B cells: intro

Question 1

How are B cells activated

Answer 1

Via tfh

Question 2

Signal 1

Answer 2

P:bcr

Question 3

Signal 2

Answer 3

Tcr:pmch2
Cd40l:cd40
- involves tfh

Question 4

What else needed to activate B cell s

Answer 4

Additional signals - tfh secreted cytokines like il21 and others to tell B cells which abs to be produced
Also concept = linked recogniiton

Question 5

Hummoral immunity

Answer 5

Abs promote pathogen neutralization, opsonization, complement activation (c1q

Question 6

What do tfh do

Answer 6

Secrete il21 and cytokines typical of type 1 - ifny, type 2 - il4 or type 3 - il17 responses
= signal activates B cells to produce specific types of abs
Tfh interacts direct with B cells
IN RSPONSE TO ALL TYPES OF PATHOGENS

Question 7

Describe Igm - gen function for B cells

Answer 7

Immunoglobulin M = ab class that serves as receptor on naive B cells

Question 8

What is B cell

Answer 8

Type of lymphocyte
Lymphoid lineage

Question 9

Where do B cells arise

Answer 9

In bone marrow

Question 10

Name 3 key roles in adaptive immunity

Answer 10

Antigen specific
B cells clonotypic - to clear infection = clonal selection and expansion
Progenitors of ab producing plasma cells and plasma blasts

Question 11

define plasma cells

Answer 11

Activated and differentiated B cells
Main ab secreting cells

Question 12

Define plasma blasts

Answer 12

B cells in lymph node that already show some features of plasma cells- can secretes abs but also have membrane bound bcr

Question 13

Bcr is..

Answer 13

Membrane bound

Question 14

What happens when B cell activated

Answer 14

Secretes B cell receptor = ab (immunoglobulin)

Question 15

Describe clonal selection and expansion

Answer 15

Process of clonal selection
Activated B cells undergo proliferation an differentiation
Outcome = plasma cells that secrete abs
(Clonal selection and expansion if match ag, clonal deletion if autoreactive)

Question 16

What do naive B cells do

Answer 16

Circulating in periphery - pass through lymph nodes and spleen regularly

Question 17

How do naive B cell enter lymph node

Answer 17

High endothelial venues

Question 18

What happens if B cell in lymph node does not encounter antigen

Answer 18

Leaves via efferent lymphatics
If still hasn’t encountered ag after months = dies via apoptosis - cell turn over

Question 19

What happens if B cell in lymph node encounters antigen

Answer 19

Provides survival signal = signal 1

Question 20

What does B cell look for

Answer 20

B cells look for ag not p:mhc

Question 21

How do antigens arrive in lymph node

Answer 21

Ag from pathogens arrive in lymph node via efferent lymphatics
- especially if small - many end up in lymphatics system

Question 22

What can at be linked to as comes into Ln

Answer 22

Ag can be covalently linked to complement protein - opsonzied

Question 23

Describe what can happen to opsonzied antigens in lymph node

Answer 23

Ag can then be retained in ln by scs macrophages and follicular dendritic cells
(Macrophages have receptors for those complement proteins = anchors them)

Question 24

Describe subscapular sinus macrophages- binding

Answer 24

After opsonzied ag enters ln
Scs Macrophage = expresses complement receptor on surface = can bind complement protein on opsonzied ag and retain ag in ln

Question 25

Describe scs macropahes - what do they do

Answer 25

Retain ag on their surface in ln - not like other macrophages Have low endocytic and degradative activity - do not phagocytose easily

Question 26

Are all ags in lymph node retained by scs macrophages

Answer 26

No Some ags free floating in ln But most retained by scs macrophages

Question 27

What does bcr bind specifically to

Answer 27

To epitope on ag

Question 28

What else can ag be bound to in lymph node

Answer 28

Ag can also be transported onto surface of follicular dc - resident dc = important for later stages in B differentiation

Question 29

Describe bcr binding ag

Answer 29

Specific interaction

Question 30

What else does B cell also express

Answer 30

Co receptor complement receptors = cd19 and cd21 = sometimes pathogens coated with complement protein so B cell binds this = not necessary (for signal 1) but can enhance signalling and activation

Question 31

What is bcr associated with

Answer 31

Igalpha and igbeta = these have itam motifs that become phosphorylated by src kinase Signalling can also occur via co receptor complex complement proteins = can be phosphorylated too

Question 32

Describe signalling outcome of bcr - gen

Answer 32

Multiple signalling pathways activated bc of phosphorylation of itam motifs on igalpha and igbeta

Question 33

Describe signalling outcome of bcr - name 3 outcomes

Answer 33

Transcription factors activated —> gene transcription (lead to B cell survival prolfiertaion and differentiation) Survival signal (enhanced if have complement protein binding to recpetor) Cytoskeletal reorganization (bc endocytosis)

Question 34

What happens to bcr ag

Answer 34

Endocytosed

Question 35

Describe internalization and presentation of ag by B cell

Answer 35

Endocytosed Once signalling begins = bcr ag complexes internalized Internalized ag processed and presented on mhc Pmhc = can then interact with tcr - tfh cell on surface

Question 36

Signal 2 = name the 2 types of antigens

Answer 36

Thymus dependent Thymus independent

Question 37

Describe thymus dependent antigens

Answer 37

More common Td ag Signal 2 provided by activated cd4+ tfh cell Specific ab and provide memory

Question 38

Describe thymus independent antigens

Answer 38

Does not need T cels, less likely Ti ag Signal 2 provided by tlr signalling Such ag are typically highly repetitive molecules like lps Only for some B cells:B-1 marginal zone B cells (less diversity and give rise to primary igm abs) - mainly found in spleen

Question 39

Describe signal 2 - tfh

Answer 39

Signal from mhc bound to tcr and co recpetor on tfh cell Signal from cd40 on B cell bound to cd40l on tfh cell = signalling and activation of tfs —> activation differentiation (to plasma cell or memory B cell or germinal centre B cell) proliferation —> ab secretion

Question 40

Describe signal 2 - other signals

Answer 40

Cytokines = tells B cell which type ab to secrete

Question 41

What makes bcr diff from tcr

Answer 41

Bcr recognizes ag in natural form

Question 42

Describe linked recognition - rule

Answer 42

For a tfh to be able to activate B cell = epitopes recognized by B cell and tfh must be from same antigen - from same source

Question 43

Describe linked recognition - describe more

Answer 43

Tfh recognizes fragment of same ag that is recognized by B cell Peptide recognized by tfh = likely to diff from protein epitope recognized by bcr - peptide processed and presented to tfh but natural for B cell bcr = BUT FROM SAME SOURCE AG

Question 44

Describe image of linked recognition

Answer 44

EPitope specific cd4 t cell = recognize ag in context mhc, taken up by conventional dc - exogenous B cell =most likely epitope on viral envelope

Question 45

Compare what b vs T cell recognizes for linked recognition

Answer 45

T cell = epitope represented by mhc on dc (could be a peptide from protein inside viral particle) Eptiope diff but same virus!!!! B cell = epitope (could be from native structure of a protein on viral surface)