B Cell and Antibody Immunity (Lec 6.5) Flashcards
1
Q
B-cell activation
A
- Antigen interactions with IgM-BCRs on a B cell surface bring multiple BCRs close
together = cross-linking - this allows for phosphorylation of BCR
- triggers signalling cascades and once threshold is reached, activation occurs
2
Q
Co-Receptors in B-cell activation
A
- can also bind to antigens along with BCRs
- Antigen binding both BCRs and coreceptors increase the signal by 1000-10000 fold = increased sensitivity to the antigen
- lowers threshold of activation
3
Q
B cells 1st activation signal
A
- Specialized cells catch and hold antigens that reach the lymph node for B cells to interact with
- B cells that interact with and bind antigen on FDCs receive 1st activation signal (recognizing and binding antigen)
4
Q
B cell 2nd activation signal
A
Activated B cells move closer to T cell zone: B cell follicle
boundary and present antigen to activated Helper T cells to receive 2nd activation signal
5
Q
How are cognate pairs formed?
A
- antigen-activated B cells present antigen to effector TFH cells, forming cognate interactions
- helper TFH cell conjugates with the B cell and begins to synthesize cytokines and CD40 ligand
- helper TFH cell reorients its cytoskeleton and secretory apparatus toward the B cell
- cytokines are secreted into narrow space between TFH cell and the B cell
- this forms an immunological synapse with allows T cells to give B cells cytokines it needs to get 2nd activation
6
Q
What is the benefit of T & B cell pairing up?
A
- they recognize the same pathogen
- B cell presents what it is recognizing on MHC class 2
- T cell recognizes MHC class 2 peptide, then can provide help to B cell
7
Q
Activated B cells and Germinal Centers
A
Activated B cells go through two stages within germinal centers:
1. Centroblasts (in dark zone) = proliferating B cells
- multiplying and mutating B cell receptors
2. Centrocytes (in light zone) = interact with antigen-presenting FDCs to test the quality of the BCR in response to antigen
- tests if mutations were beneficial
8
Q
Formation of Germinal Centers
A
- cognate pairs remain in
contact and proliferate to form germinal centers - B cells move back and proliferate in the B cell area
- expansion of antigen-activated B cells in the primary follicle creates the germinal center
9
Q
Somatic Hypermutation of Activated B Cells
A
- BCR quality is changed and assessed due to somatic hypermutation (point mutations generated in variable regions)
- can improve, have
no effect, or reduce antigen binding by BCR - mediated by Activation-induced cytidine deaminase
(AID) - longer the cell remains in germinal centers, the more mutations it accumulates
- cells that have improved binding survive due to binding more antigen
10
Q
Affinity maturation
A
- process by which B cells produce antibodies with increased binding strength (affinity) for a specific antigen
- happens mainly in germinal centers
- after undergoing somatic hypermutation, B cells with higher-affinity antibodies are preferentially selected for survival
- Low-affinity or non-functional B cells die by apoptosis
- Over time, the antibody pool shifts toward higher-affinity antibodies for the antigen
11
Q
Isotype switching
A
- mediated by activation-induced cytidine deaminase (AID)
- process by which B cells change the antibody isotype (or class) they produce without altering antigen specificity
- Switch sequences or Switch regions flank the different constant region (immunoglobulin class) options
- allow for DNA editing and class switching
12
Q
IgM
A
- first BCR and secreted antibody that is made
- Pentamers help activate complement but make it less efficient for entering tissues and neutralizing
12
Q
IgD
A
- second BCR made
- dominant BCR on the surface of anergic B cells
- does not have a typical switch gene but has been found as a secreted antibody in upper airways
13
Q
IgA
A
- main antibody produced in
our associated lymphoid tissues - keeps commensal bacteria in check
- Most abundant class of antibody
- forms dimers
- protects us from gastrointestinal pathogens
- can only make it after B cell has been activated
14
Q
Transcytosis of IgA
A
- Transcytosis = receptor mediated transport from one side of a cell to the other
- IgA binds to receptor on epithelial cell
- undergoes receptor-mediated endocytosis
- gets transported to apical face of epithelial cell
- receptor is cleaved and IgA becomes bound to mucus through secretory piece
15
Q
Why does IgA become bound to a secretory piece?
A
- tethered to a secretory piece to prevent mucus from washing it away from the site
- it stays attached to the epithelial cell in the lumen to trap pathogens
16
Q
IgA and microbiome population
A
IgA is produced to keep population growth of commensal microbes in check (neutralize) and prevent it
from overgrowing and infecting us
17
Q
IgE
A
- recruits granulocytes and induces effector functions (degranulation)
- involved in allergens
- helped us evolve methods to eject/eliminate parasitic pathogens
18
Q
IgE-Mediated Pathogen Killing
A
- IgE acts as a cell surface receptor
- Pathogen binding to IgE cross-links it and causes degranulation of the host immune cells
- Granules can increase blood vessel vascular permeability to flush out parasite
- can also attack the
parasite itself and kill it because the contents are toxic
19
Q
IgG
A
- most abundant in our body fluids (lymph and blood)
- most important
- Most flexible of the immunoglobulin family due to hinge region, which helps them interact with pathogens really well
20
Q
Antibody Dependent Cell-mediated Cytotoxicity (ADCC)
A
- Natural Killer (NK) cells can recognize human cells that are coated with specific
IgGs and kill them - can help deal with immune cell cancers
