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IMMUNOLOGY: CMOD-Week 1 > (03) Antibody Diveristy and B Cell Developement > Flashcards

(03) Antibody Diveristy and B Cell Developement Flashcards

1
Q

What does antibody repertiore refer to?

A

Complete collection of B cell receptor specificities that exists in the secondary lymphoid tissues of the host

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2
Q

What process is responsible for generating the 10^11 unique specificities of B cells?
- Genes that mediate this process

A

Somatic Recombination

  • RAG-1 and RAG-2 (Recombination Activation Genes) mediate somatic Recombination
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3
Q

What are the light chain coding regions composed of?

- what are the 2 sets of light gene segments, that contain each of these 3 parts?

A
  1. Single Variable Gene Segment
  2. Single Joining Gene Segment
  3. Single Constant Gene Segments

**Kappa and Lambda

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4
Q

What are the heavy chain coding regions composed of?

- are there 2 sets of gene segments coding?

A
  1. Single Variable Region (V)
  2. Single Diversity Region (D)
  3. Single Joining (J) segment
  4. Single Constant (C) region
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5
Q

Where are the light and heavy chain genes located in the genome?

A

Lambda Light Genes = Chromosome 22

Kappa Light Genes = Chromosome 2

Heavy Chain genes = Chromosome 14

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6
Q
  • *What do RAG-1 and RAG-2 do?

- what happens if you don’t have these enzymes?

A

Catalyze double stranded breaks and recombination events that make V-D and V-D-J recombinations

Lack of Enzymes = SCID (severe combined immunodeficiency)

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7
Q
  • *What does TdT do?
  • what processes is involved in?
  • why is this important?
A

Catalyzes the addition of “N” nucleotides in the junctions between rearranging gene segments during somatic recombination

Processes:

  • HEAVY CHAIN somatic recombination
  • ß-chain rearrangements in T-cells

Importance:
- changes in the coding region cause even more variability in the number of specificities

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8
Q

T or F: any light chain produced can be paired with any heavy chain produced

A

True

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9
Q

T or F: somatic recombination is antigen dependent

A

False, this process occurs regardless of the presence of antigens

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10
Q

What are the two antigen dependent mechanisms of B cell development?

A
  1. Affinity Maturation (binding diversity)
    - aka somatic hypermutation
  2. Class Switching (functional Diversity)
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11
Q

What is somatic hypermutation?

  • steps that lead to it?
  • Where does it occur?
A
  1. B Cell Receives activation stimuli and begins to proliferate
  2. High rates of mutation occur IN RECOMBINED regions during proliferation
  3. Some mutated antibodies have higher affinity and some lower

Location:
- Germinal Center of B cell follicles of 2˚ lymphoid tissues

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12
Q

T or F: a POSITIVE selection method is used in affinity maturation/somatic hypermutation?

A

True, higher affinity cells are positively selected

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13
Q

What is the general outcome of somatic hypermutation?

A

The immune response improves over the course of the infection

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14
Q

T or F: all B cell initially produce IgE antibodies.

A

False, they produce IgM antibodies

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15
Q

What does class (isotype) switching do?

- Why is this efficient?

A

Changes the constant region of the antibody WITHOUT changes the variable region

THIS CHANGES FUNCTIONALITY NOT SPECIFICITY

  • ONLY 1 B cell needs to be activated and it can do class switching to make IgG, IgE, IgA antibodies etc.
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16
Q

What is the order of constant regions?

A
  • IgM
  • IgD
  • IgG3
  • IgG1
  • IgA1
  • IgG2
  • IgG4
  • IgE
  • IgA2

MD. GGAGGEA

17
Q

What enzyme is required for both Class Switching AND for Somatic Hypermutation?

  • what does an enzymes deficiency in this cause?
  • Deficiency in which process is more detrimental?
A

AID - Activation-Induced Cytidine Deaminase

Causes:

  • Hyper IgM syndrome
  • Patients are susceptible to bacteria, fungi, and parasites as well as some viral pathogens such as the Flu

**Problem results from failure of Class switch NOT Hypermutation

18
Q

Somatic Recombination

  • 2 factors that cause variation
  • dependency on antigen
A

Variation caused by:

  • Imprecise end joining
  • random combos of heavy and light chains

*Antigen Independent

19
Q

Class Switching

  • What does it allow for
  • dependency on antigen
A

Allows immune system to pick the best antibody for the invading pathogen

*Antigen Dependent

20
Q

Somatic Hypermutation

  • purpose
  • dependency on antigen
A

Allows for fine tuning of antibodies

*Antigen Dependent

21
Q

Which of the following affect specificity and which affect functionality?

  • somatic recombination
  • somatic hypermutation
  • class switching
A

Specificity

  • somatic recombination
  • somatic hypermutation
Functionality
- class switching
22
Q

IL-7 (interleukin-7) what cell type makes these?

  • what cell receives?
  • why are they needed?
  • what happens if no IL-7 or IL-7 receptors are absent?
A

IL-7
Made by:
- Stromal Cells in Bone Marrow

Received by:
- B-cells

Need:
-Critical to growth and development of B-cells

No IL-7 or IL-7 receptors then patients have a normal amount of B-cells but they’re ineffective

23
Q

T or F: immature B cells already have IgM on their surface

A

True, this means they have already rearranged their heavy and light chain genes

24
Q

What is BTK and what is it needed for?

- what happens if you lack this enzyme?

A

BTK = Bruton’s Tyrosine Kinase

  • Needed for proper signal transduction from surface receptors during B cell development

NO BTK = very few B-cells

25
Q

Allelic Exclusion

  • what is it
  • How it works
A
  • Only 1 chromosome is worked on at a time

If chromosome 14a fails it will move to chromosome 14b for a heavy chain gene
If chromosome 2a kappa fails then chromosome 2b kappa will be used
If these fail it will move to Lamba

26
Q

What would happen if B cells that bound host antigens were not killed?

A

Autoimmune disease

27
Q

What are the 4 possibilities of what can happen to a B-cell when it is allowed to interact with self antigens?

A
  1. Binds Self Antigens
    - Apoptosis
  2. Binds tightly to soluble molecules
    - becomes anergic (unresponsive to antigenic stimuli) and DIES
  3. Binds weakly to self Antigens
    - migrates to periphery
  4. Doesn’t bind anything
    - migrates to periphery
28
Q

What binds the Fc region of antibodies?

A
  1. Phagocytes

2. Complement proteins

IMMUNOLOGY: CMOD-Week 1 (10 decks)

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