Fundamentals I Test 4 Burrows – Flashcards
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In what two forms are Ab's found? |
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Attached to B-cell membranes or Secreted by Plasma cells |
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T/F; Edelman ; Porter used ultracentrifugation, Papain digestion, Pepsin digestion, ; Mercaptoethanol to break down IgG and discover it's structure. |
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True |
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What connects the heavy and light chains of IgG? |
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Disulfide Bonds |
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On what end of the light chain do you find the constant & variable regions? In which region do you find kappa or lambda types? |
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Constant: C-terminal, kappa & lambda Variable: N-terminal |
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How many basic sequence patterns are found on the heavy chain constant region? |
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5 |
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What defines the isotype of an Ab? |
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The heavy chain type (IgM, IgG, IgA, IgD, IgE) |
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What are the Ag-binding sites of Abs, and where are they found? |
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Hypervariable or Complementary-Determining Regions; on the variable portion of the heavy & light chains |
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T/F CDR's are not found adjacent on the primary structure, but they are adjacent in the secondary structure. |
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True; they fold to be in the same area |
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What is the term for the Ag Determinant binding site? |
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Epitope |
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What gives the Hinge region its flexibility, what is it susceptible to, and in what Ig's is it found? |
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Flexibility - Proline Residues; Susceptible - Proteolytic Enzymes; IgG, IgD, and IgA |
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What is the most abundant Ig in serum? What is its structure? |
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IgG; monomer of 2γ H-Chains and 2κ or λ L-Chains |
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How many subclasses does IgG have & what makes them different? |
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4 (numbered by their serum concentration); size of hinge region & number and position of interchain S-S bonds b/w H-chains |
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Which Immunoglobulin molecule is pentameric and has 10 potential Ag-binding sites? |
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IgM |
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Which Ab is the first produced during primary immune response and is the Ag receptor on B cells? |
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IgM |
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What is the predominant Ig class in mucosal secretions? In what forms does it exist? |
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IgA; monomeric in serum & dimeric/tetrameric in secretions |
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What is the main effector Ab in mucosal secretions, and how is it formed? |
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S-IgA; IgA binds pIgR and is internalized, a portion is then cleaved leaving the other portion bound to IgA which forms S-IgA |
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Which type of Ab mediates Type 1 hypersensitivity reactions and binds Fc receptor of basophils & mast cells? |
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IgE |
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What induces degranulation and releases histamine? |
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Cross-linking or receptor bound IgE by Ag |
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Which two Immunoglobulins are membrane-bound and co-expressed on mature B cells? |
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IgD and IgM |
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T/F Multiple Ab's can recognize the same Ag because there are many different epitopes on a single Ag. |
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True |
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What is the Ab response to an Ag which induces a mixture of Abs to one Ag?; What does this result in? |
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Polyclonal Ab Response; Ab heterogeneity = increases immune protection |
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What is the Ab response to a single epitope? |
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Monoclonal Ab (mAb) |
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T/F; It is feasible to purify monoclonal Ab from polyclonal Ab. |
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False; it is NOT feasible |
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What two cells are fused in the preparation of mAbs? |
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Ab-producing B cell ; plasmacytoma |
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Describe the Ag-Ab Interaction. |
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Reversible ; Non-covalent Van der Waals interactions |
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What is defined as the measure of the strength of the binding ease of association or dissociation? |
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Affinity |
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What is defined as an increase in affinity due to multivalent binding or the summation of multiple affinities? |
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Avidity |
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What is a substance able to generate antibody or T cell responses? |
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Immunogen |
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What are the three most important characteristics of a good antigen? |
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Size: larger is better Chemical Composition: Proteins ; Carbohydrates ; Lipids Similarity to self-antigens: multiple differences are better |
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What is an important characteristic for T cell Ag response? |
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Degradability |
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What is the term for a Non-immunogenic substance, usually low molecular weight, that can induce Ab formation when coupled to a larger "carrier" molecule? |
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Hapten |
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Which three Hapten examples can you make monoclonal Ab's to? |
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Cortisol, Estradiol, & Testosterone |
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What is the term for Ab's binding Ag's & sticking together? |
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Agglutination |
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T/F Antibodies can inhibit attachment of bacteria to cells. |
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True |
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What does a bacteria tagged with Ab's bind to on the macrophage cell surface? |
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Fc receptors |
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What is the term for any molecule that acts as a binding enhancer for the process of phagocytosis? |
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Opsonization (via Fc Receptor) |
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Is it typical to find a peptide on an MHC?; What are the two possibilities for it? |
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Always has a peptide; usually from self, but if it is a foreign peptide it alerts T cells |
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What are the four good Ag-Ab reactions In Vivo? |
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Neutralization, Opsonization, Complement Lysis, ; Prevention of Adherence |
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What test is used to see if a person has been infected with a virus such as HIV? |
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Enzyme Linked ImmunoSorbent Assay; (ELISA); first line assay/preliminary test |
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After an ELISA test is preformed what is done to determine which viral G's the patient has made Ab's to? |
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Western Blot (second line assay) |
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Is it possible to have Ab's without being exposed to a particular virus? |
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Yes, because some viral Ag's are cross-reactive |
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What is screened for in a pregnancy test? |
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Human Chorionic Gonadotrophin; prevents Ab's from agglutinating |
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After Ab binds Ag, the outcome depends on what? What determines effector functions? |
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Constant region of the heavy chain; Ab isotype |
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At what level does diversity operate? |
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lymphocyte level |
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What causes isotype switching? |
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Ag binding |
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Describe the parts found in an original DNA sequence. (as it relates to isotype switching) |
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Leading Region, Variable Regions, Joining Regions, Constant Regions, and Introns |
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Describe the parts of an mRNA strand. |
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Leading region, Variable region, and Constant region (no introns) |
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What is the process of splicing together segments of genes in order to generate tremendous diversity without monopolizing the genome? |
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Ig or TCR gene rearrangement |
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What are the segments found in light chains? |
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κ and λ light chains each have; Leading, Variable, Joining, and Constant |
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What are the segments found in heavy chains? |
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Leading, Variable, Diversity, Joining, and Constant |
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Describe the mechanism of Immunoglobulin Gene Recombination. |
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(also called Somatic Recombination) Gene segment forms a loop that is then excised leaving the outer portions adjacent to each other |
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T/F Cells continue to proliferate between each step in Somatic Recombination resulting in even more possibilities for differentiation. |
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True |
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How many possible Ab's can be made?; How many different Ab's are produced by each B cell or plasma cell? |
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3 million; only ONE |
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What regulates Isotype Switching by Somatic Recombination? |
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cytokines produced by T cells (T cells regulate B cells) |
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T/F Cells that do not undergo isotype switching may still respond to Ag. |
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False; only cells that switch will respond to Ag |
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In what order and what amounts are the immunoglobulins produced in a Primary Response? |
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IgM followed by IgG in approximately equal quantities |
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In what order and in what amounts are different isotypes expressed in a secondary response? |
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IgM and IgG about the same time; much more IgG than IgM (b/c cell remembers how to make IgG) |
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What is the Ag-binding portion of the T Cell Receptor? |
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Variable alpha & beta regions |
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Can TCR exist in secreted form? |
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No, only as a transmembrane Ag receptor |
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In what organ do TCR's undergo somatic gene recombination? |
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Thymus |
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What are the parts of the gene segment that codes for TCR variable region? |
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Variable, Joining, Constant |
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Can B cells recognize intact protein Ag's? What about T cells? |
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B cells - Yes; T cells - No (must be degraded) |
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What results in autoreactive B and T cells that are not eliminated? |
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Autoimmune Disease |
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What can result from chromosomal translocations arising during VDJ recombination or isotype switching? |
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Lymphoid Malignancies |
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What are the major differences between B & T cell Ag Receptors? |
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B cell: Immunoglobulin, B cell Transmembrane protein, plasma secreted effector T cell: TCR, T cell Transmembrane protein, CD4 Th, CD8 Tc |
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Where are proteins denatured to be presented? What denatures them? |
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Lysozyme; proteases |
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T/F B cell antibodies can operate at a distance. |
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True |
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Do B cells recognize intact Ag's or bound peptides?; What about T cells? |
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B cells: Intact Ag's T cells: degraded peptides on MHC |
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T/F Ag-specific T cell function requires MHC contact, but does not require cell-to-cell interaction. |
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False; requires MHC and cell-to-cell contact |
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What cells express MHC Class I? To which cells do they present? |
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All nucleated cells; CD8 T cells (Cytotoxic killer cells and kills virus infected cells) |
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What cell have MHC Class II and to what cells do they present? |
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APC's (dendritic cells, B cells, MQ's); CD4 T cells (T helper cells) |
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What occurs after T helper cells are activated? |
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B cells proliferate, differentiate, & isotype switch and help activate MQ's to kill intracellular pathogens |
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How do CD4 T cells help B cells? |
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T ; B cell form very close contact and T cell secretes IL-4 into the pocket b/w the cells to induce isotype switching in the B cell |
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Is it possible for a B cell to express MHC class I and class II? |
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Yes; if it is presenting an Ag |
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Describe T cell screening. |
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T cells go from cell to cell scanning the self-peptides on MHC Class I until it finds an MHC Class II with foreign Ag |
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Is the peptide binding cleft found on the membrane proximal or distal domain of MHC classes I and II? |
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Distal |
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In what portion of the MHC does the peptide sit?; How does it differ between class I and II? |
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Beta Sheets; MHC class I is surrounded on all sides by the MHC, Class II runs the full lenth of the MHC |
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How does the structure of MHC differ between classes I and II?; What are the subclasses of each? |
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Class I: 3 ; and 1 ; chain with A, B, ; C types Class II: 2 ; and 2 ; chains with DP, DQ, ; DR types |
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What is described as allelic variation in MHC genes and is concentrated in the peptide binding regions of Class I and Class II? |
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MHC Polymorphism |
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How many MHC genes does each individual inherit? |
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9 maternal and 9 paternal |
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What are the consequences of MHC Polymorphism? |
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Organ tissue transplants are difficult; change peptide binding specificity of MHC; pathogens could mutate to avoid immune detection by MHC's |