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ImmunologyFinal
| Question | Answer |
|---|---|
| Effector Response | eliminates/neutralizes invader |
| Memory Response | b & t cells; immune system reacts faster after each exposure |
| Innate Immunity | mechanisms predeployed before infection & poised to prevent or eliminate it |
| Adaptive Immunity | acquired & specific; develops in response to infection |
| Variolation | dried crusts from small pox postules were inhaled through nostrils or inserted into small cuts in skin |
| Edward Jenner, 1798 | noticed that milkmaids who contracted cowpox seemed immune to smallpox; deliberately inoculated an 8-yr old first with cowpox, and after he recovered, with smallpox. As he predicted, the boy did not develop smallpox. |
| Louis Pasteur | worked with chicken and fowl cholera (strain of Vibrio cholerae). He arrived at an attenuated strain on accident, and determined that it could confer immunity. He called it a vaccine in honor of Jenner's work with cowpox. |
| Attenuated | organism is altered, no longer able to cause disease |
| Pasteur, 1881 | He successfully used an attenuated strain of the anthrax bacterium (Bacillus anthracis) on sheep). |
| Pasteur, 1885 | He successfully used attenuated rabies virus preparations to inoculate a boy. |
| Matchnikoff, 1883 | He showed that phagocytic cells contributed to the immune state of an animal |
| Von Behring & Kitasato, 1890 | They showed that serum could transfer an immunized state from animal to animal |
| 1930's | During this time period, it was demonstrated that gamma globulin fraction (aka immunoglobulines) was responsible for the protective effect of serum seen earlier. |
| Humoral Immunity | Based on antibodies found in blood, based on B-lymphocytes |
| Cell-Mediated Immunity | some cells can also transfer immunity from one organism to another, based mainly on T-lympohocytes (also need APCs) |
| Opportunistic Infection | A normal human wouldn't likely be affected; only if innate immunity compromised, health impaired, etc. (not considered a true pathogen) |
| B-lymphocytes | made in bone marrow, mature in bone marrow; have membrane-bound immunoglobulin molecules on their surface that bind antigen specifically |
| T-lymphocytes | made in bone marrow, mature in thymus; have T-cell receptors which are also able to bind antigen spcifically |
| APC's | include macrophages, B-cells, and dendritic cells; are able to present Ag in association with MHC class II; are also able to deliver a co-stimulatory signal necessary for TH activation |
| cytokine | chemical produced by a cell to communicate with another cell; includes TNF, IL, Interferons... |
| Class I MHC | Class of MHC molecules that are expressed on the surface of nearly all nucleated cells |
| Class II MHC | Class of MHC molecules that are expressed on specialized cells, the APC's |
| exogenous Ag | when this antigen enters the cell, it is processed and a portion of it is presented on the surface of the APC attached to a class II molecule, and then recognized by a TH cell |
| endogenous Ag | When this type of antigen is produced, portions are presented on the surface of the cell attacked to a class I MHC molecule, and then can be recognized by a TC cell |
| TH cell | type of T cell that is MHC class II restricted |
| TC cell | type of T cell that is MHC class I restricted |
| histocompatibility Ag | antigen that causes the rejection of foreign tissue |
| Human Leukocyte Antigen | HLA |
| Class III MHC | MHC class that includes secreted proteins such as TNFalpha, TNFbeta, and Complement proteins |
| polymorphic | each locus has numerous potential alleles |
| haplotype | each set of alleles of an MHC haplotype = |
| Beta2 microglobulin | structure of MHC class I; an invariant protein, made from a gene on a different chromosome |
| alpha chain peptide-binding cleft | MHC class I structure that can hold an 8-10 amino acid residue peptide |
| dimer of the alphabeta heterodimer | one MHC class II molecule = |
| alpha/beta peptide-binding cleft | can hold 13-18 amino acid residue peptides |
| Class I MHC peptide interaction | bind via anchor residues near/at N-terminus & C-terminus - the rest of the peptide arches away from the MHC binding site |
| Class II MHC peptide interaction | bind like a hot dog in a bun, no arching; hydrophobic residues and prolines are important |
| proline | imino acid |
| LMP2 & LMP7 | 2 genes in class II MHC region that encode proteasome subunits |
| TAP1 & TAP2 | 2 genes in class II MHC region that encode peptide transporters |
| proteasomes | help in cytoplasmic degradation of endogenous proteins into small peptides |
| Endoplasmic Reticulum | location of association with new MHC class I |
| peptide transporters | transfer peptides from cytoplasm into ER |
| IFN-gamma, IL4 | cytokines that help regulate expression |
| IFN-gamma | cytokine that helps increase MHC class I and II expression |
| IL4 | cytokine that increases expression of MHC class II by resting B cells |
| cytomegalovirus | virus that causes a type of mononucleosis; one of the viral proteins binds to beta2-microglobulin, preventing its assembly with an alpha chain |
| adenovirus | virus that causes the common cold; causes a decrease in transcription of TAP1 and TAP2 (inhibits viral peptide attachment to MHC class I) |
| CD4+ | TH cells that are self-class MHC restricted |
| CD8+ | TC cells that are self-class I MHC restricted |
| dendritic cells | the best professional APC's; constitutively express high concentrations of MHC class II & high concentrations of co-stimulatory molecules |
| Macrophages | professional APC's that need to phagocytose microbes prior to expressing MHC class II and co-stimulatory molecules |
| B cells | professional APC's that constitutively express class II MHC; need to be activated in order to express co-stimulatory molecules |
| cytosolic proteins | whether abnormal proteins or normal, are target for proteolysis by the attachment of a chain of small proteins, each called ubiquitin |
| ubiquitin | tagged proteins that are degraded by large protease complexes termed proteasomes |
| TAP (transporters associated with Ag-processing) | a transporter protein that transports peptides from cytosol to RER |
| calnexin | molecular chapterone that TAP must associate with before class I alpha chain association with beta2-microglobulin |
| ERp57 | binds itself to tapasin and calreticulin to help them release MHC class 1/peptide |
| calreticulin and tapasin (TAP-associated protein) | alpha-chain/b2-microglobulin assoiates with these to allow class I molecule to capture and bind to an antigenic peptide brought into the ER via TAP. |
| vesicle-golgi-vesicle-cell surface | pathway of which the class I MHC molecule/peptide leaves the RER |
| Invariant chain (Ii) | prevents class II from binding endogenous peptides; helps get class II MHC from RER to Golgi to endocytic pathway |
| CLIP (class II-associated invariant chain peptide) | small fragment remaining after Ii is gradually degraded; prevents premature binding of Ag-peptide |
| HLA-DM | molecule that helps remove CLIP and replace it with an Ag-peptide |
| glycolipid Ag | presented by CD1 molecules |
| CD1 | nonclassical class I-type molecules; associate with beta2-microglobulin; NOT in the MHC cluster (different chromosome) |
| Mycobacterium tuberculosis and Mycobacterium leprae | presented glycolipid cell wall component examples |
| Doherty & Zinkernagel, mid-1970's (Nobel Prize 1996) | Their research led to the discovery of self-MHC restriction of TCR's |
| Kappler & Marrack, 1981 | their experiment demonstrated specificity for both MHC and Ag resides in a single receptor (Altered-self model correct) |
| CDR1 & CDR2 (Complementary Determining region) | T-cell receptor structures that mostly interact with MHC |
| CDR3 | T-cell receptor structure that contacts the antigenic peptide in the middle |
| transmembrane region | region on TCR's that is mostly hydrophobic, but also has several (+)-charged amino acid residues that allow for interaction with CD3 |
| reverse transcription of TCR genes | process that clones 32P-dNTPs into 32P-cDNA |
| cloned 32P-cDNA | used as a probe on Southern blots of genomic DNA |
| alpha & gamma | chains that have V & J genes for V-protein regions (similar to light) |
| beta and S | chains that have V, D, & J genes for V-protein regions (similar to heavy) |
| CD3 | involved in signal transduction; alpha-beta or gamma-S heterodimer are only expressed with this. |
| ITAMS (immunoreceptor tyrosine-based activation motif) | located on cytoplasmic tails of all CD3 molecules; important for signal transduction |
| CD4 & CD8 | coreceptors that are important for adhesion and signal transduction; increase avidity between TCR and peptide/MHC complex |
| CD4 | single polypeptide; transmembrane IMP, binds to beta2 domain of class II |
| CD8 | alphabeta heterodimer (disulfide linked); binds to alpha3 domain of class I |
| other locations for ITAMS | Ig-alpha/Ig-beta heterodimer of B-cell receptor complex; Fc receptors for IgE & IgG are other locations for.... |
| Ag-Independent phase | phase of B-cell maturation, involving Ig-gene rearrangement, occurs in bone barrow |
| Ag-Dependent phase | phase of B-cell activation and differentiation, occurs in secondary lymphoid organs |
| 4-8 weeks | naive B-cell life span |
| 10% | percentage of potential B cells that reach maturity and exit the bone marrow |
| Progenitor B-cell (pro-B cell) | B-cell state during a stage of maturation that expresses CD45R |
| IL7 | Transformation of pro-B cell to a pre-B cell in bone-marrow stromal cells depends on the production of this |
| Precursor B cell (pre-B cell) | B-cell state during a stage of maturation that expresses u chain |
| productive light chain rearrangement | this must occur for tranformation of a pre-B cell to an immature B cell |
| Immature B cell | B-cell state during a stage of maturation that expresses mIgM |
| RNA processing changes to get both mRNAs | this must occur for tranformation of an immature B-cell to a mature B cell |
| mature B cell | B-cell state during a stage of maturation that exprsses mIgM & mIgD |
| allelic exclusion, proliferation of pre-B cells, maturation to immature B-cell state | pre-B cell receptor important for: |
| negative selection | part of the 90% reduction in the population of B cells is attributable to this; occurs when B-cells (with BCRs that bind self-Ag) are induced to apoptose |
| editing/rearrangement of L chain genes (Kappa to Lambda) | way to rescue self-reactive immature B-cells from apoptosis, causing them to produce mIgM with different specificity (no longer self-reactive) |
| plasma B-cells and memory B-cells | B-cell activation and proliferation generates: |
| TD (T-Dependent) Antigens | require direct contact with TH cells to activate the B cell |
| TI-1 (T-Independent type 1) Antigens | molecules tend to activate B cells non-specifically, and are considered mitogens at high concentrations |
| mitogen | a mitosis generating molecule |
| LPS (Gm-; outer membrane, lipopolysaccharide) | T-Independent Type 1 examples |
| highly repetitious molecules like PG (Gm+ & Gm-; bacterial cell walls, peptidoglycin) & bacterial flagellin | T-Independent Type 2 examples |
| TI-2 (T-Independent type 1) Antigens | work by extensively crosslinking the mIg receptor, activate B-cell (need Th-cytokines to get efficient B-cell proliferation & for class switching) |
| generally weaker, no memory cells are formed, IgM is main Ab (little class switching) | characteristics of T-Independent Ag responses |
| signal 1: crosslinking BCRs signal 2: part of above for TI (1 signal), CD40/CD40L (on TH) for TD (2 signals) | competence signals that move mature B-cell (G0) to early G1 |
| totipotent | able to give rise to entire organism |
| Hematopoiesis | formation and development of RBCs and WBCs and plateltes from STEM cells |
| STEM cells | These type of cells are pluripotent and self-renewing |
| apoptosis | programmed cell death |
| bcl-2 (B-cell lymphoma) | gene that produces a protein that prevents apoptosis; overproduction can result in leukemia; expressed in lower levels by activated lymphocytes |
| B-lymphocytes | named for their site of maturation in birds (Bursa of Fabricus) |
| T-lymphocytes | named for their site of maturation in the thymus |
| TH1 response | results in a cytokine profile that activates mainly Tc cells and macrophages |
| TH2 response: | results in a cytokine profile that activates mainly B cells |
| Null cells | lymphocytes that fail to express membrane molecules that distinguish T or B cell lineages |
| Natural Killer Cells (NK cells) | subpopulation of null cells that display non-specific cytotoxicity against tumor cells, can make Ab-independent contact with a tumor cell, and can exhibit ADCC (Ab-dependent cell-mediated cytotoxicity) |
| CD16 | expressed on NK membranes, and is able to interact with the C-terminal end of the IgG molecule, which is specifically bound to its Ag; Fc Receptor |
| alveolar macrophages | macrophages found in lung |
| histiocytes | macrophages found in connective tissues |
| Kupffer cells | macrophages found in liver |
| mesangial cells | macrophages found in kidney |
| microglial cells | macrophages found in brain |
| monocytes | found in blood |
| macrophages | found in other tissue, derived from monocytes that left the blood |
| IFN-gamma | one of the most potent activators of marophages; secreted by activated TH cells |
| phagolysosome | phagosome fused with a lysosome = |
| opsonization | increases likelihood of being phagocytosed; phagocytosis is more effective if foreign cells are coated with antibodies or complement |
| IL1 | helps activate TH cells; promotes inflammation and fever |
| complement proteins | these proteins help via opsonization, cause cell lysis, and promote inflammation |
| Neutrophil (aka PMN, polymorphonuclear leukocyte) | Granulocytic cell with multilobed nucleus, that is phagocytic and responds to chemotactic factors to exit the blood; first used to arrive at an inflammatory site |
| Eosinopil | Granulocytic cell with bilobed nucleus that is phagocytic, responds to chemotactic factors and extravasates; important for defense against parasitic organisms |
| eosin | acidic dye used to stain eosinophil granules |
| Basophil | Granulocytic cell that has a bilobed nucleus, is non-phagocytic, and releases granule contents in allergic responses |
| methylene blue | basic dye used to stain Basophil granules |
| mast cells | similar origin and function as basophils; differentiate after leaving the blood to go to other tissue |
| dendritic cells | best APCs; always express high MHC class II concentration and the costimulatory molecule B7 |
| Langerhans cells | dendritic cells found in epidermis and mucous membranes |
| Intersitial dendritic cells | dendritic cells found in many organs |
| Interdigitating dendritic cells | dendritic cells found in T-cell area of secondary lymphoid tissue, thymic medulla |
| Circulating dendritic cells | dendritic cells found in blood and lymph |
| Follicular dendritic cells | dendritic cells found in B-cell area of lymphoid tissue; do NOT express MhC class II, and are NOT APCs |
| Thymus, bone marrow, Bursa of Fabricus | Primary Lymphoid Organs |
| Primary Lymphoid Organs | where lymphocytes acquire specificity and tolerance to self is achieved |
| Thymus | Primary lymphoid organ located in thoracic, mediastinum cavities that has several lobes arranged into lobules |
| outer cortex | part of thymus that has relatively immature developing cells called thymocytes |
| inner medulla | part of thymus that has more mature thymocytes |
| 95-99% | percentage of thymocyte progeny that end up apoptosing |
| Bursa of Fabricus | Primary lymphoid organ found in the dorsal wall of the cloaca (common exit of intestinal and genitourinary tracts of birds |
| Bone Marrow | Primary lymphoid organ that consists of islands of hemopoietic cells and stromal cells that interact with B cells |
| spleen, lymph nodes, and mucosal-associated lymphoid tissue (MALT) such as tonsils, Peyer's patches, appendix... | Secondary Lymphoid Organs |
| Secondary Lymphoid Organs | regions where lymphocytes talk to eachother and immune responses are disseminated from |
| Lymph Nodes | Secondary Lymphoid organ that mounts immune responses to Ag circulating in lymph, absorbed either through skin or from internal viscera; filter lymph before it eventually enters the blood in the subclavian vein, located mainly in strategic cluster (2-10mm |
| Spleen | Secondary Lymphoid organ located in upper left abdomen, behind stomach; arranged into white and red pulp |
| cortex | B-cell area of lymph nodes |
| paracortex | T-cell area of lymph nodes |
| central medulla | region of lymph nodes that has both B & T cells, plasma B cells, and macrophages |
| white pulp | section of spleen that has separate B and T-cell areas; some APCs present Ag to B-cells here |
| red pulp | section of spleen that contains macrophages, RBCs, platelets, PMNs, lymphocytes, including plasma B-cells; site where old latelets and RBC's are destroyed |
| MALT | Secondary Lymphoid organs that are aggregates of non-encapsulated lymphoid tissue; more Ab-producing plasma cells here than in the spleen, lymph nodes, and bone marrow combined (secretoryIgA is important here) |
| tonsils, Peyer's patches | 2 MALT organs that respond to Ag which have penetrated the surface mucosal barriers |
| M cells | MALT cells that are specialized to carry Ag from the lumen to lymphoid tissue in the lamina propria |
| Cutaneous-Associated Lymphoid Tissue | considered a tertiary lymphoid tissue; can import lymphoid cells during an inflammatory response (contains Langerhans cels that can become interdigitating dendritic cells, and intraepidermal lymphocytes) |
| skin (epidermis, dermis), mucous membraines, cilia, low pH (stomach, slightly low skin pH) | Anatomical Barriers |
| Psoriasin | protein produced by skin, has antibacterial activity against E. coli (probably good against Gm- enterics in general) |
| PRRs (pattern recognition receptors) | recognize broad structural motifs which are highly conserved within a microbial species, but generally absent in a host; tend to never confuse self/nonself, unlike the acquired immune system which is prone to auto-immune diseases |
| PAMPS (pathogen-associated molecular patterns) | motifs recognized by PRRs (Ex. sugar combinations, certain proteins, some nucleic acid motifs, N-f-met on bacterial proteins |
| MBL (Mannose Binding Lectin) and CRP (C-reactive protein) | 2 soluble players which help to sense foreign invaders (initiators of the complement system) |
| TLRs (toll-like receptors) | receptors on immature dendritic cells and macrophages that help sense foreign invaders, detect microbial products; stimulate phagocytic activity, production of cytokines |
| IL-1, IL-6, and TNF-alpha | secreted by activated macrophages; help induce and support inflammatory responses |
| acute inflammation | type of inflammation that responds to tissue damage, which combats the early infection stages and begins repair processes |
| chronic inflammation | type of inflammation that leads to pathologic consequences like arthritis, tissue wasting |
| tumor | inflammation that infolves swelling |
| rubor | inflammation that involves redness |
| calor | inflammation that involves heat |
| dolor | inflammation that involves pain |
| edema | inflammation that involves fluid accumulation |
| vasodilation | results in more blood volume, bringing warmth and redness |
| increasae in vascular permeability | results in more fluid leakage |
| chemokines | large subgroup of cytokines that are known to act as chemoattractants |
| cytokines | during leukocyte extravasation, these act on the endothelium of local blood vessels, increasing expression of CAMs (cell adhesion molecules) |
| neutrophils | during leukocyte extravasation, these are the first to bind to inflamed endothelium and to extravasate; attach loosely to the endothelium via mucin to selectin weak attachments |
| defensins | soluble molecules that are cationic with several disulfide bonds that kill a variety of bacteria |
| Interferons, Defensins, Cathelicidins | soluble molecules produces at the infection site that act locally |
| APR (acute phase response)proteins | soluble molecule produced at distant sites that travels via blood; promote phagocytosis and C-mediated attack upon activation; liver is major site of synthesis |
| complement proteins, C-reactive proteins, proinflammatory cytokines (MBL,TNF-alpha, IL1, and IL6) | APR proteins |
| MBL, CRP, Complement, LBP (LPS-binding protein), NOD proteins (nucleotide-binding oligomerization domain) | soluble receptors |
| LBP | soluble receptor that recognizes LPS, part of the outer cell membrane of Gm- bacteria, NOT part of the outer wall |
| NOD proteins | soluble receptor that is cytosolic, recognizes products from bacterial PG cell walls |
| SRs (scavenger receptors), TLRs (Toll-like Receptors) | membrane-bound PRRs |
| SRs | membrane-bound PRR found on macrophages, dendritic cells; help bind, internalize Gm+ and Gm- bacteria, apoptotic host cells |
| TLRs | membrane-bound PRR discovered in 1980-1990's in Drosophila; has transmembrane proteins with LRRs (Leucine rich repeates) in the EC region. |
| Neutrophils | first cells to migrate blood to infection site |
| superoxide, O2-; H2O2; HOCl, hypochlorous acid | ROS (reactive oxygen species) |
| nitric acid and superoxide | RNS (reactive nitrogen species) |
| proteases, lysozyme, defensins, cathelicidins | Non-oxidative attack via: |
| immunogenicity | the ability to induce a humoral and/or cell-mediated immune response |
| antigenicity | ability to combine specifically with either Ab and/or cell-surface receptors |
| Foreign | immunogen property that describes any molecule that was not exposed to developing lymphocytes |
| adjuvant | substance mixed with antigen and co-injected to enhance its immunogenicity |
| Aluminum potassium sulfate, Freund's incomplete adjuvant (oil, emulsifying agent) | examples of Adjuvants used for human vaccination |
| haptens | small, organic, antigenic but NOT immunogenic |
| epitopes | the discrete, small sites on an Ag to which an Ig or a TCR binds specifically to; often involves primary, secondary and tertiary structures |
| B-cell epitopes | type of epitopes that often have hydrophilic aa on protein surface, accessible to membrane-bound or free Ab |
| T-cell epitopes | type of epitopes that can be on outside or inside of proteins because they are recognized after processing and presentation |
| agretope | site that binds MHC needed along with the epitope for presented peptide |
| Porter & Edelman, 1972 Nobel Prize | they determined the basic Ig structure |
| N-termini | variable regions (VH & VL) |
| C-termini | constant regions (CL, CH1, CH2) |
| Domains | units of tertiary structure of Ig that help form functional domains in quaternary structure; held together via disulfide linkages |
| Hypervariable (HV)regions, framework regions | Variable region domains |
| hypervariable (HV) regions | variable regions that form the Ag-Binding site; aka CDRs (complementary-determining regions) |
| framework regions | variable regions that don't vary much; a scaffold to support the HV loops |
| CH1 and CL | Constant-region domains |
| Constant-region domains | Ig domains that extend Fab arms, increase maximum rotation, and hold together H & L chains with interchain S-S bonds |
| Hinge Region | region in gamma, S, and alpha heavy chains that is rich in proline, flexible, and vulnerable to cleavage with proteases (pepsin and papain); has cysteine residues, H-H chain S-S bonds |
| oligosaccharide side chains | side chains used to separate CH2 domains of Igs A, D, and G; important for activation of complement components |
| terminal domain | domain that has s(secretory)Ig with hydrophilic ends and m(membrane)Ig with extra hydrophilic spacer, hydrophobic transmembrane sequence, and short cytoplasmic tail |
| IgG | Ig class that is most abundant in serum (80%), readily crosses placenta to protect the fetus, activates complement, and binds to Fc receptors on phagocytic cells; functions as an opsonin |
| IgM | Ig class that makes up 5-10% of sesrum (as a pentamer) and has 5 units held by disulfide bonds between Cu4 and Cu3 domains |
| IgM | class of Ig that has a J (joining) chain which helps hold the Fc regions together and is the first Ig produced in a primary Ag response, and first Ig produced by a nenonate |
| IgM | The best agglutinating class of Ig due to high valency; can bind 10 small haptens (or small Ag), can only bind 5 larger Ag due to steric hindrance, better than IgG at neutralizing viruses and at C activation |
| IgA | class of Ig that makes up 10-15% serum and is the main Ig in secretions such as milk, saliva, tears, mucous; is a monomer usually in serum, and a dimer or tetramer in secretions (secretory IgA) |
| IgE | class of Ig that has a very low concentration in serum (~.002%) and mediates immediate hypersensitivity reactions responsible for hay fever, asthma, hives, anaphylactic shock; binds to Fc receptors on mast cells and basophils |
| histamine, seratonin | allergic mediators |
| IgD | class of Ig that has a low concentration in serum (~.2%) and is a major mIg along with mIgM expressed by mature B cells |
| Isotypic | category of epitopes that includes C-region determinants, is the same within a species, and anti-isotypic Ab are produced by injecting Ab from one species into another species |
| Allotypic | category of epitopes that is due to different alleles for C-region genes, occurs in some members of a species, and can produce anti-allotypic Ab by injecting Ab from one member of a species into another with different allotopes |
| Idiotypic | category of epitopes that is due to VH and VL domains and is based on sum of individual idiotopes (each individual Ag determinant of the V region) |
| Ig Superfamily | group of structurally-related, often membrane-bound glycoproteins, have typical domains of antiparallel B-pleated sheets (more common than parallel) |
| Monoclonal Ab | Antibodies that are all specific for a single epitope; most Ag will induce a heterogenous mixture of Ab; production is allowed byclones of B-cell hybridomas |
| B-cell hybridoma | fused plasma cell and myeledoma |
| detecting pregnancy, measuring blood levels of drugs, diagnosing numerous pathogenic microbes, detecting Ag shed by certain tumors, and making immunotoxins | uses for Monoclonal Ab |
| immunotoxins | tumor-specific monoclonal Ab coupled to a lethal toxin |
| heteroconjugates | hybrids of 2 different Ab, 1 with specificity for a tumor, one with specificity for a surface molecule on a cell such as an NK, CTL, or activated macrophage |
| abzymes | catalytic Ab, Ab + enzyme) useful to cut peptide bonds as specific amino acid residues |
| Dryer and Bennett, 1965 | they discovered the 2-gene model; one gene for C-region, one for v-region, they must come together at DNA level; contradicted one-gene-one polypeptide hypothesis |
| Tonegawa and Hozumi, 1976, 1987 Nobel Prize | they showed that Kappa-chain mRNA hybridized to 2 DNA pieces from embryonic DNA, but to only 1 piece from myeloma DNA |
| signal (leader) sequence | found at the end of each V gene; guides nascent polypeptide to RER |
| Lambda chain | chain with about 100V, 6J, and 6C genes in humans |
| Kappa chain | chain with about 100 V, 5J, and 1 C gene in humans |
| Diversity chain | D |
| Joining | J |
| Heavy Chain | chain with about 100 V, 30 D, 6 J, and several CH |
| heavy-chain V-region genes | in B cells, these genes rearrange first |
| isotype switching | later rearrangement of H-chain C-region genes is termed: |
| transcription and intron removal | this must occur for the promotor/leader sequence/VJ/C gene to rearrange to leader sequence/VJ/C |
| translation | this must occur for gene to rearrange from leader sequence/VJ/C to leader peptide-V-J-C |
| into RER, leader peptide cut off | this must occur for gene to rearrange from leader peptide-V-J-C into V-J-C |
| RSSs (recombination signal sequences) | flank each germ-line V, D, J gene segments; signals for recombination |
| recombinase | helps bring sequences together |
| non-functional Ab/nonproductive rearrangement | joining of sections not-in-frame causes stop codons to come early, resulting in this |
| productive rearrangement | joining in-frame sections results in this |
| Allelic exclusion | only one H-chain gene is used, other isn't or only one L-chain is used, other 3 aren't |
| Junctional Flexibility | generation of Ab diversity mechanism in which some segments are jointed imprecisely, resulting in alternative amino acid at each coding joint |
| P-nucleotide addition | generation of Ab Diversity mechanism that occurs during cutting and joining of gene segments (variable cutting of a hairpin end) can result in a ss end, which when repared leaves a Palindromic sequence |
| Palindrome | reads the same forwards and backwards |
| N-region nucleotide addition | generation of Ab diversity mechanism in which random nucleotides (up to 15 each) are added to V-D and D-J junctions by TdT |
| Terminal deoxynucleotidyl transferase | TdT |
| somatic hypermutation | generation of Ab diversity mechanism that occurs in V-region segments (especially CDRs) at a much faster mutation rate than in other genes; mostly substitutions; is partly responsible for affinity maturation |
| cytokines | activated TH cells secrete these to influence which recombinases are produced, which dictates which isotypes are switched to |
| 5' 7-MeG cap & 3' poly-A tail (added by poly-A pol. ~15-30 nucleotides downstream of AAUAAA signal) | these 2 structures are added during RNA processing from the primary transcript to mRNA |
| removal of introns, splicing together of exons | these also must occur when processing the primary transcript into mRNA |
| cytoplasm | after processed from primary transcript, the mRNA is sent here. |
| secreted u | if first poly-A site of primary u chain transcript is used, splicing generates this |
| membrane-bound u | if second poly-A site of primary u chain transcript is used, splicing generates this |
| membrane S chain | if poly-A site 4 is cut, this is the result |
| poly-A sites 2 and 4 | These two sites must be cut simultaneously in order for the cell to express mIgM and mIgD |
| secreted IgM | If poly-A site 1 is cut, this is the result |
| secreted IgD | If poly-A site 3 is cut, this is the result |
| promoter | this site is found near the +1 transcription start site and initiates, giving RNA pol II the direction |
| enhancer | this site is much farther upstream or downstream, binds to regulatory proteins that then increase transcription efficiency |
| silencer | site found far up or downstream, decreases transcription efficiency |
| affinity | the strength of the total non-covalent interactions between a single Ag-binding site on an Ab and a single epitope |
| low affinity | level of affinity that binds weakly, dissociates readily |
| high affinity | level of affinity that binds tightly, ramins bound longer |
| avidity | the strength of multiple interactions between a multivalent Ab and Ag |
| cross-reactivity | occurs when two different Ag share an identical epitope or if Ab specific for one epitope also binds to an unrelated epitope with similar chemical properties |
| precipitation reactions | reaction that occurs when Ag-Ab cross-link, forming a lattice; depends on valencies of both Ab and Ag |
| equivalence zone | area of maximal precipitation with an optimum ration of Ab to Ag |
| interface (ring, Ascoli) precipitin test | this method can be used as a rapid test for the presence of Ag or Ab; dilution series of Ab in test tube, layer Ag on top |
| radial immunodiffusion (Mancini diffusion) | precipitation reaction in which the Ag is placed in a well and diffuses out into agar containing Ab; precipitate ring is proportional to Ag concentration |
| double immunodiffusion (Ouchterlony diffusion) | precipitation reaction in which both the Ag and Ab are in wells and diffuse toward each other, forming precipitate line at equivalence zone; pattern of precipitate lines indicates whether or not they share epitopes |
| Identity | pattern resulting from Ouchterlony diffusion indicating shared identical epitopes |
| Nonidentity | pattern resulting from Ouchterlony diffusion indicating no shared epitopes |
| Partial identity | pattern resulting from Ouchterlony diffusion indicating some shared epitopes |
| immunoelectrophoresis | used to detect presence/absence of proteins in serum (rocket and 2-D) |
| agglutination | interaction between Ab and particulate Ag, leads to visible clumping; more sensitive than precipitation b/c less Ag is needed to get a visible reaction |
| Hemagglutination | type of agglutination used to blood type |
| IgG & IgM | anti-A Ab and anti-B Ab have mixtures of these to Igs, thus are effective in agglutinating RBCs quickly, obtaining LARGE aggregates |
| IgG | anti-Rh has only this Ig, which doesn't overcome the zeta-potential so agglutination reaction is slower and with much SMALLER aggregates |
| zeta-potential | repulsive force between RBCs due to a negative ion cloud |
| bacterial agglutination | type of agglutination that can detect Ab against bacterial surface Ag, also quantitates serum Ab titer of the patient; also used to type bacteria |
| RIA (Radioimmunoassay) | can detect Ab or Ag, quantitate it, even at very low concentrations; involves competitive binding of labeled Ag and unlabeled Ag to a high affinity Ab |
| ELISA (Enzyme Linked Immunosorbent Assay) | detection is based on an enzyme conjugated to an Ab, enzyme cuts colorless substrate into a colored product which is readily detected; also very sensitive and quantitative; several types |
| Indirect ELISA | type of ELISA in which the wells are coated with Ag, primary Ab is added, then enzyme-conjugated secondary Ab, then substrate |
| Direct ELISA | type of ELISA in which Ab is bound to wells, Ag is added, then enzyme-linked Ab for a different epitope, then substrate |
| Competitive ELISA | type of ELISA in which Ag is bound to wells, Ab is bound to Ag in separate solution, mixtures is added to wells, along with enzyme-conjugated secondary Ab and substrate |
| Western Blotting | includes electrophoresis of proteins, blotting to nylon or nitrocellulose, incubating blot with labeled Ab, adding secondary enzyme linked anti-isotypic Ab, and visualizing via autoradiography or colorimetrically |
| signal is amplified, economy | 2 Advantages of Indirect ELISA |
| Immunoflourescence | generally use dyes like fluorescein and rhodamine; used to detect cell subpopulations, identify bacterial species, sort cells with a FACS (fluorescence activated cell sorter) |
| Immunoelectron Microscopy | accomplished by conjugating an electron-dense label to the Fc portion of an Ab, either the primary or secondary one |
| Cl1, Clr, Cls, C4, C2, C3, C5, C6, C7, C8, C9 | Classical Pathway order |
| zymogens | classical pathway component that are proenzymes which require proteolytic cleavage to become active |
| C3 cut into C3a(small fragment, generally diffuses away) and C3b(larger portion, generally works in pathway) | cleavage products of the classical pathway |
| C3, FB, FD, C3, C5, C6, C7, C8, C9 | Alternative pathway order |
| C1q, 2 C1r, 2 Cls | C1 subunits of classical pathway (5 of them) |
| autocatalysis | C1r undergoes conformational changes termed" |
| Lectin Pathway | this pathway does not depend on Ab-binding for its activation, but is activated by binding of MBL to mannose residues on glycoproteins or carbohydrates on microbial surfaces |
| MASP1 & MASP2 | these 2 MBL-associated serine proteases bind to MBL |
| DAF (decay accelerating factor) | this factor accelerates the dissociation of C4b2a and C3bBb (the C3 convertases) |
| Factor I | this factor cleaves C4b or C3b inactivating them |
| S-protein | this protein binds to solule C5b67 before membrane insertion and prevents its insertion into the cell membrane, making it hydrophilic |
| MIRL (membrane inhibitor of reactive lysis)/HRF (homologous restriction facter) | these to regulators bind to C5b678 on autologous cells, blocking binding of C9 |
| Target cell lysis | effective against cells and enveloped viruses; more effective against Gm- than Gm+ bacteria |
| C3a, C4a, & C5a | anaphylatoxins that bind to receptors on basophils and mast cells and induce degranulation (3 of them) |
| C3a, C5a, & C5b67 | help to get neutrophils and monocytes to undergo chemotaxis to the site of complement activation in the tissues (3 of them) |
| Opsonization | C proteins coat surface of target, making it more easily phagocytosed. |
| C3b & C4b | most effective for opsonization (2) |
| Viral neutralization | prevents a virus from binding to host cell by binding complement and/or Ab creating a thick coating which does not allow viruses to bind to their target cells; formation of large aggregates reduces the # of single viruses, viruses are opsonized |
| Solubilization | clearing of Immune Complexes; binding of C proteins (Especially C3b) to immune complexes helps clear them from the tissues |
| ITAMS (immunoreceptor tyrosine-based activation motifs | these can be found in Ig-alpha/Ig-beta tails and they associate with Src and Syk tyrosine kinases |
| kinases | these add phosphates from ATP to tyrosine |
| Ag + mIg | competence signals for TI-1 & TI-2 |
| mIg crosslinking + TH interaction (CD40, CD40L) | competence signals for TD Ag |
| signal transduction pathway | After competence signal, phosphorylation and de-phosphorylation activate this pathway |
| phospholipase C | This converts PIP2 (phosphetidyl inositol diphosphate) to IP3 (unositol triphosphate) |
| IP3 (unositol triphosphate) | This mobilizes Ca2+ stores |
| PKC (protein kinase C, aka Ca2+-dependent protein kinase) | After phospholipase converts PIP2 to IP3, this is activated |
| B-Cell Co-Receptor Complex | this complex can intensify the activating signal resulting from cross-linkage of the BCR |
| transmembrane IMPS (integral membrane proteins) | B-Cell Co-receptor complex is made of several proteins called: |
| interacts with Ig-alpha/Ig-beta & helps amplify the activation of signal-transduction pathway | These two activities are accomplished by the B-Cell Co-receptor complex |
| Golgi apparatus | TH cells reorganize this in order to direct the release of cytokines toward the Ag-specific B cell during a humoral response |
| to get rid of those self-reactive B cells which express mIg specific for self-Ag that did not have access to the bone marrow | What is the purpose of negative selection of mature, self-reactive B cells? |
| peripheral lymphoid tissue | Where does negative selection of mature, self-reactive B cells need to occur? |
| anergic | What is the term used to refer to B cells that are functionally nonresponsive? |
| spleen for blood borne Ag & lymph nodes for tissue Ag | What are the two sites for induction of humoral response? |
| afferent vessels | By what means do Ag or Ag/Ab enter node during induction of humoral response? |
| paracortex | This is the site for intitial activation of B&T cells that contails lots of macrophages & interdigitating dendritic cells (IDCs) |
| foci | These are formed by activated and proliferating B cells at the edge of T-cell rich zone, and differentiate into plasma cells |
| IgM or IgG | foci tend to secrete either one of these 2 Igs |
| IgG | foci will secrete this Ig if isotype switching occurred |
| primary follicles to secondary follicles | a few days after the foci secrete either IgM or IgG, a few activated B & T cells migrate from foci to these, which then develop into these. |
| FDCs (Follicular dendritic cells) | These are also important in secondary immune response and release membrane-derived molecules coated with immune complexes |
| iccosomes (immune complex coating-somes) | FDCs release these which are membrane-derived and coated with immune complexes |
| germinal center | activated B cells, along with some activated TH cells, migrate to the center of follicle, forming this, and then proliferate. |
| centroblasts | proliferating activated B cells are termed: |
| centrocytes | centroblast progeny that are small, nondividing cells that express mIg are called: |
| plasma-blasts or small memory B cells | centrocytes whose mIgM bind to ag presented by FDCs differentiate to form either one of these two |
| up to 100-10,000 fold | How much does Affinity maturation increase affinity? |
| Somatic Hypermutation | This affects in both H & L variable regions and occurs in germinal centers of follicles, mainly in the 3 CDRs (hypervariability regions) |
| apoptosis | this happens to cells with low or no affinity |
| BCl-2 | High affinity centrocytes express this which helps inhibit apoptosis |
| IL-1 & CD23 | These two are needed to generate plasma cells from centrocytes |
| CD40/CD40L | This interaction is needed to generate memory B cells from centrocytes |
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