Chapter 9 (Exam 3) Flashcards
Functions of Antibody Response
Neutralization
Opsonization
Complement Fixation
Signaling in B cells
Clustering of Receptors
B cell coreceptor
Activation of intracellular kinases
How is signaling generated in B cells?
Crosslinking Igs with repetative epitopes of antigens
Causes clustering and aggregation of Iga and Igb
B cell signaling is increased with
Coreceptors
Thymus-Independent (TI) Antigens
Repetitive carbohydrate or protein epitopes at high density on pathogen surface
TI antigens are able to
Activate B cells without Ag-specific helper T cells
Mostly B-1 cells
Antibodies most produced by TI activation and why?
IgM
no SHM or isotype switching
B cells must interact with ____ to survive
Follicular dendritic cells (FDCs)
Follicular Dendritic Cells (FDCs)
Help create B cell follicles in lymph node
On dendrites, ____ and ____ hold complement-coated antigens and pathogens.
CR1
CR2
Immune complexes
held on surface, not degraded
B cells home to lymph nodes by
CCL21 and CCl19
Drawn to primary follicle by CCL13
Cognate Interaction
(conjugate pair)
B and T cell specific for different epitopes of same pathogen
Events required for B cell activation
Surface Ig binding to antigen
T cell help
What cytokines induces B cell differentiation?
IL-5, IL-6, IL-21 from Tfh cells
How do B cells become plasma cells?
Conjugate pair moves into medullary cortex
cells divide to form primary focus
B cells secrete IgM
IL-5, IL-6, IL-21
Induce terminal differentiation
Primary focus
Produce first Ab
Secondary focus
Produce many B cells with affinity matured, switched Abs
Germinal Centers
Germinal Center Reaction
Swollen Glands
B and T cell proliferation in secondary follicle
Centroblasts
in dark zone
Proliferate
Do not express surface Ig
Cannot interact w FDC
undergo SHM and switching
Centrocytes
in light zone
no proliferation
express affinity matured, switched Ig
Centrocytes undergo _____ unless surface Ig binds antigen and ____ is bound by ____ ligand.
Apoptosis
CD40
CD40
When does B cell express Bcl-xL?
B cell induced by FDC to internalize, process, and present Ag to Tfh cell
Affinity matured centrocytes selected to survive will become
plasma cells
long-lived memory cells
Genetic deficiency in CD40 ligand
hyper-IgM syndrome
IgM activates
classical pathway of complement
Functions of circulating IgM, IgG, and IgA
Defend all tissues reached by blood
Prevent blood-borne infection
Dimeric IgA
Transported to child trough breast milk
Passive transfer of immunity
Lowest levels of IgG
age 3-12 months
Most susceptible to infections
IgG is delivered to tissues using
FcRn
poly-Ig
Binds constant domains of dimeric IgA and IgM
Cell types involved in IgE response and what they express
Mast cells, eosinophils, basophils
Express FceRI to bind constant region
Antibody Effector Functions
- Neutralization
- Activation of Complement
- Uptake and degradation of pathogens vis Fc
- Facilitate killing of targets by NK cells
- IgE response
Neutralizing Abs to prevent VIRUS entry
Bind on surface of cells with influenza hemagglutinin
Virus cannot infect
Neutralizing Abs to prevent BACTERIA entry
F protein binds fibronectin
Abs prevent attachment to tissues
IgG and IgA Abs neutralize
toxins and venoms
Treatment for venoms
passive immunization of Abs raised in animals
IgM can activate classical complement effectively due to
Pentameric structure
5 binding sites for C1q on IgM
What other isotype can activate classical complement pathway?
IgG
Removal of immune complexes
by erythrocytes
Fc receptors are expressed on
neutrophils, basophils, mast cells, dendritic cells, macrophages, FDC, and NK cells
a single mast cell has bound IgE molecules
specific for many different antigens
cross linking of FceRI
by IgE binding and clustering triggers rapid mast cell granule release
mast cell, basophil and eosinophil granule contents are
inflammatory mediators
what do inflammatory mediators do in an IgE response?
induce contraction of SM cells
increase blood vessel permeability
attack parasite directly
what are the natural targets of IgE
unicellular protozoa
multicellular invertebrates (worms, flukes)
ticks
mites
ITAMs on g chain
signal to interior
targets of IgE are ________________ than microbial pathogens so _____________________ are needed for removal
much larger
different mechanisms
FcgRI signaling
needs to be crosslinked by Ab
Signaling from FcR’s bound to Fc regions of Ab’s trigger
engulfment which eliminates pathogen and allows for processing and presenting
eosinophils ________________ large parasites coated with IgE
directly attack
in developed countries, the IgE response against _________________ is not frequent, so IgE responses in ________________ is much more common
parasites
allergies
ITIM
Suppresses signaling
helps control response
if the immune system is unstimulated,
it can respond in unexpected ways
purpose of RhoGAM
inhibits primary immune response to Rh so fetal erythrocytes are not destroyed and babies are healthy
Why have a variety of low-affinity Fc receptors for IgG?
Help control immune responses
receptors with ITIM motifs
FcaRI binding to monomeric IgA
medium-affinity
FceRI binding to IgE
very high affinity
mast cells, eosinophils, basophils
if a Rh- mother is carrying a second child that is Rh+ and does not take RhoGAM, what happens to the baby?
secondary immune response with high affinity IgG
massive destruction of fetal erythrocytes triggered by anti-Rh IgG
hemolytic anemia of the newborn
ADCC
Antibody dependent cell-mediated cytotoxicity
if a Rh- mother is carrying her first child that is Rh+ and does not take RhoGAM, what happens to the baby?
low affinity IgG and IgM
minor destruction of fetal erythrocytes
healthy newborn baby
purpose of the FcgRIIB1 receptor
crosslinks with Ig and sends an inhibitory signal to prevent naive B cell activation
is there a FcgRIIB1 receptor on memory B cells?
no!
so they can get activated!
Therapeutic use of ADCC
Rituximab eliminates B cells and tumors by ADCC
monoclonal Ab targeting CD40
