Immunology 6 Flashcards
what is the function of a B cell?
to give rise to plasma cells that secrete antibodies capable of binding to an organism, microbe, or molecule
the secreted antibodies have antigen binding sites…
identical to those of the receptor molecules on the B-cell surface
antibodies belong to the class of proteins known as ?
immunoglobulins
B cells develop first from hematopoietic stem cells, and then into common lymphoid progenitors under the influence of ?
IL-7
B cells are released into circulation as ?
immature, naive B cells
B cells develop from common lymphoid precursors into
Pre-pro B cells
As the pro-B cell matures to a pre-B cell, it will express an ?
immature BCR (B-cell receptor)
If this BCR is ? the B cell passes the pre-B cell checkpoint and becomes a pre-B cell
productive
If this BCR is ? the B cells will undergo apoptosis
unproductive
Prior to maturation into an immature B cells, the Pre-B cell goes through a second checkpoint.
At this point the BCR is checked for ?
self-reactivity
Explain if Pre-B cells is positive for self-reactivity
○ If (+): Pre-B cells tries to rearrange light chain genes of the BCR and will be checked again for self-reactivity
§ If still (+) -> Pre-B cell will undergo apoptosis
Explain if Pre-B cells is negative for self-reactivity
If (-) -> becomes a immature (aka transitional) B cell and leaves the bone marrow
From the bone marrow immature (aka transitional) B cells travel to the ?
spleen
once in the spleen, the immature B cell begins expressing:
- CD21 - the complement co-receptor
- IgD in addition to IgM as the isomer of the portion of the BCR
From general circulation, the B cell will migrate to ?
a lymphoid follicle within a lymph node
what are bean-shape structures encapsulated with a reticular network and packed full of lymphocytes, macrophages, and dendritic cells
lymph nodes
what are the 3 main regions of lymph nodes
- cortex
- paracortex
- medulla
what is in the cortex region?
Contains lymphocytes (predominantly B-cells), macrophages and follicular dendritic cells arranged into primary follicles
what is in the paracortex region?
contains mostly T-lymphocytes and dendritic cells
what is in the medulla?
- More sparsely populated with lymphoid-lineage cells
○ Often plasma cells actively secreting antibody molecules
Within a lymph node, a naïve B-cell encounters an antigen in 1 of 2 ways:
- The antigen flows into a lymph node through afferent lymphatics and binds to the BCR
- Macrophages or dendritic cells encounter an antigen in the periphery and bring it to a lymph node
- Here they will “present” the antigen to a B cell and the antigen binds to the BCR
The antigen binds to the BCR with the help of:
B-cell co-receptor:
- CD21: co-receptor that binds an antigen bound to the complement component C3d
- CD19: signal transduction protein
Once the B-cell has presented it’s antigen it will also increase its expression of co-stimulatory molecules:
- CD80/86
- ICOSL
- CD40
CD80/86 on B-cell binds to CD28 on T-helper cells for ?
T-cell activation
ICOSL on B-cell Binds to iCOS on T-helper cells to induce
Cytokine productions
CD40 on B-cells binds to CD40L on T-helper cells to ?
increase antibody production
Then the B-cell will present it’s antigen to which type of T-helper cell?
Tfh
Under the influence of ?, the B cell will proliferate and begin to produce antibodies
IL-2, IL-4 (by Tfh cell), and CD40-CD40L interaction
What will result in production of high-affinity antibodies?
somatic hypermutation
During antibody class switching, ? may be switched to a different class
the original antibody (IgM)
what secreted by the T-helper cells will induce class switching
different cytokines
T-helper 1 cells secrete INF-y which stimulates class switching to ?
IgG subtypes
TGF-beta stimulates class switching to ?
IgA
T-helper 2 cells secrete IL-4 and IL-5, which stimulates class switching to ?
IgE
what are the steps of somatic hypermutation?
- The B cell starts in the dark zone of the germinal center where it will loses its HLA expression and mutate it’s BCR genes
- The BCR moves into light zone of the germinal center and samples follicular dendritic cells for the antigen
Following B-cell selection in germinal center for high-affinity antibodies, the B cell differentiates into either:
- plasma cells
- memory B cells
what do plasma cells do?
No longer have BCR and secrete a large number of antibody molecules
what do memory B cells do?
Circulate in the periphery: Once they re-encounter their specific antigen, they will proliferate and differentiate into plasma cells
what is the structure of an antibody?
2 heavy chains and 2 light chains, and has constant and variable regions
what regions undergoes genetic shuffling for antibodies
variant regions
what are the 6 categories of antibody functions?
- Neutralization
- Agglutination
- Opsonization
- Complement activation
- anti-body dependent cell mediated cytotoxicity
- degranulation
what are the 5 main classes of antibodies?
- IgM
- IgG
- IgD
- IgE
- IgA
what is the first class of antibody secreted during the primary immune response
IgM
what is IgM secreted as ?
a pentamer
IgM tends to have a higher or lower affinity for its antigen?
lower
what are the functions of IgM?
- Very good at activating complement
- Good at agglutinating pathogens - immobilizes the pathogens allowing for phagocytosis
what is the most common antibody found in serum?
IgG
IgG is secreted as a ?
monomer
what are the variety of different classes of IgG?
IgG1, IgG2, IgG3, IgG4
what are the functions of IgG?
- Opsonization
§ Bind the Fc receptor on phagocytes and enhances phagocytosis - IgG1 and IgG3 are good at activating complement
- IgG2alpha is good at triggering antibody-mediated cytotoxicity by Natural killer cells
what is predominantly found as a dimer secreted into tears, saliva, breastmilk, and mucus?
IgA
what are the functions of IgA?
- Neutralizing pathogens
- Agglutinating pathogens
IgE is secreted as ?
a monomer in small quantities
what is the function of IgE
Binds to cells with and Fc receptor for IgE triggering degranulation of granulocyte
IgD is secreted as ?
a monomer in very small quantities
IgD is most prevalent in secretions of the ?
upper respiratory tract
IgD binds to ?
basophils and mast cells
