Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 107

the TCR-induced increased density of the 70-kDa TCR ζ -chain-associated protein

(ZAP70). In the thymus, CD4 cells arise from distinct subsets

of double-positive thymocytes that possess different kinetics and sensitivities to
stimulation of T-cell receptors. ZAP70 kinase determines the cell sensitivity to TCR
stimulation, thereby enabling the selection of CD4

+ and CD8 +

+ and CD8 + fate [ 204 ].

3.9.2 Sensing of Endo- and Exogenous Molecules

Immunocyte receptors are able to sense microbial components (danger signals) as
well as endogenous molecules generated during injury (damage signals) such as
ribonucleoprotein complexes released from dead cells. Self nucleic acids must not
be mistaken for microbial products to avoid autoimmunity. Endogenous agonists
of Toll-like receptors TLR2 and TLR4 probably trigger signals distinct from those
of microbial ligands, hence may not activate adaptive immune responses due to
the engagement of different coreceptors. On the other hand, tumor cells produce
small-molecular-weight fragments of hyaluronic acid, biglycan, and versican that
can stimulate TLR2 and/or TLR4 receptors [ 205 ].
T cells can recognize 3 types of substances [ 206 ]: (1) ligands of MHC-related
and -unrelated T-cell receptors, such as MHC class-1-like CD1c plasmalemmal

glycoprotein and phosphoantigens; (2) various types of cell-surface molecules,
such as retinoic acid early transcript RAE1 and MHC class-1 polypeptide-related
sequence MICA that engage natural killer receptors (NKR; e.g., NK group-2
member-D [NKG2d] that is also called killer cell lectin-like receptor KLRk1); and
(3) danger- (DAMP) and pathogen (PAMP)-associated molecular patterns sensed by
pattern recognition receptors, such as Toll-like receptors and dectin-1. 95
Pathogen-specific innate immune recognition activates antigen-specific adaptive
immune responses. Pattern recognition receptors (Vol. 3 - Chap. 11. Receptors
of the Immune System) of the innate immune system detect relatively invariant
molecular patterns found in most microorganisms of a given class, the so-called
pathogen-associated molecular patterns.
Microbial pattern recognition receptors can be categorized into [ 205 ]: (1)
secreted (collectins, ficolins, and pentraxins); (2) transmembrane (Toll-like recep-
tors and C-type lectins); and (3) cytosolic types (retinoic acid-inducible gene RIG-
1-like [RLR] and nucleotide-binding domain and leucine-rich repeat-containing
[NLR] receptors).
Cytosolic pattern recognition receptors — RLRs — detect viral material such as
RNA, recruit adaptor Mitochondria antiviral signaling protein (MAVS), and activate
nuclear factor-

γδ

B and interferon regulatory factor IRF3 [ 205 ].
Intracellular sensors — NLRs — recognize degradation products of peptidogly-
cans and microbial products, among others.

κ

95 I.e., dendritic cell-associated C-type lectin; a.k.a. C-type lectin domain family-7 member CLec7a
and

β -glucan receptor.