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Immunology > Week 5: B Cell Activation > Flashcards

Week 5: B Cell Activation Flashcards

1
Q

What do mature B cells have?

A
  1. BCR (Ig)
  2. Circulate in the blood, lymph, and the lymphoid organs until they encounter antigen (Ag)
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2
Q

What happens to the B cell when antigen is stimulated?

A

B cell will create many clones bearing the same Ag receptor (BCR,Ig) undergoing clonal selection and expansion

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3
Q

What do B cell clones do?

A

Become plasma cells and memory B cells bearing the same Ag receptor

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4
Q

Describe the process of antibody production by B cells?

A
  1. DC take antigen to draining LN and activate antigen-specific naive T cells
  2. T cells proliferate and differentiate to effector T cells
  3. Tfh stay in LN and interact with activated B cells
  4. Gives rise to plasma cells that secrete antibodies specific to antigen
  5. Antibodies exit the draining LN through efferent lymphatic vessel and into circulation
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5
Q

What are the goals of the B cell response?

A
  1. Following B cell activation and clonal expansion, some of these B cells will quickly make antibody (low affinity IgM antibody is made first)
  2. B cells then undergo a series of changes in order to generate higher affinity and isotype-switched antibodies
  3. Memory cells are generated to provide long-term protection
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6
Q

What is an epitope?

A

The part of antigen that an antibody/BCR binds

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7
Q

What are the components of an epitope?

A

Protein, carb, lipid

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8
Q

What is a multivalent antigen?

A

An antigen that contains more that 1 epitope or multiple copies of the same epitope

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9
Q

What are the outcomes multivalency?

A

Increased avidity that combines strength of binding of multiple interactions

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10
Q

How many CDRs does an antibody have?

A

6

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11
Q

How does the number of CDRs affect the antibody?

A

Used to contact a given antigen varies based on the properties of the antigen

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12
Q

What are the groups of epitopes?

A

Linear and discontinuous

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13
Q

What is a linear epitope?

A

Composed of several successive amino acid residues

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14
Q

What is a discontinuous epitope?

A

Formed from 2 or more parts of the protein antigen that are separated in the amino acid sequence but are brought together in the tertiary structure of the folded protein

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15
Q

Describe the process of cross linking of surface Ig?

A
  1. Surface IgM (BCR) on a naive B cell binds to protein, lipid, or carb epitopes of the antigen on the surface of a microbe
  2. Multivalent antigens are able to bind to multiple membrane bound IgM (mIgM) causes cross linking
  3. Clustering and aggregation of the BCRs are due to cross linking leading to the sending of signals to the inside of the B cell through IgA and IgB of BCR
  4. Signaling leads to gene expression changes that intimate B cell activation
  5. Additional signals are required to activate the B cell
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16
Q

Describe the components of the B cell co receptor?

A
  1. CR2-(CD21) can bind complement components fixed on pathogen
  2. CD19-acts as the signaling chain in interactions with Iga and Igb of BCR
  3. CD81-brings CD19 to the surface and organizes the co-receptor on the membrane
  4. Increases the signal through the BCR by 1000 to 10,000 fold and increases the B cells sensitivity to the antigen.
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17
Q

What are B cell response by distinct antigen types?

A

T dependent responses
T independent responses

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18
Q

What is TD response?

A
  1. Requires help from T cells (CD4+)
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19
Q

What is TI responses?

A

Doesn’t require T cell help (TI-1 and 2 antigens)

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20
Q

What is a T independent antigen?

A

Stimulates antibody production without the need for T cell help

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21
Q

What are the classes of B cells that mediate with T independent antigens?

A
  1. B1-B cells
  2. Marginal zone B cells
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22
Q

What are B1-B cells?

A

Produce IgM antibodies independent of T cell help that bind a broad spectrum of Ag with low affinity

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23
Q

What are marginal zone B cells?

A

Specialized to respond to blood-borne Ag entering interacting with the immune cells in the spleen

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24
Q

Where are the typical TI 1 antigens found?

A

Bacterial cell walls: LPS on G- bacteria

25
Q

Describe the interaction between TI cell and 1 antigen?

A
  1. Antigen binds to the BCR
  2. Antigen binds to innate immunity pattern recognition receptors (PRRs) on all B cells
  3. Primarily Toll-like receptors: TLR4 recognizes LPS and is associated with septic shock
  4. Generates antibodies that are not highly specific for the TI-1 antigen: Polyclonal antibody response
26
Q

Where are the typical TI 2 antigens found?

A
  1. Polymeric protein antigens
  2. Capsular bacterial polysaccharides
  3. Polymeric flagellin
27
Q

Describe the binding between TI b cells and TI-2 antigens?

A
  1. TI-2 antigens bind to and crosslink many IgM BCRs
  2. TI-2 antigens typically have bound complement fragments (i.e. C3d, iC3b)
  3. TI-2 antigens can crosslink BCR and CR2 (CD21) of the B cell co-receptor
  4. Interaction with T cells can push TI-2 activated cells to produced isotypes of antibody other than IgM
28
Q

Describe the 2 responses of TD-Bcells when they migrate to the lymphoid follicles?

A
  1. B cells can interact with antigen and become activates
  2. If the B cell does not come into contact with their antigen, the B cell recirculates through the blood and lymphatic systems and then travels back to the lymphoid follicle.
29
Q

What are the pathways of TD activation?

A
  1. Antibody producing plasma cells (primary focus)
  2. Low affinity memory cells
  3. Enert germinal center to participate in the germinal center reaction
30
Q

Where do naive B cells migrate to, to achieve TD responses?

A

Lymphoid follicles

31
Q

What is produced in the primary focus?

A

IgM antibodies

32
Q

What is produced by low affinity memory cells?

A

IgM-bearing memory cells

33
Q

What does the B cells do in the germinal center?

A
  1. Clonal expansion of B and Tfh cells
  2. Somatic hypermutation (SHM): generating high-affinity antibodies
  3. Isotope switching: generates isotopes other that IgM
34
Q

Where are antigens most concentrated?

A

LN and spleen

35
Q

Describe the encounter of antigen in LN and spleen?

A
  1. FDC concentrate antigen to activate B cells
  2. T cells encounter antigen presented by DCs, proliferate and differentiate into effector T cells (TFH cells)
  3. When the BCR binds its antigen, it undergoes receptor mediated endocytosis to present antigen in MHC class II molecule
36
Q

Describe the process of TD B cell prior to binding to BCR?

A
  1. B cell is now acting as an APC.
  2. Protein antigen bound to BCR and is endocytosed and digested in the lysosome into peptides.
  3. Peptides loaded on MHC class II molecules and then travel to the surface of B cells.
  4. T cells move to boundary between B and T cell area.
  5. B cells present antigen through MHC II
  6. B cells form conjugate pairs with TFH with same antigen specificity
37
Q

Describe TD B cell activation when bound to antigen?

A
  1. Antigen binds and crosslinks BCR
  2. CD40 on B cells binds to CD40L on T cell
  3. Tfh cell secretes activating cytokines inducing division and differentiation of the B cell: Some activated B cells will become IgM-secreting plasma cells and others will go to the germinal center.
38
Q

What are the components of Antigen BCR crosslinks?

A
  1. MHC class II presents the peptide antigen to TH cells (primarily TFH cells)
  2. CD28 (activating co-stimulation signal) on T cell binds to B7 (CD80) on B cell
39
Q

What is a primary follicle?

A

B cell area of the LN

40
Q

Where does the TD B cell go once activated?

A

Primary follicle

41
Q

Describe the morphology of a primary follicle?

A

Becomes a secondary lymphoid follicle containing a germinal center

42
Q

When would germinal centers appear?

A

1 week after infection

43
Q

What occurs in the germinal centers?

A

B cells become centroblasts, large rapidly proliferating cells that are undergoing somatic hypermutation and isotype/class switching (dividing every 6 hrs)

44
Q

What are centrocytes?

A

Centroblasts that slowly mature and divide

45
Q

What are the outcomes of having centrocytes with high affinity?

A

Isotope switched Ig’s become plasma cells and memory cells

46
Q

Describe the process of somatic hypermutation?

A
  1. introduces point mutations in V regions to produce changes in the antibody binding region of the Ig.
  2. The goal is to make an Ig with better avidity
  3. Clones that fail to produce an Ig that can bind antigen after SHM are eliminated by apoptosis
47
Q

What is affinity maturation?

A

Mutated B cells with high affinity for the antigen are selected for survival and expansion

48
Q

What is the purpose of isotype/class switching?

A

Allows B cells to produce antibodies with a variety of effector functions

49
Q

Describe process of isotype switching?

A
  1. The distribution within the body and the effector function of the antibody is dependent on the heavy chain of the antibody.
  2. Does not affect antigen specificity! (Determined by V region)
  3. Requires CD40 on B cell to be bound to CD40L on T cell.
    4, Cytokines made by TFH cells determine which isotype is produced.
  4. Cytokines stimulate transcription of the heavy chain Constant (C) region gene
50
Q

What happens to antigen receptors that undergo SHM induced affinity maturation?

A

Antigen receptors improve and have increasing affinity for their antigen over the course of an infection

51
Q

What occurs after the second exposure of an antigen?

A

memory B cells possessing high affinity antigen receptors will respond

52
Q

Doe the affinity maturation process terminate after second exposure?

A

Continues upon each subsequent exposure to the antigen

53
Q

How does Tfh cells help differentiate B cells and plasma cells?

A
  1. Centrocytes in the GC will be influenced by cytokines produced by TFH cells to generate plasma cells or memory B cells.
  2. TFH cells produce IL-10 which allows for the differentiation of centrocytes into plasma cells which secrete high affinity antibodies.
  3. In the later stages of an infection, centrocytes are influenced by IL-4 secretion by TFH cells to differentiate into long-lived memory B cells.
  4. These memory B cells are isotype-switched and have high affinity antigen receptors
54
Q

Describe the difference between short lived (plasma blasts) and long-lived plasma cells?

A

S: produce IgM in the medullary cords on the secondary lymphoid tissue: has the capacity to proliferate
L: Produce high affinity isotope switched Ig

55
Q

Describe the general characteristics of plasma cells?

A
  1. Highly specialized cells for antibody secretion
  2. Secreted antibody is produced by a change in processing of the heavy chain mRNA (removes the transmembrane domain)
  3. No longer express surface Ig or MHC class II and therefore are unresponsive to antigen or T cells
  4. No longer undergo cell division
56
Q

Describe the properties of memory B cells?

A
  1. B cells that persist for a long period of time.
  2. Are generated from centrocytes in the germinal center as the primary immune response subsides
  3. Require only intermittent stimulation in a primary follicle
  4. Possess high-affinity isotype-switched antigen receptors
  5. Remain quiescent until reactivated by a subsequent encounter with the same antigen
  6. Allow a much quicker and stronger response to antigen than in the primary response
  7. Result in a repertoire –a collection of diverse B cell specificities
  8. Provide protection for a lifetime
57
Q

What occurs during primary response (initial exposure)?

A
  1. B cells become activated
  2. Differentiate to effector cells
  3. Secrete IgM
  4. Helper T cell interaction with B cells causing isotope switching
  5. Primarily this induces isotope switching from IgM to IgG
  6. At mucosal surfaces (gut, lungs), the switch is from IgM to IgA or IgE
58
Q

What occurs during secondary response (second exposure)?

A
  1. Due to memory B cells that have already undergone isotype switching.
  2. Memory B cells express more MHC II and costimulatory molecules so that they can more effectively present antigen to TFH cells.
  3. These memory B cells can re-enter the GC and undergo additional isotype switching, SHM, and generate higher affinity antibodies
59
Q

How does primary differ from secondary responses?

A

P: usually 5-10 days, smaller peak response, IgM>IgG, Lower affinity, more variable
S: 1-3days, Larger peak response, Increase in IgG by heavy change isotope switching, higher affinity (affinity maturation)

Immunology (17 decks)

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