1 Antibody Structure and Function Flashcards
T-F–antigen receptors expressed by adaptive cells recognize a small diversity of antigens?
False–large diversity
Does the innate or adaptive immune system use pattern recognition as the infection sensing system?
Innate–receptors are limited and have fixed specificities and recognize only a finite number of microbial products
What molecules within B cell receptor complexes mediate antigen recognition and cell activation?
antibody molecules
What component dictates the antigen specificity of the BCR?
membrane-bound forms of antibodies component –variable region is key to diversity
Does engagement of one BCR complex by antigen lead to activation and the generation of antibodies?
No-multiple complexes engaging signal transduction along with other signals
What is the antigen specificity of antibodies determined by in developing B cells?
Gene rearrangement
What stage of B cell development rearrange genes encoding antibody components?
B cell progenitors– [more about this is later lecture]
T-f–each B cell clone expresses an antibody with a unique antigen specificity?
True
Are there a few different B cell clones produced or many? Why?
Millions
-produce antibodies specific to virtually any antigen
coding sequences assembled by gene rearrangement make up what in the BCR complex?
antibody antigen binding sites
T-F—antibodies recognize a variety of molecule as antigens?
True—proteins, nucleic acids, carbs, lipids
[NOTE: BROAD SPECIFICITY INCREASES ABILITY TO DETECT AND COMBAT MICROBIAL INFECTIONS]
T-F—TCRs can recognize a variety of molecules as antigens?
False—only recognize peptide-MHC complexes as antigens
Engagement of the BCR by antigen and activation of B cell leads to the production of what?
soluble antibodies
What is the main role of B cells in immune response?
recognize and respond to antigen and produce soluble antibodies?
What is the role of antibodies?
seek out and bind to antigens which initiates pathways to remove bound material
T-F— costimulatory signals are not needed in B cell activation?
False
Activated B cells proliferate and differentiate into?
antibody secreting cells
How do soluble antibodies distribute throughout the body?
passage through bloodstream
Antibodies are what shaped molecules?
Y
What is the makeup of the main shape of the antibody?
2 identical heavy chains
2 identical light chains
What holds the molecules together between anybody chains?
disulfide bonds
What do covalently linked carbohydrate chains to heavy chains do?
maintain antibody structure and stability—can influence function of the molecule
What are the 2 distinct functional domains of antibodies?
variable[Fab] and constant[Fc]
How many variable regions are there in antibodies?
2
amino acids in V regions are encoded by ?
randomly joined gene segments
T-F–constant region formed by N termini of heavy chains?
False–C-termini
What dictates the mulimerization state, anatomic localization and effector function?
Constant region
What does Fab stand for?
fragment of antigen binding
What does Fc stand for?
fragment crystallizable—form crystals when stored at cold temperatures
T-F—at the gene level, V regions are encoded by portions of the heavy and light chain genes that are generated by gene rearrangement?
True
T-F—within the V region, the C-termini of the heavy and light chains form a composite surface that mediates antigen binding?
False—it is the n-termini
What are segments in V regions that are highly diverse in the A.A. content and mediate direct contact with antigens?
complementarity determining regions (CDRs)
How can the antigen affinity of V regions be increased?
somatic mutation
affinity maturation
What alters DNA sequences encoding V regions, resulting in AA changes within the antigen binding pocket?
somatic hypermutation
What selects for B cell clones expressing antibodies with high affinity for antigen due to somatic hypermutation?
affinity maturation
What does high affinity for antigen increase?
stability and duration of antigen-antibody interactions
What do C regions dictate?
tissue distribution
multimerization state
antibody effector function
How are human antibodies classified?
based on constant regions
Where are IgM mostly found?
blood
What is the most abundant Ig in body?
IgG– distributes to blood and tissue
Where is IgE mostly found?
little in blood mostly in tissues bound to mast cells
Where is IgA mostly found?
some in blood, but mainly secreted across epithelial layers lining respiratory and digestive tracts
What Ig is expressed by mature B cells, integrated into BCRs and secreted very little?
IgD
What do naive B cells express?
IgM and IgD
Antibody secreting cells express?
IgG, IgA or IgE
Activated B cells with T cell help will do what to heavy chain?
will recombine DNA encoding the heavy chain
T-F—generally, B cells that undergo class switching also undergo somatic hypermutation and affinity maturation
True
What antibody is transferred across placenta?
IgG
What Ig forms pentamer?
IgM
What Ig forms dimers?
IgA
Infants receive what Igs from mother?
IgA (breast) and IgG (placenta)
What type of bonds holds together antibody dimers and pentamers? Where does the multimerization occurs?
- cysteine bonds with the J chain help
- occurs during transit through ER and Golgi
What are the 5 pathways antibodies promote clearance of microbes?
- agglutination
- neutralization
- activation of complement cascades
- Fc Receptor-mediated opsonophagocytosis
- antibody-dependent cytotoxicity
What traps microbes in a complex preventing cell-cell contact and colony formation/replication?
agglutination
What blocks contacts with host molecules and cells impeding attachment or entry into cells?
agglutination
Agglutinated materials are targets for what?
phagocytes
What Ig is very effective for agglutination?
IgM–10 antigen sites per pentamer
What does antibody neutralization do?
- block interactions with host cell receptors and eventual entry
- prevent toxins from entering cells
Neutralized material will eventually…?
be ingested by phagocytes
Are monomers better for neutralization?
Yes
Antibodies bound to surfaces can be recognized by what component of the complement system?
C1q
Antibody-C1q interaction induce a conformation change in the C1 complex…what does this activate?
C1s and C1r proteases
What does C1s generate?
C4b and C2a creating classical C3 convertase
The C3 converses lead to what deposition?
C3b
Deposition of C3b will drive formation of what?
- membrane attack complex—>cell lysis
- macrophage and neutrophil phagocytosis
T-f—antibodies alone on the surface can be recognized by Fc receptors expressed on phagocytes?
True—multiple contacts will lead to phagocytosis
Can monomeric or soluble antibodies activate cells via Fc receptors?
No
T-f—infected cells often express microbial antigens on their surface?
True
T-F—NK cells have Fc receptors that can recognize bound antibodies?
True—activation leads to cytotoxic function of NKs
[imporatant for virus or intracellular bacteria]
What antibody is critical for early antibody responses and defense against extracellular microbes?
IgM
Does IgM have a high or low affinity for antigen?
relatively low
Surface bound IgM activates what>
complement pathway cascade
Do IgG have a high or low affinity?
High—-have a long half-life
What are the main differences between IgG subtypes?
- hinge region
- ability to fix complement
- affinity for Fc receptors
IgG3, IgG2, IgG4 and IgG1 is ordered in what order for ability to fix complement?
IgG3>IgG1>IgG2>IgG4
IgG antibodies can engage 5 of 5 major B cell effector pathways?
false—4 of 5
- complement pathway
- Fc mediated phagocytosis
- neutralization
- Ab dependent cytotoxicity
Does IgA have high or low affinity?
generally high
How does IgA chiefly function (main effector model)?
neutralization
IgE has high or low affinity?
High
T-F—IgE bind constitutively to IgE receptor expressed on mast cells
True—multiple IgE antigen contacts leads to activation
