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BISC 450 > Chapter 10 > Flashcards

Chapter 10 Flashcards

1
Q

What is required of naïve B-cell activation?

A
  • antigen recognition through the B-cell immunoglobulin receptor
  • clustering of membrane immunoglobulins on the cell surface
  • costimulatory signal to properly activate
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2
Q

What are the three polypeptides that makeup the B-cell coreceptor and their function?

A
  1. CR2: responsible for the binding required for costimulatory signal with iC3b and C3d
  2. CD19: contains a cytoplasmic domain that activates signaling cascades
  3. CD81: aids in the stabilization of the coreceptor complex
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3
Q

What must occur for CR2 to bind to the patohgen?

A

C3b that was fixed on the pathogen must be cleaved by the plasma protein factor 1 and CR1 to produce C3d.

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4
Q

How are ITAMs phosphorylated?

A

ITAMs on Igα and Igβ are phosphrylated by Blk, Lyn, and Fyn and allows for the recruitment of Syk

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5
Q

What follows the recruitment of Syk?

A

initiates two of three pathways through the activation of C-γ (PLC-γ) or phosphorylates and activates guanine-nucleotide exchange factors (GEFs)

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6
Q

What is the function of C-γ (PLC-γ)?

A

cleaves phosphatidylinositol bisphosphate to DAG and IP3

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7
Q

What is the pathway for IP3?

A
  1. IP3 activates calcium channels
  2. calcium activates clacineurin
  3. calcineurin removes phosphates from transcription factor NFAT
  4. dephosphorylated NFAT translocates to the nucleus and activates genes invovled in B-cell activation
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8
Q

What is the pathway for DAG?

A
  1. DAG leads to the activation of PKC
  2. PKC leads to the activation of NFκB by phosphorylation of IκB
  3. NFκB translocates into the nucleus and transcribe genes involved in B-cell activation
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9
Q

What is the pathway for GEFs?

A
  1. GEFs activate the small GTPases Ras and Rac
  2. triggering signaling through MAP kinase cascade
  3. activating Fos and Jun to form AP-1
  4. AP-1 translocates into the nucleus and transcribes genes involved in B-cell activation
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10
Q

What is the pathway for Igα and Igβ?

A
  1. Protein kinases Blk, Lyn, and Fyn phosphorylate ITAMs
  2. Phosphorylated ITAMs recruit protein kinase Syk to the membrane
  3. Syk phosphorylates C-γ (PLC-γ)
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11
Q

What signals the B cells to migrate from lymphoid tissue to lymphoid follicle?

A

follicular dendritic cells secrete CXCL13 to signal B-cell migration to the lymphoid follicle

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12
Q

What type of cells become activated without T-cell help?

A

T-independent (thymus-independent):
* B-1 cells
* Marginal-zone B cells

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13
Q

What is the mechanism of TI-1 antigens?

A

bind to an immunoglobulin and a pattern recognition receptor such as TLRs on the surface of the B cell

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14
Q

What is the mechanism of TI-2 antigens?

A

cause immunoglobulin clusters on the cell surface when enough immunoglobulin receptors bind with the antigen; are typically formed of repetitive units such as repeating polysaccharides

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15
Q

What type of cells become activated with T-cell help?

A

T-dependent (TD) B-cells
* B-2 B cell

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16
Q

What is the mechanism for TD antigens?

A
  • cannot activate B cell antibody production without T cell help
  • reocgnized by the B-cell receptor and internalized and processed via MHC class II processing
  • recognized by a T cell with a receptor capable of recognizing the same antigen
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17
Q

What signals must the T-helper cell provide to activate TD antigen-recognizing B cell?

A
  • cytokine signaling (IL-4)
  • cell-surface interaction between CD40 on the B cell and CD40 ligant on the T cell
18
Q

What do B cells have on the cell-surface to recognize TI-1 antigens?

A
  • cell-surface immunoglobulin (B-cell receptor)
  • pathogen associated molecular pattern (PAMPs) receptors
19
Q

What must B cells have to trigger B-cell activation after recognizing TI-2 antigens?

A
  • clustering of membrane immunoglobulins in close proximity
  • costimulation of the B-cell receptor
20
Q

What signals must B-cells have to trigger the degradation of TD antigens?

A
  • B cells takes up the antigen via receptor-mediated endocytosis
  • antigen is them processed and loaded on MHC class II molecules, which display peptides to CD4 T cells
  • if the T-cell receptor recognizes the MHC-peptide complex, the T cell causes B-cell activation
21
Q

What is the pathway of B and T cells to activation?

A
  1. B and T cells enter secondary lymphoid tissue through high endothelial venules (HEVs) and migrate to primary follicle
  2. Cells migrate to the T-cell zone, where they interact with APCs
  3. Activated B cells migrate to the cortex, while activated T cells undergo clonal expansion
  4. Activated B and T cells interact at the cortex, where they become a conjugate pair
22
Q

What are the characteristics of a conjugate pair?

A
  • CD40 ligand on the T cell binds to CD40 molecule on the B cell
  • Induces ICAM-1 expression on the B cell which then binds to LFA-1 on the T cell
  • T-cell cytokine secretion targets the B cell, leading to its activation
23
Q

What are the two fates after a conjugate pair forms?

A
  1. conjugate pair migrates from the secondary lymphoid tissue to the medulla, where B cells differentiate into plasma cells
  2. conjugate pair migrates from the secondary lymphoid tissue to the medullary cords and then to the lymphoid follicles, where B cells differentiate into centrocytes
24
Q

What is the primary focus?

A
  • conjugate pair migrates into the medullary cords
  • both cells are activated and undergo clonal expansion
  • B cell differentiates into a plasma cell that begins to express and secrete soluble IgM
25
What is the secondary focus?
* some conjugate pairs migrate to the lymphoid follicle * signals from follicular dendritic cells and the T cell of the conjugate pair drive B-cell activation and proliferation * signals provided to the B cell drive rapid division and differentiation into centrocytes * rapid division makes up the germinal center which causes lymphoid tissue swelling * AID begins to be expressed, activating somatic hypermutation and isotype switching
26
What is the purpose of somatic hypermutation within germinal centers?
alters the binding affinity of the original immunoglobulin on the B cell
27
What is the mechanism of somatic hypermutation in the germinal centers?
* activity of AID is random toward cytosine bases in the variable regions of the immunoglobulin genes * base changes can have a positive or negative effect on immunoglobulin affinity for its antigen
28
How are germinal centers tested for positive/ negative selection?
T cells, follicular dendritic cells, and macrophages within the germinal center all present antigens
29
What is positive selection in germinal centers?
* B cells with the highest affinity immunoglobulin gain survival signals (BAFF) * these cells process and present bound antigen from the follicular dendritic cells to helper T cells * helper T cells provide survival signals and inhibit apoptosis through expression of Bcl-XL
30
What is negative selection in germinal centers?
* self-reactive B cells within the germinal center that significantly interact with TH cells must be removed (apoptosis) or rendered inactive (anergy) to prevent autoimmune disease
31
How do centrocytes undergo isotype switching?
* cytosine deamination in switch regions of immunoglobulin heavy chain loci can drive isotype switching * AID activity requires single-stranded DNA as a substrate (DNA regions actively undergoing transcription or replication) * requires cytokines IL-4, IL-5, or TGF-β to direct transcription
32
What are the major functions of immunoglobulins?
* neutralization * protection of internal tissues * activation of innate immune cells * complement activation * clearane of small immune complexes
33
What is the mechanism of neutralizing antibodies?
* neutralizing antibodies can interact with both toxins and cell-surface molecules on pathogens to prevent them from interacting with target cells * bind to viral surface proteins and prevent their interaction with molecules in the cell membrane, blocking the life cycle of the virus * block exotoxin action by binding and preventing interactions with the target cell molecule
34
What are the Fc regions?
* constant regions of the heavy chains * drives effector function through Fc receptors on the surface of innate immune cells * Fc receptor binding to immunoglobulins enhanves the function of the cells expressing these receptors
35
What is the mechanism of phagocytic cells?
* phagocytic cell contain Fc receptors that recognize IgG Fc portions * binding of FcγRI receptors to immunoglobulins on pathogen surfaces facilitates phagocytic uptake by macrophages and neutrophils via phagocytosis
36
What is the mechanism of granulocytes?
* induces forceful expulsion via inflammatory mediators * mast cells expressing FcεRI receptors bind to IgE at the cell surface * a single granulocyte can bind many different IgE with different antigens
37
What is the mechanism of NK cells?
* use Fc receptor, FcγRIII, to recognize IgG immunoglobulins * target these cells for apoptosis through antibody-dependent cell-mediated cytotoxicity
38
What is the mechanism of transport of antibodies
1. IgG binds to FcRN, IgA and IgM binds to poly-Ig receptor 2. The receptor and immunoglobulin are engufed via receptor-mediated endocytosis 3. Digestion within the lysosomal vesicle degrades the poly-Ig receptor to its secretory component 4. Vesicle transport moves the immunoglobulin and secretory component
39
What is the mechanism for complement activation?
1. The flexibility of IgM allows it to bind to repeating epitopes and convert to the staple form/ or at least two IgM molecules must bind 2. The staple form binds with C1q/r/s 3. C1q/r/s cleaves the complement proteins C2 and C4 into classical C3 convertase C4bC2b 4. C3 convertase cleaves C3 into C3a and C3b
40
What are small immune complexes?
* complexes formed from C1 binding and C3b fixation * binds to erythrocyte CR1 * RBCs deliver the complexes to macrophages in the liver and spleen for clearance * immune complexes persisting in the bloodstream aggregate and precipitate within small blood vessels

BISC 450 (5 decks)

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