Immunity mediated by B cells and antibodies Flashcards
B cell activation requires ___
2 signals
What 2 signals are required?
- Antigen binding B receptor
- Helper T Cell delivers 2nd Signal – CD40
Cytokines also help
Describe the Antigen Binding signal
- B cells become cross-activated when receptors are linked
- Clustering allows receptor ass. kinases to Phs. ITAMs
- Syk binds double P’d ITAMs, is activated
- Changes in gene expression
3 B Cell components of Co-receptor complex
CR2
CD19
CD81
What does CR2 bind?
C3d
What is the purpose of the coreceptor complex?
To lower the threshold of B cell activation
Four Activities Following B Cell Activation
Proliferation
Somatic Hypermutation (Affinity Maturation)
Isotype Switching
Dev. of Memory and Plasma cells
What B cells are present in the Mantle Zone?
Naive Unactivated
What B cells are present in the Germinal Centers?
Active, Proliferating
What do B Cells need to enter the LN (via afferent lymphatic)
Actual Antigen
Antigen goes from the afferent lymphatic into the ______
Subcapsular Sinus
How does antigen get from the subcapsular sinus into the Node?
Macrophage pickup using CR2
How do Peyer’s Patches/Tonsils let in antigen?
Specialized epithelial cells for transport
Steps of Naive B Cell Activation
- Naives look for their antigen on FDC
- Antigen Activated Bs go to Boundary region
- AA Bs present ant to effector T-fh cells - form pair
- Bound pairs migrate to medullary cords, EXPANSION
- Bound pairs migrate to Primary Follicle, 2dary EXPANSION
- Expansion of Primary Follicle generates Germinal Center
Germinal centers are full of what cell?
What does this cell do?
Follicular Dendritic Cell
CR1 and CR2 on FDCs holds antigen in place for several months
How is a follicular dendritic cell different than a DC?
Fibroblast lineage, Not from BM
No MHC II
How does somatic hypermutation work?
Activated B cell mutates V regions
Different versions of the B cell compete for binding to the antigen on the Folicular cell
No Binding = Death, Higher Affinity Bs bind, receive anti-apoptotics from helper T.
Two important signals a B gets from a T helper
- CD40 triggers isotype switching
2. Cytokines afterward influence what switching will occur
IFN-gamma drives what B cell type expression?
IgG2a, IgG3
TGF-beta and IL-5 trigger what diff in B cells
IgA, IgG2b
Il-4 triggers what kind of differentiation?
IgE, IgG1
Antigen selected centrocytes will tend to become plasma cells if exposed to _____ or memory cells if exposed to _______>.
Plasma – IL-10
Memory – IL-4
Mutation of CD40L will cause…
Hyper-IgM syndrome
Lack of Isotype Switching
Inheritance of Hyper-IgM syndrome?
X linked
What is seen in the blood of a Hyper-IgM syndrome patient
No IgG, IgA
Increased IgM
How do TI-1s activate B cells?
Via a non Ig receptor, for example using TLR4 to activate upon exposure to LPS
How to TI-2s activate B cells
Chains of epitopes that cause extensive cross linking signaling of Ig on B cell surface
What do TI-2s tend to target?
Polysaccharids, sometimes proteins
Why is it important that TI-2s can act without help from T cells?
Ts recognize peptide fragments.
Polysachharide aren’t processed that way, so no CD4s
T-dependent, TI-1, TI-2. Who is present in athymic people?
TI-1, TI-2
T-dependent, TI-1, TI-2. Who does idotype switching?
Only T-dep
T-dependent, TI-1, TI-2. who makes memory cells?
Only T dep
T-dependent, TI-1, TI-2. Who works in infants?
Tdep and TI-1
How do conjugate vaccines work?
Polysaccharide target is bound to a peptide toxoid
B cell binds antigen, toxoid is presented to Thelper
Activated B differentiates into plasma cell against polysac.
Three bacteria targeted by Conjugate polysaccharide vaccines?
Haemophilius influenzae
Streptococcus pneumoniae
Neisseria meningitidis
What is streptococcus pneumoniae?
Gram? Symptoms? Serotypes?
G+
Upper Resp. Inf, Otitis Media, Pneumonia
Over 90 serotypes
Problems with using a vaccine against only the most common disease types?
Increases in prevalence of non-vaccine types
Unique movement of IgA and IgG?
IgA – Across Epithelials into Mucosal Secretions
IgG – Across Endotheliams into Extravascular Space and across placenta
What receptor mediates IgA travel across epithelial cells?
Polymeric Immunoglobulin Receptor
What receptor mediates IgG travel across endothelial cell
Brambell Receptor (FcRB
How does IgA get across epithelial cells?
Binding to poly-Ig rec. on the basolateral face
Endocytosis + Transcytosis
Receptor Cleaved
IgA bound to Mucus through Secretory Piece
Poly-Ig receptor can transfer which two antibodies
IgA and IgM (but almost always does A)
How big is A1 hinge region? A2?
26 aa
13 aa
Role of secretory componeny in IgA dimer?
Wraps around J Chain – May help prevent protease activity
IgA2 is most found…
In the digestive tract (esp. Ileum+Colon)
Shorter chain makes harder to cleave there
How does IgG get across endothelial cells?
Binding to FcRB, transcytosis
Mostly active transport
At birth, what antibodies does an infant have?
Which come along later?
Maternal IgG and Fetal IgM
Fetal IgA and IgG
Name three effector functions of antibodies.
Neutralization
Opsonization
Complement Activation
Who expresses Fc-gamma receptors?
Neut, Mac, B Cells, FDCs, NKs
Purpose of Fc-gamma receptors?
Opsonization and Antibody-dependent cell-mediated cytotoxicity
Purpose of Fc-epsilon receptors? Who expresses them?
Important in allergic reactions
Expressed on Mast Cells and Basophils
FcR1 is on _____ and has a high affinity for ___
Describe its action.
Mac and Neut. IgG1 and IgG3
FcR1 binds the lower hinge/CH2 of Ig, Ig binds antigen
More efficient phagocytosis
Which Fc has the strongest relative binding strength to IgG1?
Fc-gamma R1 (CD64)
Which Fc-gamma receptors are inhibitory
RIIIB2, RIIIB1
CD32
How does antibody dependent cell mediated cytotoxicity work?
Antibody binds target
Fc receptors of NK cells recognize Ab
Crosslinked Fc receptors signal NK cell to kill the target
Apoptosis
Describe the relationship of IgE and Mast Cells
IgE binds onto Fc-gammaR1 on mast cells
On second exposure, antigen binding to bound antibodies will trigger degranulation
IgG3 is unique for…
Long Hinge
Large Heavy Chain + many disulfide bonds
Very susceptible to clevage, so short half-life
Great ability to activate complement
What is IgG4 good at?
Allergen Response
How long do untriggered naive B cells live?
3-8 weeks
Short lived plasma cells in the medulla generate….
IgM for approx. 5 days
Forms initial response to infection
What happens in secondary response if Naive B binds to a path coated in antibody?
Negative signal is given to naive B
Activation prevented
What happens in secondary response if Memory B cell binds a pathogen coated in Ab?
Memory B is activated
Becomes a plasma cell
Produces high-affinity IgG, A, and E