In which a B cell responds to a protein antigen

:Mature but naïve B cell leaves the spleen with its new & shiny IgM and IgG:

:It is looking for its missing piece! And it is hungry:

:enters a LYMPH NODE paracortex through a high-endothelial venule:

:TH cells waiting in the paracortex eye him with interest, but when they see he is not expressing MCH II they look away:

:B cell occupies a dormant primary follicle in lymph node cortex, ready for action:

:When it gets bored it enters circulation again and searches:

:The follicles in the Spleen are positioned around a central arteriole, giving him a good view of circulating molecules:

B cell recognizes its protein epitope!

:Binds, endocytoses the suspecious protein;

B: ‘yum!’

:rips it apart inside his tummy

binds its identifying characteristics to MHC II molecules;

(even pieces that he does not recognize as suspicious, just in case someone else does)

and displays the peptide-MCH II complexes on his membrane surface:

Now to find a T cell that recognizes this threat!

In anticipation, he synthesizes & expresses B-7, CD40, and some cytokine receptors

[SCENE: a lymph node; at the junction of cortex and paracortex]

:B enters the room:

B: ‘HEY!’

B: ‘LISTEN!’

:A naïve mature CD4+T cell recognizes its epitope bound to MHC II:

T: ‘HEY!’

B: ‘MHC II! EPITOPE! ALSO, CD40! AND OH YEH, CD40!’

T: ‘OMG. CD40L. CD28’

:The two naïve mature cells are activated simultaneously:

:The T cell synthesizes IL2 and IL2R:

:The T cell releases cytokines that bind its own membrane receptors!:

The T cell begins clonal expansion

All its offspring have the same epitope recognition site

They differentiate into effector or memory T cells

The effector clones differentiate into TH1 or TH2 cells, based on cytokines that bind them

The differentiated effector TH clones venture forth to the circulation to patrol for antigens bound to MHC II!

:IL2 also lands on the B cell, as well as other cells, maybe:

:The room is filled with mitotic and differentiating lymphocytes:

 

≫>This part requires IL4, and I’m not sure where it comes from

≫>But since this CD4+ cell was activated by a B cell, it’s definitely time for a humoral immune response:

:The T cell levels up!:

Mature naïve TH cell has become an effector TH2 cell!

:The TH2 secretes IL4 and IL5:

:They land on the B cell’s receptors:

The B cell begins to proliferate by mitosis

The room is filled with lots of little (not really) B cells with the exact same BCR!

:The progeny B cell clones mostly differentiate into PLASMA CELLS:

:some become MEMORY CELLS:

:The Plasma cell clones all express identical IgM BCRs:

MUTATION TIME!

:IL4 from a TH2 cell binds a Plasma clone:

:The Plasma cell undergoes a isotype switch!:

:Its inherited VDJ gene segment detaches from the μ heavy chain segment!:

:The VDJ gene segment recombines with the downstream ε heavy chain segment!:

:The Plasma clone has a new effector function!:

IgE-mediated ADCC with Eosinophils, Mast cells and Basophils

The result is inflammation

:IL4 + IL5 from TH2, +IL2 from TH1 lands on a Plasma clone!:

:Its variable region gene segment recombines with μ heavy chain segment!:

:It already had that isotype! How boring!:

IgM binds the antigen and provides a binding site for complement proteins, which perforate its membrane and kill it

:There are now more TH2 cells competing for dominance with TH1:

:TH1 secretes IFN-γ:

:A Plasma clone switches isotopes to IgG:

IgG is an opsonin! They coat the invader and provide binding sites for Phagocytes, which swallow it whole.

I don’t feel like talking about IgA and I’m pretty sure it doesn’t show up til later anyway.

:The newly-armed Plasma cells only have 3-6 days to live!:

:But before they mobilize, it’s time to play a game:

:The clones crowd into a follicle in the cortex of the lymph node:

:or maybe they were already there, IDK:

FOLLICULAR DENDRITIC CELLS are waiting

They have collected ANTIGEN  by grabbing complement fragments (C3b, C3d) and IgG bound to it

Their job is to test the antigen-binding ability of the mutated immunoglobulins

:The primary follicle activates into a GERMINAL CENTER:

 (it may have activated back at proliferation but it’s more fun this way.)

:The timer starts:

:Suddenly all the clones receive an APOPTOSIS SIGNAL:

:If they do not bind tightly to antigen in time,

they will experience PROGRAMMED CELL DEATH:

:The Germinal Center swells with activity:

:The clones scurry about, playing musical chairs FOR THEIR LIVES:

The FOLLICULAR DENDRITIC CELLS, once satisfied with a clone’s binding abilities,

delivers a signal that blocks the apoptotic pathway

:Everywhere clones are exploding:

:Cytoplasm is everywhere:

:The time is up:

:The strongest have survived:

:They receive little trophies:

:Some of them are memory cells, I forgot to mention that:

:Net result: a population of B cells that produce Ig with high affinity for its epitope:

:They exit the follicle, which is now just a dormant primary follicle once more:

:Stepping (rolling?) across the shredded bodies of their fallen comrads:

The Plasma B cells mobilize throughout the body system

They occupy ‘Extrafollicular sites’ at peripheral lymphoid organs

Because the memory of the game still haunts them

They synthesize and secrete antibodies into the stream

The antibodies work with lymphocytes in destroying the invading antigen

The threat is eradicated

Everyone dies

The End.

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s