Immunology Exam Ii

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define Homing

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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

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define endothelium

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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.

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C Regions

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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.

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V Regions

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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]

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Fab region

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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.

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Fc

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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

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Which chain determines isotype of Ig?

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Heavy chain

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Light chain:

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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.

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Heavy chain:

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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

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Affinity maturation

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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

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Isotype switching

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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

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Cross-reaction:

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Antibodies produced against 1 antigen may bind to another, structurally similar, antigens.

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Affinity:

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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

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Avidity:

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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.

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Epitope:

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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

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Hybridoma

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A cell like derived by cell fusion or somatic cell hybridization, between normal lymphocyte and an immortalized lymphocyte tumor line

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Monoclonal antibody:

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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

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Positive selection

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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.

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Negative selection

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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

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VDJ recombination:

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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.

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Combinational diversity:

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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.

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Junctional diversity

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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.

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Allelic exclusion:

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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.

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What structures are responsible for signal transduction from the Ig to the B Cell?

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Igalpha and beta

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What structures are responsible for mediating signaling functions in the T cell?

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CD3 and zeta, associated with the TCR

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What portion of the secreted Ig mediates the effector functions of the Ig?

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Constant (C) regions

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Function of IgA

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mucosal immunity

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Function of IgD

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Naive B Cell antigen receptor

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Function of IgE

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Mast cell activation and defense against helminths

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Function of IgG

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Opsonization, complement activation, ADCC, neonatal, feedback inhibition of B cells

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Function of IgM

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Naive B cell antigen receptor, complement activation

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What are the apoptosis points a naive B or T Cell has to make it through?

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- 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)

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what is a double negative Pro-T Cell

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A naive T Cell between the stem cell and pre- T Cell phase. It does not have either receptor

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What is a double positive immature T Cell?

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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

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which antigen binding molecule has a rapid on rate and variable off rate?

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Ig

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which antigen binding molecule has a slow on rate and off rate?

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TCR

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which antigen binding molecule has accessory molecules involved in binding?

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TCR (CD4 or CD8 simultaneously binds).

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Which Antigen binding molecule has a stronger affinity of antigen binding?

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Ig; increases with immune response

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define CDR

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Complimentarity Determining Region (IG -> 3 heavy and 3 light; TCR -> 3 alpha and 3 beta)

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P. falciparum:

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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.

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Clonal expansion:

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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.

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Differentiation:

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Differentiation: Results in the conversion of naïve T cells, function → recognize microbial antigens, into a population of effector T cells, function → eliminate microbes.

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Memory T cells:

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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.

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Integrins:

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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.

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Costimulation:

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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]

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Adjuvant:

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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

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ITAMs:

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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.

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ITIMs:

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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.

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Immunologic synapse:

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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

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true or false? The elimination of intracellular microbes is the main function of the T cell arm of the immune response?

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False. every 5 min, mutant cells killed by CTLs

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DTH:

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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]

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Activated macrophages:

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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

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Granzyme:

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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.

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Perforin:

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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.

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Mycobacteria:

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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.

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HSV:

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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.

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CMV:

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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.

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EBV:

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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

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Pox virus:

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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.