Toll-like receptors Scavenger Receptors Part of the innate immune response. Let´s talk first. Innate Immunity Pathogen recognized by receptors encoded in the germline: p attern r ecognition r eceptors
Part of the innate immune response
Let´s talk first...
Pathogen recognized by receptors encoded in the germline: pattern recognition receptors
Receptors have broad specificity, i.e., recognize many related molecular structures called PAMPs (pathogen-associated molecular patterns)
No memory of prior exposure
Pathogen recognized by receptors generated randomly: B-cell (BCR) and T-cell (TCR) receptors for antigen
Receptors have very narrow specificity; i.e., recognize a particular epitope after processing
Slow (3 -5 days) response (because of the need for clones of responding cells to develop)
Memory of prior exposure
Anatomical barriers: Skin, Intestinal movement, Oscillation of broncho-pulmonary cilia
N. B. All components of the non-specific immune system are modulated by products of the specific immune system, such as interleukins, interferon-g, antibody, etc.
How does the host organism detect the presence of infectious agents and dispose of them without destroying self tissues? How non-specific is innate immunity really ?
Innate Immune Recognition via Patterns
Functions of membrane bound lectins
produced by dendritic cells and
- MMR, DEC-205 (CD205), and Dectin-2:
Antigen Uptake, DC trafficking.
- Dectin-1 and DC-SIGN (CD209):
T-cell interaction, DC trafficking.
! C-type lectin receptors also recognize
glycosylated virus envelope proteins but
some viruses appear to utilize these
as attachment (& entry?) receptors.
Peiser Infect Immun. 2002;
70 (10): 5346–5354
FIG. 3. EM of N. meningitidis uptake. WT and SR-A-/- BMM were incubated for various times with 150 live MC58 bacteria per cell at 37°C.
At various intervals, the cells were washed to remove extracellular bacteria before being processed and analyzed by EM.
The fields chosen are representative of the whole M population
TLR signaling pathways
Involvement of TLR in Linking Innate Immunity to Adaptive Immunity
Nature Immunology 2001 2:675
Van Crevel, Clin Microb. Rev 15, 294-309, 2002
Phagocytosis and immune
recognition of M. tuberculosis.
Tailleux et al., J Exp Med. 2003;197(1):121-7. : „DC-SIGN is the major Mycobacterium tuberculosis receptor on human dendritic cells“.
Complement receptor (CR)3 and mannose receptor (MR), which are the main M. tuberculosis receptors on macrophages, appeared
to play a minor role, if any, in mycobacterial binding to DCs.
The mycobacteria-specific lipoglycan lipoarabinomannan (LAM) was identified as a key ligand of DC-SIGN.
Zhang and Ghosh: Toll-like receptor-mediated NF-kB activation:
a phylogenetically conserved paradigm in innate immunity
J Clin Invest 107, 13-19, 2001
C-type lectins as DC antigen receptors
C-type lectins in DC trafficking