Action & characteristics of pathogens Flashcards
Where do bacteria try to hide from immune response?
- Sites poorly protected by immune cells: e.g., cholera in GI tract, salmonella in intestinal and biliary tracts
- w/in cells (intracellular bacteria) – in macrophages (Brucella, Listeria, M. leprae, M. TB) or other cells (Yersinia, Shigella, Listeria, E. coli)
How do intracellular bacteria survive in macrophages
- Salmonella secrete products that alter environment of phagolysosome
- N. gnorrhoeae, Brucella bortus, S. aureus produce catalase and superoxide dismutase to destroy toxic oxygen products produced by the hexose monophosphate shunt
- S. aureus also produces cell-bound pigment (carotenoid) that quenches singlet oxygen
- Some bacteria escape cell –> secrete lysins to break down phagosome membrane and bacteria are relased into cytoplasm to multiply
- Some prevent phogosome-lysosome fusion (TB, T. gondii)
Surface coats as a pathogen defense mechanism
Polysaccharide Capsule that suppress complement activation to inhibit phagocytosis, also have surface receptors to bind host cells, and toxins (e.g., e coli)
Important consideration when treating hypermutable genes like pseudomonas
- Need TWO antibiotics. W/in 24-48 hrs, producing a strain resistant to first abx. You see them getting better then suddenly fever back and WBC back. C&S shows resistant to abx
- Esp important if pt is immune compromised, pseudomonas – potential for shock. IF you miss it, give 2 new ones.
Important factors that affect bacterial virulence and infectivity
- Iron – needed to multiply
- Polysaccharide capsules
- Toxin production
- Presence in blood (bacteremia or septicaemia)
What do bacteria need from the host to multiply and how does this sometimes manifest in the host?
- Must have iron to multiply – they have siderophores (iron receptors)
- Septic patiens sometimes present with false iron-deficient anemia:
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Examples of pathogenic bacteria that normally reside in humans w/o causing disease
Streptococcus pyogenes (pharyngitis), S. pneumonia (pneumonia, meningitis), Neisseria meningitides (meningitis), Haemophilus influenzae type b (meningitis)
Gram pos vs Gram neg bacteria
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- Gram neg
- thin peptidoglycan capsule.
- LPS coat (an endotoxin), causes most of immunogenicity
- Gram +
- thick peptidoglycan layer
- surface protein on top of peptidoglycan layer
- both capable of mobility
Action and characteristics of exotoxins
- Enzymes released during bacterial growth causing specific responses
- Include cytotoxins, neurotoxins, pneuotoxins, enterotoxins, hemolysins
- Immunogenic
- Elicit antitoxin production (Abs try to neutralize)
- –> vaccines available for many exotoxins
- Elicit antitoxin production (Abs try to neutralize)
Action and characteristics of endotoxins
- Lipopolysaccharides contained in the cell walls of gram-negative organisms
- Lipid A component responsible for toxic effects
- Pyrogenic effects –> why they’re called “pyrogenic bacteria”
- Can be released during bacterial membrane during growth or tx w/antibx, so antibiotics cannot prevent toxic effects
- Activates almost every aspect of inflammation!!
- Behind gram- sepsis/septic shock!
What type of toxins are behind septic shock?
- Gram negative! (most often)
- The lipopolysaccharides/endotoxins elicit a number of responses – activate coagulation cascade (DIC), induce release TNF-alpha (cachectin) by macrophages
Image: What do macrophages do in response to LPS exposure?
- Try to eat. Produce lots of TNF and IL-1 which lowers iron and induces fever. TNF and IL-1 also incite T cells to release INF-gamma, which stimulates macrophages to get more involved.
- TNF, IL-1, IFN-gamma circle is very important!
Effect of LPS on PMNs
Mobilize PMNS –> significant inflammation in epithelial cells –> increased vascular permeability
Effect of LPS on mast cells
IgE mechanisms from LPS triggers mast cell mediators –> vascular permeability.
Effect of LPS on PLTs
- Release of mediators leading to vascular permeability
- Leads to DIC thrombosis
Effect of LPS on liver
Hypoglycemia
LPS and DIC thrombosis
d/t interaction btwn LPS, PLTs and clotting factors
What cytokines does LPS trigger
- Successive waves of cytokine production
- TNF, IL-1, IL-6, IL-8
- Also NO, PAF, other mediators
How do macrophages interact with LPS?
- LPS binding protein presents bound LPS to toll-like receptors on the macrophages
- In conjunction with CD14, they create a complex capable of producing IL-1, TNF, IL-6, IL-8 and PLT activating factors (macrophages are what get platelets involved!)
Role of macrophages in LPS
Center piece responsible creation of all mediators and eventual septic shock. This is why recent ICU weapons are anti-TNFs
Book: what does LPS trigger at low, moderate, and high quantities of mediators?
- Low: local - monocyte/macrophage/neutrophil activation, endothelial cell activation, complement activation (C3a, C5a)
- Moderate: more systemic inflammatory responses – fever, acute phase reactants, leukocytosis
- High: septic shock and death– low cardiac output, low peripheral resistance, blood vessel injury, thrombosis, DIC, ARDS
Bacteremia or septicemia
- Presence of bacteria in the blood due to a failure of the body’s defense mechanisms
- Toxins released in the blood cause the release of vasoactive peptides and cytokines that produce widespread vasodilation
What type of bacteria usually causes bacteremia or septicaemia?
Gram negative
Common gram positive organism
Staphylococcus aureus
Common infections of Staph aureus
Infection produced may depend on toxin produced
Folliculitis
- Scalded Skin Syndrome (Exfoliative Toxin) (SSS)
- Food Poisoning (Enterotoxins A-G)
- Toxic Shock Syndrome (TSST-1):
- Endocarditis
- Pneumonia
- Carbuncle, Furuncle
- Impetigo
- Wound Infection (esp DM)
Concern with folliculitis d/t Staph aureus
If toxic, can lead to scalded skin syndrome
Enterotoxin: presentation and duration
not that dangerous but looks like it. Lots of cramps, feel like death. Appears w/in hours of ingestion, lasts 7-8hrs.
Pneumonia d/t S. aureus: characteristics
- Uncommon in community
- only common if hospital acquired – then MRSA
- presents bilaterally w/some lobar consolidation and effusion
UTI: S. saprophyticus vs staph aureus
- S. saprophyticus often UTI in young healthy female. Fairly benign. Or staph epidermis from skin, foley cath;
- But staph aureus in urine, remember came from the blood! = staph bacteremia until proven otherwise
Infective endocarditis: acute vs subacute course
- acute course; Health individual Came to hospital for CA Pneum, or line placement, S.a. introduced à
- signif fever, chills, deterioration w/in 24-48hrs. At risk for rupture & death.
- Subacute: IV drug users. Weeks of fever, chills, weight loss. Do echo and see huge vegetation on valve. Survive after IV antibx. Needle exchange programs reduce risk.
- Irony: healthy host dies, IV drug user lives. They survive b/c mortality is often from immunogenicity of staph aureus that kills! IV drug user has had number of low dose repeat exposures, so immune response is blunted and we see subacute course.
Viral replication cycle, with image
- Bind
- penetrate
- uncoat
- multiply in nucleus
- either burst cells or use cell export mechanisms to infect other cells
HIV tx all target one of these steps
Characteristics of fungi: size & cell wall
- Large microorganisms with thick cell walls
- Eukaryotes
- Exist as single-celled yeasts, multicelled molds, or both, or dimorphic
