Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PH2502- immunology > Lec 7- B cell development and immunity > Flashcards

Lec 7- B cell development and immunity Flashcards

1
Q

B cell development- 6 phases

A

1) Repertoire assembly- Generation of diverse and colonially expressed B-cell receptors in bone marrow
2) Negative selection- alteration, elimination or inactivation of B-cell receptors that bind to components of the human body
3) Positive selection- Promotion of fraction of immature B cells to become mature B cells in the secondary lymphoid tissue
4) Searching for infection- recirculation of mature B cells between lymph, blood and secondary lymph tissue
5) Finding infection- activation and clonal expansion of B cells by pathogen derived Ag in secondary lymph tissue
6) Attacking infection- Differentiation to Ab-secreting plasma cells and memory B cells in secondary lymph tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Early development depends on stromal cells

A
  • Lymphoid progenitor cell (must have CAMs; VLA-4 and VCAM-1 binding)
  • Early pro-B cell (Bone marrow stromal cell)
  • Late pro-B cell (Bone marrow stromal cells release IL-7 which is a growth factor)
  • Pre-B cell (Some development of Ig
  • Immature B cell- IgM
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

B cell development is coupled to BCR

A
  • Heavy chains are rearranged (D-J then VDJ) first (no surface Ig)
  • Light chain gene activation doesn’t occur until the cell is a small pre-B cell
  • At small pre B cell Mu chain is at surface and then moves intracellular
  • Once VJ rearrangement has occurred in light chain IgM is expressed
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

B cell testing -Release to periphery or retain in BM

A

-Immature B cells in bone marrow
-No reaction with self Ag
+Immature cell moves into the blood and expresses IgG and IgM
-If there is a reaction with self Ag (must have cross linking)
+Immature B cell is retained in bone marrow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Self reactive B cells are edited

A
  • Self Ag ligates immature B cells IgM
  • Immature B cell continues to rearrange light-chain genes
  • If it is no longer reactive it is then released into the body
  • If successive new receptors (up to 4) are self reactive. No further rearrangement can occur and therefore the immature B cell undergoes apoptosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Anergy- Means alive but not very reactive

A
  • IgM of immature B cell binds soluble univalent self Ag
  • B cell is signalled to make IgD and to become unresponsive too Ag
  • Enters the peripheral circulation but doesn’t survive for long
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Tolerance

A
  • Essential
  • A state of non-responsiveness to certain Ag (i.e. self)
  • Self reactive B cells- 3 fates
    1) Receptor editing= live
    2) Apoptosis= die
    3) Anergt= live (short time)
  • Central tolerance in the bone marrow
  • Peripheral tolerance (No receptor editing, must go down apoptosis)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Tolerance 2)

A
  • Not perfect tolerance - some self Ag are inaccessible normally, revealed after infection or trauma (free up self Ag not previously present)
  • Self reactive B cells may be released that will respond to these
  • Anti-DNA antibodies made in lupus
  • Autoimmunity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

B cells leave the bone marrow when mature

A

-And circulate looking for Ag and T cell help

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

B cell circulation

A
  • 1st stage in the lymph nodes
  • B cell enter through the blood vessel
  • HEV (high endothelial venule), this enters the T cell area, passes through and enters the primary lymphoid follicle
  • This will then pass out the efferent lymphatic vessel
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

B cell circulation

A
  • Chemokine (released from stromal cells) CCL21 attracts immature B cells to HEV
  • Chemokines CCL2 and CCL19 attracts B cell into lymph node
  • Chemokine CXCL13 attracts B cells into the primary follicle (FDC display Ag to drive B cell maturation)
  • Interactions with follicular dendritic cells (FDC) and cytokines drives the maturation of immature B cells- B cells have the optimum form of immunoglobulin (BAFF- B cell activating factor
  • Mature B cells recirculate between, lymph, blood and secondary lymph tissue (Mature B cells circulate ‘naive’
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

B cell activation has different pathways

A
  • One when it enters the HEV from the circulatory system it comes into contact with B cells that have already, they will then go and form germinal centres with other B cells and plasma cells
  • Another way is that it can be in contact with its Ag while circulating then once it enters the HEV it comes into contact with Th cells, It will then turn into plasma cells, germinal centers
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

B cell + Th + Ag= activation

A 
Germinal centers 
-Class switching= IgM --> IgE 
-Mutation to optimise Ab 
Plasma cells 
-To secrete Ab 
-Ab is same specificity as surface Ig of B cells 
Memory cell 
-To be ready for the future
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Cytokines drive class switching

A 
IL4 
-Inhibit: IgM, IgG3, IgG2a 
-Induces: IgG1, IgE 
IL5 
-Augments production of IgA 
IFN-gamma 
-Inhibits:IgM, IgG1, IgE
-Induces: IgG3, IgG2a 
TGF-b 
-Inhibits: IgM, IgG3
-Induces: IgG2b, IgA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

B cell mediated immunity

A

-Neutralising antibodies inactivate pathogens or toxins
+prevent interaction of pathogens with cells
-Opsonising antibodies coat pathogens
+Facilitates phagocytosis
+Antibodies can immobilise organisms by agglutination (formation of aggregates= easier to identity and engulf)
-Antibodies bound to bacterial surfaces will activate complement and lead to lysis of bacteria
-Can activate NK cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

IgM, IgG, and IgA protect internal tissues

A 
IgM 
-Immobilises pathogens 
-Activates complement 
IgG 
-Improved Ab delivery to tissue 
-Small and rapid diffuse 
Monomeric IgA 
-Support IgG
17
Q

FcRn- transport IgG across the endothelium

A
  • Fluid-phase endocytosis of IgG from the blood by endothelial cells of the blood vessels
  • The acidic pH of the endocytic vesicle causes the association of IgG with FcRn, protecting it from proteolysis
  • On reaching the basolateral face of the endothelial cell, the basic pH of the extra-cellular fluid dissociate IgG from FcRn
  • This pathway is similar to what happens with breast feeding mothers and their babies
18
Q

Dimeric IgA protects mucosal site

A
  • Binding of IgA to receptor (poly-Ig receptor) on basolateral face of epithelial cell (transcytosis- transport across a cell)
  • Receptor-mediated endocytosis of IgA
  • Transport of IgA to apical face of epithelial cell
  • Receptor is cleaved, IgA is bound to mucus through the secretory piece, little bit of the poly Ig receptor is left on the molecule which will keep it anchored to the epithelial layer
19
Q

IgE allows rapid ejection of pathogens

A
  • Binds to an Fc receptor (FceR1)
  • Awaits a pathogen
  • Cross-linking activates mast cell degranulation
  • D and V
  • We will revisit this in hypersensitivity
  • Resting mast cells have pre-formed granules containing histamine and other inflammatory mediators
  • Multivalent Ag cross-links IgE antibody bound at the mast- cell surface, causing release of granule contents
20
Q

IgE allows large parasite defence

A
  • IgE opsonised pathogen
  • Eosinophils can recognise via FceRI
  • Degranulation: death of parasite
21
Q

IgG mediates cell killing

A
  • ADCC antibody-dependant cell cytotoxicity
  • IgG and Fc(gamma)RIII (CD16)
  • NK cell activation= apoptosis
  • Antibody binds Ag on the surface of target cell
  • Fc receptors on NK cell recognises bound Ab
  • Cross linking of Fc receptors signals the NK cells to kill the target cell
  • Target cell does by apoptosis
22
Q

Ab distribution caries throughout the body

A
  • MUCOSAL AREAS: dimeric IgA

- Brain and eye: nothing there

23
Q

Herpes virus why is it recurrent

A
  • Virus infects and body fights it
  • Body makes the conditions for the virus not favourable and symptoms go away
  • body thinks virus is dead but in actual fact it has just retreated to an immunocompromised area (somewhere your immune system can’t access it) i.e. within axon of neurones
  • When conditions become more favourable it re-presents
24
Q

Ab can neutralise

A

-Prevent adhesion of
+Bacteria to host cells- IgA binds to pathogens and so can’t effects cells so move straight through the gut and excreted
+Toxins to receptors- neutralising Ab blocks binding of toxins to cell-surface receptors

25
Q

Ab can activate complement (classical pathway): which Ab

A
  • IgM and IgG3 are the best (if asked give IgM as the example)
  • IgG1 is good at activating
  • IgG2, IgA1, IgA2 are all ok at activating but not creating
  • IgD, IgG4, IgE cannot activate complement
26
Q

Ab can fix complement (classical pathway) how

A
  • Pentameric IgM binds to epitopes of the pathogens Ag
  • This allows C1 to fit on the stable IgM
  • C4 and C2 then come in to form C3 convertase
  • C3a initiates phagocytosis
  • C3b opsonises pathogen C5-9 lysis of pathogen
27
Q

Fc receptors permit Ig Opsonised uptake

A
  • Ab binds to bacteria
  • Ab-coated bacterium binds to Fc receptors on cell surface (macrophage can identify macrophage)
  • Macrophage membrane surrounds bacterium
  • Macrophage membranes fuse, creating a membrane-bound vesicle, the phagosome
  • Lysosomes fuse with phagosome, creating phagolysosome
  • Complement receptors permit complement-opsonised uptake

PH2502- immunology (16 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions