1
Q
Innate immune defense mechanisms
A
- Physical barriers
- Phagocytic cells
- NK cells
- Plasma proteins incl complement, APRs, cytokines
2
Q
How microorganisms cause disease
A
- Contact OR enter host cells + directly cause cell death
- Release of toxins / enzymes that cause damage
- Induction of host immune response -> additional
tissue damage
3
Q
Tropism
A
= affinity of a virus to infect certain cells + NOT others
4
Q
Factors affecting tropism
A
- Expression of host cell receptors for the virus
= major determinant - Presence of cellular transcription factors that
recognise viral enhancer + promoter sequences - Anatomical barriers
- Local temp / pH / local defenses
5
Q
MoA of viral inj
A
- Direct cytopathic effects
- Antiviral immune responses (mostly mediated by
cytotoxic T lymphocytes) - Transformation of infected cells into benign OR
malignant cells
6
Q
Biofilm
A
Communities of bacteria form a viscous layer of extracellular polysaccharides that adhere to host tissues or devices such as IDC or prostheses
Increase adherence to host tissues
Increase virulence of bacteria by making them inaccessible to immune effector mechanisms + increasing their resistance to antimicrobials
7
Q
MoA of bacterial inj
A
- Bacterial adherence to host cells
- Virulence of intracellular bacteria
- Bacterial toxins
8
Q
Endotoxin
A
Lipopolysaccharide = large component of outer membrane of gram -ve bacteria
Activates protective immunity
However, +++ LPS -> septic shock / DIC / ARDS
- Through induction of excessive cytokines
e. g. TNF / IL-1 / IL-12
9
Q
Exotoxin
A
Secreted proteins cause cellular inj + disease
- Enzymes
- Alter intracellular signalling OR regulatory pathways
- Neurotoxins
- Super antigens
10
Q
5 major histologic patterns of tissue reaction in infections
A
- Suppurative inflamm. (purulent)
- Mononuclear + granulomatous inflamm.
- Cytopathic / cytoproliferative
- Tissue necrosis
- Chronic inflammation + scarring
11
Q
Factors affecting pathogenicity
A
- Age
- Nutritional state
- Hygiene
- Immune status
- Presence of foreign devices
- Microbial factors
12
Q
Example of resistance to phagocytosis
A
S.pneumoniae - polysaccharide capsule inhibits phagocytosis
S.pyogenes - M protein inhibits phagocytosis
13
Q
Virulence factors
A
- Colonisation factors
- Adherence / attachment
- Surface receptors / target sites
- Invasion factors
- Toxigenicity
- Resistance of phagocytosis
14
Q
Superficial surgical infection
A
Confined to the skin + / or subcutaneous tissue
15
Q
Deep surgical infection
A
Involving fascia or muscle
16
Q
Organ / space surgical infection
A
Any part of the body, eclipsing skin / fascia / muscle, that is opened OR manipulated during operative procedure
17
Q
Example of enterotoxin
A
E.Coli toxin O157:H7
Produces haemorrhagic colitis / HUS
18
Q
Enterotoxin
A
= subclass of exotoxin
Extracellular bacterial proteins that exert their activity in the GIT
19
Q
Peptidoglycans
A
Carbohydrate stalks X-linked w/ transpeptides
Confers characteristic cell shape + provides mechanical protection to the cell
Transpeptide X-links are the target for B-lactam ABx
20
Q
LPS
A
Found on the surface of the outer plasma membrane of gram -ve bacteria
Composed of lipid A core + polysaccharide O Ag
Released upon lysis of bacterial cell
Lipid A = endotoxin activity -> SIRS in gram -ve septicaemia
21
Q
Morphology of S.aureus
A
Gram +ve (purple) cocci in clusters
22
Q
Morphology of S.pyogenes
A
Gram +ve (purple) cocci in chains
23
Q
Morphology N.gonorrhea / N.meningitidis
A
Gram -ve (pink) diplococci
24
Q
Contributing factors toward ABx resistance
A
- Inappropriate use - prophylaxis vs. Rx
- Failure to complete courses
- Hospital overcrowding
- Lack of isolation facilities
- Failure in environmental cleanliness / general
infection control measures
25
Colonisation sites of S.aureus
Nose + perineum
Varies w/ age - young >old
26
S.epidermidis
Coag -ve staph
Skin commensal
Normally = non-virulent
FBs are susceptible to non-virulent commensals e.g. prosthetic joints
27
B lactam ABx
Bactericidal = interference w/ X-linking of peptides w/ peptidoglycan backbone
Widely distributed into joints / pleura / pericardium / bile / saliva etc
Renally excreted
28
Penicillin resistance
Production of B-lactamase enzyme -> breakdown of B-lactam ring -> non-functional
29
Methicillin
Lab indicator ABx to detect fluclox resistance
30
TSS CFs
1. Generalised erythematous rash -> desquamation
2. Renal failure
3. Hypotension
4. High temps
31
Path of TSS
Production of super Ag (exotoxin)
Binds to conserved portion of MHC + T cells -> massive activation of T cells -> overwhelming cytokine release
Mimics septic shock caused by LPS in gram -ve sepsis
32
Vancomycin
Glycopeptide ABx
Bactericidal = inhibits cell wall synthesis
NOT absorbed by the gut
33
SE of vancomycin
1. Ototoxicity
| 2. Nephrotoxicity
34
Main groups of strep
1. Pyogenic strep = B haemolytic, GAS / GBS
2. Enterococcus = y-haemolytic, GDS
3. Pneumococcus = a-haemolytic, no lancefield
4. Viridans = multiple strains, N flora of PO cavity
35
Types of haemolysis (strep)
a = partial haemolysis (green)
b = complete haemolysis (clear)
y = no haemolysis
36
Causative organisms for necrotising fasciitis
1. S.pyogenes
2. Progressive bacterial synergistic gangrene
- Gram -ve bacillus (e.g. coliforms) / S.pyogenes
37
Clinical presentations for necrotising fasciitis
1. Fournier's gangrene = perineum
| 2. Meleney's disease = abdominal wall
38
C diff path
Disturbance of normal gut flora (mainly anaerobes)
-> C diff overgrowth
Largely secondary to broad-spectrum ABx affecting normal gut anaerobes
Clindamycin + 3rd gen cephalosporins
39
C diff spread
Via spores that are EXTREMELY resistant to death
Resistant to:
- Heat
- Stomach acid
- EtOH based hand rubs
40
C.tetani
Gram +ve bacilli w/ terminal spores giving the appearance of drumsticks w/ gram staining
Grows in soil, manure + rust
41
C.tetani path
Release exotoxin (tetanospasmin), which prevents GABA release
Results in blocking inhibitory nerve impulses -> localised OR generalised tetanic spasms
42
Tetanus prone wounds
1. Puncture type if contaminated w/ soil / manure
2. Extensive tissue devitalisation
3. Containing FBs
4. Development of sepsis
5. Compound #'s
6. >6h between injury + surgery
43
C.perfringens
Gram +ve bacilli that lives in soil
Obligatory anaerobe
Produces many exotoxins (n=14), produce gas gangrene
44
B.fragilis
Gram -ve bacilli
Normal flora of the gut, non-spore forming anaerobe
45
M.tuberculosis
Acid fast bacillus, poor gram stain (ZN stain)
Obligate aerobe
Infects macrophages + resists fusion of phagosome w/ lysosome
46
TB pathology
1. Endocytosed by macrophage
2. Replicates inside macrophage
- Resists destruction by preventing fusion of
phagosome + lysosome
3. <3/52 bacteria proliferate in pulm alveolar
macrophages / airspaces
4. @ 3/52 -> Th1 response mounted -> produce IFN-y ->
activates bactericidal macrophages
5. Th1 also facilitates formation of caseous necrosis /
granulomas
6. Macrophages coalesce to from giant cells
7. Either immune response halts infection or is insufficient +
progression of causation / cavitation
47
Ghon focus
Area of grey white inflammation with consolidation secondary to FX of Th1 (epitheliod granuloma formation)
48
Ghon complex
Combination of parenchymal lung lesion + nodal involvement
Undergoes progressive fibrosis w/ calcification -> Ranke complex
49
N.gonorrhoea
Gram -ve diplococcus (coffee bean appearance)
Usually sexually transmitted
Aerobic
Can cause reactive arthritis (Reiter's syndrome)
50
Bacteria that grows on "chocolate" agar
Neisseria spp
Aerobic bacteria w/ stringent nutritional requirements + grows best on enriched media -> lysed sheep's blood agar = "chocolate" agar
51
N.meningitidis
Gram -ve diplococcus
Colonizer of oropharynx -> infects resp epithelial cells -> septicaemia -> meninges
Major cause of bacterial meningitis <2yo
52
C.trachomatis
Small gram -ve bacteria
Obligate intracellular parasite
Most common STD in the world
53
Path of chlamydia
x2 forms:
1. Infectious form = elementary body
- Metabolically inactive, spore-like structure
2. Metabolic form = reticulate body
- Replicates + forms new EB
54
Fitz Hugh Curtis Syndrome
Rare Cx of PID involving liver capsule inflamm (perihepatitis) -> creation of adhesions
55
Structures of a virus
1. Envelope
2. Capsid - made up of structural units called
capsomeres
3. Genome - RNA OR DNA
56
Serology techniques
1. ELISA
2. Immunofluorescence
3. Complement fixation
4. Agglutination
57
Detection of viruses / virus particles
PCR
58
Hep B
DNA virus
Endocytosed into cells then replicates using reverse transcriptase
Acute infection ranges from asymptomatic hepatitis to fulminant hepatic failure
10% progress to chronic infective state - either as asymptomatic carrier or chronic hepatitis
59
HBsAg
Surface Ag
Indicator of infection (active or chronic)
60
HBeAg
Forms part of core Ag
Indicates active replication + high infectivity
61
Categories for equipment disinfection / sterilisation
1. Critical = enters sterile tissue + MUST be sterile
2. Semicritical = contacts mucus membranes + requires
high level disinfection
3. Non-critical = comes in contact w/ intact skin +
requires low level disinfection
62
Critical items
MUST be sterilised
Steam sterilisation if possible
If heat sensitive -> other options e.g. hydrogen peroxide gas plasma, ozone, ethylene oxide
63
Liquid chemical sterilants
NOT ideal unless absolutely necessary
Because:
1. Can only produced sterility if cleaned prior to
treatment
2. May require washing w/ H2O (which may not be
sterile)
3. Difficult to maintain sterility following processing +
during storage
64
General method of sterilisation
1. High temp
2. Low temp
3. Liquid immersion
65
Semicritical items
Used for contact w/ mucus membranes / non-intact skin
Minimum requirement = high level disinfection using chemical disinfectants
Assoc. w/ re-processing erros as margin of safety < than sterilisation
E.g. hydrogen peroxide, glutaraldehyde
66
x3 categories for Dx of infection
1. Identification of microorganisms by isolation + culture
2. Identification of specific microbial product
e. g. cell wall Ag / toxins / specific gene sequences
3. Detection of specific Ab to pathogen
67
Time for culture to produce a result
18h
68
ELISA
Enzyme linked immunosorbent assay
Employing an enzyme label to detect a particular Ag through binding to Ab
69
Non-cultural techniques for lab Dx
Microscopy
Detection of microbial Ag
DNA probes
PCR (DNA amplification)
70
Dark field microscopy
Useful for observing motility + thin cells such as spirochete
71
Detection of microbial Ag
1. Detection of Ag by interaction w/ specific Ab -> clumping
2. Detection of microbial toxins
+ve = rapid
-ve = sensitivity NOT great, false +ve possible secondary to cross reacting Ag
72
Solid agar media
Bacteria
Fungi
73
Liquid agar media
Parasites
74
Basic micro identification
1. Gram reaction
2. Cell morphology (coccus / bacillus) + arrangement (chains / pairs / clusters)
3. Aerobic vs. anaerobic growth
4. Growth requirements (simple / fastidious)
75
Advanced micro identification
1. Enzyme detection tests
2. Metabolism of sugars
3. Ability to use a range of substrates
76
Sulfonamides
Inhibit folate synthesis in bacteria
Bacteriostatic = inhibits growth of bacteria
e.g. Sulfamethoxazole
77
Trimethoprim
Inhibit folate synthesis in bacteria
Bacteriostatic = inhibits growth of bacteria
Can add in combination w/ sulfamethoxazole -> co-trimoxazole = greater effect
78
Detailed MoA of B lactams
Binds to penicillin-binding protein on bacteria + inhibits transpeptidation enzyme that X-links peptide chains attached to the backbone of the peptidoglycan
79
Cephalosporins
Interference w/ peptidoglycan synthesis after binding to B-lactam binding proteins
80
Alternate MoA for B-lactam resistance other than B-lactamase
Reduced penetration of ABx as a result of:
1. Alterations to outer membrane proteins
2. Mutations of bind site proteins
81
Carbapenems
Act in the same way as other B-lactams
Very broad spectrum of antimicrobial activity
82
Tetracyclines
Bacteriostatic = inhibits protein synthesis after active transport into bacterial cell
SE = photosensitivity, GI upset
e.g. doxycycline
83
Aminoglycosides
Bactericidal = inhibit protein synthesis
Rely on O2 dependent active transport (therefore, minimal effect on anaerobes)
Enhanced by agents that interfere w/ cell wall synthesis
E.g. doxycycline
84
SE of aminoglycosides
Ototoxicity
Nephrotoxicity
85
Gentamicin SE
More likely to interfere w/ vestibular function rather than auditory function
Nephrotoxicity
86
Macrolides
Bactericidal = inhibit protein synthesis by an effect on translocation
Binds to 50S ribosome
e.g. Clarithromycin / Erythromycin / Azithromycin
87
Lincosamides
= clindamycin active against gram +ve cocci
Inhibition of protein synthesis similar to macrolides
Used to Rx staph inf of bones + joints (wide distribution in tissues)
88
Clindamycin SE
GI upset
C.diff infection
89
Fluoroquinolones
Inhibits topoisomerase II (bacterial DNA gyrase)
- Enzyme permits transcription OR replication
- Interferes w/ supercoiling of DNA
Broad spectrum gram +ve / gram -ve coverage best for facultative + aerobic gram -ve rods + cocci
Antacids (Al + Mg based) interferes w/ absorption of the quinolones
Pathology
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