Antibody Mediated Humoral Immunity - Bowden (Completed) Flashcards
What are the co-receptors of a B cell? 6
CD19
CD81
CR2 (CD21)
What are the two major subsets of B cells? 6
Follicular B cells
Marginal B cells
What is a marginal B cell? 6
Resides in the spleen
Identifies blood-borne polysaccharide Ags
What is a follicular B cell? 6
Recirculating B cells
Make up the majority of B cells
What happens each time a naive B cell enters a lymph node? 7
They receive a survival signal (FDC), if they don’t receive this signal they degenerate
What is the first B cell signal? 9
Ag binding to membrane-bound Igs
must occur with 2 or more BCRs to conduct the signal
How B cell intracellular signaling differ from T cell intracellular signaling? 9
The ONLY difference is the initial Src kinase that interacts with Igα and Igβ
Lyn
Fyn
Blk
Besides cross-linking with two membrane Ig’s how else can the first B cell signal be generated? 10
Cross-linking can occur between a mIg and CR2 (complement receptor)
What changes does a B cell undergo after binding Ag w/ two BCRs? 11
Expression of survival proteins
Increased B7 expression
Increase cytokine receptor expression
Increased CCR7 expression (integrin)
Newly activated B cells secrete low levels of what? 12
IgM
In T-independent B cell activation what is lacking? 13
No class-switching
No memory formed
What is the second signal for B cell activation? 14
CD40L - from T cell
Bound to
CD40 - from B cell
+ cytokines
What happens first, class switching or affinity maturation in B cells? 16
They both happen at the same time
After activation from T helper cell where do B cells head? 17
They change their chemokine receptors and head to the follicular area where germinal centers are established
In reference to B cells, what are the two functions of T helper cytokine secretion? 18
To induce heavy chain class switching
Augment B cell differentiation and proliferation
How does switch recombination happen in B cells? What causes this? 19
Caused by CD40:CD40L and cytokines
DNA of heavy chain is opened up and a different C region is expressed which will be a C region downstream because IgM/IgD are the first constant regions
What is affinity maturation? 20
Introducing point mutations in variable regions to raise their affinity to specific Ags
What enzyme facilitates affinity maturation (somatic hypermutation)? 20
AID - activation-induced deaminase
What does activation-induced deaminase do in Somatic hypermutation? 20
AID converts cytosine to uracil allowing for Ape I to create ds breaks in DNA
After a B cell is activated and undergoes somatic hypermutation how is it able to survive within the lymph node? 23
If they’re able to bind a follicular DC presenting they will receive survival signals
Speaking to B cells, which recognizes protein vs polysaccharide? Which produces memory cells? 25
T-dependent B cells –> memory, recognizes proteins
T-independent B cells –> lack of memory, recognizes polysaccharides
What changes does a Plasma cell make to its cluster differentiation expression? 26
Decrease: CD19, 20, and HLA Class II
-they aren’t APCs anymore
Increase: CD27, CD38, and CD138
What is the effector molecule of the humoral immunity? 26
Abs
How are memory B cells able to survive for such a long time period? 28
By expressing more Bcl-2 (anti-apoptotic protein)
What are the surface markers for Memory B cells? 28
CD27
CD45R
What happens if Ags are fully bound to secretory IgG (IgG>Ag)? 30
If the Fc regions of IgG binds a BCR it shuts down and inhibits the B cell
Fc region bound by an Fc receptor on the B cell with a single ITIM
What is the principle defense against extracellular pathogens? 32
Humoral immunity
Which cells have Fc receptors on their cell surface? 34
NKs
Macrophages
B cells
What is the primary Ab present in the blood? 34
IgG
What Ab isotype is predominant in primary antibody response vs secondary? What about affinity? 35
Primary antibody response - first infection: Usually IgM>IgG with a lower average affinity
Secondary antibody response - second infection: Usually >IgG (IgA or IgE) with a higher average affinity
What are the effector functions of Abs? 36
Neutralizes microbes and toxins
Opsonization & phagocytosis
Ab-dependent cellular cytotoxicity (NKs)
Inflammation
Lysis of microbes
What two distinct functions does the Fc region serve? 37
It delivers Ab to inaccessible anatomical sites
Serve as a bridge between Ag and Effector cells for that Ags destruction
What do C3b and IgG have in common? 38
Both act as opsonizer
What FcRs have high affinity for Ig? What cells would these receptors be found on? 39
FcγRI (CD64) –> Macrophages, neutrophils, eosinophils
FcεRI –> mast cells, basophils, eosinophils
What is Ab neutralization? 40
The idea that Abs can inhibit toxins and microbes simply by binding to them and stopping them from:
Binding receptors
Moving through membranes
How does complement fulfill the role of waste management? 42
Erythrocytes bind immune complexes containing C3b and C4b with its CR1 receptor
Erythrocyte heads to spleen and liver
Phagocytes within liver and spleen remove complexes and RBC re-enters circulation
What transports IgG from maternal circulation, across the placenta, into fetal circulation? 50
IgG Fc receptor bound by FcRn of the endothelial cell
What’s the difference if the first signal for B cell activation comes from two membrane Igs or a membrane Ig and CR2? 10
If C3d (from C3b) binds CR2 and causes complement cross-linking the attached Ag will be 1000x more immunogenic (aka better activation of the immune system)
What is one major way Abs resemble complement? 38
Abs bound to Ag can be bound by FcRs to act as opsonizers
What FcRs have low affinity for Ig? 39
FcγRIIA (CD32)
FcγRIIB (CD32)
FcγRIIIA (CD16) - NK cells (Ab-dep. cellular cytotoxicity - ADCC)
What does ADCC stand for? What state/condition is the body in when ADCC is active? 43
Antibody-dependent cellular cytotoxicity
Active when the body is in an anti-viral state
What is the most effective fixer of complement (C’)? Why? 44
IgM becuase it contains five Fc regions that can be bound by CR receptors
What is the therapeutic role of IVIg? How does it serve this role? 45
In treating autoimmune/inflammatory disease
Engages the inhibitory FcγRIIB (B cell) and the FcR of DCs suppressing the immune response
What two Abs are lacking at birth and have a lag time of 6-12 months leaving the infant immunocompetent? 51
IgG and IgA (newly synthesized)
What are three mechanisms of humoral immune evasion? 52
Ag variation - Ag not recognized
Inhibition of C’
Blocking via Hyaluronic acid capsule
