Receptor and Cytokines Flashcards
What is an immunogen?
A substance capable of eliciting an immune response. All immunogens are antigens, but some antigens are not immunogenicity
Some very small molecules called happens can bind to antibodies or TCR, but they cannot initiate an immune response
What are antigens
Any substance that binds specifically to an antibody or a T-cell receptor
What’s an epitope
The portion of an antigen that is recognized and bound by an antibody or TCR/MHC complex
What is an Hapten?
A low molecular weight molecule that can be made immunogenic by conjugation to a suitable carrier
How do the receptor-ligand interactions occur (2)
- Occurs via multiple non covalent bonds (hydrogen bonds, ionic bonds, van Der Waals interactions, hydrophobic interactions, and ionic bonds)
- Its occurs via receptors and ligands
What is Kd?
Dissociation constant (Kd) is a measure of strength of ligand binding. The lower the Kd, the higher the affinity of the interaction.
What is multivalent, affinity, and avidity
Multivalent: Having more than one ligand binding site
Affinity: the strength of an individual bond
Avidity: the combined strength of binding of multiple interactions
Ligand-receptor binding induces WHAT molecular changes in the receptor?
Receptor alterations induce WHAT cascades of intracellular events?
- Conformational (structure of receptor changes)
- Dimerization/clustering (they combine)
- Location in the membrane (cause localization of receptors)
- Covalent modifications
- Activation of enzymes
- Changes in intracellular locations of molecules
What is aggregation?
An enhancement in ligand binding Kd due to the aggregation of receptors
What does extended contact facilitate?
Extended contact facilitates signal transduction and exchange. It allows the cytokine to do more work
What is cytoskeletal reorganization?
This can occur from extended binding and allows the other receptors to come in and increase affinity to cytokine
What is the T-cell receptor structure?
The T-cell receptor (TCR) complexes with co-receptor involved in antigen recognition
- CD3contains ITAMs that transmit signal to cell
- CD4, CD8 function in increasing avidity of peptide binding by TCR
- CD28 engages CD80 or CD86 on APC to fully activate a naive T cell
What are some characteristics of immunoglobulin?
Immune receptors bear immunoglobulin domains.
- Immune receptors can be transmembrane, cytosolic, or secreted.
- Immunoglobulin lacking the carboxyl terminus transmembrane segment is secreted.
What type of specificty do BCR, TCR, CD4, and CD8 receptors have
- A B-cell receptor (BCR) contains an antibody of defined specificity.
- T-cell receptor (TCR) specificity is for peptides derived from antigens that are degraded and presented by antigen-presenting cells (APCs) within major histocompatibility complex (MHC) molecules.
- CD4and CD8are T-cell coreceptors that define different subsets of T-cell functions.
What type of protein is an antibody?
Antibodies are quaternary proteins with two identical heavy chains and two identical light chains.
How is specificty determines for an antigen regarding an antibody
Antigen specificity is by the interaction between light-and heavy-chain variable regions.
What is the antibody effector activity function?
The antibody effector activity, for example, phagocytosis and complement fixation, is a function of the interaction of the constant regions of the heavy chain.
Antibody effector functions are an important part of the humoral immune response and form an essential link between innate and adaptive immunity. Most of these effector functions are induced via the constant (Fc) region of the antibody, which can interact with complement proteins and specialized Fc-receptors.
What are complementarity-determining regions?
They are CDR1, CDR2, and CDR3. They are the three hypervariable regions of amino acids which are location in the variable heavy (Vh) and variable light (Vl) chain. Together they are known are the antibody combining site.
Interspersed near each CDR is an invariant amino acid, what does it do?
It forms the framework region and is responsible for the folding of the CDRs to form the antibody combining site
What is an isotype and what are they?
Antiserum to the constant region of the heavy chain identifies five distinct classes of antibody called isotypes.
* IgA: alpha (α) heavy chain
* IgD: delta (δ) heavy chain
* IgE: epsilon (ε) heavy chain
* IgG: gamma (γ) heavy chain
* IgM: mu (μ) heavy chain
Light-chain isotypes are
* kappa (κ)
* lambda (λ)
Which immunoglobulin has subtypes and what are they?
IgG and it has 4 subtypes: IgG1, IgG2, IgG3, and IgG4
What co-receptors does BCR require
Antibody molecules form a B-cell receptor (BCR) complex with molecules involved in signal transduction.
- Igα and Igβ transduce signals via ITAMs.
- CD19, CD81, and CD21 transmit and relay signals to the cell interior.
Do TCRs bind only to the antigen?
No, TCR recognizes and binds both antigen-derived peptide and MHC to which peptide is bound
How is the TCR similar to the BCR in structure
Protein chains are structurally similar to immunoglobulin domains.
* Two subunits, αand β, each have a constant region and a variable region.
- Variable regions have three CDRs that form a peptide-specific binding site.
- The constant regions each contain transmembrane regions.
Define endocrine, paracrine, and autocrine?
They can act in several different ways…
* Endocrine action ‒ released into the bloodstream to effect distant cells
* Paracrine action ‒ released to effect nearby cells
* Autocrine action ‒ released, but then bind to receptors on the cell that produced them
Define pleiotropic, redundant, synergy, antagonistic, and cascade regarding cytokines and chemokines
- Pleiotropic activity induces different biological effect dependent on target cell
- Redundant activity mediates similar effects on target cell
- Synergy effect combines two cytokine activities to be greater than additive effect
- Antagonistic effect inhibits one cytokine’s effect by another’s action
- Cascade effect of one cytokine on one target cell to produce additional cytokine(s)
What are the six cytokine families
What is the major difference between common cytokine receptor of the unique receptor
The two form one receptor. However, if a cell loses the common receptor subunit a cell cannot use any unique receptor that requires it. If a cell loses the unique receptor, others may fill in due to redundancy
What is the JAK-Janus kinase pathway
Class I and Class II cytokine receptors signal by a rapid pathway using receptor-associated kinases to activate specific transcription factors.
Binding of a cytokine induces dimerization of the receptor subunits, which leads to the activation of receptor subunit associated JAK tyrosine kinases by reciprocal phosphorylation. Subsequently, the activated JAKs phosphorylate various tyrosine residues, resulting in the creation of docking sites for STATs on the receptor and the activation of the one or more STAT transcription factors. The phosphorylated STATs dimerize and translocate to the nucleus, where they activate transcription of specific genes. (Abbreviations: JAK = Janus kinase; STAT = signal transducer and activator of transcription. JAKs and STATs each exist in multiple isomeric forms, and each cytokine receptor signals through a pair of Janus kinases that may be either homo- or heterodimeric. A
Give an example of how cytokines function in the innate immune system
Give an example of how cytokines can be beneficial but also detrimental
The release of TNF-αby macrophages induces local protective effects, but TNF-αcan have damaging effects when released systemically (septic shock).
Give an example of how cytokines can create induce different responses
Give an example of how cytokines function in acquired immunity
