BIO 343 Lecture Notes - Lecture 9: Phagocytosis, Immune Complex, Extracellular Fluid
Immunology Chapter 9: Immunity Mediated by B cells and Antibodies
Hayden Casassa
• Antibodies are found in blood, lymph, and extracellular fluid
o They function to neutralize pathogens, link to Opsonization, and activate the classical
complement system
o Ab production begins about one week after infection
o TFH effector cells remain in lymph nodes to activate B cells
o First priority during initial response to pathogens is speed of production, resulting in low-affinity
IgM antibodies
o The second priority is to improve quality of the Ab
▪ Increase the Ab affinity and change the isotype
• Cross-likig of atige eeptos BCR’s togethe is the fist step i B ell atiatio
o B cell signaling requires that multiple BCRs be bound together by repetitive epitopes of the Ag
o This causes clustering and aggregation of BCR and results in signal transduction
o This is eause thee ae poal at least , BCR o oe ell… all spe. fo sae pathoge
▪ In order to send signal, we need to take 2+ BCR and be forced together
o In order for signal to be sent Ig-a and Ig-b need to force 2+ BCR together and prevent from
moving
▪ Multiple epitopes keep them together which allows signal transduction to start
• Signaling requires Ig-a and Ig-b
o Thei toplasi tails otai AA seuees ITAM’s that eoe phospholated tosie
kinases
o This then initiates signaling that leads to changes in gene expression and B cell activation
• Cross-linking of the BCR by Ag generates a signal that is necessary but often not sufficient to activate
most naïve B cells
o One additional signal is delivered by the B cell co-receptor
o The B cell co-receptor is expressed on the B cell membrane and consists of the proteins CR2,
CD81, and CD19
o These 3 proteins make up the B cell co-receptor and are on all B cells
• B cell co-receptor components
o CR2—complement receptor that binds a breakdown product of C3b called C3d
o CD81---required for surface expression
o CD19---generates intracellular signals that synergize with BCR signaling
• Simultaneous ligation of the BCR and co-receptor enhance B cell signaling 1000-10,000 fold
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o This greatly enhances sensitivity to the antigen
• Effective activation of most naïve B cells requires the BCR, B cell co-receptor, and cognate interactions
with the CD4 Effector TFH cells that provide membrane-bound CD40L and secreted cytokines
• B cells activated by antigen in the B cell area move to area boundary where they are helped by antigen
specific effector TFH cells coming from the T cell area (shown below)
• “to to the paels aoe….
o Lymphocytes get to the node via the capillary and cross the HEV and T cells here move to
paracortex while B cells move to cortex. Antigen comes in and in case of T cell they undergo
clonal expansion similar to b cells. Myeloid (regular/yellow) dendritic cell activates CD4 T cell by
pesetig atige ia a MHC lass patha. I the pia follile, the FDC does’t present
the antigen per-say as it presents the whole antigen on arms to activate naïve B cell. This
initiates the Activation of the B cell
▪ FDC’s aptue Cd-bound proteins and particles using complement Receptor CR2 as
detailed below
▪ Atiges tagged ith Cd ete ia affeet lph ad the FDC’s id ia CR. The
antigen is screened by naïve B cells arriving from blood or afferent lymph
o Naïve CD4 T cells come in and those specific for MHC undergo clonal expansion. They then
expand and differentiate into TFH cells. Simultaneously, B cells in cortex take up antigen on FDC
via endocytosis and process via class 2 MHC. They then travel to boundary region.
o Clonally expanded TFH cells meet Ag presenting B cells and adhesion molecules become
expressed.
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• What happens after??? → TFH cells help Ag-specific activated B cells by expressing CD40L (on T cell)
and cytokine secretion
o This causes the B cells to move to medullary cords (with the T cell) and differentiate into plasma
cells secreting IgM that leaves via the efferent lymph and is an early Ab source to fight the
infection
o Some members of each clone return to follicle for B cell expansion leading to massive
proliferation of Ag-specific B cells (centroblasts). The follicle becomes the germinal center
which is now where somatic hypermutation and isotype switching occurs
o Cetotes oe ito light zoe of geial ete ith highe desit FDC’s ad TFH ells
▪ They are programmed to die apoptosis uless thei BCR’s eogize specific Ag on
FDC o thei CD is oud to CDL o TFH ells… the opete ith eah othe
• Cetolasts ae loated i dak zoe… ad aïe B ells lookig fo Ag ad suial sigal fo FDC ae
in hat’s alled the atle zoe
• Affinity Maturation
o Result of somatic hypermutation of rearranged V-region and consequent selection of mutated
B cells that make B cells of higher affinity for antigen
• Antigen-mediated selection of centrocytes drives Affinity maturation
o TFH cells via CD40L and cytokines induce centroblasts to undergo somatic hypermutation
▪ This auses etotes podued to hae diesit of BCR’s ith age of affiities fo
Ag to which founder b cell was specific
• Centrocytes that express mutat IgM BCR’s ith high affiit outopete othe etotes idig
to Ag on FDC → leads to whats detailed in picture above
o CD40L from TFH cells induce the centrocytes to make TF Bcl-XL which rescues from apoptosis
and causes them to further differentiate into plasma cells
• Cytokines made by helper T cells determine how B cells switch their immunoglobulin isotype
o Isotype switching also requires that B cells in germinal center bind CD40L expressed by T cells
o IgG are very good at Opsonization
Those ith lo affiit IgM BCR’s a’t
opete ad a’t eeie suial sigal die
via apoptosis
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