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45 Cards in this Set
- Front
- Back
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...-any molecule that binds to a receptor
...-strength of interaction ...-collective affinities of multiple receptors |
Ligand
Affinity Avidity |
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Receptor-ligand Interactions:
... responses are elicited when there is an interaction between a ligand and its receptor -cells correlate information from multiple activated receptors to generate either a positive or negative signal ligand is any molecule (including antigens, cytokines and cell adhesion molecules) that ... to a receptor -ligand may be displayed on the cell-surface or a soluble molecule (as is true for the receptors) effective binding of the ligand to its receptor increases with the ...(strength) of the interaction -affinity determined by the shape and intermolecular interactions |
immune
bind affinity |
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What is this?
-any organism, molecule or part of a molecule that binds specifically to an antibody (antibody generating) or T-cell receptor -may be simple or complex in nature -may be of protein, carbohydrate of synthetic origin |
Antigen
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... (or antigenic determinant)
site on an antigen recognized by an antibody or antigen receptor -T-cell ... are short peptides derived from a protein antigen -B-cell ... are antigenic determinants recognized by B cells (discontinuous in the primary structure) |
Epitope
epitopes epitopes |
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What is this?
-any molecule that can elicit an immune response upon injection -only proteins are fully ... because only proteins are recognized by T lymphocytes |
Immunogen
immunogenic |
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What is this?
-usually of nonbiologic origin -molecules that can bind antibody but cannot by themselves elicit an immune -when coupled/crosslinked to a immunogen can elicit both an antibody and T-cell response |
Hapten
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The players in antigen recognition:
Two receptors -... receptors found on B lymphocytes -... receptors found on T lymphocytes Antigen presenting molecules -Major histocompatibility complex (MHC) types I and II *Also referred to as ... -Type I found on all ... cells -Type II found on ... antigen presenting cells: dendritic cells, macrophage, B cells and some thymocytes |
B-cell
T-cell human leukocyte antigen (HLA) nucleated professional |
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Major effector function of B cells is to ...
remember! Effector mechanism (function) is the destruction and clearance of ... |
secrete antibodies
pathogen |
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Do T-cells have an effector mechanism?
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No
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Antibody composition:
antibodies are glycoproteins composed of four ... chain -two identical ... chains (H chains) and two identical ... chains (L chains) assembly of the H and L chains are into a ... structure -each arm of the ‘Y’ is a complete L chain paired with the N-terminal part of the H-chain covalently linked by a ... bond -the stem of the Y is composed of the C-terminal portions of the H chains that are also linked by disulfide bonds area between arms and stem is called the ... region and is quite flexible allowing for the ‘movement’ of the arms |
polypeptide
heavy light Y disulfide hinge |
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Amino acid sequence:
... is the reason for the great diversity of antigen-binding specificity sequence differences are concentrated in the N-terminal region of each chain called the ... -the pairing of the V regions of the H and L chains form the ... site -every antibody has 2 IDENTICAL ... remaining sequence exhibits little variation and is referred to as ... |
variability
variable (V) region antigen-binding antigen-binding sites constant (C) region |
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... fragments are commonly known as the arms of the antibody and the ... the stem.
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Fab
Fc |
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Breaking the antibody:
-Early experiments helped elucidate the associations between the chains and the functions of the different regions -Digestion with two plant proteases -... cleaves at the hinge region create three fragments: 2 identical Fab (fragment, antigen binding) and Fc (crystallizable) -... cleaves below hinge region creating two fragments: F(ab’)2 and Fc |
Papain
Pepsin |
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H and L chains:
the L and H chains consist of a series of repeating homologous units each repeating unit is about 100-110 amino acid residues in length -each unit folds independently in a globular motif called an ... domain |
immunoglobulin (Ig)
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H Chain Isotypes:
5 heavy chain isotypes γ, µ ,δ, α , and ε, correspond to Ig isotype IgG, IgM, IgD, IgA and IgE - IgD, IgE and IgG are monomeric, IgA can be monomeric or a dimer while IgM ONLY forms pentamers ... determines location and function of the Ig differences in H chain C regions, disulfide bond locations, presence of hinge region, distribution of N-linked carbohydrate |
isotype
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L Chain Isotypes:
-2 isotypes kappa (κ) and lambda (λ) -no functional difference between an antibody containing either a κ or a λ chain -an antibody will contain either a κ chain or a λ chain, not both -both isotypes will associate with all ... chain isotypes -in humans 2/3 of antibodies carrying the ... chain |
H
kappa |
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Ig globular domains:
the ... chain is composed of a single variable domain (VL) and a constant domain (CL) the ... chains each have a single variable (VH) domain that have 3-4 constant (CH1-4) domains a complete immunoglobulin is formed when the 4 polypeptides chains are paired ... distinct globular regions are identifiable -two corresponding to the ... arms and a third to the ... stem. -each globular domain consists of 4 immunoglobulin domains (you will see 6 in the Fc stem of IgM and IgE) |
L
H three Fab Fc |
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Of special note: Immunoglobulin domains were first discovered in ...
Subsequently, Ig-like domains were identified in other cell surface and secreted proteins common to the immune system. These proteins function in recognition, adhesion and binding. Proteins contains Ig-like domains become members of the Ig superfamily. Some famous member are: TCR, MHC Class I/II, and CD4/8. |
antibodies
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The Variable Region:
comparison of V domains from a large number of H and L chains reveals differences in amino acid sequences -difference found in defined, concentrated regions called ... regions *HV regions also called ... *refers to HV regions providing a binding surface that is complementary to that of the antigens -regions are flanked by less variable ... regions pairing of the VH and VL bring together the hypervariable loops to create a composite ... surface forming the antigen-binding site |
hypervariable (HV)
complementarity-determining regions (CDRs) framework (FR) hypervariable |
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Each V domain has ... hypervariable (HV) regions flanked by ... framework (FR) regions
The HV regions are located on 3 of the loops located farthest from the ... region The FR regions correspond to the ... sheets and the remaining loops The Package: Localized ... in a structurally constant framework |
3
4 constant β variability |
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Antibodies binding to epitopes:
The Polio virus has ... proteins in pink, blue and yellow to which antibodies could potentially bind. VP1, shown below the viral particle, has several ... (white) that are recognized by specific antibodies. |
envelope
epitopes |
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Macromolecules and pathogens are normally ... than the antibody
The antibody will bind to a smaller portion of the antigen called the antigenic determinant or ... ... antigen is any antigen that has more than one epitope or more than one copy of the same epitope |
larger
epitope Multivalent |
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Antigen binding
antigen-binding sites vary in size and shape to fit the ... of the epitope to which they are binding antibody:antigen binding is through ... forces - hydrogen bonds, van der Waals forces, electrostatic forces and hydrophobic interactions (easily reversed) two antibodies can bind the same epitope (same specificity) with different ... - small differences in shape and chemical properties of the binding site The better the fit between antibody and antigen, the ... the interaction (the greater the affinity) ... - linear sequence of amino acid within the primary structure Conformational (...) epitope- formed by separate regions in the primary amino acid sequence brought together by protein folding-antigen must be in native conformation (the major type of epitope binding seen) |
specificity
NONCOVALENT affinities stronger Linear epitope discontinuous |
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Immunoglobulin:
Secreted form is ... Bind epitopes on a ... range of intact molecules: proteins, carbohydrates and lipids Bind antigen and serve in ... functions |
antibody
wide effector |
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T-cell receptor:
Absence of ... form Only recognize antigen in form of peptides presented by ... molecules Only function in binding antigen, NO ... function |
secreted
MHC effector |
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Ig and TCR:
similar structures highly variable and diverse in their antigen specificity -broad specificity generated by gene ... through the process of somatic recombination diversity is generated prior to ... exposure during development of -B and T cells develop in the bone marrow and thymus, respectively further diversity is generated in the Ig after antigen exposure via somatic ... -does NOT occur with the TCR TCRs do not undergo isotype switching after antigen exposure, as does Ig -sole function as an ... molecule |
rearrangement
antigen hypermutation antigen binding |
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T-cell receptor
Consists of 2 different polypeptide chains: T-cell receptor α chain (TCRα) and T-cell receptor β chain (TCRβ) TCR α and β chains organized into ... regions and ... regions like Igs α and β chains folded into discrete Ig domains The ... antigen binding site formed by the Vα and Vβ domains |
V
C SINGLE |
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T-cell receptor
TCR is a membrane-bound glycoprotein that resembles a single arm (Fab) of an ... molecule (single antigen binding site) composed of 2 polypeptide chains forming a ...: α chain and β chain -each chain consist of a V domain, C domain and a membrane anchoring domain -α and β chains have similar structural organization to Ig heavy and light chains with regards to the V and C regions each mature T cell expresses one functional α chain and one functional β chain together defining a unique ... molecule |
Ig
heterodimer TCR |
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Sequence variation
V region amino acid sequence variation is clustered in ... regions the HV regions correspond to the loops of the polypeptide chain at the domain ... from the membrane Have same number of hypervariable regions |
HV
farthest |
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A TCR α:β heterodimer associates with invariant sequence proteins forming the ...
The associated proteins include a ... complex and a ζ chain The TCR is involved in ... The CD3 complex and the ζ chain are involved in ... |
TCR complex
CD3 antigen recognition signal transduction |
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The TCR complex:
composed of the TCR and four ... sequence proteins -three proteins form the CD3 complex (CD3γ, CD3δ, CD3ε) and the fourth called the ... chain that forms a homodimer -the negatively charged aspartic acid residues are found in the transmembrane segments of the CD3 complex and the ζ chain *noncovalent binding with the positively charged residues of the transmembrane region of the TCR like Ig, TCR cannot make it to the cell surface without hitching a ride from some companion ... proteins (can't be expressed by themselves) |
invariant
ζ (zeta) membrane |
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The two classes of T cells:
classes defined by the expression of either the ... or ... co-receptor |
CD4
CD8 |
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CD4 (helper T cells):
glycoprotein composed of four Ig-like domains with hinge between second and third domain -general function is to ‘...’ other cells of immune system -... activates macrophage to phagocytose and secrete cytokines -... stimulate B cells to produce antibodies |
help
TH1 TH2 |
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CD8 (cytotoxic T cell):
glycoprotein composed of an α chain and β chain (each with Ig-like domain), linked by a ... bond Sole purpose: ... infected cells preventing spread of pathogen and further infection of healthy cells |
disulfide
kill |
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γ:δ Receptor:
Binds antigen like intact or organic proteins not presented by MHC molecules on professional ... Most do not express CD8 or CD4 as they do not recognize MHC γ:δ T cells develop in the ... and migrate to body tissues ... recirculate between blood and lymph nodes (account for ~ 5% of T cells in blood) |
APCs
thymus Do NOT |
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The γ:δ Receptor-the second TCR
the TCR is composed of either α:β heterodimer or γ:δ heterodimer the γ:δ heterodimer is similar in structure to the α:β heterodimer -formed by two different protein chains termed γ and δ -γ resembles … and δ resembles … |
α
β |
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Functionality of γ:δ T lymphocytes
-bind certain kinds of ligands, including heat-shock proteins and nonpeptide ligands such as phosphorylated ligands or mycobacterial lipid antigens -not restricted by ‘…’ MHC class I and class II molecule -bind free antigen, as do immunoglobulins, and/or may bind peptides or other antigens presented by … MHC-like molecules (these proteins resemble MHC class I molecules but are relatively nonpolymorphic) |
Classical
nonclassical |
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MHC class I present antigen (from an … origin) to T-cells that express CD8 on there surface
MHC class II present antigen (from an … source) to T-cells that express CD4 on there surface |
Intracellular
Extracellular |
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MHC Class I and II molecules
membrane glycoproteins that function to bind … and present them to T cells share similar 3-D structures: -two pairs of extracellular Ig-like domains -one pair forms the peptide binding site -the other provides support for the peptide binding site and are the binding sites for the CD4 and CD8 co-receptors |
antigen
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MHC class I molecule
composed of a transmembrane heavy chain (α chain) non-covalently complexed to a β2-microglobulin present antigen (from an intracellular origin) to T-cells that express … on there surface viruses, protozoa, any cell with a nucleus |
CD8
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MHC class II molecule
composed of two transmembrane chains (α and β), each of which contribute one domain to peptide binding site present antigen (from an extracellular source) to T-cells that express … on there surface. For cells to phagocytose (ex. Macrophage, dentritic) |
CD4
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“Rule of Eight”
… X MHC Class II = 8 … X MHC Class I = 8 |
CD4
CD8 |
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The α and β chains of CD8 each have one Ig-like domain with an extended region connecting it to the transmembrane region
CD8 binds to the α3 region of the MHC class … The two most distal domains of CD4 bind to the MHC class … β2 domain |
I
II |
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MHC Peptide Binding Site
the binding is the result of between the peptide and the MHC … helices of the binding site the binding site is capable of binding peptides of many different amino acid sequences (… binding specificity) binding constraints dictated by structure of the … -MHC class I binds peptides of limited length (8-10aa), peptides bound by their ends -MHC class II binds peptides of longer length (~13-25aa), ends are not pinned down into pocket |
α
degenerate groove |
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Locations of MHC Molecule
virtually all nucleated cells of the body express MHC class … molecules constitutively -susceptible to … infection. -constant surveillance by … cell for infected cells exception is…, where you see persistent infection with malaria parasites. MHC class II molecules are expressed primarily on the professional … -B cells, macrophages, dendritic cells, and epithelium of the thymus. Certain cells can be induced to MHC class II |
I
viral cytotoxic T RBC APC |
