Notes
Principles of Infectious Disease, Part 1
Sections
Overview
Virulence
Is a measure of how much damage a pathogen can cause.
Determined by virulence factors, which vary by organism; for example, bacterial adhesions and toxins facilitate host invasion and pathogenic effects.
Asymptomatic Carriers
Infections can be asymptomatic, aka, subclinical, which means that the pathogen exists but does not cause disease symptoms.
Individuals with asymptomatic infections are called "carriers," because they can carry, and, therefore, transmit the infection to others.
Exogenous vs Endogenous
Exogenous infections occur when the pathogen is acquired from the external environment;
– For example, influenza is caused by a virus that individuals "catch" from viral particles in their surroundings.
Endogenous infections are caused by opportunistic pathogens that are members of the host's normal microbial flora.
– For example, the bacteria Staphylococcus aureus, which can cause significant pathology, is commonly found in the human nares.
Be aware that the distinction between exogenous and endogenous infections is sometimes difficult to discern, and can depend on what is considered "normal" microbial flora.
Common routes of pathogen entry:
Skin
Typically blocked physically, by the stratified epithelium of the epidermis, and chemically, by antimicrobial defensins and fatty acids.
When these barriers fail, microorganisms from the surface of the skin, such as the bacteria Staphylococcus aureus, gain entry.
Other organisms take a more aggressive approach: for example, the larvae of the parasitic flatworm Schistosoma release enzymes to destroy keratinocyte bonds, thus actively creating their own means to entry.
Respiratory Tract
Protected by mucus and cilia that clear harmful materials, and by phagocytic alveolar macrophages in the lungs.
However, some microbes have adaptations to override these protections:
– The influenza virus uses hemagglutinins to bind respiratory epithelial cells.
– The bacteria Mycobacterium tuberculosis survives the phagolysosomes of the alveolar macrophages.
Gastrointestinal Tract
Epithelial lining of the gastrointestinal tract provides multiple sources of protection: the gastric glands produce a viscous layer of mucus, acids, and enzymes to trap and disable pathogens.
The normal gut flora prevents pathogenic microorganisms from colonizing.
However, when antibiotics kill the microbial flora, Clostridium difficile can flourish, leading to diarrhea.
Poliovirus is an example of a microorganism that gains entry by "high jacking" normal host physiology: it appears that gut lymphoid tissue, which naturally pulls antigens into the circulation, may likewise take up poliovirus and facilitate its spread.
Urogenital Tract
The vagina is protected by microbes that maintain an acidic pH.
However, when these microbes eradicated by antibiotics, the yeast Candida albicans can flourish.
The urinary tracts of both males and females are protected by thick layers of epithelia, as we can see in the histology sample; furthermore, urination "flushes" microbes from the urethra.
However, the bacteria Escherichia coli has special adhesion molecules that allow it to adhere to the urothelium; attachment is especially likely if urination is obstructed.
Dissemination:
Entry: Pathogens enter through a breach in the epithelia or mucosa.
Peripheral Nerves: Inside the host, some pathogens infect peripheral nerves and travel along their axons.
For example, the Varicella-zoster virus, which is responsible for chickenpox, can lead to serious central nervous system complications, especially upon later reactivation.
Cellular & Plasma Travel: Other pathogens travel within macrophages and other cells, or move freely in the plasma.
Dissemination: the lymph and blood vessels can deliver pathogens that cause systemic infections or organ-based pathologies.
Tropism
Some pathogens, especially neurotropic viruses and certain parasites, are tissue trophic.
Infect specific tissues, are therefore associated with characteristic disease patterns.
Stages of Infectious Disease:
Incubation stage
– The time between the acquisition of the pathogen and the onset of symptoms.
Prodrome stage
– Nonspecific symptoms, such as fever or tiredness, occur.
Disease-specific symptoms
– Increase rapidly
Recovery
– As the host immune system and/or treatments effectively reduce the number of pathogens, symptoms decrease (also called the convalescence stage).
Health
– Ultimately, symptoms disappear and the individual returns to health.
– However, some individuals may become chronic carriers of the infectious agents or develop latent infections that can reoccur.
Immune system evasion:
Antigenic Variation
Allows microbes to change their surface antigens to evade antibody recognition.
Peptides & Pores
Some microbes, such as Staphylococcus aureus, resist pore insertion or eject the peptides of innate immune system defensins.
Phagocytosis Avoidance
Some microbes use their external capsules to avoid phagocytosis, disrupt phagolysosome fusion within neutrophils, or even directly kill phagocytes.
Block Complement Pathway
Some microbes block the complement pathway, and, therefore, prevent formation of the membrane attack complexes (MACs) that provoke lysis.
Decoy receptors
Some viruses have evolved "decoy" receptors that weaken INF effects; another tactic is to inhibit pathways downstream of the IFN receptors.
Latency
Some viruses, including herpes simplex and Epstein-Barr, hide in latency, potentially re-activating when opportunities arise.
Infect Lymphocytes
HIV virions infect CD4+ lymphocytes, which ultimately suppresses the immune response.
The host's own immune response to pathogens is often a significant source of damage in infectious disease.