-20°C], mesophiles [20-45°C] and thermophiles [50-70°C]).
• Competition: simultaneous demand for limited resources and physical space by multiple organisms
• Host Immune System: cells and tissues involved in recognizing and eliminating foreign substances.

Acquiring Infectious Agents

• Portal of Entry/Exit: Ingestion, Inhalation, Direct Penetration (trauma, surgical procedure, needlestick, arthropod bite, sexual transmission, transplacental)
• Colonization: successful occupation of a new habitat by a species
• Adherence (attachment) of bacterial to host cells is dependent on receptors on target sites. Adhesins are structures on the bacterial cell that promote attachment
• Invasion: entering and spreading throughout host tissues. Invasins are structures that facilitate invasion.
• Multiplication: the organism's ability to reproduce during an infection. This is influenced by factors like the underlying disease state, immune response, antibiotic treatment, and nutrient availability.

Transmission of Disease

• Entrance, Colonization, Penetration: factors like age, sex, nutrition, host's immunologic state and general health, and bacterial virulence factors.
• Vector: an animal that transfers an infectious agent from one host to another (e.g., arthropod).
• Carrier: a symptomless host to a pathogenic microorganism, who can transmit it to others.
• Nosocomial Infections: hospital-acquired infection typically occurring within 72 hours of admission

Epidemiology

• Epidemic: disease occurring suddenly in numbers clearly exceeding the normal expectancy
• Endemic: disease present or usually prevalent in a geographic area
• Pandemic: widespread epidemic distributed or occurring widely throughout regions, countries, or globally

Emerging Infectious Diseases

• Emerging infectious diseases (EIDs): new or re-emerging diseases with increasing incidences.
• Causes of EIDs: antibiotic/pesticide use, climate change, travel, lack of vaccination, insufficient case reporting
• Surveillance and disease responses are crucial for emerging infectious diseases, and the CDC, NIH, and WHO play this role

Pathogenicity vs. Virulence

• Pathogenicity: ability to cause disease and produce pathologic changes
• Virulence: a measure of pathogenicity, assessed by the severity of disease caused or by determining the dosage required to cause a specific degree of pathogenicity (e.g., LD50 or lethal dose 50%)
• Dosage: number of pathogenic microorganisms entering the host
• True Pathogen: any microorganism capable of causing disease
• Opportunistic Pathogen: usually harmless microorganism that becomes pathogenic under favorable conditions

Infection vs. Disease

• Infection: colonization and/or invasion and multiplication of pathogenic microorganisms with or without the manifestation of disease
• Disease: abnormal condition of body function(s) or structure that harms the host.

Benign vs. Malignant

• Benign: non-life or non-health threatening condition
• Malignant: disease tending to become progressively worse and potentially result in death
• Morbidity: illness
• Mortality: death

Koch's Postulates

• Four criteria for identifying the causative agent of a specific disease
• Presence in all cases, isolation, replication/growth in pure culture and re-isolation from an animal model with resultant disease
• Four steps for determining causation of disease

Bacterial Virulence Mechanisms

• Adherence (Colonization): invasion, degradative enzymes, exotoxins, endotoxins, induction of inflammation, evasion of immune clearance, byproducts of growth (e.g., gas, acid), superantigen, resistance to antibiotics

Microbial Pathogenicity- Virulence Factors

• Colonization Factors: specific recognition of receptor sites
• Capsule, Surface Receptors/Target Sites

Microbial Pathogen- Adhesins and Receptors

• Tables of specific bacterial pathogens, adhesins, and receptors used to classify them

Virulence Factors (cont.)

• Invasive Factors/Invasins: enabling entry and spread of microorganisms through tissues; specific recognition of receptor sites on target cells
• Degradative Enzymes: class of proteins capable of catalytic reactions - Bacterial & host enzymes involved
• Toxigenicity: ability of a microorganism to cause diseases determined by toxin
  • Endotoxin: complex bacterial toxin (LPS) released upon cell lysis; protein, lipid, and polysaccharide components
  • Exotoxins: potent toxic substances formed and secreted by certain bacterial species

Basic Effects of Endotoxin

• Fever
• Leukopenia/Leukocytosis
• Metabolic Effects
• Release of Lymphocyte Factors

Basic Effects of Endotoxin- Severe Cases

• Cellular death & Septic Shock
• Disseminated Intravascular Coagulation (DIC)
• Organ Necrosis

Exotoxins (cont.)

• Two-Component (Bipartite) A-B Toxins
  • Binding domain (B subunit) associated with absorption
  • Enzymatic/active domain (A subunit) disrupts cell function
• Bacterial cytolysins (with cell membrane targets): hemolysis, tissue necrosis, and intravenous administration may be lethal depending on concentration and route

Examples of Bipartite A-B Toxins with Intracellular Targets

• Diphtheria toxin, Pseudomonas toxin, Cholera toxin, Enterotoxigenic E. coli toxin, Tetanus neurotoxin, Botulinum neurotoxin

Bacterial Cytolysins with Cell Membrane Targets

• Hydrolyze membrane phospholipids (e.g., phospholipases), thiol-activated cytolysins (e.g., oxygen-labile), detergent-like activity on cell membranes

Endotoxins vs. Exotoxins

• Integral part of cell wall vs. released from the cell
• Lipid A (toxic) vs. Protein
• Heat stable vs. Heat labile
• Questionable immunogenicity vs. Antigenic and immunogenic
• No toxoids produced vs. Toxoids produced
• Multiple effects on host vs. Effects specific to the target
• Produced by gram-negative only vs. Produced by gram- positive and gram-negative

Microbial Pathogenicity (cont.) - Resistance to Host Defenses

• Encapsulation, Antigenic Mimicry, Masking or Shift
• Evasion or Incapacitation of Phagocytosis
• Resistance to Humoral and Cellular Factors

Microbial Pathogenicity (cont.) - Damage to Host

• Direct damage (tissue damage from toxins, enzymes)
• Indirect damage (responses to immune system reaction- hypersensitivity reactions)

Host Resistance

• Tolerance: Suppression of symptoms or endurance to large doses of a drug, toxin, or protein
• Hypersensitivity: Increased or specific susceptibility to an antigen—leading to allergic reactions
• Immunity: the body's ability to resist an infection—by immunological factors or a biological condition

Hypersensitivity Reactions

• Type I (Anaphylactic): life-threatening, immediate hypersensitivity reaction to antigen
• Type II (Cytotoxic): specific destructive action against cells by the invading agent—mostly antibody mediated
• Type III (Immune Complex): deposition of circulating immune complexes in small vessels with complement activation
• Type IV (Cell-mediated): delayed-type hypersensitivity through T-cell mediated responses

Immunopathological Response with Tissue Reactions (cont.)

• Type I, Type II, Type III, Type IV Hypersensitivity Reactions and a breakdown of tissue reactions from each
• Example details for each type of hypersensitivity

Host Defense Mechanisms

• External (Primary): physical barriers, mechanical factors, and physical factors (sweat, fatty acids, pH, indigenous competitive flora, peristalsis, hair, cilia, flushing, mucus, tears, nasal secretions, saliva, semen, mucosal antibody (IgA))
• Internal (Secondary): immune response to pathogens that penetrated the external barriers, including phagocytosis and inflammation, mononuclear phagocytes, Reticular Endothelial System with phagocytic cells.
• Other: Non-specific (oxygen metabolites, host-generated proteins— lysosomes, lipid mediators, prostaglandins, histamine, and heat shock proteins), and cellular and humoral responses (phagocytosis, T-lymphocytes, cytokines, complement protective system, B-lymphocytes, antibody production).