immune receptor-ligand interactions Flashcards
how does cell communication occur?
via cytokines and receptors, soluble factors, surface molecules, and antigen presentation
what are PAMPs?
pathogen-associated molecular patterns, i.e., a piece/fragment of a bacterial pathogen (ex. LPS on Gram-negative bacteria). They are recognized by pattern recognition receptors (PRRs) or sensors. PAMPS binding to PRRs initiates an immune response
what are Toll-like receptors?
TLRs are a type of PRR that are located on the cellular membranes of leukocytes involved in innate immunity mechanisms. They are trans-membrane signal receptor proteins
how many different TLRs do humans have?
10 (lack TLR11, TLR12, TLR13)
what is the function of extracellular TLRs?
to detect molecules found outside of the cells
where are intracellular TLRs found?
in the wall of endosomes, located inside the cell
what is the effect of TLR activation?
cell signalling activation/repression, gene expression, production of inflammatory mediators including cytokines, chemokines, etc.
what is the definition of a cytokine?
a low-molecular weight protein that regulates cell function and shapes the immune response
what do sensor cells do?
constantly monitor host tissues for any foreign body/pathogen, i.e., constantly looking out for any stress or danger in the host.
When they sense something wrong, they activate the production of cytokines
autocrine
the cell producing the cytokine is its own target cell
paracrine
the target cell is in close proximity to the cell secreting the cytokine
endocrine
the cytokine needs to travel through the bloodstream to reach the target cell
what is pleiotropy?
different biological effects that are induced depending on the nature of the target cell
what is redundancy in regards to cytokine attributes?
two or more cytokines mediate similar functions
what is synergy?
combined effect of two or more cytokines on cellular activity is greater than the additive affects of the individual cytokines. induces a class switch to IgE
what is antagonism?
effect of one cytokine inhibits the effect of another
what is cascade induction?
action of one cytokine on a target cell causing that cell to produce one or more additional cytokines
how does the immunity system avoid an infinite feedback loop where there is uncontrolled inflammation?
production of anti-inflammatories such as IL-10, non-immunity related hormones, and soluble or membrane-bound TNFs
what is the role of chemokines?
provide signals to immune cells to help them traffic to site of inflammation, homing to organs/tissues
what are the cytokine receptor types?
- interleukin-1
- class 1 cytokine receptors
- class II cytokine receptor family
- TNF receptor family
- chemokine receptor
what are Il-1 receptors?
monomeric and inhibitor ligands with only the heterodimeric receptor able to transduce a signal. Il-1 receptors change in ratio of functional and inhibitor receptors to modulate the immune response
Class I cytokine receptors
receptor that most cytokines bind to, and are made up of at least two subunits: alpha and beta subunits. these subunits explain the redundancy and antagonism of some cytokines
class II cytokine receptor
also known as the IFN (interfeuron) family. Made up of three types of IFNs and are characterized as heterodimers. the family consists of 12 different receptor chains that in their various assortments, bind to at least 27 class II cytokines
TNF receptor family
cytokines that are trimers and can either be membrane-bound or soluble. these receptors can also act as decoys, preventing cytokines from binding to membrane-bound receptors.
Il-17 receptor family
mostly proinflammatory, IL-17 cytokines are secreted as dimers, and receptors are either dimeric or trimeric, and can be homo or hetero dimers/trimers
what is the role of chemokines? what are characteristics of chemokines
influence cell movement, i.e., chemotaxis. chemokines have a tertiary structure which is determined by the presence of highly-conserved disulfide bonds; the position of these bonds determine classification
what receptors do chemokines act on?
G protein coupled-receptors
what happens in consequence to cell signaling upon ligand binding?
production of cytokines, receptor expression, cell polarization, change in cell metabolism
what is mediator of the negative feedback loop to ligand binding?
SOC3, prevents tyrosine phosphorylation of STAT
what are the varying levels of cytokine receptors based on?
strength of signal binding and transduction, based off number of subunits within one receptor
what do varying levels of cytokines influence during hematopoeisis?
proliferation and differentiation, as well as cell polarization and functions