Pathogenesis Flashcards
Colonization vs. infection
Colonization - without harming the body
Infection - microbes damage tissues (directly via proliferation or actions of virulence factors or by stimulating the immune response)
Possible outcomes of infection
Horizontal transmission
Pathogen transmission
- Inhalation
- Ingestion
- Wound
- Sex
- Blood-to-blood
- hand/hand, hand/eye, hand/mouth, or mouth/mouth
Vertical transmission
Pathogen transmission
Pathogens passed from mother to fetus or infant - can occur in utero (antenatal/prenatal) or in the days/weeks immediately before, during, or after birth (perinatal), or after birth (postnatal)
Arhtropod vectors
mosquitoes, ticks, fleas, and mites
Quorum sensing
Mechanisms microbes use to assess the density of the local cell population allowing them to coordinate virulence factor production
Important to biofilm formation becuase it regulates polysaccharide matrix production
QSM compounds: usually acylated homoserine lactones, peptides, or alcohols
A/B subunit toxins
B - binds to host cell surface
A - enters host cell and performs the action of the toxin
B binds
A has activity
Intracellular Pathogen Cytopathic effects (CPE)
- Cell lysis
- Vacuolation
- Inclusion body formation
- Cell fusion
- Parasitophorous vacuole (PV)
- Transformation
Botulinim toxin action
A/B subunit toxin
Cholera toxin action
A/B subunit toxin
B - binds to ganglioside GM1 on intestinal epithelial cells
A - enters cell and activates adenylate cyclase - increases cellular cAMP - results in the secretion of electrolytes and water into the intestinal lumen
Cytolethal distending toxins
A/B subunit toxin
Cause host cell DNA damage - cause senescence in immune cells, but also increases the possibility of cancer-causing mutations
Pore forming toxins
Hemolysins are one type of bacterial pore forming toxins - leak or lyse RBCs
Superantigens
Cause non-specific activation of T cells and professional antigen presenting cells which results in systemic release of inflammatory cytokines
i.e. S. aureus secretes a superantigen - causes toxic shock syndrome
What immune cells target intracellular pathogens
Cytotoxic T cells, neutrophils and NK cells
Pro-inflammatory mediators
Type I interferons (IFN-alpha/beta) and inflammatory cytokines (IL-6, IL-1beta, and TNF-alpha)
Systemic Inflammatory response syndrome (SIRS)
Systemic circulation of DAMPs/PAMPs results in cytokine storm and other mediators - in which disseminated intravascular coagulation and severe hypotension can lead to shock, ischemic tissue damage, multiorgan failure, and death
How do pathogen virulence factors transform host cells?
- Inactivate the host cellular growth suppressors p53 and Rb
- Increase activity of host cell growth activators (hormones and cytokines)
- Inhibit apoptosis - pathogens inhibit p53 and/or other apoptosis pathway factors - or by inducing mutations in host genes encoding these regulatory proteins
- Producing genotoxins that damage host cell DNA, cause incomplete host cell chromosome segregation, or induce host epigenetic changes
- Increasing host cell oxidative stress
Candida albicans
Normal flora distribution
Mouth, colon, vagina
Methods of dissemination
- Direct spread between cells or tissues using virulence factors
- Transversion across epithelial barriers at sites of mucosal associated lymphoid tissues (MALT)
- Hematogenous spread in the bloodstream and/or lymphatics is most common mechanism for systemic dissemination
- Neuronal - some virsues
What age pop. is there the strongest immune response?
Young adults
i.e. chicken pox can be life-threating in a young adult
Direct spread of Listeria monocytogenes
Expresses a virulence protein at one end of the bacterial cell to stimulate polymerization of host cell actin. These “actin comet tails” push the bacteria through the cytoplasm into neighboring cells or the surrounding tissue
Multi-nucleated giant cells
This type of cytopathic effect is typically observbed in host cells infected with enveloped viruses - VAPs/viral fusion proteins are inserted into the host cell plasma membrane
Syncitium
Common cytopathic effect
Fused cells (multinucleated giant cells)
Syncitium
Common cytopathic effect
Fused cells (multinucleated giant cells)
Mechanisms by which pathogens can promote cancer
Immune Mediated Tissue Damage in Response to Pathogen
- CD8+ CTL and NK cell killing of infected cells
- Molecular mimicry and autoimmunity
- Immune complex deposition
- Inflammatory mediators
Host cell mimicry in S. pyogenes infection
IgG/IgM mad against M proteins (streptococcal cell wall proteins) are able to cross react with cardiac tissue - cause rheumatic fever
Activates complement proteins C3a and C5a