Humoral Immunity: Antibodies And The Life Cycle Of B Cells Flashcards

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1
Q

What is the basic structure of a antibody/immunoglobulin?

A

Variable reigon - different

Constant reigon - same for all same class

Antigen binding site

Light - 2 types make two chains

Heavy - 4 chains (9 different types of chains including variants of alpha and gama chain) that make 2 chains

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2
Q

What are the five classes of heavy chain?

A

Micro

Delta

Alpha

Gamma

Epson

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3
Q

What are the two domains of the light chain?

A

Variable region and constant region

NH3 nd on variable reigon

COO- on the control end

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4
Q

How are the variable region of the the light and Harvey chain different?

A

They have different shapes

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5
Q

What are the four different antibody functions?

A

Virus and toxin neutralisation - prevents pathogen host binding

Opsonisation + ADCP - phagocytosis

Complement fixing/ MAC formation (CDC) - phagocytosis or lysis

Opsonisation + ADCC - NK induced apoptosis

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6
Q

What are the different classes of antibodies?

A

IgG - iconic antibody structure

IgD

IgE

IgA - has a J chain and a secretory component - secreted in mucus and good for respiratory infections - 2 molecules

IgM - has a J chain - 5 molecules together

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7
Q

What defines the different classes of antibodies?

A

The heavy chain

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8
Q

What heavy chain does igM have?

A

Micro/mu

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9
Q

What heavy chain does IgD have?

A

Delta

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10
Q

What heavy chain does IgG have?

A

Gamma

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11
Q

What heavy chain does IgA have?

A

Alpha

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12
Q

What heavy chain does IgE have?

A

Epsilon

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13
Q

What is the function of IgM?

A

Main Ab of primary response

Best at forming immune complexes and fixing compliment

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14
Q

What is the function of Ig D?

A

BCR

Indicated mature B cells

Only AB not secreted

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15
Q

What is the function of IgG?

A

Main Ab of secondary responses,

neutralise toxins,

opsonisation

80% of total Ab in serum

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16
Q

What is the function of IgA?

A

Secreted onto mucous, tears, saliva, colostrum

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17
Q

What is the function of IgE?

A

Allergy

Anti-parasites

Smallest percentage of Ab in serum

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18
Q

When can heavy chain class switching occur?

A

Only effects heavy chain constant region

Different effector functions

Minor: Differential splicing (mRNA level) - IgM and IgD

Major : DNA recombination
- igM to IgG, IgA, IgE
- IgG to IgA, IgE

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19
Q

What is class switch recombination (CSR)?

A
  1. Cytokine signal
  2. Switch regions
  3. AID and DSB repair

Recombination between switch regions

Switching only proceeds down stream

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20
Q

Why does antibody class switching occur?

A

In response to antigen stimulation and costimulatory signals

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21
Q

Describe a overview of the B cell life cycle

A

Antigen independent stage (BONE MARROW)
- Stem cells differentiate to pro B cells
- then pre B cells when recombination makes the heavy chain variable region
- immature B cell forms after light chain develops
- expression of igM and igD by differential splicing

Antigen dependent stage (BLOOD STREAM AND LYMPH NODE)
- reside in spleen until pathogen is detected
- class switching occurs
- receptors because igG or igA
- some will turn into plasma cells
- memory b cells remain in blood

22
Q

What is somatic recombination ?

A

Alteration of the genetic information at DNA level

  • VDJ recombination
  • Tdt nucleotide addition
  • somatic hypermutation
  • class switching
23
Q

What is differential splicing?

A

Changes made on the mRNA

  • igM and igD
  • membrane bound and secreted ig
24
Q

What happens on the life cycle of a B cell?

A
  1. Stem cell is converted to pro-b cell (heavy chain develops)
  2. Pro b cell becomes a pre-b cell (light chain develops
  3. Immature B cell
  4. Quality control occurs with differential splicing of igM nd igD - mature B cells form
  5. Mature B cells. Then leave the be marrow and enter the spleen and lymph node
25
Q

How many antibody genes are inherited?

A

None! No complete genes re inherited, only gene segments

The gene segments in different combinations generate many ig sequences

26
Q

What re the three genetic loci encoding ig?

A

Two for light chain - kappa and lambda locus

One for heavy chain

Located on different chromosomes

27
Q

What are. Recombination signal sequences (RSS)?

A

Conserved sequences upstream or downstream of gene segments

28
Q

What is the on-turn/two-turn rule (12/23 rule)?

A

Recombination only occurs between 12bp spacer and 23bp spacer

29
Q

What are the number of different combinations the antibody Haines can have/

A

1.98 x 10^8

30
Q

What are the processes that can abuse antibody diversity?

A

Multiple germaline V,D and J gene segments

Junctional flexibility

P nucleotide addition

N nucleotide addition

Combination association of heavy and light chains

Somatic hypermuutation during affinity maturation

31
Q

What is junctional diversity?

A

Junctional flexibility during VDJ recombination, P and N nucleotide recombinations

Good for antibody diversity

Bad: non-productive rearrangements - wasteful process

32
Q

Describe the mechanism of junctional diversity?

A
  1. RAG1 and RAG2 bind to the terms on either end pulling them together to form a hairpin structure
  2. DNA is nipped and forms a hairpin at the ends of the gene set
  3. Enzymes process these ends and form a coding joint of the desired genes and a signal joint
  4. Signal joint contains other genes that were between the two gene segments

5.

33
Q

Describe what occurs during hair opening and joining

A

The hairpin opens using the enzyme Artemis
And the DNA ends will be processed by exonuclease and TdT

The DNA ends are Joined by a series of enzymes

34
Q

What is junctional flexibility?

A

Removal of nucleotides between gene segments during VDJ recombination

Exact mechanism unknown

Involves Exonuclease - removes mismatched nucleotides

35
Q

Describe roughly what occurs during junctional flexibility

A
  1. two different hairpins are cleaved at a random parts
  2. Leading for one hairpin to turn into 2 DNA strands
  3. P Nucleotides and N nucleotides are added to the ends of the DNA strand
  4. The strands from each hairpin at the start join by terminal deoxynucleotidyl transferase (Tdt)
  5. Forming 2 long DNA strands that contain one P Nucleotide and one N nucleotide
36
Q

What is allergic exclusion?

A

Two copies for each ig gene - one paternal an one maternal

Both genes are expressed

Antibody genes different - only on heavy chain and one light chain allele Is expressed

37
Q

What is the order of rearrangement of allelic genes?

A

Heavy > kappa > lamba: 1st allele then 2nd allele

38
Q

Describe what occurs during the Life cycle B cells

A
  1. Lymphoid progenitor cells in the bone marrow is converted into a mature B cells and T helper cells
  2. Mature B cells enter the spleen + lymph node and blood
  3. T helper cells migrate to the thymus
  4. Once the mature B cell enters the spleen it enters the germinal center
  5. In the dark zone of the germinal centre the mature B ell undergoes clonal expansion + somatic hyper mutation
  6. In the light zone the cells undergoes selection + class switching occurs
  7. After this the mature B cells now have Ig on their surface and leave the spleen/lymph node an enter the blood
  8. The B cells then differentiate into memory cells or plasma cells
39
Q

What occurs in T cell INDEPENDENT B cell activation?

A
  1. Antigen on pathogen binds to B cell
  2. Triggering clonal expansion and IgM secretion
40
Q

What occurs in T cell DEPENDENT B cell activation?

A
  1. Antigens on pathogen bind to dendritic cells
  2. Dendritic cells then bind to T helper cells
  3. The T helper cells then bind to B cells using (TCR + MHC2) (CD40 + CD40L)
41
Q

What are the 3 signals required for B cell activation?

A
  • Antigen binding to BCRs
  • Co-stimulation by activated Th cell specific to some antigen
  • Th Cell-deprived cytokines
42
Q

How are B cells activated by the T cell transduction pathway?

A

The B cell receptor binding activates tyrosine kinase, which phosphorylated proteins

Signal transduction pathway for cell proliferation, differentiation and survival

43
Q

Define affinity maturation

A

To fine tune antibody affinity to antigen

44
Q

What occurs during clonal expansion?

A
  1. B cell that can bind to the pathogen the best will get activated
  2. B cell then makes clones of itself
  3. B cells then undergo finite maturation
45
Q

What occurs during affinity maturation?

A

Process to. Improve affinity of antibody to antigen

Antibody binds at low affinity - antibody takes longer to bind or binds loosely

Once B cell is activated mutations occur in the antibody which allow it to have higher affinity - shapes the area of the variable region to fit the antigen better

46
Q

Where does the affinity maturation take place?

A

In the germaline centre of the lymph node

47
Q

What are follicular dendritic cells (FDC)?

A

Not your normal dendritic cells but are antigen presenting

Are present n the germalne centres of the lymph node

48
Q

When does class switching occur?

A

In the light zone of the germinal center of the thymus

Occurs to the B cells with the highest affinity after affinity maturation

49
Q

What is somatic mutation?

A

Point mutations that occur in the clonal expanded B cells

50
Q

Describe how antibody finite changes through the cycles of affinity maturation

A

The antibody finite increases with the number of rounds of affinity maturation