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OPHTH Immunology > B lymphocytes > Flashcards

B lymphocytes Flashcards

1
Q

How many days does it take for the adaptive immune response to develop + become effective?

A

4-7 days

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2
Q

What are 2 forms forms of the adaptive immune response?

A
  1. Humoral: B cells, antibodies
  2. Cell-mediated: T cells, cytokines, lysis of pathogens
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3
Q

Where do B cells mature?

A

one marrow, whereby they express specific B cell receptors (BCR)

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4
Q

Where does antibody production following B cell activation and differentiation occur?

A

peripheral lymphoid organs

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5
Q

What are the 4 stages of B cell maturation?

A

Pro-B Cell -> Pre-B Cell -> Immature B Cell -> Mature B Cell

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6
Q

What is the B ell receptor?

A

transmembrane protein complex composed of: mIg + Igα/Igβ

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7
Q

What is the function of mIg that forms the B cell receptor?

A

central larger immunoglobulin molecule, cytoplasmic tail too short so not involved in signalling

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7
Q

What is the function of mIg that forms the B cell receptor?

A

central larger immunoglobulin molecule, cytoplasmic tail too short so not involved in signalling

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8
Q

What are Igα/Igβ that form the B cell receptor?

A

dil-sulfate linked heterodimers, contain immunoglobulin-fold structure. cytoplasmic tails of Igα/Igβ long enough to interact with intracellular signalling molecules

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9
Q

Which structures forming the B cell receptor interact with intracellular signalling molecules?

A

Igα/Igβ - cytoplasmic tails. mIg cytoplasmic tail too short

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10
Q

Which structures forming the B cell receptor interact with intracellular signalling molecules?

A

Igα/Igβ - cytoplasmic tails. mIg cytoplasmic tail too short

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11
Q

What does the unique binding site of B cell receptors bind to?

A

antigenic determinent/ epitope

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12
Q

How are BCR coded for on chromosomes?

A

kappa and lambda light chains and the ehavy chain are encoded by separate multigene families on different chromosomes - during maturation, segments are rearranged and brought together to form BCR (immunoglobulin gene rearrangement)

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13
Q

What are 4 types of segments within genes responsible for encoding the BCR chain?

A
  • variable, V
  • diversity, D
  • joining, J
  • constant, C
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14
Q

Which chain of the BCR is the diversity gene segment responsible for?

A

heavy chain only

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15
Q

In summary what generates the diversity of the B cell lymphocyte repertoire?

A

immunoglobulin gene rearrangement - occurs during maturation of B cells in the bone marrow

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16
Q

What type of DNA is involved in the synthesis of prototypical B cell membrane proteins?

A

Genomic DNA -> transcription -> primary transcript RNA/pre-mRNA -> Splicing -> Mature mRNA -> trnalsation -> membrane protein

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17
Q

What is the process resulting in light chain synthesis?

A

Germline DNA -> rearrangement of V and J segments involving VDJ recombinase -> B cell DNA -> transcription -> primary trancript RNA/pre mRNA -> splicing -> mature RNA -> translation -> light chain polypeptide (kappa or lambda)

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18
Q

Which enzyme is important in rearrangement of V+J segments of germline DNA important for heavy and light chain synthesis?

A

VDJ recombinase

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19
Q

What happens to unused DNA during joining of gene segments for light chain synthesis?

A

looped out and removed

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20
Q

What is the process of heavy chain synthesis from gene encoding?

A

Germline DNA –> rearrangement of V and J segments involving VDJ RECOMBINASE –> B cell DNA –> Transcription –> Primary transcript RNA/pre-mRNA– (Alternative Splicing) –> Mature mRNA –> (translation) –> Heavy chain polypeptide

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21
Q

Which DNA are B cell receptor membrane proteins derived from?

A

genomic DNA

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22
Q

Which DNA are B cell receptor heavy and light chain proteins derived from?

A

germline DNA

23
Q

Which DNA are B cell receptor heavy and light chain proteins derived from?

A

germline DNA

24
Q

What is meant by alternative splicing?

A

involved in heavy chain synthesis - results in different mature mRNA, as mRNA express different genes (e.g. may have different constant region genes present)

25
Q

What happens to a B cell if it doesn’t meet an antigen?

A

cell death

26
Q

What can happen to antibody specificity and class over time?

A

may keep specificity but change class

27
Q

What is clonal expansion?

A

mature lymphocytes (T or B) migrate to periphery, unique specific antigen receptor binds antigen - activates cell + proliferates to clone of cells with same receptor

28
Q

What is the difference between a plasma cell and a memory cell?

A

plasma cells produce lrage amounts of antibodies, while memory cells remember antigens and create secondary immune responses

29
Q

What do naive antigen-specific lymphocytes need to be activated by antigen?

A

Cannot be activated by antigen alone, require accessory signals either from:
1. microbial constituents - thymus independent
2. helper T cells - thymus dependent

29
Q

What do naive antigen-specific lymphocytes need to be activated by antigen?

A

Cannot be activated by antigen alone, require accessory signals either from:
1. microbial constituents - thymus independent
2. helper T cells - thymus dependent

30
Q

Which class of immunoglobulin can be produced by thymus independent accessory signals + antigen activation to lymphocytes?

A

IgM only

31
Q

Which class of immunoglobulin can be produced by thymus dependent accessory signals + antigen activation to lymphocytes?

A

all immunoglobulin classes

32
Q

Which type of antigen activation of lymphocytes forms memory cells?

A

thymus dependent only - not formed wih thymus independent signalling

33
Q

What is the main difference between the process of thymus independent accessory signalling with antigen ativation vs thymus independent?

A
  • independent: antigens directly activate B cells without the help of T cells
  • dependent: membrane bound BCR binds with antigen, is internalised + delivered to intracellular sites
  • antigen is degraded into peptides, peptides associated with self MHC class II form complex which is expressed at cell surface
  • T cells with compleentary TCR recognises the complex, then secretes lymphokines
  • B cell then enters cell cycle, forming clone of cells with identical BCRs + differentiating into plasma + memory cells
34
Q

What are the 7 stages of how T cells aid B cells in thymus dependent antibody production?

A
  1. Antigen cross link with BCR induces signal 1- ↑MHC II, ↑B7
  2. Antigen is internalised and degraded, and the peptide-MHC II complex is presented
  3. T cell recognises complex and co-stimulation by B7 and CD28 interaction -> activation of T cells
  4. Activated T cell expresses CD40L -> the interaction between CD40L and CD40 (expressed by B cell) induces signal 2
  5. Activated B cells (CENTROBLAST) express cytokine receptors
  6. T cell derived cytokines bind to receptors on B cells
  7. B cells proliferate and differentiate into antibody secreting plasma cells
35
Q

Which 2 things are upregulated in the B cell as a result of signal 1 in the thymus dependent antibody production?

A

MHC II, B7

36
Q

What 2 things activate T cells during thymus dependent antibody production?

A
  1. B7
  2. CD28
37
Q

What do T lymphocytes increase their production of during thymus dependent antibody production?

A

CD40L

38
Q

What process induces signal 2 in thymus dependent antibody production?

A

interaction between CD40L (expressed by T cell) and CD40 (expressed by B cell)

39
Q

Which part of immunoglobulins remains constant and which changes during class switching?

A

variable region (hence specificity) remains constant, but constant region changes from the original IgM

40
Q

Which 2 Ig classes are induced by IL-4?

A
  1. IgG1
  2. IgE
41
Q

What is the action of IL-5 on antibody switching?

A

augments production of IgA

42
Q

Which 2 immunoglobulins are induced in antibody switching by IFN-gamma?

A

IgG3 and IgG2a

43
Q

Whcih 2 immunoglobulin classes are induced by TGF-beta in antibody switching?

A

IgG2b and IgA

44
Q

What are 3 ways in which the secondary immune response i.e. subsequent encounters with an antigen differs from the primary response?

A
  1. more rapid
  2. higher amount of antibody produced
  3. higher affinity for antigen
45
Q

Which cells are responsible for the secondary immune response?

A

memory B cells

46
Q

What is the lag period for the primary immune response vs secondary immune response?

A
  • primary = 4-7 days
  • secondary = 1-3 days
47
Q

What is the time of peak response for the primary immune response vs secondary immune response?

A
  • Primary = 7-10 days
  • Secondary = 3-5 days
48
Q

Is antigen processing thymus independent or dependent for the primary immune response?

A

both

49
Q

Is antigen processing thymus independent or dependent for the secondary immune response?

A

dependent

50
Q

What is meant by polyclonal antiserum?

A

all antigenic epitopes induce an immune response -> many different B cells activated -> different antibodies produced i.e. mixture of antibodies directed to several antigenic determinants

51
Q

How can monoclonal antibodies be extracted?

A

combining plasma cells with myeloma cells to form hybridomas

52
Q

What is a plasma cell?

A

a fully differentiated B-lymphocyte (white blood cell) which produces a single type of antibody.

53
Q

What is ap plasmacytoma?

A

clone of malignant plasma cells

54
Q

What provides the genetic variability allowing the body to generate an immune response to every pathogen during its lifetime?

A

The hypervariable regions of receptors achieve their diversity through** genetic recombinations during development (in utero**). These include V, D, and J gene rearrangements, with random addition of nucleotides by terminal deoxyribonucleotidyl transferase.

OPHTH Immunology (8 decks)

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