Immunology Overview Flashcards
Downstream TLR mediators
NOD-1 and NOD-2
Cytosolic proteins containing N-terminal CARD (caspase related) domains. They are specific for bacterial peptidoglycans, which are common components of bacterial cell walls. They both activate the NF-κB transcription factor. Some polymorphisms of the NOD2 gene are associated with inflammatory bowel disease; the underlying mechanisms remain poorly understood.
NLRP-3
NOD-like receptor family, pyrin domain containing 3
A cytosolic NLR that responds to many unrelated microbial structures or pathologic changes in the cytosol. It contains an N-terminal pyrin domain (so named because it is present in receptors that induce the production of fever-causing cytokines). NLRP-3 recognizes microbial products, ATP, uric acid crystals derived from nucleic acids, and changes in intracellular potassium ion (K + ) concentration; and endogenous substances that are deposited in cells and tissues in excessive amounts (e.g., cholesterol crystals and free fatty acids).
After recognition of these varied substances, NLRP-3 oligomerizes with an adaptor protein and an inactive (pro) form of the enzyme caspase-1, resulting in generation of the active form of the enzyme. Active caspase-1 cleaves a precursor form of the cytokine interleukin-1β (IL-1β) to generate biologically active IL-1β. This cytosolic complex of NLRP-3 (the sensor), an adaptor protein, and caspase-1 is known as the inflammasome. There are also other caspase-1 activating inflammasomes that contain different sensor proteins besides NLRP3.
NLRP-3 Inflammasome Activation
NLRP-3 and Gout
The deposition of urate crystals that is characteristic of gout may also result in chronic NLRP-3 activation and IL-1b-mediated inflammation.
RIG-like receptor Family
recognizes RNA produced by viruses in the cytosol and activates signaling pathways that lead to the production of type I interferon (IFN)
Cytosolic DNA sensors
Several structurally related proteins that recognize cytosolic viral DNA and also induce type I IFN production
Lectin receptors
Receptors in the plasma membrane are specific for fungal glycans (these receptors are called dectins) and for terminal mannose residues (called mannose receptors); they are involved in the phagocytosis of fungi and bacteria and in inflammatory responses to these pathogens.
Innate lymphoid cells
Produce cytokines and perform functions similar to those of T lymphocytes but do not express T cell antigen receptors.
ILCs have been divided into three major groups based on their secreted cytokines; these groups correspond to the Th1, Th2, and Th17 subsets of CD4 + T cells. The responses of ILCs are often stimulated by cytokines produced by epithelial and other cells at sites of infection. ILCs provide early defense against infections and also guide the subsequent T cell response.
NK Cell Effector Mechanisms
NK Cell Activating Ligands
IL-15
IL-12
Type I IFNs
IL-15 is important for the development and maturation of NK cells, and type I IFNs and IL-12 enhance the killing functions of NK cells.
NKG2D
NK Cell activating receptor
Recognizes molecules that resemble class I major histocompatibility complex (MHC) proteins and are expressed in response to many types of cellular stress.
antibody-dependent cellular cytotoxicity
NK cells are the principal mediators of ADCC.
Fc receptors on NK Cells are crosslinked and their ITAMs are activated. ITAMs activate downstream tyrosine kinase cascades and lead to cytotoxic granule exocytosis and IFN-γ production.
Families of NK Cell Inhibitory Receptors
killer cell immunoglobulin-like receptors (KIRs)
CD94/NKG2
Both families bind Class I MHC and contain ITIMs, which activate tyrosine phosphatases.
NK-T cells
Express TCRs with limited diversity and surface molecules typically found on NK cells. They are present in epithelia and lymphoid organs. They recognize microbial lipids bound to a class I MHC–related molecule called CD1.
