4 Humoral Immunity II Flashcards
What type of antigen contain molecular moieties that are recognized by pattern recognition receptors that serve as signal 2?
Type I TI antigens
What type of antigens must recruit elements of innate immunity that provide signal 2?
Type II TI antigens
T-F–innate-derived signals and cytokines collaborate with BCR signals to activate B cells?
True
What type of antigen do not contain molecular structures that can activate innate immunity and are primarily protein?
TD antigens
What type of antigen require require CD4+ T helper cells to provide necessary signals?
TD antigens
T-F—since T cells recognize protein derived peptides, TD antigens don’t need to contain a protein component?
False–they need to contain a protein component
What is the key element of TD antigens?
protein that can be ingested and processed on MHC II molecule
What antibodies are primarily induced by TI antigens
IgM
Are TD or TI antigens associated with long lasting responses, memory, high affinity, class switching?
TD
What are chemical moieties that by themselves are not immunogenic, but can be bound by Abs?
Haptens
What does a hapten need to be chemically coupled with to induce an Ab response?
large protein–carrier [becomes a TD antigen]
What type of haptens are among the most useful in studying B cell responses?
Phenol Ring
T-F—– T cell-driven B cell activation only occurs when the B cell and T cell epitopes are covalently linked on the same molecule?
True–linked recognition
[Look at slide 7 and 8 for more explanation about the mouse model experiment]
What is signal 1 of a primary adaptive immune response in Tcell?
flu peptides on MHCII of DCs bind to CD4 T cells
What is signal 2 of a primary adaptive immune response in T cell?
DCs have CD80/86 which engage CD28 on T cells
[costimulation]
What is signal 3 of a primary adaptive immune response in T cell?
DCs provide cytokines to direct CD4 to differentiation
What is a very important key attribute of activated T helper cells to activate B cells?
ability to express CD154 [ligand for CD40]
What is signal 1 of B cell activation?
BCR bind antigen—crosslinked—induce signal cascade
In addition to triggering signal 1, crosslinked B cell antigen receptor complex lead to what?
ingestion of Ag-BCR complex and presented as MHC class II
What is the main difference between the ingestion and presentation of MHC class I molecules of B cells and antigen presenting cells?
B cells can only ingest and present what their specific BCRs can bind
What CD complex initiates signal cascaded upon BCR cross linking?
CD79
What CD is constitutively expressed on surface of B cells?
CD40
Activated T and B cells co-express CCR7 and CXCR5 forcing what?
recruitment by CCL19/21 and CXCL13–forcing Their movement to the border to respective zones
What is signal 2 of B cell activation?
a second set of signaling cascades due to CD154 and CD40 interaction.
What is signal 3 of B cell activation?
cytokines from T follicular helper cells essential for expansion and differentiation
What interaction results when T cells can recognize their specific antigen on the surface of B cells?
cognate interaction
what syndrome– mutations of the CD154 gene, x chromosome, normal TI response, but no TD response?
Hyper IgM Syndrome
Upon B cell activation, what 2 subsets are formed?
- antibody producing cells [plasma cells]
- seeds for germinal center response
T-F—-antibody producing cells are long lived, affinity maturation and have great isotope switching ability?
False– short lived, limited switching, and no affinity maturation
T-F —Ag-specific T follicular helper cells are found in germinal centers.
True
T-F— germinal centers can form in non-lymphoid tissues under pathologic conditions?
True- often autoimmune antibodies
What are the key B cell processes in the germinal center?
- Proliferation
- Isotype Switching
- Affinity Maturation
- Terminal differentiation into plasma or memory B cells
Light zone of germinal center contains?
Fewer B cells and enriched in follicular dendritic cells. Also contains CD4 T cells and macrophages are at midline
Where are macrophages situated in germinal centers?
between dark and light zones—highly phagocytic
The human heavy chain locus contains which key constant genes?
mu delta 4 C gamma 2 C epsilon 2 C alpha (NOTE: The first C epsilon is mutated and is non functional)
What cytokine is key to class switch of IgE?
IL-4
What largely dictates which downstream switch region is made accessible during class switching?
cytokine mixture from T helper cell
T-F—lymphocytes are the only somatic cells in the body where DNA rearrangements on a huge scale are the norm?
True
Isotype switching leads to what antibody changes?
- B cell receptor with different constant region
- Identical heavy chain VDJ
- Identical Light chain
During hypermutation (one bp change per 10^3 bps) where are the nucleic acid interchanges focused?
VDJ region of heavy cain and the light chains
What are the 3 outcomes of hypermutation initiated by T follicular helper cells on B cells?
- no change of binding affinity
- loss of binding affinity
- gain in binding affinity
What 3 key proteins are involved in somatic hypermutation?
-activation induced cytidine deaminase
-uracil-DNA glycosylase
-error prone DNA polymerase
(U-G can also be identified by mismatch repair and repaired in that method with similar results)
What happens to B cells without cognate interactions with T follicular helper cells?
They die
What do follicular dendritic cells display in light zone of germinal center?
limiting amounts of original Ag—->[B cells can ingest , process and present fresh MHC II peptides and attract cognate interactions and survival—they are in direct competition for this…hence affinity maturation offers an advantage]
What is a critical cytokine that keeps B cells from undergoing apoptosis during interaction with T cells?
BAFF [Blys]
B cells of the highest affinity after somatic mutation have what?
A clear SELECTIVE ADVANTAGE—only their progeny will become plasma and memory cells
What are Ab factories specialized for producing one product for export?
plasma cells
Where are plasma cells initially found? eventually found
-lymphoid organs proximal to the germinal center
-move to bone marrow surviving for years, they stay switched
(NOTE: these are plasma cells differentiated in the germinal center)
What immune cells have isotope switched, have high affinity, are long lived, and recirculate and are distributed throughout secondary lymphoid organs>
memory B cells
Note: plasma cells nestle in bone marrow and memory B cells recirculate through secondary lymphoid organs
When are memory B cells rapidly called upon?
same Ag re-enters—secondary adaptive immune response
What does vaccination with TD antigens induce?
T cell-driven B cell activation
[germinal center reactions, high affinity, long lived plasma and memory B cells]
An OVA protein and a reactive TNP =?
TNP-OVA conjugate
Why will injecting TNP-rabbit IgG and OVA separately lead to an MHCII display that will fail to attract the attention of OVA specific T cells?
The TNP-specific B cells will be presenting Rabbit IgG peptides in their MHCII instead of OVA peptides [LINKED RECOGNITION LOOK TO SLIDE 33]
What is the most effective means to attack encapsulated bacteria?
anti-carbohydrate Abs (Type II TI response)
Who particular fail to generate a type II TI response?
young children
What is the solution to children’s inability to form Type II TI response?
generate TD antibody to carbohydrate Ags [treat carbohydrates as haptens and link to protein carrier= conjugates—-> ie Hib conjugate vaccine]
For B cell help what is required in a primary adaptive immune response in T cell?
T-follicular helper cells
