790 immunology of infectious disease 3 7 2013 bieneke bron n.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
790 Immunology of Infectious Disease 3/7/2013 Bieneke Bron PowerPoint Presentation
Download Presentation
790 Immunology of Infectious Disease 3/7/2013 Bieneke Bron

Loading in 2 Seconds...

play fullscreen
1 / 32

790 Immunology of Infectious Disease 3/7/2013 Bieneke Bron - PowerPoint PPT Presentation


  • 71 Views
  • Uploaded on

Sailing on the cell surface. 790 Immunology of Infectious Disease 3/7/2013 Bieneke Bron. Outline. Background Trypanosoma Antigenic variation Hydrodynamics Paper Figures Summary Discussion. Trypanosoma bruceii.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about '790 Immunology of Infectious Disease 3/7/2013 Bieneke Bron' - wenda


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
outline
Outline
  • Background
    • Trypanosoma
    • Antigenic variation
    • Hydrodynamics
  • Paper
    • Figures
    • Summary
  • Discussion
trypanosoma bruceii
Trypanosomabruceii

http://www.ilri.org/InfoServ/Webpub/fulldocs/Ilrad88/Trypanosomiasis.htm

  • Unicellular hemoflaggelate
  • Vector: tsetse fly
  • Disease: sleeping sikcness
    • Human & livestock
    • Africa, Asia, South America
trypanosoma life cycle
Trypanosoma life cycle

1960 almost disappeared

Surveillance relaxed

40.000 – 300.000 cases/year

1990 new efforts to control the disease started

2009 <10.000

No vaccine

trypanosoma survival strategies
Trypanosoma survival strategies

Antigenic variation of surface coat

Clearance of surface bound antibodies

Immune suppression

cyclus antigenic variation
Cyclus: Antigenic variation

Nature Reviews Microbiology10, 431-438

hydrodynamics
Hydrodynamics

the branch of science concerned with the mechanical properties of fluids

http://www.no.adeptnordic.com/products/dataanal/tecplot/showcase/studies/2005/gwu.htm

paper main question
Paper – main question

How are antibody – VSG complexes sorted on the cell surface?

How are they cleared from the cell surface?

Thus this give immunological protection?

figure 2
Figure 2

37C

24 C

☐ 18 C

12 C

6 C

figure s1
Figure S1

VSG

IgG

conclusion figure 1 2
Conclusion: Figure 1 & 2

Direction movement of cell surface IgG-VSG toward the posterior end of the cell and the subsequent rapid endocytosis provides a very efficient mechanism to clear immune complexes from the surface.

table 1
Table 1

Clearance on population

=

Clearance on single cell

figure 5
Figure 5

Forward swimming

Reversed swimming

take home figure 3 4 5
Take home figure 3,4,5
  • Immune complex redistribution:
    • Provides resistance to complement*
    • Dependent on directional motility of the trypanosoma
    • Independent of
      • Endocytosis
      • Actin skeleton
  • Do we agree?
hydrodynamics for dummies
Hydrodynamics for dummies

r = radius of the IgG 7.5 nm

R = mean diameter of tryp. 3 um

v = mean velocity of the IgG TBD

vt = mean velocity of tryp. 20 um/s

n = viscosity of bloodstream 0.03 kg/(s*m)

Assuming no slip conditions and a cylinder shaped trypanosoma

v = r vt/ R

v = 7.5*10-3 * 20 / 3 = 0.05 um/s

v = 15*10-3 * 20 / 3 = 0.1 um/s

hydrodynamics for dummies1
Hydrodynamics for dummies

Mean velocity of IgG in no slip conditions = 0.05 um/s

Average length of trypanosoma = 20 um

Estimate of T ½ IgG = (0.5 * 20) / 0,05 = 200 seconds

Estimate of T ½ +/-IgM = (0.5 * 20) / 0.1 = 100 seconds

Not even close..

table 11
Table 1

Larger structures

Shorter half-life

summary
Summary
  • Direction movement of cell surface IgG-VSG toward the posterior end of the cell and the subsequent rapid endocytosis provides a very efficient mechanism to clear immune complexes from the surface.
  • Immune complex redistribution:
    • Provides resistance to complement*
    • Dependent on directional motility of the trypanosoma
    • Independent of
      • Endocytosis
      • Actin skeleton
  • Hydrodynamic drag force is a good model for the complex movement over the cell (sailing on the cell surface).
  • Thus: T. brucei evolved another subtle defense strategy besides antigenic variation, in which directional cell motility and plasma membrane recycling function cooperatively in the removal of host antibodies from the cells surface.
discussion
Discussion
  • Why would the endocytosis of stumpy cells increase?
  • What could be an explanation for just having one location for endocytosis?
discussion1
Discussion
  • If you were a bloodborne parasite, what immune evading strategy would you use of this repertoire or what would you add to make it more efficient?
  • What could be the next step of this research?
    • For medicine development
    • For academic curiosity