Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 108

Secreted pattern-recognition receptors bind to microbe surfaces, activate
classical and lectin pathways of the complement system, and opsonize pathogens
for phagocytosis by macrophages and neutrophils.
Transmembrane pattern recognition receptors reside either in the plasma mem-
brane or on endosomes and lysosomes. Plasmalemmal TLRs recognize conserved
microbial patterns accessible on the cell surface, such as lipopolysaccharides of
Gram bacteria, bacterial lipopro-

teins (TLR1-TLR2 and TLR2-TLR6), and flagellin (TLR5) [ 205 ]. Endosomal
TLRs detect microbial nucleic acids, such as double-stranded RNA (TLR3), single-
stranded RNA (TLR7), and dsDNA (TLR9). C-type lectin domain-containing
proteins CLec7a and CLec6a (dectin-1 and -2) sense

− bacteria (TLR4), lipoteichoic acids of Gram +

β -glucans and mannan on

fungal walls, respectively [ 205 ].
Most, if not all, pattern recognition receptors activate the transcription factors
nuclear factor-

B, interferon regulatory factors, or nuclear factor of activated T cells
to induce both T- (e.g., T H1 ,T H17 ,andCD8

κ

T-cell responses) and B-cell responses
(IgM, IgG, and IgA immunoglobulin-antibody responses) [ 205 ]. Secreted and some
endocytic pattern recognition receptors, such as scavenger and mannose receptors,
cannot induce adaptive immunity by themselves.
Three signals are required for cross-priming that permits dendritic cells to
present exogenous antigens to responding antigen-specific CD8

+

T cells. 96 Sig-
nal 1 (MHC-AG-TCR) constitutes the complex made of peptidic antigen and
major histocompatibility complex class-1 molecule that targets the relevant TCR.
Signal 2 (costimulator) refers to costimulatory molecules such as B7-family
members that ligate T-cell-specific surface glycoprotein CD28. Signal 3 (inflam-
matory cytokine) corresponds to triggering soluble factors, such as interleukin-12
and interferon-

+

α and- β . However, this process needs help that is provided by

CD4 T cells, plasmacytoid dendritic cells, and natural killer T cells that stimulate

chemokine release from cognate dendritic cells (signal 0 : chemokine gradient), i.e.,
upstream from signal 1, to attract CD8

+

+ T cells [ 207 ].

3.9.3 Resistance to Oxidizing Environment

Lymphocytes are exposed to oxidizing environments during inflammation. Helper
T lymphocytes become progressively less sensitive to an oxidizing environment
after differentiation into effector T cells, which affects their ability to proliferate,
differentiate, and secrete cytokines.
In human helper T lymphocytes, calcium influx through Orai family member-
based channels is involved in the cell activation, proliferation, and differentiation.

96 Cross-priming refers to the stimulation of naive CD8 + cytotoxic T cells by cross-presentation,
i.e., when antigen-presenting cells take up, process, and present extracellular antigens with MHC
class-1 molecules.