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129 Cards in this Set

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A substance, distinct from antigen, that enhances T cell activation by promoting the accumulation of APCs at a site of antigen exposure and by enhancing the expression of costimulators and cytokines by the APCs.
What is affinity maturation?
The process that leads to increased affinity of antibodies for a protein antigen as a humoral response progresses. Affinity maturation is the result of somatic mutation of Ig genes followed by selective survival of the B cells producing the highest affinity Abs.
Allelic exclusion
The expression of only one of two inherited alleles encoding immunoglobulin heavy and light chains and T cell receptor beta chains. Allelic exclusion occurs when the protein product of one productively recombined antigen receptor locus on one chromosome blocks the rearrangement of the corresponding locus on the other chromosome.
What is an allogeneic graft?
An organ or tissue graft from a donor who is of the same species but genetically not identical to the recipient (also called an allograft).
What is the alternative pathway of complement activation?
An antibody-independent pathway of activation of the complement system that occurs when the C3b protein binds to microbial cell surfaces. The alternative pathway is a component of the innate immune system and mediates inflammatory responses to infection as well as direct lysis of microbes.
What are the anaphylatoxins?
The C5a, C4a, and C3a complement fragments that are generated during complement activation. The anaphylatoxins bind specific cell surface receptors and promote acute inflammation by stimulating neutrophil chemotaxis and by activating mast cells.
An extreme systemic form of immediate hypersensitivity, also called anaphylactic shock, in which mast cell or basophil mediators cause bronchial constriction, massive tissue edema, and cardiovascular collapse.
Clonal Anergy
Anergy is a state of unresponsiveness to antigenic stimulation. Lymphocyte anergy is the failure of clones of T or B cells to react to antigen, and this may be a mechanism of maintaining immunologic tolerance to self antigens. (In clinical practice, anergy refers to a generalized defect in T cell-dependent cutaneous delayed-type hypersensitivity reactions to common antigens.)
A type of glycoprotein molecule, also called immunoglobulin (Ig), produced by B lymphocytes, that binds antigens, often with a high degree of specificity and high affinity. The basic structural unit of an antibody is composed of two identical heavy chains and two identical light chains. Amino-terminal variable regions of the heavy and light chains form the antigen binding sites, whereas the carboxy-terminal constant regions of the heavy chains functionally interact with other molecules in the immune system. In any individual, there are millions of different antibodies, each with a unique antigen-binding site. Secreted antibodies perform various effector functions, including neutralizing antigens, activating complement, and promoting phagocytosis and destruction of microbes.
Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC)
A process by which natural killer (NK) cells are targeted to IgG-coated cells, resulting in the lysis of the antibody-coated cells. A specific receptor for the constant region of IgG, called FcγRIII (CD16), is expressed on the NK cell membrane and mediates the binding to the IgG.
What happens when antigen-antibody complexes simultaneously engage B cell membrane Ig and Fcγ receptors?
This process, called antibody feedback, results in the downregulation of antibody production. This is an inhibitory negative feedback mechanism. The cytoplasmic tails of the Fcγ receptors deliver inhibitory signals to the B cell.
Distinguish between antigens seen by B and T cells.
Antigens are molecules that bind to an antibody or a TCR. Antibodies can bind to all sorts of molecules, and can recognize the 3D structure of a protein. TCRs only recognize peptide fragments of proteins complexed w/ self MHC. MHC I peptides are 9 amino acids in length, and bind via P2 and P9, with tethered ends. MHC II peptides can be a bit longer, bind via P4 and P6, and have free ends.
What is the Arthus reaction?
A localized form of experimental immune complex-mediated vasculitis induced by injecting an antigen subcutaneously into a previously immunized individual that has been given IV antibody specific for the antigen. Circulating Abs bind to the injected Ag, forming immune complexes that deposit in the walls of small arteries at the injection site, giving rise to a local cutaneous vasculitis with necrosis.
What is Atopy?
The propensity of an individual to produce IgE Abs in response to various environmental Ags and to develop strong immediate hypersensitivity responses. People who have allergies to environmental allergies such as pollen or house dust are said to be atopic.
Autoimmune Disease
A disease caused by a breakdown of self-tolerance such that the adaptive immune system responds to self antigens and mediates cell and tissue damage. Autoimmune diseases can be organ-specific (e.g., thyroiditis or diabetes) or systemic (e.g., SLE).
What is an autologous graft?
A tissue or organ graft in which the donor and recipient are the same individual. (Autologous bone marrow and skin grafts are commonly performed in clinical medicine.)
What is Avidity?
The overall strength of interaction between 2 molecules, such as an Ab and Ag. The avidity depends on both the affinity and the valency of interaction. Therefore, the avidity of a pentameric IgM antibody, with 10 antigen binding sites, for a multivalent antigen might be much greater than the avidity of a dimeric IgG molecule for the same Ag. Avidity can also be used to describe the strength of cell-cell interactions, which are mediated by many binding interactions between cell surface molecules.
Where do B cells mature and develop?
B cells develop in the bone marrow. Mature B cells are found mainly in lymphoid follicles in secondary lymphoid tissues, in bone marrow, and in low numbers in the circulation.
Describe the BCR complex.
The BCR complex is a multiprotein complex expressed on the surface of B lymphocytes that recognizes antigen and transduces activating signals. It includes membrane Ig, which is responsible for binding Ag, and the associated Igα and Igβ, which initiate signaling events.
What is Bare Lymphocyte Syndrome?
An immunodeficiency disease characterized by the lack of class II major histocompatability complex (MHC) molecule expression, leading to defects in antigen presentation and cell mediated immunity. The disease is caused by mutations in genes encoding factors that regulate MHC Class II transcription.
C3 Convertase
C3 convertase is a multiprotein enzyme complex generated by the early steps of complement activation, which cleaves C3, giving rise to C3a and C3b.
C5 Convertase
A multiprotein enzyme complex generated by C3b binding to C3 convertase, which cleaves C5 and initiates the late steps of complement activation.
What are caspases?
Intracellular cysteine proteases that cleave substrates at the carboxy-terminal sides of aspartic acid residues, and are components of enzymatic cascades that cause apoptotic death of cells. Lymphocyte caspases may be activated by two distinct pathways: (1) associated with mitochondrial permeability changes in growth-factor deprived cells; and (2) cell murder from signals from (Fas-FasL, etc.) in the plasma membrane.
Cell-Mediated Immunity
The form of adaptive immunity that is mediated by T lymphocytes and serves as the defense mechanism against microbes that survive within phagocytes or infect nonphagocytic cells. Cell-mediated immune responses include CD4+ T cell-mediated activation of MΦs and CD8+ cytolytic T cell killing of infected cells.
Central Tolerance
A form of self-tolerance that is induced in generative ("central") lymphoid organs as a consequence of immature self-reactive lymphocytes recognizing self-antigens, leading to their death or inactivation. Central tolerance prevents the emergence of lymphocytes with high-affinity receptors for ubiquitous self antigens that are present in the bone marrow or thymus and are likely to be present throughout the body.
Chediak-Higashi Syndrome
A rare autosomal recessive immunodeficiency disease due to a defect in cytoplasmic granules of various cell types that affects the lysosomes of neutrophils and macrophages, as well as the granules of CTLs and NK cells. Patients show reduced resistence to infections with pyogenic bacteria.
What is special about chemokine receptors?
Chemokine receptors are cell surface receptors for chemokines that transduce signals, which stimulate migration of leukocytes. These receptors are members of the 7-transmembrane GPCR family. Cytokine receptors are generally TRKs (confirm this!!)
Chronic Granulomatous Disease
A rare inherited immunodeficiency due to a defect in the gene encoding a component of the phagocyte oxidase enzyme, which is needed for microbial killing by PMNs or MΦs. The disease is characterized by recurrent intracellular bacterial and fungal infections, often accompanied by chronic cell-mediated immune responses and the formation of granulomas.
Chronic Rejection
Allograft rejection characteried by fibrosis with loss of normal organ structure occurring over a prolonged time period. Often the major pathological event in chronic rejection is graft arterial occlusion that occurs due to the proliferation of intimal smooth muscle cells (graft arteriosclerosis).
Class II-Associated Invariant Chain Peptide (CLIP)
A peptide remnant of the invariant chain that sits in the class II MHC peptide-binding cleft and is removed by action of the HLA-DM molecule before the cleft becomes accessible to peptides produced from endocytosed protein antigens.
Describe the classical pathway of complement activation.
Initiated by the binding of of Ag-Ab complexes to the C1 molecule, inducing a proteolytic cascade involving multiple other complement proteins. The classical pathway is an effector arm of the humoral immune system that generates inflammatory mediators, opsonins for phagocytosis of antigens, and lytic complexes that destroy cells.
What is clonal ignorance?
A form of lymphocyte unresponsivness in which self antigens are ignored by the immune system, even though lymphocytes specific for those antigens remain viable and functional.
What is the Clonal Selection Hypothesis? (note: has been proven, isn't technically an hypothesis)
A fundamental tenet of the immune system stating that every individual possesses numerous clonally derived lymphocytes, each clone having arisen from a single precursor, and being capable of recogniing and responding to a distinct antigenic determinant. When an antigen enters, it selects a specific PRE-EXISTING clone and activates it.
A family of proteins including mannose-binding lectins, that are characteried by the presence of a collagen-like domain and a lectin (carbohydrate-binding) domain. Collectins play a role in the innate immune system by acting as microbial pattern recognition receptors, and they may activate the complement system by binding to C1q.
Describe the three pathways of complement activation.
There are three pathways of complement activation that differ in how they are initiated. The classical pathway is activated by antigen-antibody complexes, the alternative pathway by microbial surfaces, and the lectin pathway by plasma lectins that bind to microbes. Each complement pathway consists of a cascade of proteolytic enzymes that generate inflammatory mediators and opsonins and leads to the formation of a lytic complex that inserts into cell membranes.
CR2 (Complement Receptor, Type 2)
A receptor expressed on B cells and follicular dendritic cells that binds proteolytic fragments of the C3 complement protein, including C3d, C3dg, and iC3b. CR2 functions to stimulate humoral immune responses by enhancing B cell activation by Ag and by promoting the trapping of Ag-Ab complexes in germinal centers. CR2 is also a receptor for EBV.
CDR (Complementarity-Determining Region)
Short segments of the Ig and TCR proteins in which most of the sequence differences among different Abs or TCRs are confined and which make contact with Ag. There are 3 CDRs in the variable domain of each Ag receptor polypeptide chain and 6 CDRs in an intact Ig or TCR molecule. These "hypervariable" segments assume loop structures that together form a surface that is complementary to the 3D structure of the bound Ag.
Constant (C) Region
The portion of the Ig or TCR polypeptide chains that does not vary in sequence among different clones of B and T cells and is not involved in Ag binding. The C regions are encoded by DNA sequences in the Ig and TCR loci that are spatially separate from the sequences that encode the variable (V) regions.
What is Contact Sensitivity?
The propensity to develop a T cell-mediated, delayed-type hypersensitivity rxn in the skin on contact w/a particular chemical agent. Chemicals that elicit contact sensitivity bind to and modify self proteins or molecules on the surfaces of APCs, which are then recognized by CD4+ or CD8+ T cells.
What are the main coreceptors on B and T cells?
A lymphocyte surface receptor that binds to a part of an Ag and that delivers signals required for optimal lymphocyte activation. CD4 and CD8 are T cell coreceptors that bind nonpolymorphic regions of an MHC complex concurrently with TCR binding to polymorphic residues and the displayed Ag peptide. The type 2 complement receptor (CR2) is a coreceptor on B cells that binds to complement-coated Ags at the same time that membrane Ig binds an epitope of the Ag.
What is costimulation in the context of T cell activation?
A molecule on the surface of an APC that provides a stimulus ("second signal") required for activation of naive T cells, in addition to antigen (the "first signal"). Examples include the B7-1 (CD80) and B7-2 (CD86) molecules on APCs that bind to CD28 on T cells. [Note that CTLA-4 BLOCKS costimulation by binding to B-7, inactivating effector T cells. CTLA-4Ig is helpful in the inactivation of T cell-mediated autoimmunity by binding to B7 molecules on APCs and starving T cells for costimulation.]
What is cross-presentation (cross-priming)?
A mechanism by which a professional APC displays the antigens of another cell (a virus-infected or tumor cell) and activates or primes a naive CD8+ T cell. This occurs when an infected and damaged cell is ingested by a professional APC and the microbial Ags are processed and presented in association with MHC II, just like any other phagocytized antigen. The professional APC also provides costimulation for the T cells.
How does cyclosporin prevent allograft rejection?
Cyclosporin is an immunosuppressive drug used to prevent allograft rejection, which functions by blocking T cell cytokine gene transcription. Cyclosproine binds to a cytoplasmic protein called cyclophilin, and the cyclosporin-cyclophilin complexes bind to and inhibit the phosphatase calcineurin, thereby inhibiting activation and nuclear translocation of the transcription factor NFAT.
What is a Cytotoxic T Lymphocyte (CTL)?
A type of T lymphocyte whose major effector function is to recognize and kill host cells infected with viruses or other intracellular microbes. CTLs express CD8 and recognie microbial peptides displayed by MHC I. CTL killing of infected cells involves release of cytoplasmic granules whose contents include membrane pore-forming proteins and enzymes.
What are Defensins?
Cysteine-rich peptides produced in epithelia and neutrophil granules, which act as broad-spectrum antibiotics that kill a wide variety of bacteria and fungi.
Delayed-Type Hypersensitivity
An immune reaction in which T-cell dependent MΦ activation and inflammation cause tissue injury. A DTH reaction to subcutaneous injection of Ag is often used as an assay for cell-mediated immunity (e.g., the PPD test for Mycobacterium Tuberculosis)
What is "Desensitization"?
A method for treating immediate hypersensitivity disease that involves repetitive administration of low doses of an Ag to which individuals are allergic. This process often prevents severe allergic reqctions on the subsequent environmental exposure to the antigen. (Mechanism? Acts by gradual cross-linking the IgE on the surface of mast cells and causing degranulation so that the stores are used up.)
What is the major source of immune deficiency in DiGeorge Syndrome?
Causes a T cell deficiency due to a congenital malformation that results in defective development of the thymus, parathyroid and other structures that arise form the third and fourth pharyngeal pouches.
What is Direct Antigen Presentation (in the context of an allogeneic graft)?
Presentation of cell surface allogeneic MHC molecules by graft APCs to the recipient's T cells, leading to T cell activation, with no requirement for processing. Direct recognition of foreign MHC molecules is a cross-reaction of a normal TCR, which was selected to recognize a self MHC molecule plus foreign peptide, with an allogeneic MHC molecule plus peptide. (Contrasts with 'indirect presentation' of alloantigens.)
What are Diversity (D) segments on TCR and Ig heavy chain loci?
Short coding sequences between the variable (V) and constant (C) gene segments in the Ig heavy chain and TCR β and δ loci, which, together with the J (joining) segments, are somatically recombined with V segments during lymphocyte development. The resulting combined V-D-J DNA codes for the antigen receptor V (variable) region.
Double Negative Thymocyte
A subset of developing T cells in the thymus that express neither CD4 nor CD8. Most double-negative thymocytes are at an early stage of development and do not express antigen receptors. They will later express both CD4 and CD8 during the intermediate "double positive" stage before further maturation to single-positive T cells expressing only CD4 or only CD8.
Double-Positive Thymocyte
A subset of developing T lymphocytes in the thymus at an intermediate developmental stage, which express both CD4 and CD8. Double-positive thymocytes also express TCRs and are subject to selection processes, the survivors of which mature to single-positive T cells expressing only CD4 or only CD8.
What is the role of endosomes in processing of antigen for display in conjunction with MHC?
An endosome is an intracellular membrane-bound vesicle into which extracellular proteins are internalized during Ag processing. Endosomes have an acidic pH and contain proteolytic enzymes that degrade proteins into peptides that bind to class II major histocompatibility complex (MHC) molecules. A subset of class II MHC-rich endosomes (called MIIC) plays a special role in Ag processing and presentation by the class II pathway - these endosomes fuse with the phagolysosome and allow the MHC II to bind an appropriate peptide antigen (displacing CLIP) and make its way up to the plasma membrane surface.
What is Endotoxin and who makes it?
Endotoxin is a component of the cell wall of gram-negative bacteria, also called LPS, which is released from the dying bacteria and which stimulates many innate immune responses, including the secretion of cytokines and the induction of microbicidal activities of macrophages and the expression of adhesion molecules for leukocytes on the endothelium. Endotoxin contains both lipid components and carbohydrate (polysaccharide) moieties.
What is an Epitope?
The specific portion of a macromolecular antigen to which an Ab binds. In the case of a protein Ag recognized by a T cell, an epitope is the peptide portion that binds to an MHC molecule for recognition by the T cell receptor.
Discuss Epstein-Barr Virus.
EBV is a dsDNA virus of the herpesvirus family that is the etiologic agent of infectious mononucleosis and is associated with some B cell malignancies and nasopharyngeal carcinoma. EBV infects B lymphocytes and some epithelial cells by specifically binding to the complement receptor type 2 (CR2 or CD21).
F(ab')2 Fragment
A proteolytic fragment of an IgG molecule that includes two complete light chains but only the variable domain, first constant domain, and hinge region of the two heavy chains. F(ab')2 fragments retain the entire bivalent antigen binding domain of an intact IgG but cannot bind complement or IgG Fc receptors.
Fab fragment
A proteolytic fragment of an IgG antibody molecule that includes on complete light chain paired with one heavy chain fragment containing the variable domain and only the first constant domain.
Fas (CD95)
A member of the tumor necrosis factor receptor family, which is expressed on the surface of T cells and many other cell types and which initiates a signalign cascade leading to the apoptotic death of the cell. The death pathway is initiated when Fas binds to Fas Ligand expressed on activated T cells. Fas-mediated killing of T cells (called activation-induced cell death) is important for the maintenance of self-tolerance. Mutations in the Fas gene cause systemic autoimmune disease in mice.
Fas ligand
A membrane protein that is a member of the tumor necrosis factor family of proteins, which is expressed on activated T cells. Fas ligand binds to Fas, thereby stimulating a signaling pathway leading to apoptotic death of the Fas-expressing cell. Mutations in the Fas ligand gene (like mutations in Fas) cause systemic autoimmune disease in mice.
Fc (fragment crystalline)
A proteolytic fragment of antibody that contains only the disulfide linked carboxyterminal regions of the two heavy chains. The Fc region mediates effector functions by binding to cell surface receptors of phagocytes and NK cells or the C1 complement protein.
Fc Receptors
A cell surface receptor specific for the carboxy-terminal constant region of an Ig molecule. Typically multichain protein complexes that include Ig-binding components and signaling components. There are different types of Fc receptors including those specific for different IgG isotypes, IgE, and IgA. Fc receptors mediate many of the effector functions of Abs, including phagocytosis of Ab-coated opsonized molecules, Ag-induced activation of mast cells, and activation of NK cells.
A high affinity receptor for the carboxy-terminal constant region of IgE molecules which is expressed on mast cells and basophils. FcεRI molecules on mast cells are usually occupied by IgE, and antigen-induced cross-linking of these IgE-FcεRI complexes activates the mast cell and initiates immediate hypersensitivity reactions.
Fcγ Receptor
FcγR is a specific cell surface receptor for the carboxy-terminal constant region of IgG molecules. There are several different types of Fcγ receptors, including the high affinity FcγRI that mediates phagocytosis by MFs and PMNs, the low affinity FcγIIb that transduces inhibitory signals in B cells, and the low affinity FcγIIIB that mediates targeting and activation of NK cells.
Follicular Dendritic Cells
These cells are found in lymphoid follicles and express complement receptors, Fc receptors, and CD40 Ligand and have long cytoplasmic processes that form a meshwork that is integral to the architecture of lymphoid follicles. Follicular DCs display antigens on their surface for recognition by B cells and are involved in the activation and selection of B cells expressing high-affininty membrane Ig during the process of affinity maturation.
Where are the major generative organs of B and T cells?
Bone marrow (B cells) and Thymus (T cells)
What is glomerulonephritis?
Inflammation of the renal glomeruli, often initiated by immunopathologic mechanisms such as deposition of circulating Ag-Ab complexes in the glomerular basement membrane or binding of Abs to Ags expressed in the glomerulus. The Abs can activate complement and phagocytes, and the resulting inflammatory response can lead to renal failure.
Describe the phenomonen of "Graft Arteriosclerosis"
Occlusion of graft arteries due to proliferation of intimal smooth muscle cells. This process is evident within 6 months to 1 year after transplantation and is responsible for chronic rejection of vascularized organ grafts. The mechanism is most likely the result of chronic immune response to vessel wall alloantigens.
What is Graft vs. Host Disease?
GVHD occurs in bone marrow transplant recipients. It is caused by the reaction of mature T cells in the marrow graft against alloantigens on host cells. The disease most often affects the skin, liver, and intestines.
What is Granulocyte Colony-Stimulating Factor?
A cytokine made by activated T cells, macrophages, and endothelial cells at sites of infection that acts on bone marrow to increase production of and mobilize neutrophils to replace those consumed in inflammatory reactions.
Granulocyte-Monocyte Colony-Stimulating Factor (GM-CSF)
A cytokine made by activated T cells, macrophages, endothelial cells, and bone marrow stromal fibroblasts that acts on progenitors in the bone marrow to increase production of neutrophils and monocytes.
What is a Granuloma?
A nodule of inflammatory tissue composed of clusters of activated MFs and T lymphocytes, often with associated necrosis and fibrosis. (Th1 associated pathology). Granulomatous inflammation is a form of chronic delayed-type hypersensitivity, often in response to persistent microbes, such as Mycobacterium Tuberculosis and some fungi, or in response to particulate antigens that are not readily phagocytized.
A serine protease enzyme found in the granules of cytotoxic T lymphocytes and NK cells that is released by exocytosis, enters target cells, mainly through perforin-created "holes", and proteolytically cleaves and activates caspases, which in turn cleave several substrates and induce target cell apoptosis.
HLA Haplotype
An HLA haplotype is the set of MHC alleles inherited from one parent and therefore on one chromosome.
What is a hapten and how does it work?
A hapten is a small chemical that can bind to an Ab but must be attached to a macromolecule (carrier) to stimulate an adaptive immune response specific for the chemical (because T cell help is necessary and the Th cells need to see the carrier as a peptide in the context of an MHC-peptide complex.)
Heavy Chain Class (Isotype) Switching
The process by which a B lymphocyte changes the isotype of the Abs it produces, from IgM to IgG, IgE, or IgA, without changing the specificity of the Ab. Heavy chain class switching is regulated by helper T cell cytokines and CD40 ligand and involves recombination of heavy chain VDJ segments with downstream constant region gene segments.
T Helper Lymphocytes
This is the functional subset of T lymphocytes whose main effector functions are to actiate macrophages in cell-mediated immune responses and produce B cell Ab production in humoral immune responses. These functions are mediated by release of secreted cytokines and by T cell CD40 ligand binding to CD40 on macrophages or B cells.
High Endothelial Venules (HEVs)
Specialized venules that are the sites of lymphocyte extravasation from the blood into the stroma of a peripheral lymph node or mucosal lymphoid tissues. HEVs are lined by plump endothelial cells that express unique adhesion molecules involved in binding naive T cells.
A peptide exchange molecule that plays a critical role in the MHC Class II pathway of Ag presentation. HLA-DM is found in the specialized MIIC endosomal compartment and facilitates the removal of the invariant chain-derived CLIP peptide and the binding of other peptides to class II MHC molecules. HLA-DM is structurally similar to MHC Class II molecules but is not polymorphic.
What is a Humanized Antibody?
A monoclonal Ab encoded by a recombinant hybrid gene and composed of Ag-binding sites from a murine monoclonal Ab and the constant region of a human Ab. Humanized Abs are less likely than mouse monoclonal Abs to induce an anti-Ab response in humans and are used clinically in the treatment of tumors and transplant rejection.
Hyperacute Rejection
A form of allograft or xenograft rejection that begins within minutes to hours after transplantation and is characterized by thrombotic occlusion of the graft vessels. Hyperacute rejection is mediated by preexisting Abs in the host circulation that bind to donor endothelial antigens such as blood group antigens or MHC molecules.
Hypervariable Region
Short segments of about 10 amino acid residues within the variable regions of Ab or TCR proteins which form loop structures that contact antigen. There are 3 hypervariable regions (called complementarity-determining regions) in each Ab heavy chain and light chain and in each TCR alpha and beta chain. Most of the variability between different Abs or TCRs is located in these regions.
The unique structures present in the Ag-binding regions of the Abs or TCRs produced by a single clone of lymphocytes.
Igα and Igβ
Igα and Igβ are proteins required for surface expression and signaling functions of membrane Ig on B cells. Igα and Igβ pairs are disulfide-linked to one another and noncovalently associated with the cytoplasmic tail of membrane Ig, forming the B cell receptor complex. The cytoplasmic domains of Igα and Igβ contain immunoreceptor tyrosine-based activation motifs (ITAMs) that are involved in early signaling events during Ag-induced B cell activation.
Immature B Lymphocyte
A membrane IgM (+), IgD (-) B cell, recently derived from marrow precursors, that does not proliferate or differentiate in response to antigens but may undergo apoptotic death or become functionally unresponsive. Immature B cells that are specific for self antigens present in the bone marrow are negatively selected by encounter with these antigens and do not complete their maturation.
Immediate Hypersensitivity
The type of immune reaction responsible for allergic diseases and dependent on IgE plus Ag-mediated stimulation of tissue mast cells and basophils. The mast cells and basophils release mediators that cause increased vascular permeability, vasodilation, bronchial and visceral smooth muscle contraction, and inflammation.
Immune Complexes
A complex of one or more Ab molecules with bound Ag. Because each Ab molecule has a minimum of two Ag-binding sites and many Ags contain multiple epitopes, immune complexes can vary greatly in size. Immune complexes activate effector mechanisms of humoral immunity, such as the classical complement pathway and Fc receptor-mediated phagocyte activation. Deposition of circulating immune complexes in blood vessel walls, renal glomeruli, and joint synovia can lead to inflammation and disease.
What is immune complex disease?
An inflammatory disease caused by deposition of Ag-Ab complexes in blood vessel walls resulting in local complement activation and phagocyte recruitment. Immune complexes may form because of overproduction of Abs to microbial antigens or because of auto-antibody production in the setting of an autoimmune disease such as SLE. Immune complex deposition on arteries, kidney glomeruli, and joint synovia may cause vasculitis, glomerulonephritis, and arthritis, respectively.
What is an immune privileged site?
A site in the body that is inaccessible to, or actively suppresses, immune responses. The anterior chamber of the eye, the testes, and the brain are examples of immune privileged sites.
What is an immunoglobulin domain?
A 3D globular structural motif found in many proteins in the immune system including immunoglobulins, T cell receptors, and MHC molecules. Ig domains are 110 amino acid residues in length, include an internal disulfide bond, and contain two layers of beta-pleated sheet, with each layer composed of 3-5 strands of antiparallel polypeptide chain.
Immunoglobulin (Ig) Heavy Chain
The basic structural unit of an Ab includes 2 identical, disulfide-linked heavy chains and 2 identical light chains. Each heavy chain is composed of a variable region (Ig) domain and 3 or 4 constant (C) Ig domains. The different Ab isotypes, including IgM, IgD, IgG, IgA, and IgE are distinguished by structural differences in their heavy chain constant regions.
What is an immunoglobulin domain?
A 3D globular structural motif found in many proteins in the immune system including immunoglobulins, T cell receptors, and MHC molecules. Ig domains are 110 amino acid residues in length, include an internal disulfide bond, and contain two layers of beta-pleated sheet, with each layer composed of 3-5 strands of antiparallel polypeptide chain.
Immunoglobulin Light Chain
The basic structural unit of an Ab molecule includes two identical light chains, each disulfide-linked to one of two identical heavy chains. Each light chain is composed of one variable (V) Ig domain and one constant (C) Ig domain. There are two light chain isotypes, called κ and λ which are functionally identical. 60% of human Abs have κ light chains and 40% have λ light chains.
Immunoreceptor Tyrosine-Based Activation Motif (ITAM)
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. ITAMs are present in the ζ and CD3 proteins of the TCR complex, in the Igα and Igβ proteins in the B cell receptor complex, and in signaling subunits of several Ig receptors. When these receptors bind their ligands, the tyrosine residues of the ITAMs become phosphorylated, forming docking sites for other molecules involved in propagating cell-activating signal transduction pathways.
Immunoreceptor Tyrosine-Based Inhibition Motif (ITIM)
A 6 amino acid (isoleucine-X-tyrosine-X-X-leucine) motif found in the cytoplasmic tails of various inhibitory receptors in the immune system, including FcγRIIB on B cells, and the killer inhibitory receptor on NK cells. When these receptors bind their ligands, the ITIMs become phosphorylated on their tyrosine residues, forming a docking site for protein tyrosine phosphatases, which function to inhibit other signal transduction pathways.
Indirect Antigen Presentation (in the context of an Allogeneic Graft)
Pathway of presentation of donor MHC molecules by recipient APCs using the same mechanisms used to present microbial proteins. The allogeneic MHC proteins are processed by recipient professional APCs, and peptides derived from the allogeneic MHC molecules are presented, in association with recipient (self) MHC molecules, to host T cells. This is in contrast to direct antigen presentation, which involves recipient T cell recognition of unprocessed allogeneic MHC molecules on the surface of graft cells.
Inflammatory Bowel Disease
A group of disorders including ulcerative collitis and Crohn's disease, characterized by chronic inflammation in the GI tract. Gene KO mice lacking IL-2, IL-10, or the T cell receptor α chain develop IBD.
Insulin-Dependent Diabetes Mellitus (IDDM)
A disease characterized by a lack of insulin, which leads to various metabolic and vascular abnormalities. The insuline deficiency results from destruction of the insulin-producing β cells of the islets of Langerhans in the pancreas, usually as a result of T-cell mediated autoimmunity.
Heterodimeric cell surface proteins whose major functions are to mediate adhesion of leukocytes to other leukocytes, endothelial cells, and extracellular matrix proteins. Integrins are important for T cell interactions with APCs and for migration of leukocytes from blood into tissues. The ligand-binding affinity of the integrins can be regulated by various stimuli, and the cytoplasmic domains of integrins bind to the cytoskeleton. There are two subfamilies of integrins, and the members of each family express a conserved β chain (β1, or CD18, and β2, or CD29) associated with different α chains. VLA-4 is a β1 integrin expressed on T cells, and LFA-1 is a β2 integrin expressed on T cells and phagocytes.
IFN-γ (Interferon Gamma)
A cytokine produced by T lymphocytes and NK cells whose principal function is to activate macrophages in both innate immune responses and adaptive cell-mediated immune responses.
Interleukin-1 (IL-1)
IL-1 is a cytokine produced mainly by mononuclear phagocytes whose principal function is to mediate host inflammatory responses in innate immunity. IL-1 cause induction of endothelial cell adhesion molecules, stimulation of chemokine production by endothelial cells and macrophages, stimulation of synthesis of acute-phase reactants by the liver, and fever.
Interleukin-10 (IL-10)
A cytokine produced by activated macrophages and some helper T cells whose major function is to inhibit activated macrophages and maintain homeostatic control of innate and cell-mediated immune reactions.
Interleukin-12 (IL-12)
A cytokine produced by mononuclear phagocytes (macrophages) and dendritic cells that serves as a mediator of the innate immune response to intracellular microbes and is a key inducer of cell-mediated immune response to these microbes. IL-12 activates NK (natural killer)cells, promotes IFN-γ production by NK cells and T cells, enhances cytolytic activity of NK cells and cytolytic T lymphocytes, and promotes development of Th1 cells.
Interleukin-15 (IL-15)
Produced by mononuclear phagocytes and other cells in response to viral infections whose principal function is to stimulate the proliferation of NK cells.
Interleukin-18 (IL-18)
A cytokine produced by macrophages in response to LPS and other microbial products, which functions together with IL-12 in stimulating production of IFN-γ by NK cells and T cells. IL-18 is structurally homologous to (but functionally very different from) IL-1.
Interleukin-2 (IL-2)
A cytokine produced by Ag-activated T cells that acts in an autocrine manner to stimulate T cell proliferation and also potentiates apoptotic cell death of antigen-activated T cells. IL-2 is required for both the induction and regulation of T cell-mediated immune responses. IL-2 also stimulates proliferation and differentiation of NK cells and B cells.
Interleukin-2 (IL-2)
A cytokine produced by Ag-activated T cells that acts in an autocrine manner to stimulate T cell proliferation and also potentiates apoptotic cell death of antigen-activated T cells. IL-2 is required for both the induction and regulation of T cell-mediated immune responses. IL-2 also stimulates proliferation and differentiation of NK cells and B cells.
Interleukin-3 (IL-3)
A cytokine produced by CD4+ T cells that promotes the expansion of immature marrow progenitors of all blood cells. IL-3 is also known as multilineage colony-stimulating factor (multi-CSF).
Interleukin 4 (IL-4)
Produced mainly in the Th2 subset of CD4+ helper T cells whose functions include inducing differentiation of IgE production by B cells, and suppression of IFN-γ-dependent macrophage functions.
Interleukin-5 (IL-5)
Cytokine produced by Th2 CD4+ T cells and activated mast cells, which stimulates the growth and differentiation of eosinophils and activates mature eosinophils.
Interleukin-6 (IL-6)
A cytokine produced by activated mononuclear phagocytes, endothelial cells, and fibroblasts, which functions in both innate and adaptive immunity. IL-6 stimulates the synthesis of acute phase proteins by hepatocytes and stimulates the growth of antibody-producing B lymphocytes.
Interleukin-7 (IL-7)
A cytokine secreted by bone marrow stromal cells that stimulates survival and expansion of immature precursors of B and T lymphocytes.
Intraepithelial T Lymphocytes
T lymphocytes that are present in the epidermis of the skin and in mucosal epithelia that typically express a very limited diversity of antigen receptors. Some of these lymphocytes may recognize microbial products, such as glycolipids, associated with nonpolymorphic MHC class I molecules. Intraepithelial T lymphocytes may be considered effector cells of innate immunity and function in host defense by secreting cytokines and activating phagocytes and by killing infected cells.
Invariant Chain (Ii)
A nonpolymorphic protein that binds to newly synthesized MHC Class II molecules in the ER. The invariant chain prevents loading of the class II MHC peptide binding cleft with peptides present in the ER, leaving such peptides to bind to class I molecules. The invariant chain promotes folding and assembly of class II molecules and directs newly formed class II molecules to the specialized endosomal MIIC compartment where peptide loading takes place.
A type of antibody determined by which of five different forms of heavy chain are present. Ab isotypes include IgM, IgD, IgG, IgA, and IgE, and each isotype performs a different set of effector functions. Additional structural variations characterize distinct subtypes of IgG and IgA.
J Chain
A protein produced in mature B cells taht binds to secreted forms of IgM and IgA molecules and brings together 5 IgM molecules or 2 IgA molecules.
What is junctional diversity?
The diversity in the Ab and TCR repertoires that is attributed to the random addition or removal of nucleotide sequences at junctions between V, D, and J gene segments.
Killer Inhibitory Receptors (KIRs)
Receptors on NK cells that recognize self class I MHC molecules and deliver inhibitory signals that prevent activation of NK cell cytolytic mechanisms. These receptors ensure that NK cells do not kill normal hose cells, which express class I MHC molecules, while permitting lysis of virus-infected cells in which class I MHC expression is suppressed. Several classes of inhibitory receptors have been described, all of which contain immunoreceptor tyrosine inhibition motifs (ITIMs) that are involved in initiating inhibitory signal pathways.
What happens when Langerhans Cells traffic to the lymph node?
Immature dendritic cells found as a continuous meshwork in the epidermal layer of the skin, whose major function is to trap and transport protein antigens to draining lymph nodes. During their migration to the lymph nodes, Langerhans cells mature into lymph node DCs that can efficiently process and present Ag to naive T cells.
What is the late phase component of the immediate hypersensitivity reaction?
Ensues several hours after mast cell and basophil degranulation and is characteried by an inflammatory infiltrate of eosinophils, basophils, neutrophils, and lymphocytes. Repeated bouts of late phase reactions can cause tissue damage.
Lck is an Src family nonreceptor tyrosine kinase that noncovalently associates with the cytoplasmic tails of CD4 and CD8 molecules in T cells and is involved in early signaling events of Ag-induced T cell activation. Lck mediates tyrosine phosphorylation of the cytoplasmic tails of CD3 and ζ proteins of the TCR complex.
Lectin Pathway of Complement Activation
A pathway of complement activation triggered, in the absence of Ab, by the binding of microbial polysaccharides to circulating lectins like plasma mannose-binding lectin (MBL). MBL is structurally similar to C1q and activates the C1r-C1s enzyme complex (like C1q) or activates another serine esterase, called mannose-binding protein-associated serine esterase. The remaining steps of the lectin pathway, beginning with cleavage of C4, are the same as the classical pathway.
Distinguish between lymphocytic leukemias, myelogenous leukemias, and erythroid leukemias.
Lymphocytic leukemias are derived from B or T cell precrusors, myelogenous leukemias are derived from granulocyte or monocyte precursors, and erythroid leukemias are derived from RBC precursors. A leukemia is a malignancy of bone marrow precurosrs of blood cells in which large numbers of leukemic cells occupy the bone marrow and circulate in the blood stream.
Leukocyte Adhesion Deficiency (LAD)
A rare group of immunodeficiency diseases caused by defective expression of leukocyte adhesion molecules required for tissue recruitment of phagocytes and lymphocytes. LAD 1 is due to mutations in the gene encoding the CD18 protein, which is part of beta2 integrins. LAD II is caused by mutations in a gene that encodes an enzyme involved in the synthesis of leukocyte ligands for endothelial selectins.
A class of arachidonic acid-derived lipid inflammatory mediators produced by the lipoxygenase pathway in many cell types. Mast cells make abudnant leukotriene C4 (LTC4) and its degradation products LTD4 and LTE4, which bind to specific receptors on smooth muscle cells and cause prolonged bronchoconstriction. Leukotrienes contribute to the pathology of bronchial asthma. LTC4, LTD4, and LTE4 constitute the "slow-reacting substance of anaphylaxis."
TNF-β is produced by T cells and binds to the same receptors as TNF-α. Has proinflammatory effects, including endothelial and neutrophil activation. Critical for the normal development of lymphoid organs.
What activates macrophages?
Macrophages are activated by microbial products (endotoxin), by molecules such as CD40L (expressed on Th cells), and by T cell cytokines such as IFN-gamma. Activated macrophages phagocytose and kill microorganisms, secrete proinflammatory cytokines, and present Ags to Th cells. Macrophages may assume different morphologic forms in different tissues, including the microglia of the CNS, Kupffer cells in the liver, alveolar macrophages in the lung, and osteoclasts in bone.
What is the marginal zone in splenic lymphoid follicles?
The marginal zone is a peripheral region of splenic lymphoid follicles that contain macrophages that are efficient at trapping polysaccharide antigens. Such antigens may either persist for prolonged periods on the surfaces of marginal zone macrophages, where they are recognized by specific B cells, or they may be transported into follicles.
Mature B Cell
A mature B cell is a functionally competent IgM and IgD expressing naive B cell that represents the final stage of B cell maturation in the bone marrow and that repopulate peripheral lymphoid organs.