Exam III and IV Flashcards
Pro B cell stages
Heavy Chain rearrangement
Pre B cell
First checkpoint –> light chain rearrangement –> Second checkpoint
Immature B cell
Makes functional IgM
Survival of pro-B cell depends first on the productive rearrangement of the
heavy chain
Immature B cell can either be
u:k or u:l
how many successive attempts can be made of the kappa chain
5 successive attempts can be made of the kappa chain.
Immature B cell first undergoes
negative selection in the BM
receptor editing allows
the immature B cell more chances to make a nonreactive BCR (only editing in light chain)
B cell undergoes receptor editing
to make IgM with different specificities and not till the receptor is NOT self reactive, the B cell leaves the BM.
Maturation of B cells
immature B cells leave BM and enter circulation and secondary lymphoid organs.
Interaction with _ provides the required maturation and survival signals _
FDC; Positive selection
(competition with other B cell is the limiting factor for space in folice
enigmatic follicular dendritic cell
storage vessel for antigens ready for B cell stimulation.
CR1 and CR2 bind to intact virus particles and retain them at the cell surface
capture and display of intact antigens by CR2 expressed on
FDC and macrophages
How do B cells become activated?
When their receptors are cross linked by antigens
Much like T cell activation, B cell activation requires
Cross linking (clustering) and association with signaling adapters
B cell signaling cascade initiated from
ITAM domains in IgA and IgB
BCR triggering is greatly ENHANCED by
B cell coreceptor:
CD19/CR2/CD81
increase BCR signal intensity by 10,000 fold.
Work best with complement labeled antigens
CR2
binds to the antigen/microbe and initiates B cell activation
Binding of CR1 to C3b
bound to a pathogen facilitates its cleavage by Factor I to iC3b and C3d.
The CR2 component binds to
C3d
Two types of antigens activate B cells
T dependent: Require T cell help for production of antibodies (protein antigens)
T independent:
T dependent B cell activation
CD40/CD40Ligand interaction with T cells
Essential for T cell help
Required for isotype switching, affinity maturation
CD40:CD40L
B cells need two signals for activation by T cell dependent antigens.
To obtains T cell help, B cell must take up antigen through BCR, process and present peptide via MHC class II
T independent antigens
T1 and T2
TI1 (T independent antigens)
combination of BCR and TLR signals activate B cell
Require contribution from TLR signaling.
TI2
repetitive carbohydrate antigens present at high density on a pathogen surface, leads to extensive BCR cross linking
TI1
TLR
TI2
crosslinking
plasma cells
migrate to medullary cords or BM
- have no cell surface immunoglobulin or MHC class II, no further division, specialized for antibody secretion
primary expansion of antigen activated B cells
medullary cords –> primary follicle –> creates the germinal center
cell entire devoted to antibody production
plasma cell
germinal centers
sites where somatic hyper mutation, affinity maturation and isotype switching occurs
memory B cells
maintained and circulate through body ready to rapidly respond upon pre-exposure to pathogen.
somatic hypermutation
Changes affinity for antibody
Resting B cell
Surface Ig: Yes
MHC class II: yes
High rate Ig Secretion: no
Growth : yes
Somatic hyper M.: yes
Isotype switch: yes
plasma cell properties
Surface Ig: no
MHC class II; no
High rate Ig Secretion ; yes
Growth ; no
Somatic hyper M.; no
Isotype switch: ; no
T cells, development and selection
Thymus
B cell location and development
BM
Function of T cell
kill or make cytokines
Function of B cell
make antibodies
Like B cells, T cells generate receptors through
somatic recombination
T cells are more _ than B cells
diverse
two classes of T cell receptors
alpha/beta and gamma/delta
majority of conventional T cells
alpha beta
T cell receptor class with high degree of receptor diversity
alpha beta
alpha/beta recognize
MHC/peptides
where are alpha/beta abundant
all secondary lymphoid tissues
gamma/delta abundant in
gut mucosa
types of alpha/beta T cells
CD4 and CD8
CD4+ T helper cells
Produce cytokines to help clear infections
recognize MHC II
Antigens tend to be from extracellular sources
CD8 + Cytolytic T cells
Killer cell
MHC I though CD8
Cytoplasmic sources
CD4 consists of
D1-4