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Questions and Answers
What is one role of bacterial capsules in evading the immune system?
What is one role of bacterial capsules in evading the immune system?
All biofilms are harmful and associated with acute infections.
All biofilms are harmful and associated with acute infections.
False
Define bacteremia.
Define bacteremia.
The presence of bacteria in the bloodstream.
The formation of a population of bacteria attached to a surface is known as a ______.
The formation of a population of bacteria attached to a surface is known as a ______.
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Match the following terms with their definitions:
Match the following terms with their definitions:
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Which of the following statements about chronic infections is true?
Which of the following statements about chronic infections is true?
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Only encapsulated bacteria can evade the immune system effectively.
Only encapsulated bacteria can evade the immune system effectively.
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What is the importance of antigen presentation in the immune response?
What is the importance of antigen presentation in the immune response?
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What is the primary focus of immunopathogenesis?
What is the primary focus of immunopathogenesis?
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Vertical transmission occurs through direct contact between individuals in the same generation.
Vertical transmission occurs through direct contact between individuals in the same generation.
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Name one method through which horizontal transmission of pathogens can occur.
Name one method through which horizontal transmission of pathogens can occur.
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Pathogens must avoid the host's _____ to ensure their survival and replication.
Pathogens must avoid the host's _____ to ensure their survival and replication.
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Match the types of transmission with their definitions:
Match the types of transmission with their definitions:
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Which of the following is NOT a portal of entry for infectious agents?
Which of the following is NOT a portal of entry for infectious agents?
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Virulence factors include only toxins and do not encompass any other mechanisms.
Virulence factors include only toxins and do not encompass any other mechanisms.
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Identify one step that a pathogen must accomplish in order to cause disease.
Identify one step that a pathogen must accomplish in order to cause disease.
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What are pathogenicity islands primarily associated with?
What are pathogenicity islands primarily associated with?
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Adhesins are found on the surface of the pathogen and enable it to bind to host cells.
Adhesins are found on the surface of the pathogen and enable it to bind to host cells.
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What are the hairlike appendages that bacteria use to attach to specific host cells called?
What are the hairlike appendages that bacteria use to attach to specific host cells called?
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Salmonella contains resistance plasmids called ______.
Salmonella contains resistance plasmids called ______.
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What is the role of hyaluronidase in microbial infection?
What is the role of hyaluronidase in microbial infection?
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All strains of Salmonella contain the same pathogenicity islands.
All strains of Salmonella contain the same pathogenicity islands.
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What feature differentiates pathogenicity islands from normal chromosomal DNA?
What feature differentiates pathogenicity islands from normal chromosomal DNA?
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Study Notes
Weapons of Mass Infections
- Microbes, too small to see with the naked eye, can cause significant harm to humans.
Chapter Overview
- Host-pathogen interactions are crucial to understand.
- Microbes' attachment to host cells is a key aspect of pathogenesis.
- Toxins' effects on host functions are important to study.
- Toxin and effector deployment strategies vary.
- Pathogens' ability to survive within hosts is studied.
- Tools to examine pathogenesis in depth are employed
Introduction
- How very small organisms can kill beings much larger is the subject of study.
The Language of Pathogenesis
- Primary pathogens cause disease in healthy individuals.
- Shigella flexneri cause bacillary dysentery.
- Opportunistic pathogens cause disease in compromised hosts or following entry into unprotected sites.
- Pneumocystis jirovecii cause life-threatening infections in AIDS patients
- Infection is when a pathogen enters a host and begins to grow; it doesn't always indicate disease.
- Microbes may enter a latent stage during infection, undetectable through culture methods.
- Herpesvirus causes cold sores.
Pathogenicity
- Pathogenicity is an organism's ability to cause disease.
- Defined by infectivity (how easily the organism causes disease) and virulence (how severe the disease is).
- Genetic makeup also defines pathogenicity.
- Ebola is exceptionally virulent, while rhinoviruses are not.
Measuring Virulence
- Virulence can be estimated from experimental studies of infectious dose (ID50) and lethal dose (LD50).
- ID50 = number of pathogen cells/virions needed for infection in 50% of tested subjects.
- LD50 = amount of substance that kills 50% of the subjects in a test group.
Example of ID50
- Data on ID50 for various foodborne diseases like Hepatitis A, Norovirus, and Rotavirus exist, along with bacteria such as Escherichia coli, Salmonella, and Shigella.
Immunopathogenesis
- The immune system's response to a pathogen can damage tissue and organs, sometimes described as "friendly fire."
- Immunopathogenesis describes when the immune response contributes to disease pathology.
- To understand infectious diseases, scientists look at the pathogen's mechanisms and the symptoms of immunopathogenesis.
Infection Cycles
- Infection cycle describes transmission route of an infectious organism
- Horizontal transmission: transfer between individuals of the same generation
- Can be direct (e.g., handshake) or indirect (contaminated object).
- Fomites are nonliving objects that transmit pathogens (e.g., doorknobs).
- Vertical transmission: pathogen transfer from mother to fetus during pregnancy (transplacental) or birth (parturition).
Steps to Pathogenesis
- Multiple steps are necessary for a full-blown bacterial infection to manifest as symptoms and pathology.
- Exposure to pathogens is the first step
- Adherence to skin/mucosa
- Invasion through epithelium
- Multiplication and production of virulence factors/toxins.
- Toxicity—local effects or systemic
- Invasiveness—further growth in original and distant sites
- Tissue or systemic damage
Portals of Entry
- Infectious agents enter the body via portals specific to their pathogenesis mechanisms.
- Common portals of entry include the mouth, respiratory tract, conjunctiva/mucous membranes, wounds/injuries/skin lesions, and parenteral route (direct injection into bloodstream).
Virulence Factors
- All pathogens must attach to and damage host tissue, obtaining nutrients to replicate and evade host immune responses.
- Virulence factors are encoded within virulence genes.
- These factors include toxins, attachment proteins, capsules, and other components used in virulence.
Genetics of Virulence
- Salmonella species encode a large number of virulence factors, including several which direct invasion, clustered in the chromosome and categorized as pathogenicity islands.
- Another pathogenicity island promotes more systemic illness
- Resistance plasmids (R plasmids) are also present.
Pathogenicity Islands
- Pathogenicity islands are horizontally transmitted through conjugation or transduction.
- These islands have unique GC/AT ratios, codon biases, and inverted repeats and are found in specific strains of a species
Microbial Adherence: Adhesins
- Receptors coat pathogens and tissues, to which bacteria or viruses bind.
- Adhesins are glycoproteins or lipoproteins located on the pathogen's surface, facilitating binding to host cells.
Microbial Adherence: Pili or Fimbriae
- Fimbriae and pili are bacterial surface protein structures for attachment. Type I pili adhere statically to carbohydrates on host membranes; Type IV pili facilitate dynamic attachment with motility.
Nonpilus Adhesins
- Bacteria have adhesins that aren't pili (e.g., M protein in Streptococcus pyogenes, pertactin in Bordetella pertussis, MAM7 in Pseudomonas aeruginosa.)
Microbial Adherence: Capsules
- Capsules are thick coatings surrounding the plasma membrane and cell wall. They prevent phagocytosis, blocking opsonization. These capsules are often essential for bacterial pathogenicity, since a bacteria without a capsule are often not pathogenic. Capsules contain receptors for facilitating pathogen attachment to host tissues.
Biofilms and Infections
- Bacteria may attach to surfaces as populations to form biofilms, enabling persistent adherence, resistance to host defenses, and tolerance to antimicrobial agents
Colonization and Invasion
- Colonization is the growth of microorganisms after gaining access to host tissues.
- Steps in colonization and invasion include exposure, adherence, invasion, multiplication, toxicity, invasiveness, and tissue/systemic damage.
Colonization and Invasion: Invasiveness
- The capability of a pathogen to grow in host tissues where it can inhibit host function is considered invasiveness.
- Bacteremia (bacteria in bloodstream) can occur, but is not always harmful.
- Septicemia is a bloodborne infection that can lead to inflammation, septic shock, and death.
- Infection occurs when a microorganism (that isn't part of normal flora) establishes itself and grows in a host.
Enzymes and Toxins of Pathogenesis
- Enzymes assist tissue invasion, and toxins disrupt host functions.
- Enzymes like hyaluronidase and toxins (AB-type, cytolytic, superantigen, and endotoxins) play important roles in pathogenic mechanisms. Effector proteins and secretion systems are also key tools for pathogenesis.
Enzymes Involved in Tissue Invasion
- Hyaluronidase, coagulase, streptokinase allow pathogens to invade tissues.
Toxins Subvert Host Functions
- Bacterial toxins are broadly categorized as exotoxins (secreted proteins) and endotoxins (lipids)
- Exotoxins, like AB toxins, cytolysins, and superantigens, kill host cells and utilize nutrients.
- Endotoxins, component of lipopolysaccharide (LPS) in Gram-negative bacteria or lipoteichoic acid on Gram-positive bacteria, trigger an excessive immune response causing damage.
Bacterial Exotoxins and Endotoxins
- A Comparison table exists describing bacterial exotoxins and endotoxins (Location, Composition, Effect on Host, Heat Stability, LD50, Immunogenicity)
Categories of Microbial Exotoxins
- Microbial exotoxins are categorized based on their mechanisms of action (membrane disruption, cytoskeleton alterations, protein synthesis disruption, cell cycle disruption, signal transduction disruption, cell-cell adherence, vesicular traffic inhibition, etc.
Membrane Disruption (Cytolysins)
- Pore-forming proteins, phospholipases, some exotoxins causing cell lysis.
Two-Subunit AB Exotoxins
- AB exotoxins consist of two subunits (A and B) working together to disrupt host cell functions.
- The A subunit is the toxicity-associated factor, while the B subunit binds to the host cell to deliver the A subunit
Two-Subunit AB Exotoxins (Cholera Toxin)
- Cholera toxin is an AB5 exotoxin from Vibrio cholerae.
- The B subunit binds to intestinal cells, triggering the endocytosis of the toxin complex.
- The A subunit ADP-ribosylates a host cell target to raise cAMP levels, that causes water to be expelled from cells and create watery stools (diarrhea).
Two-Subunit AB Exotoxins (Diphtheria Toxin)
- Diphtheria toxin from Corynebacterium diphtheriae disrupts the synthesis of proteins within the respiratory tissues, and forms a layer of thickened gray cells coating the area
Two-Subunit AB Exotoxins (Neurological Exotoxins)
- Botulinum and tetanus toxins affect nervous tissue, acting as transport disrupters.
Endotoxin (LPS)
- Endotoxins, (lipid A components of lipopolysaccharides) are made only by Gram-negative bacteria.
- Released upon bacterial death, LPS triggers a strong immune response, causing fever, inflammation, and potentially shock and death.
Endotoxin (LPS) and septic shock
- Endotoxin release can lead to septic shock, characterized by widespread inflammation or potentially resulting in tissue damage or organ failure.
Important Infectious Agents Causing Sepsis and Septic Shock
- Several bacterial, viral, fungal, and protozoal pathogens can contribute with sepsis and septic shock.
Limulus Amoebocyte Lysate (LAL)
- LAL is used to detect LPS contamination.
Exotoxin and Endotoxin Comparison Tables Exist
- A comparison of exotoxin and endotoxin characteristics is commonly available
- Including their source, composition, effect on the host, heat stability, and LD values
T3SS (Type III Secretion System)
- Used by pathogens to inject virulence factors into host cells.
- Triggered by cell-cell contact.
- Involved in colonization, invasion, cytotoxicity, immune evasion and TJ disruption.
- Multiple effectors have different functions.
T2SS (Type II Secretion System)
- Homologous to type IV pilus biogenesis
- Secretion structures extend and retract like pili.
- Proteins enter the periplasm, then exit via an outer membrane pore.
T4SS (Type IV Secretion System)
- Modification of conjugation pilus, secreting proteins only or proteins plus DNA.
- Allows bacterial pathogens to inject proteins into host cells from their cytoplasm or periplasms.
- Found in Agrobacterium tumefaciens and Bordetella pertussis.
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Description
Explore the intricate relationships between microbes and their hosts in this quiz on pathogenesis. Understand how pathogens like Shigella flexneri and Pneumocystis jirovecii interact with different immune systems and the consequences of these relationships. Delve into the mechanisms of infection and the tools used to study these deadly microorganisms.
