Recognition and Response Flashcards
Signal
Any event that changes the state of a cell (usually through altered gene expression of cell)
How signals are generated
Binding of ligand to complementary membrane receptor
How cells regulate signals
Change level/expression of ligands
Change level/expression of receptors
Alter intracellular machinery that transmits signal from cell surface to nucleus
Change activity or location of transcription factors
Molecular changes to receptor caused by ligand binding
Alteration in receptor conformation
Receptor dimerization or clustering
Change in receptor location within cell membrane
Are ligand-receptor interactions covalent?
No- strong (high affinity), but need to be able to engage and disengage
Affinity
Measure of strength of interaction
Avidity
Overall strength of collective interactions
How many identical binding sites to antibodies have?
2
Most common intracellular protein modification in signalling
Phosphorylation
Usually occurs on tyrosine, serine, or threonine residues
Kinase
Enzyme that transfers a phosphate group (usually from ATP)
Phosphatase
Removes phosphate group
Reverses actions of kinase
Only isotype that is a true B cell receptor
IgM: only isotype that can send signals
B cell receptor parts
2 heavy chains, 2 light chains
Variable region at top, constant region at bottom
Molecules that are considered to be B cell receptors
Antibodies
Co-receptors required by B cell receptors to transmit signal
Ig alpha and Ig beta
Contain immunoreceptor tyrosine-based activation motifs (ITAMs) that become phosphorylated to start signal transduction
How B cell receptor activation works
Antigen-mediated clustering -> phosphorylation of Ig alpha and Ig beta -> activation of transcription factors
How T cell receptor activation works
Engagement of MHC + antigen -> conformational change -> phosphorylation of adapter proteins (collectively called CD3)
CD3
T cell receptor co-receptor (signal transmission)
Contains immunoreceptor tyrosine-based activation motifs (ITAMs)
CD 4 or CD 8
CD 4 : T-helper cells
CD 8 : T-cytotoxic cells
Co-receptors
Participate in interaction with antigen-presenting cell via interaction with MHC molecule
Receptor sharing of cytokines
Ability for increased signaling
Endocrine action
Cytokines acting on distant cell, usually of another type
Paracrine action
Cytokines acting on a neighboring cell of same or different type
Autocrine action
Cytokines act on cell that secretes them
What cytokines are used for
Cell communication
Pleiotropy of cytokines
One cytokine can act on many different cells
Redundancy of cytokines
Several cytokine types can have the same activity
Interleukin 1 family
Cytokines: inflammatory response
Produced by activated macrophages and epithelial cells
Class 1 cytokine family (hematopoietins)
Cytokines: immunocyte differentiation
Interferons (class II cytokines)
Cytokines: anti-viral responses
Tumor necrosis factor family
Cytokines: immune system development, effector functions
TNF alpha: cell killing, fever, cytokine cascades, vascular endothelial cell adhesion for neutrophils
TNF alpha is produced by macrophages and NK cells
Interleukin 17 family
Cytokines: neutrophil accumulation
Chemokines
Cytokines: chemoattractants (migration of immune cells into inflammed regions, does so through chemical gradient)
Colony-stimulating factors
Promote terminal differentiation of progenitor cells
Stromal cells
Present in bone marrow
Support lymphopoiesis and myelopoiesis
Interferon gamma
Most potent activator of macrophage immune function
Interleukin 2
Primary growth factor for T cell proliferation
Cachectin
Another name for TNF alpha
Too much activity leads to malnutrition
Elevated levels of TNF can lead to what?
Septic shock
Major source of anti-inflammatory cytokines
T helper 2 cells
