Chapter 09 Flashcards
(35 cards)
What are the similarities of immunoglobulins and the T-cell receptor?
- both are very specific
- their diversity is created through somatic recombination
- essential components of receptor complexes required for activation
What are the functions specific to soluble immunoglobulins?
antigen neutralization and removal
Who and what are the important discoveries in immunoglobulin research?
- Behring and Kitasato: used a serum against diphtheria to treat other animals
- Ehrlich: described the first theoretical structure
- Edelman and Porter: primary sequence and sensitivity to proteases such as papain
How are immunoglobulins able to function?
- bind tightly to their cognate antigen
- link the bound antigen to other effector mechanisms
What is the composition of immunoglobulins?
- two identical heavy chains and light chains
- Each light chain has a variable region and a constant region
- Each heavy chain has one variable region and three or four constant regions
- Chains are linked via disulfide bonds between cysteines
- Glycosylated domains that makes domain more accessible for interaction
What is the antigen-binding site composed of?
- a hinge region gives flexibility
- the interaction between variable regions of heavy and light chains creates an antigen-binding site
What happens when you digest an immunoglobulin with papain?
releases two types of fragments:
* two Fab pieces (fragment-antigen binding) contain a single antigen-binding site
* one Fc portion (fragment crystallizable): stem of the completed immunoglobulin
What is characteristic of each variable region in the heavy and light chains?
- hypervariable regions (complementarity-determining regions): three flexible loops of each variable region located at the junction sites of V, D, and J segments
What are epitopes and their function?
- epitope: specific location or structure where an immunoglobulin binds
- usually consists of a short sequence or structural feature of the antigen
What are multivalent antigens?
antigens that bind multiple copies of the same immunoglobulin because the antigen has either:
* repeating eptiope for the the same immunoglobulin
* multiple different epitopes for different immunoglobulins from separate B cell clones
What are two scenarios for multivalence?
- an antigen can be multivalent by having multiple epitopes
- having repeating epitopes that allows binding of more than one immunoglobulin of the same type
What is the difference between linear and conformation epitopes?
- linear epitopes are made up of macromolecule residues in sequence; remain functional when antigen is denatured
- conformational epitopes are created by the complete 3D structure of the antigen; typically destroyed when antigen is denatured
What are the similarities with T-cell receptor recombination?
- somatic recombination at the immunoglobulin loci occurs in B cells
- rearrangements begins with the heavy chain loci before continuing to rearrangement events at the light chain loci
- identical recombination process through the activity of V(D)J recombinase, RAG1, RAG2, exonucleases, and TdT
- B cells express immunoglobulins at the cell surface with short cytoplasmic tails
- must interact with cell-surface proteins Igα and Igβ to drive signal transduction
What are the differences between T-cell and B-cell recombination?
- recombination of the T-cell receptor halts after positive and negative selection in the thymus
- recombination events can occur after the B cell has finished development in the bone marrow
- B cells leave the bone marrow and undergo class switch recombination in the secondary lymphoid after activation
What is the structure of the constant regions?
preceded on its 5’ end by a switch region (denoted S) and followed by the heavy chain constant region subscript
What happens after B-cell activation?
- induces clonal expansion and differentiation into plasma cells
- triggers the production of soluble immunoglobulins
How are IgM and IgD produced in naïve B cells?
alternative splicing: the rearranged heavy chain locus of a naïve B cell that has not undergone isotype switching incorporates the variable region that has been recombined and the two closeley located constant regions μ and δ. After primary transcript is made, it is processed to include either the membrane-spanning region that is present right after the μ or δ regions.
What are the fates of naïve B cells, memory B cells, and terminally differentiated B cells (plasma cells)?
- naïve B cells and memory B cells produce membrane-bound immunoglobulins
- terminally differentiated B cells (plasma cells) produce soluble immunoglobulins
How are membrane-bound and soluble immunoglobulins produced?
RNA transcripts contain a segment that encodes a large hydrophobic sequence of amino acids
1. if the segment is retained, the immunoglobulin anchors in the plasma membrane as a membrane-bound receptor
2. if the segment is removed, the protein becomes a soluble immunoglobulin and is secreted from the cell
When are certain immunoglobulin isotypes expressed?
- IgM and IgD are expressed in naïve B-cells
- IgA, IgE, and IgE are not expressed until B-cells are activated and have undergone isotype switching
What is affinity maturation?
the process by which immunoglobulin genes gain higher affinity through somatic hypermutation of the immunoglobulin gene during B-cell activation
What is the function of activation-induced cytidine deaminase (AID)?
plays a key role by deaminating the base cytosine, creating the base uracil, activating DNA repair mechanisms and leading to point mutations
What are the three possible mechanisms that can repair the cytosine-to-uracil conversion?
- DNA replication
- Base excision repair
- Mismatch repair
What happens during DNA replication?
a cytosine-to-uracil conversion prior to DNA replication can be interpreted as a thymine base. This will result in changing of the uracil base to a thymine and the complementary to an adenine, thus mutating C-G to T-A
