genomewide characterization of host-pathogen interactions by ...

Maren Depke
Introduction
Neutrophil granulocytes are another group of phagocytes. They are found in the blood stream
and leave it only at sites of infection. During an infection, the numbers of neutrophils can
increase strongly, but these cells are only short-living. Phagocytes recognize pathogenic
structures by membrane PRRs. Binding to the pathogen initiates phagocytosis. First, the
pathogen is enclosed in the phagosomal compartment, which afterwards fuses to lysosomes.
Lysosomes bring enzymes and antimicrobial mediators to the new phagolysosomal compartment
and finally accomplish killing of the pathogen in a process called respiratory burst, during which
enzymes produce toxic reaction products like H 2 O 2 , O 2 – , and NO under consumption of O 2 , the
name-giving effect. During activation, phagocytes produce cytokines and chemokines, which lead
to a pro-inflammatory reaction and to chemotaxis of further immune cells like monocytes and
neutrophils (Janeway et al. 2002).
Aspects of Adaptive Immunity
A third type of phagocytic cells, dendritic cells, links the innate to the adaptive immune
system. These cells ingest different antigens in the peripheral tissue by phagocytosis and
macropinocytosis and and transport them to the lymph nodes, where non-activated cells of the
apaptive immune response wait for an activation trigger. Dendritic cells are the mediator cells
which relay the information of peripherally present antigens and therefore potential infection to
cells which might bear the specific receptor to these antigens. The information is transferred in a
process called antigen presentation. It involves major histocompatibility complex (MHC)
molecules. The complex is formed either by an α-chain with transmembrane domain and a noncovalently
linked beta-2-microglobulin (B2M) molecule as β-chain in class I type of MHC or by an
α- and a β-chain which are both inserted in the membrane in class II type of MHC (Fig. I.2 A).
MHC-I α-chains and MHC-II α- and β-chains form a binding groove for antigen derived peptides
and are encoded in the genome in a highly polymorph manner. Only B2M is encoded by a single
gene. The two types of this complex, class I and class II, present antigenic peptides from different
origin to subsets of T cells, which in turn possess a receptor for MHC-peptide-complexes, the
T cell receptor (TCR).
A
Fig. I.2:
Antigen presentation to T cells via MHC molecules.
A. T cell receptor (TCR) mediated recognition of a peptide antigen bound
to an MHC-derived molecule.
B. Activation of naïve T helper cells requires the presence of co-stimulatory
molecules, e. g. B7.
Abbreviations:
MHC – major histocompatibility complex; APC – antigen presenting cell
From: Andersen et al. 2006.
B
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