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Immuno > Adaptive Immune System: B-Cells > Flashcards

Adaptive Immune System: B-Cells Flashcards

1
Q

Lymphocytes in the central lymphoid tissues

A

Antigen independent differentiation

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2
Q

Lymphocytes in the Peripheral lymphoid tissues

A

Antigen dependent differentiation

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3
Q

The 8 important points about B-cells

A

Progenitor and immature are in the bone marrow or bursa fabricii in birds
Native Atg recognition (conformation epitop)
No MHC restriction
Secondary maturation occurs in the folliculi- this is stimulated by the Atg stimuli
The secondary maturation results in plasma cell or memory cell
Clonal B-Cell receptor
Cell-line marker: CD19+- is on every B-cell

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4
Q

Evolution of B-Cells- locations

A

Bone marrow
Spleen (maturation)
Periphery

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5
Q

Bone marrow: main functions

A

Production, maturation and differentiation of B-cells
One kind of specificity
Elimination of autoreactive cells
Transfer of useful B-cells to the periphery
Place of memory cells!

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6
Q

Stages of development in the bone marrow

A

Signalled by the environment- bone marrow stroma cells
Pro B-Cell: earliest expression of CD19
Pre B-Cell: express rearranged heavy chain with Cmu chain and surrogate light chain
Immature B-Cell: expresses rearranged light chain (kappa mainly) and the membrane bound IgM (mIgM)

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7
Q

Negative selection

A

The cell is capable of recognising the Atg when the heavy and light chain binds
The cells with high autoreactivity BCR should not enter circulation- they should be deleted
In the bone marrow, the autoreactive clones re-edit BCR with new recombination– receptor editing

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8
Q

Spleen

A

Maturation of B-cells in the white pulp

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9
Q

BAFF and APRIL

A 
BAFF= B-Cell activating factor 
APRIL= proliferation-inducing factor- survival of B-cells

Functions:
Plasma cell survival
T-cell independent response and isotype switching
Immature B-cell survival and isotype switching

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10
Q

Lymph Nodes: components and functions of the cortex

A

Primary follicle: B-cell activation
Secondary follicle germinal center: B-cell proliferation and maturation

Exclusively B-cells

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11
Q

Lymph Nodes: components and functions of the paracortex

A

Initial T and B cell activation

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12
Q

Lymph Nodes: components and functions of the medulla

A

Plasma cell secretion of antibody

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13
Q

Important points about Follicular Dendritic Cells (FDC)

A

In the stratum germinativum of the secondary follicles
Myeloid progenitors
FcR and complement receptors (opsonisation)
Atg is held in a native form to B-memory cells
No phagocytotic activity
No expression of MHCII

*sidenote: remember Fc is part of IgG

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14
Q

What are the 3 zones of the secondary follicle

A

Dark zone
Light zone
Mantle zone

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15
Q

What happens in the dark zone?

A

The naive B-Cell undergoes clonal expansion and somatic hypermutation

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16
Q

What happens in the light zone?

A

Desired: After the somatic hypermutation in the dark zone, the B-cell has improved affinity, undergoes selection and differentiation with FDC and T-cells
Cross-switching to become plasma cells and memory B cells

Undesired: Disadvantageous mutations leading to an apoptotic B cell

17
Q

B-Cells as APC’s

A 
Less Atg conc is effective 
Receptor mediated endocytosis 
1-6 hrs btw pathogen intake and presentation
The cells reproduce BCR within 8-24 hrs 
Conformation specific BCR (MHCII present linear Atg)
Presentation depends on: 
-CR2 (CD21) positive
-Fc gamma RIIb1 negative
18
Q

What type of phase occurs in the bone marrow?

A

Antigen INDEPENDENT phase (maturation)

19
Q

What type of phase occurs in the secondary lymphoid tissue?

A

Antigen DEPENDENT phase (activation and differentiation)

Affinity maturation
Isotype switch

20
Q

Activation of naive B-cells

A

B cell presents Ag to Th by its BCR

In return, the Th gives the B cell CD40 and cytokines- the B-Cell is now activated

21
Q

Somatic mutation and selection of B-Cells

A

Activation of B-cell and migration to centrum germinativum

Somatic Mutation:

  • Proliferation of B-Cell
  • Hypermutation of Ig’s V-gene

Selection:

  • Selection of high affinity Ig expressing B-cell
  • Apoptosis of B-Cells that do not recognise antigens

Migration of B-memory and high affinity Ig expressing B-Cell

22
Q

What is the main function of plasma cells

A

Antibody secretion

23
Q

What is the main function of IgG expressing B-cells

A

Isotype switching

24
Q

What is the main function of high-affinity Ig expressing B-Cell

A 
Affinity maturation (the connection btw Ag and Ab)
Memory B-Cell
25
Q

Plasmablast can become

A

Long-lived plasma cell

26
Q

Long-lived plasma cell

A

BM: IgG
MALT: IgA
Red pulp in the spleen: IgM, IgG, IgA

27
Q

Differentiation of activated B-Cells to plasma cells, what does it depend on?

A

Cytokines!!

Prolif cytokines: IL- 2,4,5
Differentiation cytokines: IL-2,4,5 and IFNgamma and TGFbeta

28
Q

IgG structure (6)

A 
Most common in the blood (65-80%)
Mw= 160,000 
Bivalent monomer
The gamma heavy chain is responsible for its subclasses 
Serum half life is 10-20 days 
Can cross the endothelium
29
Q

IgG Functions (6)

A 
Agglutination
Precipitation
Complement activation
Neutralisation
Opsonisatoin
Cytotoxic reactions
30
Q

IgM structure (8)

A 
5-15% of serum Ab's 
Mw= 900,000
Pentameric, disulphide bridges
Its J chain has a Mr of 15,000
Mu heavy chain
Pentavalent 
Serum half life is 5 days 
Usually does not cross the epithelium
31
Q

IgM functions

A 
Primary immune response 
BCR as monomer 
Agglutination
Neutralisation
Complement activation
32
Q

IgA structure

A 
5-10% of serum abs 
NB ON BODY SURFACES!-- mucus membranes esp
Mw=360,000
Dimeric (trimer or tetramer) but is mostly monomer in blood 
Has an alpha chain and a J chain
Has secretory component (mucin) 
Half life in serum is 2 hours 
Half life on surfaces is 2 days 
Tetravalent
33
Q

IgA Functions

A

Local immune response
Agglutination
Neutralisation
Can migrate transcellularly

34
Q

IgE structure

A 
Less than 0.05% of serum Igs 
Mw= 200,000
Epsilon heavy chain
Half life is 1-2 days 
Bivalent- can bind to metals and granulocytes
35
Q

IgE functions

A

Type I hypersensitivity- anaphylaxis and allergy

Protozoa and parasite infections

36
Q

IgD

A 
BCR- is unstable 
Monomer 
Bivalent 
Mw= 180,000
alpha heavy chain
half-life is 3 days 
Always on cell membranes

Sidenote from lecture: has a very long neck, the double chain can be destroyed therefore is not good in the blood!! is not physio found in the blood

37
Q

Memory B-Cells…

A

Do not produce antibodies, but transform easily to plasma cells

Immuno (12 decks)

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