Interplay with Adaptive Immunity

Question 1

how is T and B cell receptor diverity achieved??

Answer 1

Genetic recomibation of VDJ semgemtns using RAG proteins

Question 2

B cell activation by binding of an antigen is also referred to as….

Answer 2

thymus indepednent antigern activation

Question 3

whata are the Steps in B cell development?

Answer 3

• form from haemotpoieitc stem cells in BM
• BC progenitro remain in bone marrow to undergo matutation ( BM stomal celsl mciorneviornemt commit progentiros to B cells)
• Pre-B celsl undergo reaaragnemnt of heavy cahin VDJ by RAG
• then after heavy chain RAG is rexperssed VJ reaarnagmet lgiht cahin
• upon successful formation fo a light locus- immatur B cell si formed- expxress IgM
• here immature B cell tyest for autoreactivity
• immature B cell then migrate to spleen
  
  • undergoes splciign leads to expression of IgD and igM
• in spllen B celsl require positive signal–> cytokines BAFF, follciuclar denritic celsl to fully mature

Question 4

label this and what is it?

Answer 4

BCR

Question 5

Label this and what is it

Answer 5

Question 6

in T cell receptor gene reaarnagement which comes first

Answer 6

B chain- VDJ- D joined to J then DJ joined to V

then get cell proliferation

then A-geen reaarnagement- VJ only

alpha chian binds to B cahina on cell surface and the cells can undergo selection

Question 7

where else can variation be seen on TCR aside form A and B chains- ‘rapid responder’

Answer 7

γ:δ receptor has also been discovered

recognise antigen directly- rpaid responders (under gene replacemtn in simialr process but fewer genes- so more limited

Question 8

Describe T cell development

Answer 8

• Haemotpoieitc stem cells in bone marrow
• travlel to thymus for deevlopemt
• douvle negative for CD4 , CD8 (CD3 and TCR)
• thymic stormal celsl commit T cell progeneitors via signalling receptor (NOTCH-1) intiate TCR gene rearranegemtn
• VDJ- B chain first
• T cell begsin to express CD3- A chain also rearranges
• Positive selection- destoryed if TCr cannot respond to Self MHC
• Negative seltion- if react to self atnige ( expect Treg)
• single positiv thymocyte formation- only express Cd4 or Cd8
• mature, leave thymus travel to secodnayr lymphoud tissues

Question 9

Waht does the Activation of B cells require?

Answer 9

thymus depednent antigne activation of B cells (stronger)

thymus indepednent antigen activation of B cells

Question 10

describe thymus dependent antigen activation of B cells

Hint( TFH celsl CD40L and cytokines)

Answer 10

• B cell express MHC II that is is recognised by speciif TCR on TFH
• TFH activated expressed CD40L and secretes cytokines Cd40L interacts with Cd40 on B cell and IL21 and Il-4 cytokines alos secreted
• signals the B cell to activate- undergo proliferationa dn differentiat into plasma cells
• proliferation of B cells formation fo germianal centres( site of itnense B cell proleration, selction and amturation and death)
• eventrullay get differnetion of Matur B cells into plasma cells

Question 11

what can further production of cytokines from TFG in germianl centre lead to production of?

Answer 11

determine the type of antibody creasted

Question 12

Describe thymus indepent antigen activation

(hint TOll-like rececptors)

Answer 12

• B cell activation without helpf from TFH cells
• other surface receptors - loke toll like receptors
• recognise lignas- bacterial LPS
• crosslinking of BCR and Toll like receptors
• pro surivial signals induced

Question 13

Thymust dependent vs thymus independent

Answer 13

thymus depednent has higher adffinity, stronger immune response, Isotype switching

Question 14

what processes are used to fine tune the antibody response

Answer 14

affinity maturation by soamtic hypermutation

class switching

(antibodies induecd by micorbial agents alone have lower affinity and less functional vesaltility)- want T cell and cytokines

Question 15

Describe affinity maturation and clonal selection

Answer 15

• Activated B cells differeniate into plasma blasts and plasma cells and proliferate to form germinal centres
• produce enzyme called (AID) acitave induced cytidine deaminase and undergo somatic hypermutation
  
  • intorduce mutations into the complimentary determing region or the vairable region.- closely related clones with different affinity
  • those that have a positive effect- have hgher affinity capture and present antigne and present to MHC class II
• TFH provides survial and growth signals to these via CD40L and cytokines
• repeated until best affinity

Question 16

what is the purpsoe of clonal selection process

Answer 16

enables secondary response to an infecito. to have much hgiher affinity antibodies than pirmayr response

thymius depeendnt B cells have been show to propduce higher affinity antivoies than thymus independnt B cells due tot htis selctive process

Question 17

what is clonal expansion

Answer 17

where eahc progeny will produce identical antibodies

Question 18

Look at his diagram

Question 19

During secondary response recativation fo a memory B cell is dependne ton its interaction with its corresponding what?

Answer 19

Secondayr respons ereactivation of memory B cell is depednent on its itneraction with correspeoding memeory T cell

Question 20

what are the 4 stages of immunolgoical memory

Answer 20

niave pahse

primary response

memory phase

secondary response

Question 21

describe the niaev pahse of immunologicla memory

Answer 21

before antigen encoutner- low number of antigens epcific T cells and B cells not physically close in secondary lymphoid tissues

Question 22

describe the primary response

Answer 22

• antigen encountered, antigne speciif niave T cells in the T cell zone primed by dendirit cells migrate towardfs the B cell follicles
• antigen specific B cells encounter antigen also migrate to border of the T cell zone which allows of B and T cells ton interact
• activate B cells differentiate to either continue in germinal centre reaction or plasma cells
• low levels of antogen speicif igG production detcte 1 week after antigne challeneg

Question 23

decribe the mrmory phase of immune response

Answer 23

after antigen cleared, antigne specific memroy T and B cells egenrated

some of the memroy B cells remain clsoe to germianl centres which have now contracred

Memroy T cell derived from effector TFH cells (localised at B cell -T clel. border) or in B cell follciles

so remain in clsoe proximity

Question 24

describe the secondary response

Answer 24

T an dB celsl present - when antigen encoutnetred agian, ememory cell close proximity- acitve aeachother

get high levels of antigne specifi IgG antibodies within a few days