Dendritic cells & complement system

bridge between innate and adaptive immunity

professional antigen-presenting cell (most efficient APC)

only APC able to activate naive T-cells

constitutive MHC class II expression

antigen uptake in peripheral sites & antigen presentation

derive from common myeloid progenitor

leave bone marrow and immature circulating in the blood

in peripheral tissue also resident immature DC

activated —>maturation due to extravasation or migration to draining lymph node

exists in genetically deficient mice & observed in humans (IRF8 deficiency autosomal recessive)

loss of circulating monocytes & all types of DC

highly susceptible to infections of all kinds —>no adaptive immune response

form network of sentinel cells

waits to sense infection

conventional DC = myeloid cells

cDC1: express CD8aa, main subset involved in cross-presentation, TLR3+, produce IL-12 (Th1—>polarization & IFNγ production)

cDC2: express CD4, mostly extracellular antigen presentation bacteria to CD4+ cells, TLR3-, produce IL-23/-6 (Th17)

plasmacytoid DC (non-conventional): TLR9, virus recognition, produce type I IFNs

B-cells

monocytes

first recognized DC from the skin

express langerin (CD207)

part of cDC2

define conditions to generate wanted cell type from blood precursors

monocytes via GM-CSF & IL-4 tp Mo-DC (monocyte-derived DC)

hematopoietic pluripotent stem cell (CD34+) via GM-CSF & TNFa to Langerhans cells

intensively used for infusion in cancer patients after pulse with tumor antigens

DC activation in peripheral tissues

CCR7 induction (receptor recognizing cytokines from the lymph node)

Migration to draining lymph node (in T-cell zone)

Upregulation of MHC and costimulatory molecules (B7)

Stop processing of antigens (want antigen from tissue)

mature DC enters lymph nodes from infected tissues and transfers antigens to resident DCs

B7-positive DC stimulates naive T-cells

lymph node

mucosa-associated lymphoid tissue (MALT)

spleen

C1q interacts with pathogen surface or with Abs bound to the surface

after initial binding interaction with

• C1r (activates protein cascade, protease)

• C1s (activates protein cascade)

• C4 (surface-binding protein & opsonin)

• C2 (activates protein cascade)

mannose-binding lectin and ficolins recognize and bind carbohydrates on pathogen surface

recruitment of

• MASP-2 (protease)

• C4

• C2

properdin activates cleavage of C3 by factor D&B after binding of carbohydrates on cell surface on pathogen

all pathways generate C3 convertase cleaving C3b bound to the microbial surface & releasing C3a

—>C3a & C5a recruit phagocytic cells to the site of infection and promote inflammation

—> Phagocytes with receptors for C3b engulf and destroy the pathogen (opsonins)

—>completion of complement cascade leads to formation of a membrane-attack complex MAC disrupting cell membrane and causes cell lysis (formation of pores)

for opsonisation: CR1-4 (CR3&4 are integrins)

for inflammation C5a & C3a (chemokine-like function)

FDC

resident DC from SLO in the germinal center

no hematopoietic origin

soluble factors:

• C1 inhibitor displaces C1r/s & MASP-2 inhibiting activation of C1q & MBL

• C4-binding protein displaces C2a (cofactor for C4b cleavage of factor I)

membrane-bound factors:

• decay accelerating factor displaces Bb and C2a from C3b and C4b respectively

• Membrane-cofactor protein

• protectin inhibits MAC formation