chapter 3 Flashcards
any event that instructs a cell to change its metabolic or proliferative state
cellular signal
How are cell signals usually generated?
binding of a ligand to a complementary cell-bound receptor
How can a cell become more or less susceptible to actions of a ligand?
by increasing or decreasing expression of the receptor for that ligand
What type of bonding occurs between receptor-ligand and why?
multiple non-covalent bonds bc covalent are too strong
Describe the strength of the bond between ligand-receptor?
each individual bond is weak but deliver a total strong binding affinity
a measure of strength of ligand binding
dissociation constant (kd)
Receptor-ligand interactions may be _______valent
multivalent
Multivalency increases ____________of the interactions
avidity
the strength of an individual bond
affinity
What is avidity?
the combined strength of binding of multiple interactions
An interaction may have _______affinity but ___________ overall avidity
weak, high
Ligand-receptor binding induces molecular change in the receptor:
- Conformational
- Dimerization/clustering
- Location in the membrane
- Covalent modification
Receptor alterations induce cascades of intracellular events:
- Activation of enzymes
- Changes in intracellular locations of
molecules
Immune Receptors bear immunoglobulin:
domains
Immune receptors can be:
transmembrane, cytosolic, or
secreted
What is a fancy word for antibody?
immunoglobulin
What is the state of the immunoglobulin that is secreted?
it is lacking the carboxyl terminus transmembrane segment
contains an antibody of defined specificity
B-cell receptor (BCR)
specificity is for peptides derived from APC degraded antigen presented on MHC molecules
T-cell receptor (TCR)
T-cell coreceptors that define different subsets of T-cell function
CD4 & CD8
A quaternary protein with two identical heavy chains and
two identical light chains
antibody
Why is it called heavy/light chain?
the molecular weight is higher in the heavy chain
Antigen specificity is by the interaction between:
light/heavy chain variable regions
What are some functions of the interaction of the constant regions of the heavy chain?
antibody effector activity, phagocytosis, and complement fixation
what type of bonds holds the antibody together?
intra/interchain disulfide covalent bonds
The segment of an immunoglobulin heavy chain between the Fc and Fab regions. It gives flexibility to the molecule and allows the two antigen-binding sites to function independently.
hinge region
What does Fab stand for?
fragment antigen binding
What does Fc stand for?
Fragment crystallizable
What is found at the antibody combing site?
Three hypervariable regions of amino acids found in variable heavy (VH) and variable light (VL) regions
What is CDR1, CDR2, and CDR3?
complementarity-determining regions/antibody combining site
Interspersed near each CDR is an ___________________ that forms the framework region and is responsible for the folding of the CDRs to form the antibody combining site
invariant amino acid
What does the constant region consist of?
distinct classes of antibody called isotopes
What are the isotypes of the constant region of the heavy chain?
IgA, IgD, IgE, IgG, IgM
What are the isotopes of the constant region of the light chain?
Kappa and Lambda
transduce signals via ITAMs
Igα & Igβ
transmit and relay signals to cell interior
CD19, CD81, CD21
What complex does IgA consist of?
dimer
What complex does IgM consist of?
pentamer
What does ITAM stand for?
immunoreceptor tyrosine-based activation motif
Antibody molecules form a B-cell
receptor (BCR) complex with
molecules involved in:
signal transduction
Two TCR types _________________have diverse antigen binding characteristics
αβ (majority) and γδ
TCR recognizes and binds both ______________________ to which peptide is bound
antigen-derived peptide and MHC
Peptide sources can be from:
endogenously or exogenously processed antigens
The T-cell receptor (TCR) complexes
with coreceptor involved in:
antigen recognition
contains ITAMs that
transmit signal to cell
CD3 complex
function in increasing avidity of peptide binding by TCR
CD4, CD8
engages CD80 or CD86 on APC to fully activate a naive T cell
CD28
secreted, low-molecular-weight proteins that regulate the intensity and duration of the immune response by exerting a
variety of effects on lymphocytes and other immune cells that
express the appropriate receptor.
cytokine
cytokines are also referred to as_____________
interleukins
a group of low-molecular-weight cytokine that affect
chemotaxis of leukocytes
chemokine
describe properties of most cytokines
-soluble proteins
-released by one cell
-bind to receptors on another cell
-induce biological effects
TNF are what type of cytokine
membrane-bound
how are cytokine signals usually generated?
binding of ligand to its receptor
What type of binding is cytokine-receptor binding?
noncovalent
Cytokine-signaling end results often induce a change in the _________________________ of the target cell
transcriptional program
any event that instructs a cell to change its metabolic or proliferative state
cytokine signal
cytokine endocrine action:
released into the bloodstream to effect distant cells
cytokine paracrine action:
released to effect nearby cells
cytokine autocrine function:
released, but then bind to receptors on the cell that produced them
induces different biological effect dependent
on target cell
Pleiotropic activity
mediates similar effects on target cell
Redundant activity
combines two cytokine activities to be greater
than additive effect
Synergy effect
inhibits one cytokine’s effect by another’s
action
Antagonistic effect
effect of one cytokine on one target cell to produce
additional cytokine(s)
Cascade
-the first noninterferon cytokine to be identified
-Members of this family include important inflammatory mediators
Interleukin-1 family
Members of this large family of small cytokine molecules exhibit striking sequence and functional diversity.
Class 1 (hematopoietin) cytokine family
While the IFNs have important roles in antiviral responses, all are important modulators of immune responses.
Class 2 (interferon) cytokine family
Members of this family may be either soluble or
membrane-bound; they are involved in immune
system development, effector functions, and
homeostasis.
Tumor necrosis factor family
This is the most recently discovered family; members function to promote neutrophil accumulation and activation, and are
proinflammatory.
Interleukin-17 family
All serve chemoattractant function.
Chemokines
-promote inflammation
-stimulated by viral, parasitic, or bacterial antigens
-Secreted very early in immune responses by macrophages and dendritic cells
-Acts locally on capillary permeability and to pull leukocytes to infected tissues
-Acts systemically to signal the liver to produce acute phase proteins
IL-1 family
describe class I cytokines:
-diverse in action and cell target
-single protein family
-made up of multiple subunits
-IFN-α and IFN-β are 18–20 kDa dimers with antiviral effects
-Secreted by activated macrophages and dendritic cells
-Induce synthesis of ribonucleases and inhibit protein synthesis
Type I interferons
-Dimer produced by activated T/NK cells
-Potent modulator of adaptive immunity
Type II interferon (IFN-γ)
-Secreted by plasmacytoid dendritic cells
-Upregulate genes controlling viral replication and host cell
proliferation
Type III interferon family (IFN-λ)
regulates development, effector function, and homeostasis of cells of the skeletal, neuronal, and immune system
Tumor Necrosis Factor (TNF)
N-terminal vs C-terminal regions of TNF cytokines:
-Short intracytoplasmic N
-Longer extracellular C
Generally Type 2 transmembrane proteins form as _______________when binding to TNF receptor-1
trimers
proinflammatory and produced by activated
macrophages and other cell types
TNF-α
produced by activated lymphocytes, delivering signals to leukocytes and endothelial cells
TNF-β (lymphotoxin-α)
-proinflammatory molecules expressed on a variety of cells
- Receptors found on neutrophils, keratinocytes, and other
nonlymphoid cells
-Tend to work at the interface of innate and adaptive immunity
IL-17 family cytokines
what is the function of chemokines?
they direct leukocyte migration
describe the structure of chemokines:
-Small (7.5–12.5 kDa) proteins
-Possess highly conserved disulfide bonds that dictate both structure and category (six categories)
-Share two, four, or six conserved cysteine residues
Chemokine receptors are an example of _______________
receptors
G-protein-coupled
Chemokine receptors transduce signals via interactions with a polymeric________________
GTP/GDP-binding G protein
T/F: Many receptors can bind to more than one chemokine; and several chemokines are able to bind to more than one receptor
true
how do chemokines direct leukocyte migration?
Signaling through chemokine receptors helps cells move to different body areas
Integration of all signals received by a cell occurs______________________
at the molecular level inside the recipient cell
Antigen-mediated _______________initiates signaling in B
and T cells
receptor clustering
Clustered receptors are localized in________________
lipid rafts
an early step in many signaling pathways
Tyrosine phosphorylation
CD3 (T cells) and Igα/β (B cells) are phosphorylated on____________
ITAMs
Phosphorylated tyrosines serve as docking points for _____________molecules
adapter
Which kinases phosphorylate tyrosines?
Src-family
Antigen signaling includes:
- Bringing dendritic cells into the required locations
- Macrophages and neutrophils upregulate phagolysosome
activity and cytokine production - Dendritic cells exhibit antigen peptides on MHC class I and
MHC class II - Cytoplasmic proteasomes process antigen to peptides
- Dendritic cells induced to secrete cytokine
