Download CNS Infections

Immune Evasion and Antimicrobial Resistance
Evasion of ---/
Resistance
Strategy
Specific Mechanism
Organism
Notes
Phagocytosis/
Macrophages
Capsule
S. Pneumo, H. Flu, N.
Meningitidis, Klebsiella,
Salmonella,
Cryptococcus
neoformans
Inhibits phagocytosis
Catalase
Staph
Break down H2O2
Phagolysosome fusion
inhibited
Mycobacteria,
Legionella
Escape phagosome
Sialic Acid expression
Listeria
N. Meningitidis
Using listeriolysin (forms pores)
Inhibits C3, C5 convertase
Coated w/ IgA
N. Meningitidis
IgA antibodies don’t activate complement
M protein
Strep
Blocks C3 binding to organism and C3b
binding to complement receptors by
binding fibrin, fibrinogen to its surface
Long O Antigen chains
(LPS)
Modified LPS
“smooth” GNB
(Salmonella, E. coli
strains)
Pseudomonas
MAC prevented from accessing outer
membrane; “rough” strains (little O
antigen) not as virulent
Resists action of peptide antibiotics
Protein A
S. aureus
Binds Fc portion of IgG: camouflage
IgAases
N. gonorrhea,
meningitidis, H. flu
these extracell proteases that cleave IgA
at hinge region, fragments ineffective
IL-10 secretion
EBV
Inhibition of macrophage activation
Soluble cytokine receptor
production
Poxviruses
Immune modulator
production
Tapeworn (tenia)
Slime layer
Staph epidermidis
Phase variation
N.gonnorhea
Complement
Peptide Antibiotics
(innate immunity)
Antibody
Response
Immune
Modulation
Misc. Immune
Evasion
Block proteasomal activity
EBV, CMV
Can turn on/off exp of several Opa
proteins (antigenic variants)/diff LPS
genes by gain/loss of CTCTT repeats
(shifts reading frame)
Turn on/off fimbriae exp. (fimA) by
inversion of DNA segment w/ promoter
MHC class I affected
Block in TAP transport
HSV
MHC I affected
Remove class 1 from ER
CMV
MHC 1 affected
E. coli
Antigen
Presentation
(MHCs)
Cysticerci produce paramyosin,
taeniastatin- inhibit complement, bind
antibody, interfere w/ CMI
Exopolysaccharide secreted-resistance to
phagocytes and adherence to plastics
(entry)
Antigenic Variation
Vary Surface Antigens
E. Coli
N. gonorrhea
Influenza
HIV
Trypanosomes
Malaria
Pilin genes
Homologous recombo of pillin genes (Pil
E exp, Pil S “silent”)
Point mutations/genetic recombination of
segemented RNA genome
Hypervariable regions in nonconserved
glycoproteins (ex. exposed regions of GP
120)
VSGs (variant surface glycoproteins),
clonal expansion of organisms coated by
another VSG as immune resp develops,
variation rate 10-2-10-6, over 1000 so
“exhausts” immune sys
Var (variety) gene family encoding
PfEMP-1 proteins, every 10-6/10-7
organism shifts to diff var genes, takes
~18 months to run through family
Display host antigens
Schistisome Larvae
S. pyogenes
HIV
Treponema pallidum
Shed antigen coat
Meninges
Necrotic Tissue
Modified peptidoglycan
precursor
B-lactamases
Ameba
N. meningitidis
Clostridia
Enterococci (VRE)
Methicillin
PBP2a (on mec A gene)
S. Aureus (MRSA)
Fluoroquinolones,
tetracyclines,
macrolides
Aminoglycosides
Efflux pumps
GNB, pneumococcus
Block transport
Inactivating enzymes
GNB (gram – bacteria)
Staph
Anatomic
Sequestration
Vancomycin
Penicillin/ BLactams
S. Aureus, et al
Covered in host glycolipid, MHCs
hyaluronic acid coat mimics host surface
covered by polysacch side chains added
by host enzy
Cardiolipin, other major surf lipoproteins
thought to derive from host
D-ala-lactate not D-ala-D-ala
PBP that “went wrong”
Gram +: secrete extracell., resis cannot
be overcome by giving more drug,
Gram -: constitutive production, can
overcome resis. w/ more drug
Novel penicillin binding protein
Inactivate active trans across membrane