genomewide characterization of host-pathogen interactions by ...

Maren Depke
I N T R O D U C T I O N
INFECTIOUS DISEASES AND IMMUNE SYSTEM
Humans and animals regularly encounter microorganisms like bacteria and need to defend
themselves in order to avoid or limit damage of their own organismal integrity.
Before any possibly dangerous interaction could occur, they first aim to prevent the nearer
contact by physical mechanisms. Dry, closely connected skin surfaces impede the settlement of
microorganisms, and inner surface epithelium often uses mucus as trapping and rinsing agent or
creates unfavorable conditions e. g. by low pH in the stomach. Such physical barriers cannot
completely prevent colonization. A commensalism of certain microorganisms has been
established. But this is not a disadvantage: The occupation of interaction surfaces by apathogenic
commensals limits the available habitat for pathogens.
Additionally, the host organism has developed active defense mechanisms. On the one hand,
general defense factors are produced in advance and deposited at potential interaction sites.
Such factors, like lytic enzymes or defensin peptides, will exert their properties without further
assistance of the host’s physiological systems. These factors can additionally be further induced
after initiation of the immune response. On the other hand in case of a successful infection by a
pathogen, the host is able to start reaction cascades, which will be activated and enhanced after
contact with the pathogen. The host possesses receptors which bind conserved structures of
pathogens. This enables the host to recognize the infection, initialize alarm cascades, and
activate further antimicrobial factors, which are prepared as inactive precursors. The host also
activates the blood coagulation cascade and by this means aims to confine infection to specific
sites and to reduce spreading. Also cellular defense processes are initiated in sequence of
pathogen infiltration into the body, where a first step is pathogen-unspecific phagocytosis by
macrophages or neutrophils. In the later phases of infection, the host can adapt even more
specialized defense systems to react to the specific infecting agent on a humoral and cellular
level. This approach needs more time, but is most effective and finally enables the host to
overcome the infectious disease.
Aspects of Innate Immunity
Many pathogens possess conserved structures. These can be related to their outer structure
like peptidoglycan of the bacterial cell wall, but also to the very basic genetic information like the
double-stranded RNA constituting the genome of some viruses. Some of them are essential for
the pathogen and therefore highly conserved during evolution. In their co-evolution, both sides,
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