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186 Cards in this Set
- Front
- Back
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describe the perfect prototype antibody?
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made early in infection and binds strongly to pathogen
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during the course of an infection, antibody production ____'s with time?
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improves
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what does the faster T-cell independent response mediated by B-cells result in?
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production of low affinity IgM antibodies which can which can delay infection until T-cell activation of B cells allows for higher affinity antibody production
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what causes a B cell to recognize an antigen?
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antigen binding bring BCRs into clusters which stimulates signal transduction into the cell interior
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what are the cytoplasmic components of the BCR's associated with that effect a biological response?
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cytoplasmic protein tyrosine kinases
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what parts of the BCR communicate with the cell interior?
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proteins IgAlpha and IgBeta
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the antigen binding portion of the BCR is what immunogobulin?
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IgM
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what is the name of the cytoplasmic protion of the IgAlpha and IgBeta proteins that interact with cytoplasmic protein tyrosine kinases?
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immunoreceptor tyrosine kinases associated motifs (ICAMs)
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what interacts with phosphorylated ICAMs on the IgBeta chains?
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Syk protein kinases
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what are the 3 components of the B cell co-receptor?
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1. CR2
2. CD19 3. CD81 |
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what does CD21 do?
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binds compliment components on pathogen
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what does CD19 do?
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acts as the signaling chain from the B cell co-receptor to the cell interior
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what does CD81 do?
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unknown
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what is the ligand for CR2?
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C3d
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what happens when a BCR binds antigen and C3d is present on the antigen surface?
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CR2 binds C3d and ligates the BCR and B cell co-receptor causing the phosphorylation of the CD19 by tyrosine kinases
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what is the function of the signals created by CD19?
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synergize with signals of BCR to cause 1000-10000 fold increase in signal strength
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antigens which can activate B-cells without the the aid of T cells are called?
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thymus-independent antigens (TI antigens)
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antigens which cannot activate B-cells without the the aid of T cells are called?
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thymus-dependent antigens (TD antigens)
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what are TI antigens called which bind to other receptors on B cell surface to induce proliferation and differentiation?
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TI-1 antigens
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what is an important example of a TI-1 antigen?
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lipopolysaccharide (LPS)
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LPS is found in which type of bacteria?
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gram-negative
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to produce an activating signal, LPS must bind to what 3 surface proteins on the B-cell?
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1. LPS-binding protien
2. CD14 3. Toll-like receptors |
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in addition to activating a B cell to produce anti-LPS IgM antibodies, what else does the presence of LPS cause to happen?
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activating of B cells specific for another antigen on the bacterial surface
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Describe TI-2 antigens?
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composed of repetative carbohydrate or protien epitopes present at high density on the surface of a microorganism
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TI-2 antigens can stimulate what kind of activation?
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TI-2 can only stimulate B-cells which are specific for the TI-2 antigen unlike TI-1 antigens
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mostly which type of B cells respond to TI-2 antigen?
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B-1 cells
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whereas TI-1 antigens can only stimulate production of IgM, what can TI-2 antigens stimulate the production of?
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IgM (predominant) and IgG
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why are the antibodies produced by TI antigens not very specific?
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they do not undergo hypermutation
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what type of memory is associated with TI antigen activation of B cells?
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there is none
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binding of CD40L by the B cells CD40 receptor causes what to happen?
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production of NFcappB which upregulates expression of ICAM-1 (adhesion molecule)
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what is the cytokine secreted by TH2 cells which is essential for B cell proliferation and differentiation?
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IL-4
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what TH2 cytokines cause newly activated B cells to go to the medullary cords and develope into plasma cells?
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IL-5 and IL-6
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What do B cells which are not stimulated by IL-5 and IL-6 do?
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move into primary follicles and with the help of TH2 cells become centroblasts
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when do germinal centers appear in secondary lymphoid tissue after an infection?
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1 week
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what is the central region of closely packed dividing lymphocytes in the germinal center?
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the dark zone
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what is the less densely packed are just outside the dark zone called?
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the light zone
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what happens in the light zone?
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mature centroblasts (centrocytes) interact with follicular dendritic cells which present concentrated antigen to them for the duration of contact
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why are follicular dendritic cells different thatn professional APCs?
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the do not have MHC class II molecules and they are not of the myeloid lineage
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what does the outermost zone of the germinal center a.k.a. the mantle zone consist of?
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the B-cell which were present in the primary follicle before the B cell/TH2 conjugates arrived and pushed them to the outside
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what does the negative selection process of centrocyte hypermutation involve?
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mutated B cells must bind some of the limited antigen and present it to a TH2 cell via MHC class II molecules to survive
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how are immune complexes related to antigen binding on follicular dendritic cells?
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becuase follicular dendritic cells don't have MHC molecules the bind antigen/antibody/compliment complexes to their surfaces to present antigen to B cells
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describe the components of the first immune complexes formed during an infection?
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IgM/antigen complexes
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Later in the immune response to infection, immune complexes consist of?
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IgG/antigen
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which type of immune complex, IgM or IgG, can follicular dendritic cells bind?
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Follicular dendritic cells only of receptors for compliment or Fc regions of IgG
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what are the bundles of membrane that bud off of dendritic cells that carry immune complexes to B cells?
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iccosomes (immune-complex coated antibodies
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what happens to iccosomes?
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they internalized by B cells and the antigen they carry is displayed on MHC class II molecules on B cell surface
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what happens in the outer region of the light zone?
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centrocytes which present antigen gained from follicular dendritic cells meet up with TH2 cells
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what is the importance of the meeting of centrocytes and TH2 cells in the outer region of the light zone?
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binding of CD40L be B cells CD40 receptors allows the cells to express Bcl-XL protein which rescues the cells from apoptosis
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how does affinity play a role in the selection of B cells to be rescued from apoptosis?
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centrocytes with the highest antigen affinity bind it first and are able to be activated by TH2 cells first which excludes all lower affinity mutations
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the process by which centrocytes with the highest antigen affinity bind it first and are able to be activated by TH2 cells first which excludes all lower affinity mutations is called?
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affinity maturation
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in addition to affinity maturation, what else gives developing centrocytes an advantage?
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development of new isotypes which could possibly have higher affinities than IgM
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at the height of an immune response, most centrocytes go on to become what?
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plasma cells
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what is a macrophage in the germinal center that has recently ingested a centrocyte called?
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tingible body macrophage
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the particular isotype to which a developing B cell switches to is controlled by what?
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cytokines from TH cells
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what are the two necessary elements to induce isotype switching?
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cytokines and CD40L-CD40 action
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IL-4 induces the production of what isotypes?
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IgG1 and IgE
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IL-5 augments the production of what isotype?
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IgA
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IFN-gamma induces the production of what isotypes?
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IgG3 and IgG2a
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TGF-beta induces the production of which isotypes
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IgG2b and IgA
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what are the two distinct functions of the Fc region?
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1. delivery antibodies to otherwise inaccesible places
2. link bound antigen molecules or cells to effect their destruction |
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what allows effector cells of the immune system to bind to antibodies?
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they have Fc receptors
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how do IgM antibodies interact with each other after their secretion?
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the form a pentamer
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what is the Fc region of IgM capable of binding?
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compliment proteins only
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later in the immune response, what is the main antibody?
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IgG
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what is blood infection called?
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septicemia
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where is monomeric IgA produced?
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in secodnary lymph tissue of the lymph nodes or spleen
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where is dimeric IgA made?
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in lymphoid tissue underlying mucosal surfaces
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what is the function of monomeric IgA?
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basically the same as IgG
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what is the name of the receptor that binds dimeric IgA and some pentameric IgM on the basolateral side of epithelial cells of the bodies mucosal lining?
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poly-Ig receptor
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how does dimeric IgA cross the basolateral membrane?
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receptor mediated endocytosis
(transcytosis) |
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how does IgA leave the apical surface of the epithelial cells of the mucosa?
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proteases cleave the IgA receptor between the anchoring region and the IgA binding region
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what is the residual piece of the IgA receptor that is bound to IgA after its release from the apical surface of the epithelial cells?
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secretory component
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what is the purpose of the secretory component?
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its carbohydrates bind mucins of the mucous layers which holds IgA stationary in the mucous layer
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what is the receptor which binds IgG's Fc region on the lumenal surface of vascular endothelium?
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Brambell receptor (FcRB)
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what is the special benefit given to IgG for its ability to leave the blood stream?
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it has a longer-half life then the rest of the isotypes becuase it escapes degredation pathways of circulating protiens
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what keeps babies healthy before their immune response is sufficient to protect them?
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passive transfer of immunity involving pre-formed IgA against pathogens the mother has already experienced (transfered via breast feeding)
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what is the isotype which can cause the placental barrier from mother to fetus?
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IgG
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what facilitates the transfer of IgG into the placenta?
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Brambell receptor (FcRB)
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when do infants begin to produce their own antibodies?
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around 6 months
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during which time frame are infants most susceptible to infection?
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3-12 months when maternal IgG is degraded but the baby cannot replace it because their immune system is not compitent enough yet
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what are used as harmless analougs of bacterial toxins that are used as vaccines?
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toxoids
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describe a toxoid?
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receptor-binding peptide which allows toxin to bind to cells is intact, but the peptide with toxic function is denatured
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what is the main neutralizing antibody in extracellular spaces?
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IgG
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what is the main neutralizing antibody in mucosal spaces?
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dimeric IgA
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what is the main treatment for people exposed to venoms?
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serum infusion with antibodies against the venom from a large domestic animal
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where does the influenza virus bind to get into human cells?
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binds oligosaccharides on the cell-surface glycoprotiens of the epithelial cells of the lung
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what is the name of the receptor influenza uses to bind to the lung epithelial cells?
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influenza hemagglutinin
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what is another function of hemagglutinin that resulted in its name?
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it can bind oligosaccharides on blood cell surfaces causing agglutination (clumping) of RBC's
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what is the most important component of the Fc receptor on phagocytic effector cells?
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the alpha chain because it decides the specificity of the isotype it binds and contains the binding site for that isotype
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what is the signaling component of the Fc receptor?
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the gamma chain which is very similar to the zeta chain of the TCR complex
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what greatly increases the rate at which a pathogen is ingested by the phagocytic cells of the body?
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opsonization
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what is the receptor on phagocytic cells which recognizes the Fc regions of opsinizing antobodies?
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Fcgamma receptors
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which isotypes Fc region does Fcgamma bind?
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the Fc region of IgG
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how are phagocytic cells able to tell the difference between IgG bound to antigen and IgG the is freely moving around?
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a strong binding to pathogen by a phagocytic cells is mediated by the sume of many transient Fcgamma interactions and only a few such interaction would not be strong enough to hold the phagocyte in place
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describe the engulfment of the cell or molecule being phagocytized?
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the phagocytes membrane crawls around the object via Fcgamma binding until the membranes eventually fuse on the other side
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what happen to molecules or cells after ingestion?
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the are restricted to acid vesicles called the phagolysosomes for destruction
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describe the affinity of mast cell, basophils, and eosinophils for IgE?
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very strong affinity which is opposite that of IgG
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what is the main inflamitory molecule contained in mast cells granules?
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histamine
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what controls the release of histamine from mast cells?
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antigen binding to IgE
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describe antigen binding that causes the release of histamine?
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IgE must be able to bind to two sepperate epitopes on the antigen which will cause the crosslinking of two IgE molecules and receptors = degranulation
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how does the body rid itself of parasites which are too large for phagocytosis?
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IgE mediated release of inflammatory mediators causes smooth muscle contraction and fluid release which flushes out parasites
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what is the Fc receptor on NK cells called?
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CD16
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what is CD16 specific for?
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the Fc regions on IgG
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what is the term used to describe the action of NK cells which are stimulated by IgG molecules?
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antibody-dependentcell-mediated cytotoxicity
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in addition to tagging a pathogen for destruction, what is activated by antibody binding?
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the classical pathway of compliment
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what are the two antibody independent pathways of compliment?
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1. lectin pathway of compliment
2. alternative pathway of compliment |
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what causes activation in the lectin pathway?
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binding of plasma proteins to mannose-containing peptidoglycans on microbial surfaces
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what triggers the alternative pathway of compliment?
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direct enviromentally stimulated changes on microbial surface (stomach acids effects)
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where are all compliment components created?
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the liver
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many compliment proteins are said to be what type of protein?
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enzymes
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what is the reaction which all three compliment pathways converge into?
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splitting of C3 into C3a and C3b
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what is the most important function of the compliment pathway?
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binding C3b to the pathogen surface
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what is the binding of compliment C3b to the surface of a pathogen called?
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compliment fixation
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what are the two functions of bound C3b?
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1. tags pathogen for phagocytosis
2. nucleates protein complexes that damage the cell membrane of the pathogen |
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what is the purpose of the soluble C3a peices?
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attracting phagocytic cells to the site of infection
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what is the most abundant compliment component in the body?
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C3
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what is the first stage in the classical compliment pathway?
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binding of C1q to antibody/antigen complex
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what is the second step in the classical compliment pathway
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C1q acts as a scaffold for proteases C1r and C1s which together form the active c1 molecule
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what is the third step in the classical compliment pathway
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cleavege of C4 and then C3 by the C1 proteases
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where does C1q bind to the antibody/antigen compex?
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at the Fc region of the antibody
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when exactly is the compliment cascade activate?
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not until many antibodies are bound to a pathogen
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which isotype is most efficient at activating compliment? Which others can activate to lesser extents?
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IgM
Ig1 and Ig3 to lesser extents |
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what is required for a stable binding of antibody to compliment C1q?
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C1q must bind several sites on the associated antibodies, for IgM's pentameric structure this is easy, but for IgG monomeric means multiple antibodies must be bound
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C1r and C1s are examples of what?
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serine proteases
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which of the two serine proteases of the C1 complex cleaves C4 and C2?
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C1s
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what forms the C3 convertase?
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association of C2 and C4 compoments on the pathogen surface
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what is the large fragment of the C4 called?
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C4b
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what is the small fragment of the C4 called?
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C4a
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what happens to the exposed thioester bond in cleaved C4b fragments?
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it undergoes nucleophilic attack which covalently binds C4b to the pathogen surface and to nearby antibodies
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what is the large fragment of C2 called?
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C2a - opposite naming of all other compliment proteins... why do they do this to us :(
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what is the function of C2a?
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it is a protease
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where does C2a bind to?
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C4b
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what does the binding of C4b and C2a make?
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the classical C3 convertase
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describe the cleavage of C3?
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very similar to C4 - large fragment C3b has a thioester which upon nucloephilic attack covalently binds C3b to pathogen surface
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what are the two types of C4?
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C4A (capital suffix is important) and C4B
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which of the C4 types is preferentially attacked by macromolecules?
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C4A
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what is C4B preferentially attacked by?
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hydroxyl groups
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where are the genes for C4 protiens located?
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on the class III region of MCH
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what is a deficiency in C4A associated with?
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systemic lupus erythematosus
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what role do C4b and C3b have in common?
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the both can form C3 convertases
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what provides the protease activity to the alternative C3 convertase associated with C3b?
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factor B which is a plasma protein closely related to C2
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what are the two components of the alternative C3 convertase?
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1. C3b
2. Bb |
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what are the 4 complement receptors that can bind to C4 and C3 fragments?
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1. CR1
2. CR2 3. CR3 4. CR4 |
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what are the two structural grouping of compliment receptors?
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CR1 and CR2 in one group and CR3 and CR4 in the other
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which compliment receptor is displayed on macrophages and neutrophils?
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CR1
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what does CR1 facilitate?
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uptake and destruction of the pathogen by phagocytic cells
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what is the function of C3b and C4b in regards to CR1?
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they act as opsinizing agents
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is the interaction of CR1 with compliment protiens on the pathogen surface enough to initiate phagocytosis or intracellular killing of pathogens?
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no it must act as a compliment (hence the name) to the actions initiated by the binding ig IgG
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what does IgG bind to on a effector cells surface?
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Fcgamma
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what else besides IgG/Fcgamma interaction can initiate phagocytosis or intracellular killing of pathogens?
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TNF-gamma secreted by T cells
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where is CR2 expressed?
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B-cells and follicular dendritic cells
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what is CR2 part of at the B cell surface?
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the B cell co-receptor
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what does CR2 bind?
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degredation fragments of C3b on the pathogen surface
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what exploits CR2 to gain entry into B-cells?
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Epstein-Barr virus
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describe the structure of CR1 and CR2 molecules
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elongated molecules consisting of a string of small comapact structural modules
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what are the CR3 and CR4 called?
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Beta-integrins
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where are CR3 and CR4 found?
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on the surfaces of phagocytes
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what are the roles that CR3 and CR4 serve?
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augment activity of Fc receptors and CR1 in activating phagocytes
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binding of C3b fragments to CR3 is different that binding to CR1 because?
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it is sufficient to stimulate phagocytosis without any other stimulus
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aside from their role in initiating phagocytosis what do beta-integrins serve as?
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adhesion molecules to endothelial cells at the sites of inflammation
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what allows for the removal of small protien antigens that are too small for IgG to be recognized by phagocytic cells?
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1. Bind C1
2. Cleave C4 -> Cleave C3 -> C4b and C3b on pathogen surface 3. CR1 on erythrocytes bind complex and take it to macrophages in spleen and liver where it is destroyed |
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If immune complexes are not removed from erythrocytes, what happens?
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they can cause damage in the kindey by binding to CR1 on podocytes -> mesangial cells clean up the mess
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what happens in patients with a compliment dificiency and SLE?
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their kidneys are destroyed by immune complexes
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what happens when C3b binds to a C3 convertase?
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it forms a C5 convertase
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describe the components C5 classical convertase?
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1. C4b
2. C2a 3. C3b |
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describe the components of the alternative C5 convertase?
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1. Bb
2. 2 x C3b |
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what is the function of C5b?
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initiate formation of membrane-attack complex which forms holes in plasma membrane of pathogens
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what happens when C6 and C7 bind to C5b?
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C7 sticks its hydrophobic region into the PM of the pathogen
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what happens when C8 binds to C5b?
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its hydrophobic region inserts into the PM just like C7
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what does C8 binding initiate?
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the plyomerization of C9 which forms a pore structure in the PM
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what do the smaller soluble fragments of C3, C4, C5 do?
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increase inflammation at the site of complimentation
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when the smaller soluble fragments of C3, C4, C5 create an acute inflammatory response they are referred to as?
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anaphylatoxins
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C5a works directly on macrophages and neutrophils as a?
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chemoattractant
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what is the compliment inhibitor which blocks the action of C1r and C1s?
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C1 inhibitor (C1INH)
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in addition to its role in the compliment system what else does C1INH do?
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inhibits serine proteases of the clotting and kinin systems
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what is the disorder in which only one copy of the C1INH gene is functional?
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hereditary angioneurotic edema (HANE)
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what causes edema in HANE patients?
|
a cleavage product of C2b called C2 kinin draws fluid from blood into tissues
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what is the main product of the kinin system that is overproduced with impaired C1INH function?
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bradykinin
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what controlls the stability of the classical C3 convertase?
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C4-binding protein (C4BP)
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what happens when C4BP binds to C4b?
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it makes it vulnerable to inactivation by factor 1 (plasma serine protease)
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what facilitates the binding of factor I to the C3 convertase and its subsequent conversion to iC3b?
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Factor H
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a over production of C3 convertase by patients missing factor I result in what?
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a depletion of C3 and therefore a depletion in compliment on the surface of invading pathogens which makes it harder dor phagocytes to recognize them
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what binds to C4b and C4b causing their dissociation and inactivation?
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decay-accelerating factor (DAF)
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what has the same function as DAF, but in addition is able to make both C4b and C3b vulnerable to factor I?
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membrane co-factor protein (MCP)
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what protects self-cells from forming compliment proteins on the PM?
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CR1 disrupts C4b and C3b as well as makes them vulnerable to factor I
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For a list of soluble and surface-associated proteins involved in stopping compliment action of cell look at page 220 in parham
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Your Done :)
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