In tissues and fluids

1
In tissues and fluids 1. Complement virulenc
e mechanisms for evasion a. do not bind
and/or activate complement - polysaccharide
capsules b. cause inhibition of activation
and amplification cascade - bind factor H (M
protein of streptococci) c. degrade
complement - secrete proteases d.
complement receptor homologs (viruses) e.
secrete complement homologs C4b homolog
(vaccinia virus) inhibits C cascade
2
2. Phagocytes - beyond mucosal surface i.
EXTRACELLULAR vs. INTRACELLULAR pathogens ii.
extracellular antiphagocytic functions
?inhibit recruitment - inhibit complement,
cytokines ?kill the phagocytes - toxins
?prevent phagocytosis - prevent opsonization,
prevent binding (carbohydrate capsules) iii.
intracellular pathogen functions ?inhibit
phagosome-lysosome fusion ?escape
phago(lyso)some into cytoplasm ?inhibit
oxidative burst ?resist antimicrobial functions
3
Cytokines

• IL-1
• B13R protein of vaccinia virus inhibits ICE (IL-1
  converting enzyme), preventing formation of
  IL-1ß, down regulating inflammation and
  inhibiting apoptosis
• B15R protein of vaccinia virus - IL-1 receptor
  homologous
• TNF-a
• pox viruses secrete TNF receptor homologs that
  can bind TNF-a
• Interferons
• IFN-? receptor homologs secreted by myxoma virus
  and vaccinia virus
• IFN-a/ß receptor homologs secreted by vaccinia
  virus
• Vaccinia virus E3L and K3L proteins inhibit
  different parts of IFN-mediated intracellular
  antiviral functions

4
Figure 11-5
5
Immune Host c. Antibodies i. antigenic
mimicry - surface components look like host
?polysialic acid capsule of Neisseria
meningitidis ii. antigenic cloaking - bind host
proteins to bacterial surface ?protein A of
Staphylococcus aureus iii. antigenic variation
- change antigenic composition ?pili of
Neisseria gonorrhoea ?Hemagglutinin of
Influenza virus (shift and drift) iv. antigenic
variety -numerous serological types among strains
in the world (each strain is antigenically
stable) ?M protein of Streptococcus
pyogenes v. degrade antibodies ?IgAse of
Haemophilus influenzae
6
Figure 11-3 part 2 of 2
7
Figure 11-1
8

• d. Cell-mediated immunity
• ?alter host response from cell-mediated (Th1) to
  antibody (Th2) response - Mycobacterium leprae
• M. leprae - intracellular pathogen of macrophages
  - replicates within macrophages
• Antibodies (Th2-regulated) are ineffective and
  probably detrimental
• Cell-mediated immunity (Th1 regulated) is
  protective
• M. leprae causes some people to produce primarily
  an antibody response by affecting cytokine gene
  expression (lepromatous leprosy)
• People who make CMI responses have mild disease
  (tuberculous leprosy)

9
Figure 11-6
10
Humoral and Cell-mediated

• Latency of viruses
• hide out until the coast is clear (many Herpes
  viruses)
• Varicella zoster (chicken pox) re-emerges later
  in life as shingles after being latent in nerve
  ganglia

11
Figure 11-4