B cells

0.0(0)
studied byStudied by 0 people
learnLearn
examPractice Test
spaced repetitionSpaced Repetition
heart puzzleMatch
flashcardsFlashcards
Get a hint
Hint

how B cells work

Get a hint
Hint
  1. identify pathogen

    uses many receptors to do this

  2. decision needs to be made

    attack planned from spleen and lymph nodes

  3. coordinated approach

    cells communicate with eachother and need B cells to launch attack

Get a hint
Hint

difference between B and T cells

Get a hint
Hint

B CELLS

  • humoral immunity

  • arise in bone marrow

  • B cell receptor

  • produce antibodies for long term - only cell that does this

  • present antigen - have MHC class 1 and 2

  • release chemokines

  • antibodies released into the blood (humoral)

  • when activated can either become memory cells or plasma cells

T CELLS

  • cellular immunity

  • arise in the thymus

  • t cells recognise niaive t cell biund antigen via t cell receptors

  • long term memory

  • dont produce antibody

Card Sorting

1/29

Anonymous user
Anonymous user
encourage image

There's no tags or description

Looks like no tags are added yet.

Study Analytics
Name
Mastery
Learn
Test
Matching
Spaced

No study sessions yet.

30 Terms

1
New cards

how B cells work

  1. identify pathogen

    uses many receptors to do this

  2. decision needs to be made

    attack planned from spleen and lymph nodes

  3. coordinated approach

    cells communicate with eachother and need B cells to launch attack

2
New cards

difference between B and T cells

B CELLS

  • humoral immunity

  • arise in bone marrow

  • B cell receptor

  • produce antibodies for long term - only cell that does this

  • present antigen - have MHC class 1 and 2

  • release chemokines

  • antibodies released into the blood (humoral)

  • when activated can either become memory cells or plasma cells

T CELLS

  • cellular immunity

  • arise in the thymus

  • t cells recognise niaive t cell biund antigen via t cell receptors

  • long term memory

  • dont produce antibody

3
New cards

why do we need B cells

HYPER IgM

  • in hyper IgM syndrome patients will only produce IgM

  • patients have many infections and life expectancy is under 30

LUPUS

  • rifuximab is a treatment for lupus which decreases B cells (as pathological antibodies drive lupus)

  • people with lupus cant get vaccinated

  • B cells going wrong is the main cause

  • people with lupus cant make antibodies as theyre medicated to reduce B cells

  • therefore, b cells are essential for long term memory

4
New cards

B cell receptor

  • is a membrane bound antibody

  • b cells dont bind MHC —> can bind soluble antigen

  • can present antibody on MHC

  • antibodies on the membrane has same structure as soluble antibody

STRUCTURE

  • 2 light chains, 2 heavy (25 and 50kDa)

  • made up of the antibody the cell is making and CD79

  • CD79 chains move internal ITAM moelcules which signal to the cell to dictate function

  • variable and contant region

  • antigen binding region within variable region

  • the effector function activity is found within the contant region

  • the isotype is determines by the carboxy terminal of the heavy chain

5
New cards

ITAMs

  • immune receptor tyrosine based activation motif

  • present in b cells ad t cells

  • 2 tyrosine resides separated by 9-12AAs

  • theyre able to bind with high affinity to SH2 domains of protein tyrosine kinases

  • when phosphorylated by these kinases they can be bound by further mediators of the signalling cascade

  • activation of ITAMs is the first signal that the B cell has seen a cognate antigen

  • a phosphorylation is a quick, good signal for these cells

6
New cards

classes of antibody

  • 5 classes determined by the constant region of the heavy chain: IgM, IgD, IgG, IgA, IgE

  • each antibody has a different role, migration capacity and is expressed at different times

  • B cells are able to change what tyope of antibody is expressed

  • when they begin to mature, they express IgM and later co express IgD

  • IgD is membrane bound but all other antibodies are secreted

IgA

  • common at mucosal sites

  • good in intestine and good defence in the gut

  • lots of IgA in bodily fluids

IgG

  • 75% of blood based AB

  • 4 subclasses

  • monomeric —> can diffuse across tissues/across the placenta

  • antibody mediated cellular cytotoxicity

IgE

  • least common

  • main role is binding to mast cells and cross linking Fc receptors

  • IgE will carry our response to large pathogens such as tape worms where they must be killed by granules

  • also releases huge amount of histamine, critical for allergic response

IgD

  • small amounts secreted, usually bound to B cell surface

  • signals to mature and activate B cells

IgM

  • pentameric

  • 1st antibody made

  • good at complement maturation

  • high avidity

7
New cards

maturation of B cells

  • early B cells in the bone marrow

  • BCR locus is arranged as in T cells - heavy chain first then light chain

  • IgM is expressed on the surface

  • negative selection and receptor editing occurs befire the cells move to the periphery

  • IgD expressed on the surface

  • maturation begins in an antigen dependent fashion

  • class switching occurs as different antibody classes are made

8
New cards

role of the stromal cells

  • stromal cells (parts of the bone marrow that dont change) in the bone marrow are essential for the survival of B cell progenitors as they move from being heamopoetic stem cells and differntiate into b cells

  • first, VCAM1 on the stromal cells binds VLA4 on the B cell

  • this tethers the B cell to the stromal cell so signals can be transferred

  • the second stromal cell factor from the stromal cells binds cKit on the B cell. This triggers growth and differentiation of the cells

  • finally, IL7 from the stromal cells binds the IL7 receptor of the B cell

    • IL7 is a critical cytokine in the bone marrow and it supports the survival and proliferation of B cell progenitors

  • the B cell is then released into the periphery and VLA4 and cKit are downregulated

9
New cards

diversity of B cells

  • 10 billion different antibody molecules in each of us

  • BCR recombination drives diversity

  • only occurs in B cells at the 3 loci that make up the antibody molecule

  • unlike T cells, B cells can change what they respond to

  • the 3 stages of recombination:

    • heavy chain recombination at stem cell stage

    • heavy chain recombination at early B cell stage

    • light chain recombination (where IgM expressed)

  • RAG genes are expressed for a little longer than needed so the B cells can change their antibody

  • sometimes overhanging gaps will lead to junctional diversity

10
New cards

antibody structure

  • antibodies have 3 complementarity determinoing regions in the variable region

  • CDR1 and CDR2 fall where V gene segment is located

  • CDR3 is the most variable and is formed by the heavy chain

  • this allows them to be hugely diverse —> in 1ml of plasma can estimate 110 variable gene segments, potential of 5×10^13 antobodies

  • lots of antibodies will have the same heavy chains but different light chains

11
New cards

negative selection

  • bout 75% of early B cells generated are self reactive

  • approx 33% are removed by receptor apoptosis

  • this is because theres a less comprehensive antigen display system in the bone marrow compared to the thymus

12
New cards

4 routes when B cells are produced in the bone marrow

  1. MULTIVALENT

    • B cells recognise self antigens

    • if theyre early enough in development can recombine RAG genes and try again

    • does not happen in T cells

  2. ANERGIC

    • if they dont produce a strong signal it becomes angeric in the periphery

    • could become active again if theres an overwhelming amount of inflammation

    • cross linking causes a stronger signal

  3. CLONALLY IGNORANT

    • weak signal from a rare antigen so the B cell wont see the antigen

  4. MATURE B CELL

    • no self reaction —> normal B cell

13
New cards

receptor editing

  • if an immature B cell recognises self antigen its surface IgM will cross link which drives a stronger signal through the cytoplasm

  • most of the time this signal leads to death by apoptosis

  • but if this happens early enough the right chain rearrangement process can continue and a new BCR can be made

  • this is receptor editing

14
New cards

anergy and clonal ignorance

  • like in t cells anergy in B cells is a state where cells continue to survive but are not responsive even if they see their cognate antigen

  • this is a way to get rid of autoreactive B cells after the early receptor editing stage is passed

  • anergy is an active process that requires signalling to maintain

  • anerguc cells have a shorter lifespan

  • they can be bought out of anergy in very severe infection

  • we know that they are mature because they express IgM and IgD

15
New cards

short ived and long lived plasma cells

SHORT LIVED

  • produce lots of antibodies before apoptosis

LONG LIVED

  • become long lived plasma cells which can produce either IgA, IgG or IgE and also can become memory B cells

16
New cards

t cell help

B cells respond to antigen in the thymus in either a t cell dependent way or a T cell independent way

THYMUS DEPENDENT

  • antigen can activate the t cell but it cannot be activated any further without a t cell which is delivered through CD40

THYMUS INDEPENDENT

  • everything required to activate the B cell is delivered by the antigen itself

  • only a few types of antigen can do this

  • typically polysaccharides with repeating sequences of sugars so they have multiple repeats of the same antigen

  • sugar epitopes bind surface IgM and IgD which cluster and a strong activation signal is generated

  • B cells release IgM and small amounts of IgD

  • only happens to mature B cells in circulation

17
New cards

t cell help

  • requires t cells which recognise the same antigen as B cells (linked recognition)

  • takes a long time as it acts to conserve energy unless neccessary

  • t cell delivers signals to B cells which provides the full activation (the main one is CD40 ligand on the t cell which activated Cd40 on B cell)

  • CD40 a key cytokkine and also triggers B cell proliferation

MECHANISM

  1. BCR binds epitope to antigen

  2. it then internalises this and digests it —> proteosome —> ER —> MHC2

  3. the B cell presents the antigen specific atibodies

  4. after teh B cells have turned into plasma cells they downregulate anything they dont need (MHC2)

18
New cards

B cell proliferation in germinal centres

  • IL5 and Il6 very important for proliferation of plasma cells in germinal centres

  • t cells have seen an antigen and move into the lymph node via blood vessel of HEV

  • they remain in the t cell zone, if they see their B cell then they get their signals

  • the B cells then move to the germinal centre

  • at first the germinal centres are very small but they grow as b cells proliferate (germinal centres are not present in lymph nodes with no signals)

  • the germinal centres formed 7-10 days after infection and around the germinal centres is the mantle zone which is made up of resting B cells from previous infections which gradually get displaced by active B cells

  • in the germinal centres B cells undergo 3 processes:

    • somatic hypomutation

    • affinity maturation

    • class switching

19
New cards

somatic hypomutation

  • mutation that happens in body cells and is not passed on

  • undergoes mutation 1 billion times more frequently than other cells —> random

  • mutations occur in segments that encode the complementarity determining region

  • particularly CDR3 which binds the epitope of the antigen

  • some new CDRs will bind antigen better than the orginal antibody

  • B cells can develop receptors with increased ability to recognise antigen (affinity maturation)

  • happens because point mutations are introduced into the V region of the light and heavy chin

  • cytidine deaminase deaminates cytosine to uracil and these uracil molecules will be removed.

  • this introduces nicks in the backbone which are repaird by an error prone DNA pol

  • it requires a single strand of DNA and often targets genes that are being actively transcribed E.g: ig genes

20
New cards

affinity maturation

  • as antibody V regions are mutated, B cells are selected based off the ability to bind antigen

  • as somatic hypomutation occurs, antibodies become more specific for antigen

21
New cards

vaccination

  • if we vaccinate aginst an antigen when cells see it agin they can repsond much faster

  • as the humoral response progresses antibodies with higher affinity are produced

  • higher frequency, lower number of B cells

  • the type of antibody they release is changed and they produce the required antibody not IgM

22
New cards

class switching

  • class switching occurs through DNA recombination

  • changes to IgG, IgA, IgE during the immune response after t cell help

  • only occurs in t cell dependent B cells

  • allows different C region to be used in an antibody that has a specific antigen binding region

  • the constant region doesnt change unless the class is changed

  • in this case variable region stays the same as we still want to respond to the same antigen but we want to change the type of AB produced

  • DNA arrangements where the transcript for IgM is excised and forms a circle which is lost during mitosis

23
New cards

generation of diversity

IN THE BONE MARROW

  • antigen dependent

  • pairing of heavy and light chain

  • recombination

  • variability on the joins of the recombined gene segments

  • P & N region nucleotide addition

IN THE PERIPHERY

  • antigen dependent

  • somatic hypomutation

  • class switching and affinity maturation

24
New cards

role of antibodies

NEUTRALISATION

  • bind to soluble antigen and prvent it from working

  • swallowed up by phagocytic cells

COMPLEMENT

  • antibodies can bind and activate complement

  • causing complenet to form a membrane attack complex

OPSONISATION

  • bind bacterial cells

  • cause phagocytic cells to take up this complex

  • has Fc receptors that bind the constant region

25
New cards

Fc receptors

  • bind the Fc of Ig molecules

  • these receptors are specifc for diff antibody subclasses and isotypes

  • formed on many immune cells - Nk, mast cells, neutrophils, eosinophils

  • some of them phagocytose whatever Fc receptors triggered

  • other cells like Nk cells and mast cells release granules when Fc receptors are active

  • very specific to the subclass of antibody

  • some Fc receptors have an inhibitory negative effect on cells (ITIMs instead of ITAMs)

26
New cards

cytokine production

  • B cells much slower in cytokine production and its less of a critical function

  • niaive b cells dont make cytokines

  • produce chemokines to induce the migration of t cells as well as assist with t cell help

  • they can also produce cytokines which regulate the response of the immune cells around them

  • E.g: IL2 boosts T cell proliferation, IL2 is made by B cells

27
New cards

further maturation of B cells

  • surviving B cells within gthe germinal centres differentiate into plasma cells or memory cells

  • comtrolled by BLIMP 1 which switches off affinity maturation and proliferation

  • memory cells are long lived and have undergone affinity maturation

  • they have a BCR which is highly specific for an antigen but doesnt secrete antibody

28
New cards

plasma cells

  • secretes 2000 antibodies a second

  • downregulate MHC 2

  • dont class switch and undergo no further maturation

  • short lived

29
New cards

memory B cells

  • antigen specific memory cells respond to antigen rapidly and proliferate much faster than niaive b cells

  • the antibodies they make are higher affinity and also continues to increase throughout the secondary response

  • IgG is produced more quickly in primary challenges

  • less IgM is produced as the cells have already switched classes

30
New cards

dysregulated B cell response

  • most ommon is systemic lupus erythmatosus

  • in healthy people B cells which make antibody to self proteins are deleted but in SLF this goes wrong and B cells survive which means antibodies to nuclear components are made

  • patients have more B cells and more memory cells which have a lower activation threshold

  • the antibodies to DNA/RNA form immune complexes which miust be disposed of, most commonly in the kindey which causes tissue damage