Mechanisms of Pathogenicity
Mechanisms of Pathogenicity
Overview of the mechanisms of pathogenicity and disease classifications.
Disease Vocabulary & Classifications
Disease: Any condition in which normal structure or functions of the body are damaged or impaired.
Infection: Successful colonization of a host by a microorganism.
Signs: Objective and measurable incidents, such as body temperature, antibodies in blood serum, blood pressure, and breathing rate.
Symptoms: Subjective experiences felt by the patient, such as nausea, loss of appetite, and pain.
Syndrome: A specific group of signs and symptoms characteristic of a particular disease.
Classifications of Disease
Infectious Disease: Caused by the direct effect of a pathogen.
Communicable Disease: Can be spread from person to person through direct or indirect mechanisms; Contagious diseases are easily spread.
Noncommunicable Disease: Not spread from one person to another.
Iatrogenic Disease: Result of a medical procedure.
Nosocomial Disease: Acquired in a hospital setting.
Zoonotic Disease: Transmitted from animals to humans.
Noninfectious Disease: Not caused by pathogens.
Acute Disease: Occurs in a short amount of time.
Chronic Disease: Occurs over a long period.
Latent Disease: Pathogen is dormant for extended periods without active replication.
Periods of Disease
The disease process occurs following infection and typically follows these five stages:
Incubation Period: Time between exposure to the pathogen and the onset of symptoms.
Prodromal Period: Early signs and symptoms appear but are not specific.
Illness Stage: Disease is most severe, with specific signs and symptoms.
Decline Stage: Symptoms begin to subside.
Convalescence: Recovery phase after illness.
Etiology and Koch's Postulates
Etiology: The study of causation of disease.
Germ Theory of Disease: Proposed that infections by pathogenic microorganisms cause disease.
Koch's Postulates: Developed by Robert Koch to prove a particular pathogen causes a specific disease:
The suspected causative agent must be absent from all healthy organisms but present in diseased organisms.
The causative agent must be isolated from the diseased organism and grown in pure culture.
The cultured agent must cause the same disease when inoculated into a healthy, susceptible organism.
The same causative agent must then be reisolated from the inoculated, diseased organism.
Limitations to Koch's Postulates:
Some pathogens can’t be cultured in the lab.
Diseases may be caused by a combination of pathogens and cofactors.
Ethical considerations prevent applying Koch's postulates to human-requiring pathogens.
Molecular Koch's Postulates
Proposed revision to Koch's postulates to analyze the genetic contribution to pathogenicity:
Phenotype: Signs or symptoms of the disease should associate only with pathogenic strains of a species.
Gene Inactivation: Loss of pathogenicity should occur when associated gene(s) are inactivated.
Reversion: Restoration of disease phenotype should happen with reactivation of the inactive gene.
Pathogenicity & Virulence
Pathogenicity: The ability of a microorganism to cause disease.
Virulence: The degree of pathogenicity; higher virulence indicates a greater potential for causing disease.
Virulence Factors: Factors contributing to virulence, including:
Adhesion Factors: Help pathogens attach to host cells.
Biofilms: Communities of microorganisms that protect against the immune response.
Exoenzymes: Enzymes that aid in colonization and protect against host defenses.
Toxins: Poisonous substances produced by some microorganisms.
Antiphagocytic Factors: Mechanisms to evade phagocytosis.
ID50 and LD50
ID50 (Infective Dose 50): The number of pathogenic cells/viruses required to infect 50% of the sample population.
LD50 (Lethal Dose 50): The quantity of pathogenic cells/viruses/toxins required to kill 50% of the sample population.
Example:
Anthrax ID50 through skin = 10-50 endospores.
Shiga toxin ID50 gastrointestinal = 250 ng/kg.
Botulism LD50 in mice = 0.03 ng/kg.
Infection Types
Local Infection: Confined to a small area near the portal of entry.
Focal Infection: Localized pathogens or toxins spread to a secondary location.
Systemic Infection: Infection spreads throughout the body.
Primary Infection: Initial infection caused by one pathogen.
Secondary Infection: Follow-up infection caused by a second pathogen due to damage done by the first.
Stages of Pathogenesis
Primary Pathogens: Cause disease in hosts regardless of the host’s microbiota or immune system.
Opportunistic Pathogens: Cause disease when the host’s defenses are compromised.
The stages of pathogenesis include:
Exposure (Contact): Pathogen gains entry into the host.
Adhesion (Colonization): Pathogen attaches to body cells.
Invasion: Dissemination of a pathogen throughout local tissues or the body.
Infection: Pathogen multiplies, leading to infection.
Portals of Entry
Skin: Acts as a barrier, some pathogens can enter through openings or cuts, or by burrowing.
Mucous Membranes: Line body cavities open to the environment, providing a moist environment hospitable to pathogens; the respiratory tract is most common for entry.
Placenta: Forms an effective barrier, but some pathogens can cross the placenta.
Parenteral Route: Circumvents the usual portals of entry (e.g., insect bites).
Specific Portals of Entry Include:
Eye (conjunctiva)
Nose
Mouth
Ear
Vagina
Urethra
Broken skin
Anus
Portals of Exit
Pathogens typically leave hosts in materials the body secretes or excretes, such as:
Nose: Secretions
Tears: Eye
Milk: Mammary glands
Urethra: Urine, secretions
Skin: Flakes, secretions
Mouth: Saliva, sputum
Blood: From broken skin, insect bites, or needles
Anus: Feces
Role of Adhesion in Infection
Adhesion: The process by which microorganisms attach themselves to host cells. Necessary for establishing colonies within the host.
Adhesins: Glycoproteins or lipoproteins that bind to host receptors; the interaction can determine host specificity.
Disruption of Adhesion: Changing/blocking a ligand or its receptor can prevent infection.
Inability to produce attachment proteins can render microorganisms avirulent.
Bacterial pathogens may also attach to each other to form biofilms.
Virulence Factors: Exoenzymes
Exoenzymes: Allow pathogens to colonize tissues or evade the immune response. Examples include:
Coagulases: Form fibrin clots from blood.
Kinases: Dissolve clots formed by the body.
Hyaluronidase: Destroys hyaluronic acid in connective tissue.
Collagenase: Breaks down collagen.
IgA Proteases: Degrade IgA antibodies.
Virulence Factors: Toxins
Toxins: Poisonous substances produced by some microorganisms.
Toxigenicity: Ability of microorganisms to produce toxins.
Exotoxins: Secreted by bacteria or released during lysis; most are proteins and can destroy specific host cell functions.
Endotoxins: Lipid A from the LPS of gram-negative bacteria, released upon death or division of the bacterium and generally causes systemic effects such as fever.
Types of Exotoxins:
A-B Toxins: Have two components (A: active, B: binding).
Membrane-Disrupting Toxins: Create protein channels in host cells.
Superantigens: Trigger intense immune responses.
Pathogenesis of Viruses
Antigenic Variation: Viruses can change their surface antigens to avoid recognition by the host immune system via:
Antigenic Drift: Gradual mutations leading to slight antigen changes.
Antigenic Shift: Major changes due to gene reassortment when different viruses infect the same host.
Pathogenesis of Fungi
Mycotoxins: Metabolic products produced by fungi that can be toxic to humans; fungi can also produce proteases and may develop capsules.
Pathogenesis of Protozoa and Helminths
Protozoa: Can grow within host cells and adapt by changing their antigens to evade the immune system.
Helminths: Utilize host cells and tissues for growth, affecting host health and contributing to disease symptoms.