Antibody Mediated Immune Response Flashcards
Ig rearrangement occurs where?
bone marrow
What is the main Ag receptor isotype of the surface of most peripheral B cells?
IgD often co-expressed with IgM
Some children with periodic fever have increased levels of what?
IgD
Before a B cell can leave the bone marrow it must undergo what?
central tolerance or negative selection
negative selection prevents what?
the development of autoimmunity
the second mechanism for preventing recognition of self-ags?
receptor editing
receptor editing consists of?
reactivation of Ig gene recombination and expresses new light chain
Activation of B cells by Ag in the lymph node initiates what process:
- B cell proliferation
- B cell increases expression of: Ag (MHC class II), B7 (CD80/CD86), receptors for cytokines produced by Th cell
- Secrete low levels of IgM
Where do Ag-activated B cells migrate to within the lymph node?
from lymphoid follicle to T cell rich zones of lymph node
Which part of complement is very important at the beginning of infection when amount of microbial Ag is limited?
CR2
what does CR2 bind?
C3d, a fragment of C3b deposited on bacteria
CR2 does what to B cells?
makes B cell very sensitive to Ags
CR2 helping B cells helps to illustrate what concept of immune system?
cooperation between innate and adaptive immunity
Ags are processed and peptides produced are presented on what of B cells?
class II MHC
T cells activate B cells through?
direct contact and cytokines
CD40 is expressed on which cell?
B cells
CD40L is expressed on what cell?
T helper cells
What must happen with BCRs for the B cell to be activated?
cross-linked
what does activation of the B cells result in?
proliferation, initial antibody production, germinal center reaction
what is the first antibody produced by B cells?
IgM
Ab class is determined by which region?
Fc region of heavy chain
During B cell maturation it can switch to produce what?
IgG, IgA, or IgE
Principal effector function of IgA
mucosal immunity
Principal effector function of IgG subclasses (IgG1, IgG3)
Fc-dependent phagocyte responses; complement activation; neonatal immunity (placental transfer)
Principal effector function of IgM
complement activation
Principal effector function of IgE
immunity against helminths (eosinophil-mediated); mast cell degranulation (immediate hypersensitivity)
Mechanism of Ig class switching?
intrachromosomal recombination within G-rich tandem repeated DNA sequences called S (switch) regions located upstream of heavy chain constant region genes (except C-delta)
High rate of mutation of VDJ gene segments is referred to as?
somatic hypermutation
Where does somatic hypermutation mutate?
part of rearranged gene that encodes Ag-binding domain
Somatic hypermutation creates B cells with BCRs?
with higher affinity or stimulated more easily because they get Ag first
B cells with higher affinity proliferate…?
more robust than lower affinity receptors
Result of somatic hypermutation?
more B cells with higher affinity of BCR for Ag
B cells can become what?
plasma cell or memory cell
plasma cells travel where?
spleen or back to bone marrow
plasma cells live about how long?
5 days
Memory seems to be only activated when?
CD40-CD40L interaction occurs
Thymus-dependent antigen chemical nature?
proteins
Thymus-independent antigen chemical nature?
polymeric antigens, esp. polysaccharrides, glycolipids, nucleic acids
Does isotype switching occur with thymus-dependent antigens?
Yes
Does isotype switching occur with thymus-independent antigens?
little or no (may be some IgG)
Do antibodies of thymus-dependent antigens have affinity maturation?
yes
do antibodies of thymus-independent Ags produce secondary response (memory B cells)?
Only seen with some antigens
What are 3 properties of Thymus-independent Ags?
- polymeric structure
- resistance to degradation (persist for long periods of time and continue to stimulate the immune system)
- polyclonal activation of B cells
What do TI-Ags do to B cells?
cross-link many BCRs
TI-1 Ags are?
polyclonal activators of B cells
What kinds of molecules are normally TI-Ags?
Usually polysaccharide lipids and other nonprotein Ags
TI-2 Ags are?
(not polyclonal) are Ags with repeating epitopes for cross-linking BCRs
TI-1 Ags signaling?
1: BCR binds Ag
2: TLR
* no CD4 cell help
may be non-specific (e.g. such as LPS)
TI-2 Ags signaling?
1: BCR binds Ag
2: clustering of BCRs
* no CD4 cell help
TI-2 Ag immune responses
generated against repetitive Ags
B cells activated with TI-2 Ags by?
direct BCR cross-linking
Does TI-2 Ag immune response produce memory?
no
For TI-2 Ags what kind of Ab produced?
mostly IgM
Abs produced in response to TI-2 Ags had what kind of affinity?
relative low
What kind of belong to TI Ags?
many bacterial cell wall polysaccharides
What are the advantages of TI-Ags?
B cells can be activated right away without T cells activated
Patients with congenital or acquired deficiencies of Ab-mediated response are susceptible to infections of what?
encapsulated bacteria