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Immunology Exam 2 > Lecture 3 > Flashcards

Lecture 3 Flashcards

1
Q

What antibodies do naive B-cells express?

A

IgM IgD

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2
Q

What are the phases of the humoral immune response?

A
  1. Antigens bind to IgM and IgD (B-cell receptors) on a naïve B-cell, causing it to become activated.
  2. Under the influence of helper T-cells, and other stimuli, the activated B-cell (B-cell clone) proliferates and differentiates.
  3. Activated B-cell can:
  • a. Become plasma cells that secrete IgM
  • b. Undergo isotype switching and become a Ig-G expressing B-cell.
  • c. Undergo affinity maturation, creating antibodies with increasing affinity for the antigen.
  • d. Create memory B cells.
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3
Q

Compare our primary and secondary immune response.

A

will differ in quality and quanitity

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4
Q

What happens during our primary immune response?

A
  1. Antigens activate naïve B cells.
  2. Activated B-cell will then differentiate into plasma cells that release IgM>IgG.
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5
Q

What happens during our secondary immune response?

A

Secondary immune response- the same antigen will stimulate the memory cells that we made in our primary immune response, leading to the production of IgG>IgM.

  • More antibodies are made.
  • Isotype switching occurs
  • Affinity maturation (increasing affinity) occurs.
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6
Q
A

Secondary responses has higher average affinity due to affinity maturation.

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7
Q

[Q:] What is the predominant antibody isotype in our primary response and our secondary immune response?

A

Primary- IgM

Secondary- IgG and sometimes IgA/IgE.

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8
Q

[Q:] What induces the primary response?

A

All immunogens.

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9
Q

[Q:] What induces the secondary response?

A

Mainly protein antigens.

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10
Q

Types of B cells

A
  1. Follicular B2 cells
  2. Marginal zone B cells
  3. B1 cells
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11
Q

Follicular B2 Cells

Where are they located?

T-cell dependent/independent?

Bind:

Produces:

A
  • Circulate in spleen and other lymphoid organs
  • T-dependent
  • Bind: protein antigens
  • Becomes a long lived plasma cell that have undergone isotype switching (IgG, IgA and IgE) and have a high affinity.
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12
Q

Marginal Zone B Cell

Where are they located?

T-cell dependent/independent?

Bind:

Produces:

A
  • Circulate in spleen and other lymphoid organs
  • T-independent
  • Bind: multivalent antigen
  • Becomes short-lived plasma cell that releases IgM
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13
Q

B1 B Cell

Where are they located?

T-cell dependent/independent?

Bind:

Produces:

A
  • Located mucosal sites, peritoneal cavity
  • T-independent
  • Respond to: multivalent antigens
  • Becomes short-lived plasma cell that releases IgM
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14
Q

_____ are widely distributed throughout the body and continually replaced from the bone marrow.

A

B2 B-cells

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15
Q

Name that cell.

Diversity is high.

Memory- yes

Underwent isotype switching

A

B2B cell

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16
Q

B1 B-cells

Arise from what?

Where are they located?

A

Arise from the fetal liver by the 8th week of gestation.

Respiratory and GI system.

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17
Q

Name that cell:

Diversity is low

Memory- very little

Undergo limited isotype switching

A

B1 B-cells

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18
Q

What cells bridge the innate and adaptive immune system?

A

B1 B cell

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19
Q

In order to initiate a antibody response, the antigen must be transported where?

A

Where B-cells are located: LN or spleen

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20
Q

B2 B cells are located in follicles in our LN. How do they get there?

A

B2 B cells (aka recirculating B cell) recirculate in our blood from one to another secondary lymphoid organ.

  • Once in the secondary lymphoid organ, they go to the B-cells zones (also called follicles) using CXCL13, a chemokine secreted from follicular DCs, as a guide
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21
Q

What is CXCL13?

A

A chemokine released from follicular DC that guide B2 B cells home (into the follicles of LN).

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22
Q

How do antigens get delivered to the Follicular B2 B cell, located in the follicle of LN?

A

Antigens can be delivered in many forms and many routes.

  1. Afferent lymphatic vessels that drain into the subscapular sinus of the LN.
  2. Soluble antigens (smaller than 70kD) can interact directly with B-cells in the follicle.
  3. Large antigens are transported to the follicles by resident FDCs.
  4. Pathogens and Ag-Ab complexes are captured by subscapular sinus macrophages, and deliver the antigen to the follicle.
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23
Q

Properties of FDCs

A
  • They do not express class II MHC.
  • Do not phagocytose exogenous antigens and express them on class I MHC.
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24
Q

What do FDCs do then?

A
  1. Secrete CXCL13 to help B cells and follicular T-helper cells migrate to the follicles.
  2. Can have [immune Ag-Ab complexes] on their surface for long periods of time.
  3. They play an important role during the germinal center reaction, as they release the substrate that drives affinity maturation
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25
Q

What cells are located in the marginal zone (MZ) of the spleen?

A
  1. MZ macrophages
  2. Marginal B cells
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26
Q

What forms the framwork of the marginal zone?

A

Fibroblasts.

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27
Q

How can lymphocytes and DCs can enter the white pulp?

A

To enter white pulp:

Pass through the cells that line the marginal sinus, which forms the barrier between the marginal zone and white pulp.

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28
Q

Marginal zone B cells that are located in the spleen can send antigens into the follicular region for Follicular B2 cells. How?

A
  1. An [immune complex] binds to the C2 compliment receptor on the MZ B cell.
    • Immune complex contain and antigen and has compliment fragments
  2. MZ B-cell will then take it to the follicular region.
  3. In the follicle, FDC cells (which have a high level of CR) complete with MZ B cells for binding of the complex.
  4. Immune complex is trasferred to the FDC.
  5. MZ B cells then go back to the marginal zone.
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29
Q

How do MZ B Cells recognize antigens in the spleen?

A

MZ B cells recognize antigens in their native conformation. Thus, they are not processed by APCs.

    1. If the antigen is a part of the immune complex, it can bind to the CR2 compliment receptor.
    1. Plasmacytoid DCs take up pathogens in blood –> spleen –> take to MZ Bcells
    1. MZ macrophages in the spleen take up polysaccharide antigens and displayed them or take to MZ B-cells
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30
Q

When an antigen binds to a B-cell, what can happen?

(Antigen-dependent process)

A
  1. B-cell will express proteins that promote survival and cell cycling–> increased survival and proliferation
  2. Increased B7 expression–> causes B cell to interact with helper T-cell
  3. Increased expression of cytokine receptors–> increases responsiveness to cytokines
  4. Increased expression of CCR7–>migrates from follicle–> T-cell zone.
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31
Q

What are the components of the B-cell receptor complex?

A
  1. BCR–> transmembrane antibody
  2. Igalpha and Igbeta

Coreceptors: CD19, CD21, CD32 (not a part of the complex, but associate with the complex)

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32
Q

What BCR do naive B cells have?

A

IgM or IgD

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33
Q

If is a naive B-cell class switches, what does it switch to?

A

IgG, IgA, IgE

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34
Q

What are Igalpha and Igbeta?

How are they linked together?

How are they associated with the BCR?

What is special about them?

A

Invariant signaling molecules that are a part of the BCR receptor complex.

  • Linked together by disulfide
  • Noncovalently associated with the BCR
  • Have ITAMs on their cytoplasmic tail, which mediate the signaling molecule
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35
Q

Describe how the co-receptors associate with the BCR complex.

A

They associate with the BCR complex, especially when they are linked through [Ag-complement or Ag-Ab complex].

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36
Q

What is the purpose of co-receptors?

A

Depending on which co-receptors are used, the signaling of the complex can be enhanced or inhibited.

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37
Q

Coreceptor CD19

A

The dominant signaling component of B-cell

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38
Q

Co-receptor CD21

A

CD21 is the compliment receptor 2 (CR2)

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39
Q

Co-receptor CD21/19

A

Together, they positively regulate B cell activation and lower the Ag threshold for B-cell activation

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40
Q

CD32 (FcyRIIIB)

A

contains ITIM and negatively regulates BCR signaling

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41
Q

BCR signaling pathway to activate

A

In B-cells, to initiate a signal you need to bring together (cross-link) two or more BCR (Igs).

  1. Antigen (signal 1) + costimulatory molecule (signal 2) bind to the cross-linked BCR receptor and activate.
  2. BCR complex initiate signaling
  3. Src kinases (lyn, fyn, blk), which are lipid anchors, phosphorylate ITAMs on Igalpha and Igbeta.
  4. BCRs enter lipid rafts, where many adaptor and signaling molecules are located
  5. SH2 domains of Syk tyrosine kinases bind onto the phosphorylated ITAMS and are activated by Src kinases.
  6. Activated Syk phosphorylates tyrosine residues on BLNK (B cell linker protein).
  7. It recruits other enzymes, which activate Ras and Rac, PLCy2 and the Btk (bruton tyrosine kinase)
  8. Activates the following signaling pathways
    1. Ras-MAP kinase pathway
    2. PLC pathway
    3. PKC-B pathway

End result: activation of the B cell.

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42
Q

What is CD21 (CR2) and its role in B cell activation?

A

B-cells have a complex made up of [CR2 (CD12) compliment receptor and CD19-CD81]. CD19 contains ITAMS.

A pathogen opsonized by C3d can bind to both the CR2 receptor and BCR, greatly enhancing B-cell activation.

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43
Q

How does the microbe antigen get opsinized by C3d?

How does [microbe antigen+ C3d] become bound?

A
  1. C3 –> C3a and C3b.
  2. C3b will bind to the microbe.
  3. C3b –> C3d.
  4. CD2 (CD21) is a receptor on the B cell for C3d.
  5. Thus, [C3d+Ag] binds to B-cells, with the BCR recognizing the antigen and the CR2 recognizing the C3d.
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44
Q

CR2-CD19-CD81 is often called what?

A

B-cell coreceptor complex

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45
Q

What is the mechanism of CR2 signaling?

A
  1. When C3d-CR2 binds, CD19-CD81 moves close to the BCR associated kinases.
  2. CD19 cytoplasmic tail becomes tyrosine phosphorylated.
  3. Follows the recruitment of Lyn kinase, which amplifies BCR signaling.
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46
Q

PAMP recognition + TCR signaling can activate B-cells as well. How?

A

TLRs and their PAMPs can activate B cells by activating NF-kB signaling cascade.

Microbial antigen will bind to Ab, causing BCR signaling. At the same time, TLR can recognize PMP and undergo TRL signaling, activating the NF-kB signaling cascade.

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47
Q

Research on TLR signaling in B cells has generated enormous interest. Why?

A

Because of its potential use in vaccines.

When a Bcell is stimulated with a TRL ligand–> B-cell proliferation and differentiation–> plasma cells.

Thus, TLR signaling in B cells accounts for adjuvant (booster) effect in any immunizations.

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48
Q

Antigen stimulation induces the ____ phase of the humoral response.

A

EARLY.

Antigen activated B cells causes proliferation, differentiation and can also secrete IgM, inducing the early phase of the humeral immune response.

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49
Q

B cell activation by antigen (and other signals) initiates the proliferation and differentiation of the cells and prepares them to interact with helper T lymphocytes if the antigen is a ________.

A

PROTEIN

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50
Q

What are the functional consequences of B-cell activation by an antigen?

A
  1. Activated B-cells can express protein that increase survival and proliferation.
  2. Activated B-cells can present antigens and B7, causing them to interact with helper T-cells.
  3. Activated B-cells can increase expression of cytokine receptors to increase the responsiveness to cytokines.
  4. Activated B-cells can increase expression of CCR7, causing the migration from follicle–> T-cell zone.
  5. Activated B-cells can generate plasma cells and secrete antibodies (IgM)
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51
Q

Explain the mechanism of how B-cells present Ag to T-cell.

A
  1. Activated B cells endocytose protein antigen that binds specifically to the B cell receptor, resulting in degradation of the antigen and display of peptides bound to class II MHC molecules.
  2. The helper T-cell recognizes the MHC-peptide complex on the B-cell
  3. Activated helper T-cells begin to express CD40L and secrete cytokines
  4. Both bind to their receptors on the same B-cell and proliferation and differentiation.
    * a. Short-lived plasma cells that produce IgM are generated
  5. B cells then migrate to germinal centers and undergo germinal center reaction
  • a. Somatic mutation
  • b. Affinity maturation
  • c. Isotype switching
  • d. Generation of memory B cells
  • e. Long-lived plasma cells that make IgG, IgA, IgM, IgE.
  1. B cells that have been activated by T helper cells at the edge of a primary follicle migrate into the follicle and proliferate, forming the dark zone of the germinal center . Germinal center B cells that underwent [isotype switching and somatic mutation]à light zone, where B cells with the highest affinity Ig receptors are picked to survive and differentiate into plasma cells or memory cells, which leave the germinal center.
52
Q

Extrafollicular B-cell reaction

Occurs where?

What are the T-cells involved?

Characteristics.

A

Occurs: medullary cords of the LN, between the [T-cell zone and red pulp] of the spleen

T cells involved: extrafollicular helper T-cells

  • Limited class switching occurs
  • Somatic mutation rate is low
  • Antibody affinity is low
  • Terminally differentiated B cells: Short lived plasma cells with a life span of 3 days.
53
Q

Follicular/Germinal center B-cell reaction

Occurs where?

What are the T-cells involved?

Characteristics.

Terminally differentiated B cells:

A

Occurs: Secondary follicles

T-cells involved: TFH cells in the germinal center

  • Extensive class switching occurs
  • Somatic mutation rate is high.
  • Antibody affinity is high

Terminally differentiated B cells: long-lived plasma cells, which migrate to the bone marrow or MALT and memory cells

54
Q

generation of TFH cells requires what?

A

sequential activation of T cells by

  1. Dendritic cells
  2. Activated B cells
55
Q

After TFH cells are formed, whatt happens?

A

–>[germinal center]–> activate B cells.

56
Q

TFH cells secrete ____, which is required for GC development and generation of plasma cells.

They also secrete______, which controls isotype Th1/Th2 switching.

A

IL-21

IFN-y or IL-4

57
Q

B-cells cause previously activated T-cells to _____________

A

become TFH cells 4-7 days after antigen exposure

58
Q

TFH cells are important in GC formation and function and the activation and differentiation of B cells in these reactions. why

A

they express:

  1. ICOS (inducible costimulatory)
  2. PD-1 (programmed death-1)
  3. IL-21
  4. Transcription repressor (Bcl-6)
59
Q

The germinal center is located within the follicle of a LN and has 3 zones:

A
  1. Dark zone- contains proliferating B cells
  2. Light zone- contains follicular DC cells
  3. Mantle zone- surrounds GC and contains tightly packed small B cells of the primary follicle, pushed aside by GCs
60
Q

Activated B cells–> _______–>__________; forms a dark zone.

Here, what happens?

A

follicle–> proliferate

These B-cells undergo somativ hypermutation.

61
Q

From the dark zone, B cells –> [_____ zone] –> encounter [follicular DCs with antigen] & [TFH cells].

what happens?

A

light zone

  • isotype switching
  • affinity maturation- B cells wil highest affinity survive and become plasma cells and memory B
62
Q

what b cells survive and differentiate into

  • Plasma cells

Memory B cells

A

B cells with the highest affinity Ig

63
Q

fate of plasma cells made in light zone?

A

leave and live in bone marrow as long lived plasma cells

64
Q

fate of memory B cells made in light zone?

A

enter recirculating lympcyte pool

65
Q

Heavy-chain isotype switching is induced by a combination of _______, _______ and ______ released from ____ cells. It occurs in germinal centers and allows plasticity in the humeral immune response.

A
  • CD40L signals
  • AID (activation-induced deaminase) activation by CD40
  • cytokines

TFH

66
Q

Heavy chain isotype switching occurs in ________ and allows ____ in the humeral immune response.

A

germinal centers

plasticity

67
Q

In isotype switching, what changes?

A

Constant regions of the heavy chains are changed to switch the class of the antibody

68
Q

_____ induces IgG switching.

How?

A

IFN-y

  1. Intracellular pathogens activate Th1 cells –> IFN-y
  2. causing TFH cells–> IFN-y.
69
Q

______ induces IgE switching.

How?

A

IL4 via TH2

Helminths cause TFH cells to release IL-4, which makes Th2 type cytokines during the germinal reaction

Eliminates helminths, working with eosinophils and mastcells.

70
Q

B-cells in different anatomic sites switch to different types of antibodies, controlled by the _____ at that site.

A

cytokines

71
Q

For example, B cells in mucosal tissues will switch to _____, where they protext epithelial cells from interacting with micbrokes.

A

IgA

72
Q

_________ stimulates a switch to IgA.

A

TGF-B (made by Treg cells and macrophages)

73
Q

[Q:] What happens in immunodeficiencies related to the CD40-CD40L axis?

A

Isotype switching cannot occur.

74
Q

The molecular mechanism of isotype switching, called __________, takes the previously formed VDJ exon encoding the V domain of an Ig μ heavy chain and moves it adjacent to a down- stream C region

Both isotype switching and affinity maturation are critically depend on _____________

A

class- switch recombination

AID

75
Q

How does CSR work?

A
  • Mature B cells first produce IgM immunoglobulins
  • Occurs in constant region of heavy chain and is regulated by cytokines.
  • Every C gene is preceded by a switching (S) sequence that controls the rearrangement process. CSR is proceeded by the expression of germline transcripts. The germline transcripts open the S region and make it accessible to recombination.
  • CSR takes place between two SWITCH REGIONS (S), which has repetitive sequences of palindrome‐rich sequnces. DNA in between is cut out.
76
Q

CSR is a “SWITCH” of the immunoglobulin isotype from IgM/IgD to IgG, IgA or IgE, with ______ Ag specificity but with ______ biological properties

A

similar

different

77
Q

What is affinity maturation?

A

The process where the affinity of antibodies made in response to a protein antigen increases with prolonged or repeated exposure.

78
Q

Affinity maturation is seen only in responses what?

A

T–dependent protein antigens.

79
Q

Because of affinity maturation, the ability of antibodies to bind to a microbe or microbial antigen increases if what?

A

the infection is persistant or recurrent

80
Q

This increase in affinity is caused ____________, and particularly in the antigen-binding _________ regions, of the genes encoding the antibodies produced.

A

by point mutations in the V regions

hypervariable

81
Q

Affinity maturation occurs in the germinal centers of lymphoid follicles and is the result of what?

A

Somatic hypermutation of Ig V genes in dividing B cells, followed by the selection of high-affinity B cells by antigen.

82
Q

Why are mutations in IgV genes called somatic hypermutations?

A

In proliferating B cells in the dark zone of the GV, Ig V undergo point mutations at a extremely high rate: 1 in 10^3 base pairs, which is 1000x higher than spontaneous mutation. VH and VL genes each have about 700 nucleotides, resulting in 1 mutation/cell division.

83
Q

Ig V gene mutation occur in the progeny of individual B cells. Thus, any B cell clone can gain more mutations during the life in the germinal center. IgG anitbodies from one clone of a B-cell can have as much as ____ of its germline sequence mutated (10 aa substitutions.

A

5%

84
Q

Which have more mutations: IgM or IgG

A

IgG

85
Q

_____________ wil result from somatic hypermutation?

A

affinity maturation

86
Q

How do we select what B cells survive?

A
  • Only B cells with high affinity for antigens on follicular DCs are selective to survive.
  • B-cells can also present antigens to germinal TFH cells, which uses CD40 to help B-cells survive.
87
Q

Where do B cells die?

A

B-cells also die in germinal center because somatic mutation creates many B cells that do not have high affinity.

88
Q

B cells that have undergone somatic mutation go where?

A

Follicular DC rich light zone.

89
Q

B-cells with high affinity receptors are best able to bind the antigen when it is present at low concentration. B cells survive because of several mechanisms:

A
  1. Antigen recognition causes the B cells to express anti-apoptotic proteins of the Bcl-2 fam.
  2. They will endocytose and present the antigen to TFH cells in the germinal center, which signal via CD40L to promote the survival of B cells.
  3. Can activate endogenous inhibitors of Fas and be protected from death.

Some TFH express FasL, which recognize Fas on B cells and causes apoptosis.

90
Q

B cell lymphomas develop from B-cells located where?

A

Germinal center.

91
Q

What happens in B-cell lymphomas?

A

When DNA breaks in somatic mutation and isotype switching, oncogenes translocate (sneak) in the Ig.

92
Q

_______ may also contribute to autoimmunity.

A

Germinal center.

Somatic mutation can produce a self-reactive B cell clone in GC. Thus, SM is not perfect

93
Q

Memory cells are made in the GC for ________ protein antigens.

A

T-dependent

94
Q

Memory B cells are able to survive for long periods to time, without being stimulated by an antigen. How?

A

Express high levels of Bcl-2, an anti-apoptotic protein.

95
Q

Do memory cells B cells have BCRs?

A

They have high affinity and Ig molecules are of switched isotypes (anitbodies other than IgM or IgD).

96
Q

After secondary exposure to an antigen, antibody production ___________

A

greatly increase thanks to the activation of memory cells.

97
Q

fate of memory B cells

A
  1. stay in lymphoid organ
  2. recirculate between [blood and lymphoid organ].
98
Q

What are TI (thymus independent) antigens?

A

Many non-protein antigens, stimulate antibody production in the absence of Th cells.

They are usually low affinity and mainly consist IgM, with limited isotype switching to some IgG subtypes and IgA

99
Q

Properties of TD antigens

A
  • Proteins
  • Undergo isotype switching (IgM –> IgG, IgA, IgE)
  • Undergo affinity maturation
  • Make memory B cells
100
Q

Properties of TI antigens

A
  • Non-proteins
  • Low level of isotype switching
  • Little or no affinity maturation
  • Only some polysaccharide antigens make memory cells.
101
Q

Most TI antigens are _____valent

A

mutlvalent

Thus, they have repeated identical epitopes–> cross-linking of the BCRs–> activation without help from T-cells.

102
Q

TI Ab responses may be initiated where?

A

spleen, bone marrow, peritoneal cavity, and mucosal sites.

103
Q

-The ________ and ________ are important for antibody responses to TI antigens.

A

MZ B cells

B1 B cells

104
Q

MZ B cells in the spleen mainly respond to ______. After activation, they differentiate into what?

A

polysaccharides

short lived plasma cells–> igM

105
Q

B1 B-cells respond to TI antigens in the what?

A

peritoneum and mucosal sites

106
Q

The most important TI antigens are what?

A

polysaccharides

glyolipids

nucleic acids

107
Q

How do TI antigens (polysacharides, glycolipids and nucleic acids) activate B cells?

A

through polysaccharides activate the complement system via the alternative pathway C3b–> [binds to antigen] –> processed into C3d, which is recognized by CR2 on B cells.

-PAMP will activate TRL on B cell

108
Q

What can stimulate isotype switching in T1 responses?

Some TI antigens can induce Ig isotype switching (other than IgM). GIve an example

A
  1. Some TI antigens can cause Ig isotype switching.

Ex

pheumoccocal capsular polysaccharide induces IgG2.

  1. Cytokines. Ex. TGF-B induces IgA switch
109
Q

how do we produce AID?

A

DC and MO release BAFF.

This is facilitated by the activation of TLRs on B cells

110
Q

How do TI Antibodies protext us?

TI antibodies are antibodies that are not released in response to a CD4+ T-helper cell.

A
  1. Most TI antigens are polysaccharides of encapsulated bacteria. Humoral immunity is the major mechanism of defense against encapsulated bacteria. If people have immundeficiences of humoral immunity, they are susceptible to life bacterial infections.
  2. TI antigens also make NATURAL antibodies.
111
Q

What are natural antibodies?

A

Natural antibodies are present in the circulation of normal people without overt exposure to pathogens.

Most are low affinity anti-carbohydrates antibodies, made by peritoneal B1 cells in the GI tract and MZ B-cells in the spleen.

112
Q

Effective vaccines against microbes and toxins must: _________ and _________

A

cause affinity maturation and

form memory B cells.

113
Q

memory only occurs if the vaccine can do what

A

activate helper T-cells.

114
Q

How do we make vaccines for capsulate polysaccharide , which ccannot stimulate T cells?

A

Polysaccharide is linked to a foreign protein to form a hapten-carrier conjugate.

They then bind MHC molecule and activate the TCR directly or function as an anchor for a sugar epitope.

Such vaccines, called conjugate vaccines, more readily induce high-affinity Abs and memory cells

115
Q

Conjugate vaccines induce long-lived protective immunity. How?

A

Rapid and large secondary repsonses similar to memory (but without much isotype switching or affinity maturation) may occur on secondary exposure to the carbohydrate antigens.

116
Q

Why is B-cell activation is tightly controlled

A

to avoid collateral damage and prevent reactions against self-antigens

117
Q

Inhibitory receptors structure

A

extracellular ligand binding domain and a cytosolic ITIM motif.

When a ligand binds, ITIM tyrosine is phosphorylated by Src family kinase.

118
Q

Inhibitory r signaling on B cells

A
  1. ligand binds
  2. Src family kinase phosphorylates ITIM tyrosine.
  3. SH2 domain containing tyrosine phosphatases bind to the p-ITIM and inhibit signal.
119
Q

CD32 is also called?

A

FcyRIIB

120
Q

What does FcyRIIB do?

A
  1. Inhibitory receptor in B cells.

  1. Attenuates signaling in activated DCs and macrophages
121
Q

How are cells regulated by FcyRIIIB?

A
  1. Ag-Ab complex binds to [BCR and FcyRIIB] via the Fc portion of the antibody.
  2. Src kinases phosphorylate ITIM
  3. p-ITIM recruits SHP and SHIP (tyrosine phosphotases with an SH2 domain)
  4. PIP3–>PIP2, blocks BCR signaling and activation by inhibiting PIP3 kinase activity in [lymphocytes, NK cells, innate immune cells]
122
Q

What is antibody feedback?

A

Where a secreted antibody blocks the production of antibodies.

123
Q

Purpose of antibody feedback

A
  1. Stop the humeral immune response once we have enough IgG being made.
  2. Prevents attacks to self antigens.
124
Q

A polymorphism in in the gene that encodes FcyRIIB would lead to what?

A

Lupus erythematosus

125
Q

[Q:] If a mice had a KO gene for FcyRIIB, what would we see?

A

Uncontrolled antibody production

126
Q

We do not clear of situations where secreted antibodies provide compliment-mediated amplification or Fc receptor-mediated inhibition. What is a likely scenario?

A

A likely scenario is that IgM that activate compliment but do not bind to the FcyR are involved in amplication, wherease increasing production of IgG leads to feedback inhibition.

Immunology Exam 2 (10 decks)

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