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59 Cards in this Set

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define Homing
the directed migration of subsets of circulating lymphocytes into particular tissue sites. Regulated by the selective expression of adhesion molecules, called homing receptors, on the lymphocytes and the tissue-specific expression of endothelial ligands for these homing receptors, called addressins, in diff vascular beds. ie peyer's patches in intestines; homing is independent of antigen recognition
define endothelium
The endothelium is the thin layer of cells that lines the interior surface of blood vessels and lymphatic vessels,[1] forming an interface between circulating blood and lymph in the lumen and the rest of the vessel wall.
C Regions
Constant region. The portion of immunoglobulin or T cell receptor polypeptide chains that does not vary in sequence among different clones of B and T cells and is not involved in antigen binding.
V Regions
The antigen recognition portion of the Ig or T cell receptor. Much of the sequence variability is concentrated within short stretches, hypervariable regions, because they form the parts of the receptor the bind to the antigen [i.e. they are complementary to the shape of antigens]
Fab region
The proteolytic fragment of an IgG antibody molecule that includes 1 complete light chain bonded to the variable and the first constant region of 1 of the heavy chains. Retains the ability to bind to an antigen but cannot interact with the IgG Fc receptors on cells or with compliment.
Fc
A cell surface receptor specific for the carboxy-terminal constant region of an Ig molecule. Typically, the are multichain protein complexes that include Ig-binding and signaling components. Functions → such as phagocytosis of antibody-coated (opsonized) microbes, antigen-induced activation of mast cells, and activation of NK cells
Which chain determines isotype of Ig?
Heavy chain
Light chain:
1 of 2 types of polypeptide chains that compose an antibody molecule. The basic structural unit of an antibody includes 2 identical light chains, each linked by disulphide bonds to 1 of 2 identical heavy chains. Each light chain is composed of 1 variable Ig domain and 1 constant Ig domain. 2 isotypes: κ[kappa] and λ [lamda]. Functionally similar. About 60% of antibodies have κ chains, the other 40% contain have λ.
Heavy chain:
1 of 2 types of polypeptide chains that compose an antibody molecule. The basic structural unit of an antibody includes 2 identical, disulphide-linked heavy chains and 2 light chains. Each heavy chain is composed of a variable Ig domain and 3 or 4 constant Ig domains. 5 isotypes: IgM, IgD, IgG, IgA, IgE → distinguished by structural differences in their heavy chain constant regions. The heavy chain constant regions also mediate effector functions → such as complement activation & engagement of phagocytes
Affinity maturation
The process that leads to increased affinity of antibodies for a protein antigen as a humoral response progresses. It is the result of somatic mutation of immunoglobulin genes followed by selective survival of B cells producing the highest-affinity antibodies
Isotype switching
The process by which a B lymphocyte changes the isotype of the antibodies it produces, from IgM to IgG, IgE or IgA, without changing the specificity of the antibody. Switching is regulated by helper T cell cytokines and CD40 ligand
Cross-reaction:
Antibodies produced against 1 antigen may bind to another, structurally similar, antigens.
Affinity:
The strength of the binding between a single binding site of a molecule [ex. an antibody] and a ligand [ex. an antigen]. This can be represented by the dissociation constant, Kd. The smaller the Kd, the higher the affinity interaction
Avidity:
The overall strength of interaction between 2 molecules, such as an antibody and an antigen. It can also be used to describe the strength of cell-cell interactions, which are mediated by many binding interactions between cell surface molecules.
Epitope:
The specific portion of a macromolecular antigen to which an antibody binds [2-10 binding]. In the case of a protein antigen recognized by a T cell, an epitope in the peptide portion that is recognized by the TCR when it is displayed bound to an MHC
Hybridoma
A cell like derived by cell fusion or somatic cell hybridization, between normal lymphocyte and an immortalized lymphocyte tumor line
Monoclonal antibody:
An antibody that is specific for 1 antigen [all identical] and is produced by A B cell hybridoma. Used widely in research, clinical diagnosis, and therapy
Positive selection
The process by which developing T cells in the thymus whose antigen receptors bind to self MHC molecules are rescued from apoptosis.
Failure of positive selection → do not recognize self-antigens but fail to bind to self MHCs.
Negative selection
The process eliminates potentially dangerous lymphocytes that may be capable of reacting against self-antigens that are present throughout the body, including in the generative lymphoid organs
VDJ recombination:
VDJ recombination: A collection of enzymes that together mediated the recombination that result in the formation of functional antigen receptor genes in developing B and T lymphocytes.
Combinational diversity:
Combinational diversity: A term describing lymphocyte antigen receptor diversity due to the many different combinations of variable, diversity, and joining segments that are possible as a result of somatic recombination of DNA during T and B cell development.
Junctional diversity
Junctional diversity: The diversity in the antibody and T cell receptor repertoires that is attributed to the random addition or removal of nucleotide sequences at junctions between V, D, and J gene segments.
Allelic exclusion:
The expression of only 1 of 2 inherited alleles encoding immunoglobulin heavy and light chains and T cell receptor β chains. It occurs when 1 chromosome process shuts off recombination of Ig heavy chain genes on the second chromosome, because each B cell can only express receptors of a single specificity.
What structures are responsible for signal transduction from the Ig to the B Cell?
Igalpha and beta
What structures are responsible for mediating signaling functions in the T cell?
CD3 and zeta, associated with the TCR
What portion of the secreted Ig mediates the effector functions of the Ig?
Constant (C) regions
Function of IgA
mucosal immunity
Function of IgD
Naive B Cell antigen receptor
Function of IgE
Mast cell activation and defense against helminths
Function of IgG
Opsonization, complement activation, ADCC, neonatal, feedback inhibition of B cells
Function of IgM
Naive B cell antigen receptor, complement activation
What are the apoptosis points a naive B or T Cell has to make it through?
- Has to express pre-lymphocyte receptor
- Express antigen receptor
- Has to have weak self antigen recognition (none = failure of positive selection; or strong = negative selection, results in apoptosis)
what is a double negative Pro-T Cell
A naive T Cell between the stem cell and pre- T Cell phase. It does not have either receptor
What is a double positive immature T Cell?
has both CD4 and CD8 receptors; goes through weak positive selection to become a mature CD4+ or CD8+ T Cell; or if no recognition or strong recognition, apoptosis
which antigen binding molecule has a rapid on rate and variable off rate?
Ig
which antigen binding molecule has a slow on rate and off rate?
TCR
which antigen binding molecule has accessory molecules involved in binding?
TCR (CD4 or CD8 simultaneously binds).
Which Antigen binding molecule has a stronger affinity of antigen binding?
Ig; increases with immune response
define CDR
Complimentarity Determining Region (IG -> 3 heavy and 3 light; TCR -> 3 alpha and 3 beta)
P. falciparum:
P. falciparum: Protozoa that causes Malaria. Evades detection of immune system by invading RBCs. Since RBCs aren’t nucleated, they have no class I MHC making it hard for lymphocytes to recognize if they are infected.
Clonal expansion:
Clonal expansion: On activation of by an antigen or other stimuli, a T cell begins to secrete cytokines. Some of the cytokines stimulate proliferation of the antigen-specific T cells resulting in the rapid increase of the antigen-specific lymphocyte.
Differentiation:
Differentiation: Results in the conversion of naïve T cells, function → recognize microbial antigens, into a population of effector T cells, function → eliminate microbes.
Memory T cells:
Memory T cells: Some of the progeny T cells from proliferation develop into memory cells. They are long-lived and functionally inactive. They circulate for months or years, ready to rapidly respond to repeat exposures to the same microbe.
Integrins:
Integrins: To induce a productive response, the binding of T cells to APCs through adhesion molecules must be stabilized for a sufficiently long period that the necessary signaling threshold is achieved. The most important of these adhesion molecules belong to a heterodimeric protein called integrins.
Costimulation:
Costimulation: Done by a molecule on the surface of an APC that provides a stimulus (second signal) required for activation of a naïve T cell, in addition to the antigen (first signal). Example → CD80 & CD86 [APC] to CD28 [T cell]
Adjuvant:
Adjuvant: A substance, distinct from antigen, that enhances T cell activation by promoting the accumulation of APC at a site of antigen exposure and by enhancing the expression of costimulators and cytokines by the APCs
ITAMs:
ITAMs: [Immunoreceptor Tyrosine-based Activation Motif] A conserved motif composed of 2 copies of the sequence tyrosine-X-X-leucine found in the cytoplasmic tails of various membrane proteins in the immune system that are involved in signal transduction. Critical for signaling.
ITIMs:
ITIMs: [Immunoreceptor Tyrosine-based Inhibition Motif] A 6-amino-acid motif found in the cytoplasmic tails of various inhibitory receptors in the immune system and the killer inhibitory receptor on NK cells.
Immunologic synapse:
Immunologic synapse: The region of contact between the APC and T cell, including the redistributed membrane proteins. It was first described as first site of transduction. Effector molecules and cytokines are secreted through this region
true or false? The elimination of intracellular microbes is the main function of the T cell arm of the immune response?
False. every 5 min, mutant cells killed by CTLs
DTH:
DTH: [Delayed-Type Hypersensitivity] An immune reaction in which T cell-dependent macrophage activation and inflammation cause tissue injury. A DTH reaction to subcutaneous injection of antigen often is used as an assay for cell-mediated immunity [ex. TB test]
Activated macrophages:
Activated macrophages: Effector TH1 cell recognizes antigen on macrophages. In response, TH1 expresses CD40L to engage CD40 of macrophage and secrete IFN-γ. With combination of signals, macrophage activates. Functions → killing of phagocytized microbes using ROS & NO, Increased expression of MHC molecules and co-stimulators, secretion of cytokines causing inflammation [TNF, IL-1, chemokines], secretion of IL-12
Granzyme:
Granzyme: Enzymes that cleave and thereby activate enzymes called caspases that are present in the cytoplasm of target cells, and the active caspases induce apoptosis. Enters cell through holes created perforin.
Perforin:
Perforin: A pore-forming protein that is present as a monomer in the granules of cytotoxic T lymphocytes and NK cells. Released when CTLs and NK cells are activated. Undergo polymerization in the lipid bilayer of target cell membrane creates a pore.
Mycobacteria:
Mycobacteria: A genus of bacteria, many species of which can survive within phagocytes and cause disease. Mechanism → inhibition of phagolysosome fusion therefore can survive within phagosome.
HSV:
HSV: [Herpes Simplex Virus]
The inhibition of antigen presentation = Mechanism → HSV peptide interferes with TAP transporter therefore the protein is unable to load into MHC I.
CMV:
CMV: [Cytomegalovirus]
The inhibition of antigen presentation = Mechanism → Inhibition of proteasomal activity therefore protein won’t be able to be chewed up into smaller pieces and the removal of class I MHC molecules from ER.
EBV:
EBV: [Epstein-Barr Virus]
The inhibition of antigen presentation = Mechanism → Inhibition of proteasomal activity therefore protein won’t be able to be chewed up into smaller pieces.
Inhibition of macrophage activation = Mechanism → invades B cell, produces IL-10 which in turn inhibits macrophage and dendritic cell activation
Pox virus:
Pox virus: Block cytokine activation of effector cells = Mechanism → production of soluble cytokine receptors therefore activating cytokines, IL-1 or IFN-γ, bind to the soluble receptors rather than receptor on effector cell.