4 - Recognition and Response Flashcards
What are 2 reasons why immune cells need to interact with each other?
eliminate pathogen | activate other immune cells
What is signal transduction?
binding interaction of receptor and cognate ligand »_space;> intracellular molecular pathway »_space;> cellular response
What kind of bond do receptors must have with their ligands and why? (non-covalent or covalent)
non-covalent; if covalent = eliminates receptors since it cannot be used as there is no available binding site
What is affinity?
strength of an individual bond (one interaction)
What is avidity?
the combined strength of ligand-receptor binding of multiple interactions
What is the relationship between avidity and affinity?
an interaction may have a weak affinity but all together = high overall avidity
What are the 4 molecular changes in the receptor induced by ligand-receptor binding?
conformational change | dimerization/clustering | change location on membrane | covalent modification (phosphorylation)
What is the area called when receptors change their location on the membrane due to ligand-receptor binding?
lipid rafts
What molecule is commonly associated with lipid rafts?
cholesterol
What are the 3 forms that immune receptors can take shape?
cytosolic (not most common) | secreted | membrane-bound
What are the 3 common features of the immune receptor-ligand interactions?
have immunoglobulin domains | transmembrane, cytosolic, or secreted | no carboxyl terminus on secreted form
When would a protein lose its carboxyl terminus?
post-transcription due to splicing
What are 2 characteristics of immunoglobulin domains?
contains sticky amino acids = stick to things non-covalently | spacing = due to disulfide bonds
What cells have chemokine receptors? What do these receptors recognize?
all cells | chemokines
What cells have cytokine receptors? What do these receptors recognize?
all cells | cytokines
What kind of receptors are chemokine receptors?
G-protein coupled receptors
What are the 2 tasks that the rapid innate immune response allows PRRs to carry?
eliminate pathogen via phagocytosis/cytotoxicity | initiate adaptive immune response via cytokine/chemokine secretion
What molecules do PRRs recognize?
PAMPs
What are PAMPs? (not what it stands for)
motifs of recurring patterns on bacteria, yeast, and parasites
What are the 2 forms can PRRs take the shape of?
integral membrane proteins | intracellular proteins (not secreted)
What is antigen specificity of antibodies dictated by?
interaction between the light/heavy chain variable regions
What is the function of the constant heavy regions of the antibody?
antibody effector activity such as phagocytosis
Which region of the antibody binds to the Fc receptor?
constant region
What is the antigen binding site on the antibody called?
Fab
Which receptor has a higher avidity, TCRs or BCRs? Why?
BCRs because TCRs only bind to one MHC molecule
Which region on the antibody can change isotypes? How many isotypes are there? What are those isotypes?
constant region | 5 isotypes = G, A, M, E, D (GAMED)
Why must BCRs form a B-cell receptor complex with other molecules on the membrane that are involved with signal transduction?
BCRs do not have a cytoplasmic region
Where can peptide sources for T-cell initiation be from?
both from exogenous (foreign) or endogenous (within us) processed antigens
What BCRs complex with to induce an intracellular signal?
ITAMs
What are ITAMs? What are they composed of?
immunoreceptor tyrosine activation motif (ITAM) that gets phosphorylated during activation | Ig-alpha and Ig-beta
What is the function of Ig-alpha and Ig-beta for the ITAM?
enzymes that dimerize and phosphorylate each other = kinases
What is similar about T-cells and B-cells in terms of their receptors?
T-cell receptors also have a constant and variable region
Which region on the T-cell receptor binds to the MHC molecules?
variabe
What is the common type of T-cell? (alpha/beta or gamma/delta)
alpha/beta
What is CD3 and what does it recognize?
gene cluster, cytosolic in T-cell | recognizes T-cell receptor
What is the function of CD4 and CD8?
stabilize interaction to occur for a longer period of time until T-cell fully becomes activated
When is the only time that MHC molecules are expressed? Are they always expressed?
not always expressed — expressed/present on surface ONLY if there is a peptide bound to it
What are cytokines?
proteins that communicate among other immune cells
What is a cytokine signal?
any event that induces a cell to change metabolically or its proliferative state | cytokine signaling = change in transcriptional program of target cell
What are the 3 types of extracellular signaling?
paracrine | endocrine | autocrine
What is paracrine signaling?
affects cells nearby
What is endocrine signaling?
affects cells far away - travel via circulation
What is autocrine signaling?
cell affects itself
What are the 5 properties of chemokines and cytokines?
pleiotropic | redundant | synergy | antagonistic | cascade
What is the pleiotropic property of chemokines and cytokines?
a chemokine/cytokine can affect different cells and make it carry out different functions
What is the redundant property of chemokines and cytokines?
a chemokine/cytokine has the same effect on a target cell that other chemokines/cytokines also have
What is the synergy property of chemokines and cytokines?
a group of more than one chemokine/cytokine unite to carry out a function on one target cell together
What is the antagonistic property of chemokines and cytokines?
a chemokine/cytokine inhibits the activity of another chemokine/cytokine
What is the cascade property of chemokines and cytokines?
a chemokine/cytokine is involved with the production of more chemokine/cytokines
What kind of cytokine is interleukin-1 (IL-1)? What produces it?
innate-immune cytokine = pro-inflammatory (causes inflammation = fever) | macrophages and dendritic cells produce IL-1
What receptor must be activated to induce production of IL-1? What is it stimulated by?
PRRs | all pathogens
What are the 5 families of cytokines?
Interleukin-1 (IL-1) | Interleukin-17 (IL-17) | Class I | Interferons (IFN - classes 1 and 2) | Tumor-Necrosis Factor (TNF)
Which cytokines are antiviral? Which family and class do they belong to?
IFN-alpha | IFN-beta = Type I interferons
What secretes Type I interferons?
activated macrophages and dendritic cells
What is the function of Type I interferons?
induce ribonucleases synthesis | inhibit protein synthesis
What secretes/produces Type II interferons?
activated natural killer cells and T-cells
What is the function of Type II interferons?
activates macrophages to make them more phagocytotic and a better APC
What are the Tumor-Necrosis Factors (TNF) cytokines?
regulates development, effector function (ie: apoptosis), and homeostasis of cells of the skeletal, neuronal, and immune system
What 2 forms can TNF cytokines take the shape of?
soluble (secreted) or membrane bound
What is TNF-alpha?
pro-inflammatory role | commonly seen with IL-1 and IL-6
What is TNF-alpha produced from?
macrophages and other cell types
What is IL-17 cytokine?
pro-inflammatory cytokine more involved with mucosal tissues | transmembrane protein
Are most cytokines secreted, cytosolic or membrane-bound?
secreted - unless stated otherwise
What is the effect of chemokines on leukocytes?
directs lymphocytes to move towards chemokine signal/source via chemotactic proteins
What are chemokines?
chemotactic proteins
What signaling pathway do TCRs, BCRs, and PRRs undergo?
tyrosine phosphorylation
What signaling pathway do chemokines undergo?
Ras/MAP kinase cascade - G-coupled chemokine receptor = activates transcription
What signaling pathway do cytokines undergo?
JAK/STAT pathway = induces dimerization of receptor = activates gene expression
What are the 5 things that antigen signaling includes?
bringing dendrites to site | macrophages and neutrophils = increase phagolysosome activity and cytokine production | cytoplasmic proteosomes break down antigen = peptides | dendritic cells exhibit peptide on MHC | dendrites induced to make cytokines and chemokines
