Term
| What type of pathogens does humoral immunity deal with? |
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Definition
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Term
| What is the difference between thymus dependent and thymus independent antigens? Which is the more common? |
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Definition
-Thymus dependent antigen is much more common and requires the direct contact of the B cells with the TH cells
-Thymus independent antigens are not peptide structures and therefore cannot be recognized by TH cells (e.g. LPS)
-They may directly stimulate B cells or may also act as mitogens (mitosis promoting factors) regardless of idiotype
-Mitogens are mainly used in labs to test cell response
-The independent response is weaker; no class switching (IgM only) and no immunologic memory |
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Term
| How is a B cell activated? Give molecules on each cell, what they do, and any cytokines released? Order? |
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Definition
B cell;
-MHC class II (exogenous pathway) [to TCR & CD4]
-CD40 (proliferation signal) [to CD40L]
-B7 (induced by antigen binding, costimulatory) [to CD28]
-LFA-3 (integrin for binding) [to CD2]
T Cell
-TCR and CD4
-CD40L (expressed after activation, stimulates cytokines*)
-CD28 (binding)
-CD2 (an IgCAM for binding) [to LFA-3]
-The TH2 cell then releases IL-4,5,6,10, 13, & TGF-β which will be the final stimulatory signal |
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Term
| What are the two digestive agents we can use to degrade Igs and what molecules do they produce? Which would cause agglutination/precipitation? |
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Definition
-Papain digestion occurs above the heavy chain disulfide bond (cuts arms off) generating three fragments; one Fc fragment (fragment crystallizable), and two Fab fragments (fragment antigen binding)
-Would no longer get agglutination/precipitation
-Digestion with pepsin degrades the Ig below the disulfide bond (Fc part) and leaves one large divalent fragment called F(ab')2
-Still get agglutination/precipitation
-Agglutination happens for particulate antigens while precipitation happens for soluble proteins |
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Term
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Definition
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Term
| What is the first Ig to be produced? When isn't it first? |
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Definition
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Term
| What joins the multimeric Igs together? |
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Definition
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Term
| What does secreted IgM look like and what are it's specialties and weaknesses? What are its avidity and affinity like? What about its valence? |
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Definition
-Secreted IgM is a pentamer with a valence of 10
-It has excellent avidity (binding capacity), but since it is the first Ig secreted, it may have a weak affinity (binding strength)
-It's strength is in trapping or "sponging" of free antigen
-It is also the best activator of compliment
-However, it cannot opsonize or mediate ADCC (antibody-dependant cell-mediated cytotoxicity; more or less the result of opsonization) |
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Term
| What is the order of Ig regions on the DNA? |
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Definition
| VDJ---μ---δ---γ3---γ1---α1---γ2---γ4---ε---α2 |
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Term
| How does isotype switching work? Where? |
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Definition
-The actual DNA is excised out and degraded by activating switch regions between the segments
-This means that once a B cell switches to a downstream isotype, it cannot go back
-Occurs in the germinal centers
-This is why IgG has a higher affinity
-Note that this is different than the constitutive expression of IgM&D which makes use of RNA editing, not DNA |
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Term
| What are the germinal centers and what language do we use to describe how they become better antigen binders? |
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Definition
-This is the place in the follicles where B cells are undergoing intense proliferation and class switching
-The random mutations that result can increase binding affinity with daughter cells being better competitors for antigen; causes CLONAL SELECTION
-This leads to what's called AFFINITY MATURATION |
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Term
| What is X-linked hyper-IgM syndrome? |
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Definition
-TH cells do not have the CD40L (maps to X chrom)
-B cells therefore do not undergo class switching and no germinal centers are created
-Patients only produce IgM (in large amounts)
-Suffer recurrent respiratory infections (no IgA) |
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Term
| What does IgG look like? What is it good at/notable for? What factors stipulate IgG B cells? |
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Definition
-It is monomeric and divalent (no J chain)
-Has four subisotypes
-It is the only good opsonizing antibody, mediates ADCC, and can activate compliment, although not as well as IgM
-It is the only Ig that has transporters to go across the placenta
-Compared to IgM it has higher affinity, and lower avidity
-IgG is the major one for memory (IgG memORY)
-IL-4 + INF-γ |
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Term
| What is the structure of IgA, where do we find it and how does it get there, and how is it as an opsonin and with compliment? What cytokine dictates its production? |
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Definition
-IgA is a dimeric molecule with a valency of 4 and held together by a J chain
-We find it mostly in MALT, but can also find small amounts of the monovalent form in serum
-It crosses the epithelium using the POLY Ig RECEPTOR which binds to the J chain and becomes the SECRETORY COMPONENT that protects it in mucosa
-It is a poor opsonin and does not activate compliment
-TH2 cells release IL-5 and TGF-β to stimulate B cells to this isotype
-Basically, it interferes with antigen binding to mucosal surfaces
-Can be found in breast milk |
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Term
| What does IgE look like like, what is special about its binding ability, what dictates its production, what is its main purpose, and how is it as an opsonin and with compliment? |
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Definition
-They are the normal Y
-They can bind to mast and basophil cells without antigen to cause their degranulation (role in allergies)
-IL-4 & 13 dictate production (4-Ever)
-They respond to parasites and allergins
-They do not act as opsonins (except with paracitic worms) or in compliment activation |
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Term
| Which activate compliment? |
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Definition
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Term
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Definition
| -IgG only (rest are not so good) |
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Term
| What are receptors for naive and memory B cells? |
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Definition
-Naive have IgM & D
-Memory have one of anything but |
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Term
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Definition
-IL-5----> IgA
-IL-4----> IgE |
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Term
| Which have high avidities? |
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Definition
-IgM* and then IgA
-Dictates agglutination ability (antigen trapping) |
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Term
| What do we find in the mucosa? |
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Definition
-Mostly IgA, but IgM can get into mucosa using poly Ig transporter because it also has a J chain
-Thus, IgM will still be first on site in things like respiratory infections |
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Term
| What are the two most important functions of the compliment pathway? |
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Definition
-Inflammatory response
-Removal of pathogens and immune complexes |
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Term
| Which are the effective compliment components for recruitment of inflammatory cells? |
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Definition
-C3a, C4a, & *C5a (all free) [C3-5a]
-They are all anaphylatoxins (cause degranulation by binding directly to mast and basophil cells)
-Only C5a is a chemotactic component (attractor) |
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Term
| Which compliment protein is the opsonin? What else does it do? |
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Definition
-C3b
-Also works in eliminating immune complexes |
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Term
| What proteins compose the membrane attack complex (MAC) in all pathways? What does it do? What happens if you have a problem with one of these proteins? |
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Definition
-C5b + C6,7,8,9,9,9,. . .
-Punches holes in membrane of pathogens
-The only thing is recurrent neisseria infections (meningococcal and gonococcal); demonstrates that MAC is not the main purpose of compliment |
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Term
| What is the difference between the alternate and classic compliment pathways? |
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Definition
-Alternate does not require activation by IgM or IgG, whereas the classic response does
-Alternate is thought to be more primitive |
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Term
| Why is Lima making us learn all the steps to compliment? |
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Definition
| -Because she's out of touch with what the board expects us to know. But here goes... |
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Term
| Run through the alternate pathway? |
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Definition
-C3--->C3b (binds to path, spontaneous and unstable)
-C3b + Factor B (and then cleavage by factor D)
-C3bB-----factorD----->C3bBb (**C3 convertase**);
-C3----C3bBb---->C3b (amplification loop)
-C3bBb + C3b---->C3bBbC3b (**C5 convertase**);
-C5----C3bBbC3b---->C5b (for MAC)
-C5b + C6,7,8,9+9+9... (**MAC**) |
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Term
| What components is the alternative pathway missing? What does it have instead? |
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Definition
-Most notably, the Igs
-Also, C1,2,&4
-Has Factors B & D instead |
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Term
| Run through the classical pathway? |
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Definition
-q unit of C1 binds IgM twice, or two IgGs
-q activates r activates s
-C4----C1s---->C4b (binds to pathogen)
-C4b + C2----C1s---->C4bC2a (**C3 Convertase**)
-C3----C4bC2a---->C3b (amplification loop)
C4bC2a + C3b---->C4bC2aC3b (**C5 Convertase**)
C5----->C5b
C5b + C6-9---->MAC |
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Term
| What is the only C#a to get incorporated? Which path? What does its Cb do? |
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Definition
-C2a (the rest are all Cbs)
-Classical
-It's Cb does nothing; this is the only released particle that has no function
-C1 & C6-9 don't break and C(3-5)a all have a purpose |
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Term
| What proteins overall does the classical path have and which is it missing? |
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Definition
-Has C1-9 (all)
-Missing Factors B & D |
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Term
| Again, what is the specific interaction that causes class switching? |
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Definition
-The CD40/CD40L interaction
-Remember, the TH2 cells have the ligand |
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Term
| What calls for IgE, A, & G |
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Definition
-IgE; IL-4 + IL-13
-IgA; IL-5 + TGF-β
-IgG; IL-4 + IFN-γ |
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Term
| What is the difference between idiotype, allotype, and isotype? Which one would you look at for a paternity test? |
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Definition
-Idiotype is antigen specificity
-Allotype is various alleles existing within a population
-Isotype is IgG vs IgD etc. |
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Term
| How does the lectin pathway work? (Lima) What does this bypass? |
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Definition
-Depends on action of MBL and MAPs
-Mannose binding lectin binds to sugar on pathogen which activates membrane associated proteases
-MAPs basically constructs the C3 convertase that classical uses (C4bC2a) and lets the rest go as usual
-Bypasses need for C1 |
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Term
| What inhibits compliment and what happens when it goes bad? |
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Definition
-C1-INH (inhibits C1)
-You get hereditary angioedema
-Mucosal surfaces puff up (such as lips and larynx)
-Caused by overactive compliment |
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