EXAM 3 B Cell Mediated Immunity Flashcards
maturation into immature committed B cells occurs in the ___, and antigen-dependent proliferation and differentiation into plasma and memory cells occurs in the ___
- bone marrow
- peripheral lymphoid tissue
describe how B cells mature within and migrate through secondary lymphoid tissues
*the “mature B cell” in the yellow box is naive
B cell activation drives what 3 things?
clonal expansion, class switching, and somatic hypermutation
___ are stromal cells involved in B cell development and activation
follicular dendritic cells
follicular dendritic cells accumulate antigens via ___
complement receptors
do follicular dendritic cells have phagocytic activity?
no
___ and ___ display antigen to B cells
macrophages and follicular dendritic cells
___ is expressed on FDCs and subcapsular sinus macrophages, and its function is to capture and display ___
- CR2
- intact antigens
B cell activation involves what 3 signals?
- antibody crosslinking (via IgD) - activation
- co-receptor signaling - survival and proliferation
- cytokines - differentiation; class switching, SHM
1st and 2nd signals are requisite
what are the 2 antigen types involved in B cell activation?
- thymus-dependent antigen
- thymus-independent antigen
describe thymus-dependent antigen
- protein
- protein-associated antigen
- Th cell interaction required
describe thymus-independent antigen
- PRR-detected antigen
- complement-bound antigen
describe antibody cross-linking involved in B cell activation
- signal 1
- antibody is bound to antigen
- clustering and aggregation
- Ig-alpha and Ig-beta signaling
- ITAM phosphorylation and signal recruitment
- *don’t need to know the specific molecules in the diagram
describe B cell co-receptor signaling in B cell activation
- signal 2
- ensures target is pathogenic
- prevents anergy
- foreign or self antigen
- initiates clonal expansion
- co-receptor signals are diverse
describe how co-receptor signals are diverse in B cell co-receptor signaling
- B cell co-receptor complex
- CR2, CD19, CD81 complex
- binds to complement (C3b)
- pattern recognition receptors
- TLRs
- CD40
- CD4 T cells
describe cytokine signaling of B cell activation
- signal 3
- Tfh cells are the most common source of cytokines during B cell activation
- local cytokines can provide signals in the absence of T cell-mediated activation (TI activation)
- 4 roles of cytokine signaling (different card)
what are the 4 roles of cytokine signaling in B cell activation?
- survival and proliferation
- class switching - same epitope binding, different heavy chain
- somatic hypermutation - increases antibody specificity
- differentiation - produces plasma cells and memory B cells
Tfh cells drive what 4 things in B cells?
- activation
- proliferation
- enhanced specificity
- differentiation into plasma and memory cells
what is the most common pathway of B cell activation?
Tfh cell activation is the most common
thymus-independent activation can also happen, but it is much less common
Tfh cell activation typically yields a larger population of plasma cells and memory cells
describe how B and T cells form cognate pairs at the follicle boundary
describe the process of Tfh cells aiding in B cell activation
- B cell is first activated by antigen binding
- B cell presents antigen to Tfh cells
- CD40 induces survival and proliferation (secondary activating signal - co-receptor signal)
- cytokines
- differentiate (plasma vs memory)
- isotype switch (in germinal centers)
- most common B cell activation pathway
B cells form plasma cells in which two stages and locations?
- cognate pairs first move to the primary focus
- produce IgM expressing plasma cells for several days (allows B cells to prevent systemic infection)
- no class-switching or somatic hypermutation
- cognate pairs then move to the secondary focus and form germinal centers
- enormous proliferation (every 6H) and plasma/memory cell production
- class switching and somatic hypermutation
- selection of most specific plasma cells
where do B cells hypermutate and class switch?
germinal centers
cognate pairs form germinal centers in ___
the follicular zone
cognate pairs first form centroblasts. what are they?
- form the germinal center dark zone
- proliferating source of new B cells
- do not express surface immunoglobulins
- somatic hypermutation
- class switching
- create centrocytes
centrocytes form plasma cells and memory B cells. describe centrocytes.
- form the light zone
- divide slowly
- express surface immunoglobulin
- cannot class switch or hypermutate
- interact with and selected by follicular dendritic cells
- programmed to die
___ and ___ improve antibody specificity
class switching and somatic hypermutation
describe class switching
- RAG proteins reactivated
- change heavy chain Fc region
- cytokine induced
- classes dictate effector functions
describe somatic hypermutation
- directed hypervariable region mutation
- singla nucleotide insertions and substitutions
- produces new epitope binding region
- as centroblasts divide, more mutations are produced
- increases antibody affinity
- paired with selection process
follicular dendritic cells select ___ centrocytes
high-affinity
after centrocytes have undergone the first round of somatic hypermutation, what is the result?
- the new antibody is different than cognate B cell antibody
- activating antigen presented on FDCs
how do follicular dendritic cells select high-affinity centrocytes?
- at this point, centrocytes have undergone the first round of somatic hypermutation
- competition for FDC-presented antigen
- only centrocytes that bind FDCs can bind Tfh cells
- FDC-bound centrocytes are bound by Tfh cells - survival signal
what happens when FDC-bound centrocytes are bound to Tfh cells?
- limited Tfh cell population in the germinal center
- survival signals
- selection of centrocytes with the highest antibody affinity
- further proliferation; several rounds of affinity maturation
- differentiation into plasma cells or memory B cells
plasma cells secrete large quanitites of ___
antibody
high-rate Ig secretion (intrinsic)
give an overview of B cell activation
describe the 4 broad effector functions of antibodies
- virus and toxin neutralization - prevents pathogen-host binding
- opsonization - phagocytosis
- complement fixation, formation of MAC - phagocytosis and lysis
- antibody-dependent cell-mediated cytotoxicity - NK induced apoptosis
what are the basic functions of the different antibody isotypes?
- IgM, IgG, IgA: internal tissues
- IgA: mucosal surfaces
- IgE: parasite immunity; receptor
- IgD: B cell receptor
___ receptors bind antibodies and provide adaptive specificity to innate cells
Fc
Fc receptors allow adaptive immunity to enhance innate immunte cells specificity and function
describe how Fc receptors are widespread and diverse
- monomeric and dimeric
- often require dimerization
- expressed on most leukocytes
- IgG, IgE, IgA
- enhance innate immunity
- stimulate and inhibit effector functions
- involved in Ig transport
in what ways do Fc receptors stimulate and inhibit effector functions?
- cytokine production/release
- phagocytosis
- degranulation
- targeted killing
describe how Fc receptors facilitate IgG transport into tissues
transcytosis of IgA protects ___
mucosal surfaces
describe how transcytosis of IgA protects mucosal surfaces
___ prevent pathogen establishment
neutralizing antibodies
IgA and IgG
describe how neutralizing antibodies prevent pathogen establishment during exposure to influenza virus
describe how neutralizing antibodies prevent pathogen establishment of strep pyogenes in the pharynx
___ clear agglutinized antigens
erythrocytes
how do erythrocytes clear agglutinized antigens?
how does opsonization lead to phagocytosis?
which cells does IgE make competent?
mast cells, basophils, and eosinophils
targeted degranulation, important in allergies
how does IgE make mast cells competent?
how does IgE make eosinophils competent?
___ and ___ initiate the complement classical pathway
IgM and IgG
describe antibody-dependent cellular cytotoxicity
antibodies provide ___ immunity during development
passive
in what ways do antibodies provide passive immunity during development?
- IgG during gestation
- IgA from breastfeeding protects infant mucosal surfaces
- mother’s immunity is passed to the infant
