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immunology > Secondary Organ Antibody Synthesis and B Cell Surface Proteins > Flashcards

Secondary Organ Antibody Synthesis and B Cell Surface Proteins Flashcards

1
Q

what is the purpose of lymph nodes?

A

communicates with the lymphatics to allow for the acquisition of free and bound antigen as
well as the migration of immune cells.

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2
Q

what is located at the cortical region of the lymph nodes?

A

follicles that are rich in naïve, circulating B cells

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3
Q

what surrounds the follicles of the lymph nodes?

A

paracortex that is rich in circulating naïve T cells

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4
Q

what resides in the interspaces of the lymph node?

A

dendritic cells (APC)

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5
Q

what do dendritic cells do?

A

can easily trap free antigen, process it into numerous peptides and present it to numerous B cells and T cells to induce activation

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6
Q

define cognate epitope

A

select B cells can bind free antigen, process it and present it on its surface to the T cells, which can recognize the same peptide epitope

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7
Q

what are the T cells involved in antibody synthesis?

A

T helper cells

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8
Q

how do T helper cells recognize linear peptides presented?

A

MHC class II

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9
Q

how are helper T cells characterized via flow cytometry?

A

CD4+ T cells

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10
Q

what transcription factor are B cell clones mediated by?

A

BcL-6

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11
Q

what are the follicles that contain the germinal centers?

A

secondary follicles

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12
Q

what takes place in the germinal centers that yield both plasma cells and memory B cells?

A

isotype-switching, somatic hypermutation and affinity maturation

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13
Q

even during clonal expansion, the clones are screened and selected based on what?

A

their binding affinity

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14
Q

what forms when the non- activated naïve B cells line the periphery

A

mantle zone

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15
Q

what happens in the dark zone of germinal centers?

A

the replicating B cell clones increase the production of activation-induced cytidine deaminase (AID)

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16
Q

what is activation-induced cytidine deaminase (AID) required for?

A

somatic hypermutation and isotype-switching

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17
Q

what is the outcome of hypermutation of Ig in the dark zone?

A

large contingent of B cell clones of various binding affinities for the original cognate antigen epitope

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18
Q

what happens following somatic hypermutation?

A

the B cell clones with their modified antigen-specific binding affinity move to the light zone where they encounter the follicular dendritic cell

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19
Q

what happens to B cell clones with mutated BCRs with lower binding affinity?

A

apoptosis

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20
Q

how are failed B cell clones scavenged?

A

tingible body macrophages

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21
Q

what happens in the light zone when activated B cell encounter T follicular helper cells (TFH)?

A

upon binding and in the presence of AID can direct the activated B cells to undergo isotype-switching

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22
Q

what secretory antibody is favored to be produced by plasma cells in the bone marrow?

A

IgG, some produce monomeric IgA

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23
Q

what can be the result of genetic defects that can disrupt the formation of the germinal center?

A

unique primary immunodeficiencies

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24
Q

what major immunoglobulin is associated with humoral mucosal immunity?

A

IgA

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25
Q

what is the primary antibody secreted in the GI and respiratory tract as well as secretions (saliva and tears)?

A

IgA

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26
Q

what is the main function of IgA?

A

to bind and or cross link to the specific antigen, preventing attachment to epithelial cells, allowing for its removal out of the body

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27
Q

what structure of IgA coupled with secretory protein it acquires for it to pass through the epithelial to survive and function in harsh microenvironment of the GI and respiratory tract?

A

dimeric

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28
Q

what is the inductive site?

A

site of B and T cell activation only

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29
Q

what two cells have to be involved to make them thymus dependent (TD)?

A

T and B cells

30
Q

describe TD antigens

A

structurally complex, commonly associated with most pathogenic microbes, generating immunologic memory.

31
Q

what are peyer’s patches?

A
  • GALT secondary lymphoid tissue functioning as inductive sight
  • reside in connective tissue deep to epithelial cells and communicate with microfold cells (M cells)
32
Q

what do M cells do?

A

transcytose antigen from the lumen to resident dendritic cells that present process antigen to B and T cells

33
Q

where does B cell activation and IgA isotype switching occur?

A

peyer’s patch

34
Q

what is homing?

A

surface proteins called adhesion molecules and chemokine receptors of the activated B cells are guided back to GALT to effector site where
they complete their B cell differentiation to become terminally differentiated plasma cells
secrete IgA to be released into the lumen of the gut

35
Q

where can thymus independent (TI) antigens gain entry at?

A

MALT

36
Q

describe TI antigens

A

simple structures, not typically associated with pathogenic microbes, only induce IgM-
secreting B cells and yield no measurable memory response.

37
Q

how can TI antigens be classified as?

A

based on their ability to independently induce activation of multiple B cells to undergo replication or proliferation

38
Q

what is a benefit of TI antigens?

A

they induce a rapid IgM, which is beneficial if the TD response is impaired (i.e. dysfunctional T cells)

39
Q

what is a mitogen?

A

substance that can induce cells to
proliferate

40
Q

why are mitogens known as polyclonal activators?

A

tend to have repeating structures with many epitopes in that they stimulate multiple B cells at the same time

41
Q

what is an example of a TI-1 mitogen

A

lipopolysaccharides from gram negative bacteria (i.e. E.coli)

42
Q

what are examples of TI-2 antigens?

A

polysaccharides (i.e. dextrans, ficoll), glycolipids and nucleic acids

43
Q

what are marginal Zone B cells?

A

non-circulating, mature subset of B cells that reside in the marginal zone of the spleen and other lymphoid tissue

44
Q

what is unique about marginal zone B cells?

A

they can be rapidly recruited as part of an early adaptive response to TI antigens (i.e. blood borne or lymphoid borne pathogens, encapsulated bacteria or viruses) resulting in IgM production. They tend to have a long-life span in the tissues

45
Q

where are B-1 cells predominantly found?

A

peritoneal and pleural cavities

46
Q

what do B-1 cells express?

A

germline-encoded, polyreactive IgM antibodies utilizing minimal V gene segment usage

47
Q

why are B-1 cells linked to autoimmune diseases?

A

low affinity, polyspecific antibodies are frequently reactive with TI-2 polysaccharides and autoantigens

48
Q

true or false: B-1 cells contribute a significant amount of IgM and are likely responsible for the natural antibodies

A

true

49
Q

what is an example of natural antibodies?

A

abs to ABO blood group.

50
Q

what makes up the BCR complex?

A

antibody of a naïve B cell will be a monomeric IgM isotype that has adjacent to it the dimer Igα Igβ

51
Q

Upon antibody binding to the cognate antigen epitope and likely occurring at multiple BCRs on the B cell, what do the Igα Igβ with its transmembrane domain acts as?

A

signal transduction molecule to initiate B cell activation.

52
Q

what are the 4 surface proteins that act as activation signal enhancers once the BCR complex is activated?

A

CD19, CD21, CD81 and CD225

53
Q

CD__, C__1 are often called a complex and are believed to help prolong BCR signaling.

A

19, 21

54
Q

CD__ is a bit of an enigma in that it may facilitate the expression of CD19 during activation and yet may also have inhibitory properties.

A

81

55
Q

CD___ is a co-receptor that may help regulate CD19 expression

A

225

56
Q

what is the essential cell surface protein required for T cell recognition as it is responsible for presenting the linear peptide epitope to T cells.

A

MHC

57
Q

For the B cells that recognize TD antigens and require T cell activation for isotype-switching,
CD__ and B_ are ligands that are upregulated in activated B cells to enhance T cell activation
post MHC class II- TCR recognition and binding.

A

40, 7

58
Q

which CD is critical for isotype-switching?

A

CD40

59
Q

what is the purpose of inducible costimulatory ligand?

A

primarily interacts with CD4+ T helper cells. It helps drive the T cell into proliferation and cytokine secretion and has a role in germinal center formation.

60
Q

the binding of receptors by a specific cytokine will impact what?

A

specific heavy chain isotype that will be switched

61
Q

what 3 sets of cells surface molecules is homing attributed to?

A

integrins (i.e. CD11, CD18), selectins (i.e. CD62L) and chemokine receptors.

62
Q

what group of proteins does integrins and selectins make up?

A

adhesion molecules

63
Q

what is the purpose of adhesion molecules?

A

to allow the circulating leukocyte, in this case, the activated B cell to bind to another cell surface, like an endothelial cell, and pass through the blood vessels into the deep tissues, like a Peyer’s patch

64
Q

what do chemokines do?

A

help direct or attract the activated B cell to its tissue target

65
Q

Following binding of the antigen epitopes
to the BCR, usually more than one resulting in _______________________, the Igα Igβ undergoes a
signal transduction activating the ITAMS transmembrane domain causing a rapid
phosphorylated by cytoplasmic tyrosine kinases Fyn,Lyn.Phosphorylation of the ITAMS recruits cytoplasmic protein Syk to the site resulting in it being phosphorylated to become activated. Syk recruits another tyrosine kinase, Btk and B cell linker protein (BLNK, a carrier protein).

A

receptor cross-linking

66
Q

what activates the 3 major cell signalling pathways?

A

Phospholipase Cγ2 (PLCγ2) binds to BLNK

67
Q

describe pathway 1

A

PLCγ2 acts on membrane bound phospholipid phosphatidylinositol 4,5 bisphosphate (PIP2) breaking it down in to 2 byproducts one of which is inositol triphosphate (IP3), which drives the release of sequestered Ca+2 activating calcineurin

68
Q

describe pathway 2

A

Membrane Diacylglycerol (DAG), the second byproduct of PLCγ2, activates protein kinase C which initiates a signaling signal cascade resulting in the activation of a transcription factor NF-κB

69
Q

describe pathway 3

A

DAG also interacts with a GTPase, Ras that activates the MAP kinase cascade, a proliferation signaling cascade, leading to activation of transcription factors

70
Q

what does all 3 intracellular pathways lead to?

A
  • activation of transcription factors NF-κB, NFAT and Ap-1 leading to antibody synthesis
  • B cell proliferation
  • upregulation of cell surface protein expression.
71
Q

what happens after BCR recognition and signal transduction?

A

B cell starts proliferating and differentiating within 24-48 hour window

72
Q

If a high antibody concentration or titer
is the goal for protection, say to Rabies, then why not continuously vaccinate (boost) people
and animals with the goal to continually increase the titer?

A

There is a threshold antibody titer and once reached, B cell activation ceases. Nature has a safeguard. there is a cell surface receptor called CD32. It binds the Fc portion of the antibody molecule. So following an exposure (i.e. vaccine booster), B cell activation occurs and CD32 is upregulated. If there are sufficient secretory antibodies present to the same cognate antigen epitope for that B cell, when the BCR binds that antigen and it is already bound to
secretory antibody with an exposed Fc portion. If this Fc portion of the antibody binds to CD32,
it depolarizes a transmembrane protein associated with CD32, which activates cytoplasmic phosphatases that dephosphorylate tyrosine residues on the Igα Igβ and shuts down B cell activation

immunology (18 decks)

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