1-17 Snow Humoral Immune Respone Part 2

Front 1

Within the germinal center there are two types of B cells

Back 1

centroblasts- actively dividing- in the dark zone
centrocytes- resting B cell- in the light zone

Front 2

What is the general life cycle happening with the b cells in the germinal center?

Back 2

the centroblasts divide and then go to the light zone to rest, but they must then receive signal 1 then 2 or they enter programmed death

Front 3

How is somatic hypermutation happening?

Back 3

In the dark zone the centroblasts shed their receptors (don't want to have a mix) and using the AID enzymes do the point mutations. At a certain point they stop dividing and turn into centrocyte and express their new receptors. In the light zone they compete for the Ag- they only have ~20 hours to get it before they apoptose.

As time goes on- 8 weeks later- and Ag is low in supply, it gets very competitive and a cell must have very strong affinity to survive

Front 4

What kinds of things happen in germinal center to cause class switching?

Back 4

during the second week after some of the somatic hypermutation has already been going on, some of the higher affinity cells will take in the Ag, process it, and get cognate with helper t cell for signal 2. They can shed receptors and go back to centroblast OR they can class switch instead.

When centrocyte expresses AID does class switching- VDJ moved near other Ig isotype.

Front 5

How is class switching regulated?

Back 5

The helper cells make different cytokines combinations over time and it causes different isotypes to come out from the Ig A G E. (Ig3 then 1 2 and 4 in that order which is just down the chromosome actually)

Front 6

Plasma cells in the blood indicates what?

Back 6

you have a very sick pt- a myeloma. They're supposed to be in the bone marrow.

Front 7

After the somatic hypermutation and class switching, what's another fate the centrocyte may have?

Back 7

become a Memory B cell. The receptors/Ab they have will be whatever isotype they had from class switching. These are regulated the same for if they're receptor or Ab form. These home onto secondary lymphoid tissues throughout the body

Front 8

What happens during congenital deficiency of CD40L?

Back 8

hyper-IgM syndrome
you can't get second signal from helper T cells, so no affinity maturation, isotype switching, or memory cell generation (all these steps need signal 2 feedback for centrocyte)

Front 9

What are plasma cells like?

Back 9

they are Ab factory and they don't do anything else. They are terminally differentiated.

Front 10

So, what's the big difference between TD and TI antigen responses?

Back 10

in both you need signal 1 and 2, but only in TD can you go from parafollicular response to germinal center response for the affinity maturation, isotype switching, and memory cells

Front 11

Which Ig isotypes do you find where?

Back 11

Lots of IgG in blood and body
Lots of IgA monomeric in blood and body
Lots of IgA dimeric in mucousal surfaces (so if you ever sample these surfaces there should be a bunch- they have a problem it's all IgM)
IgM in blood
IgE on basophils and mast cells right below epitheliod barriers-- was for parasites, but now just allergies

Front 12

What Ab's go across placenta?

Back 12

All subtypes of IgG though these are passive transfer so only last a while

Front 13

What Ab's can go through breast milk?

Back 13

IgA dimeric-- so definitely recommend

Front 14

The endothelial cell receptor, ___, transports Ig_ from the bloodstream into extracellular spaces.

It's also what does.. ?

Back 14

FcRn puts out IgG

puts IgG across the placenta- that's why only IgG's go across-- this FcRn

Front 15

what is missing in the diagram?

Back 15

IgA coming across in the breast milk

Front 16

Every once in a while maternal Ab interfere with ..

Back 16

vaccines because maternal Ab's address- especially live attenuated viral vaccines

Front 17

Along your epitheliod barrier you have your immune responses which drive germinal centers to make Ig_ and Ig_ plasma cells.

Back 17

IgA and IgM

Front 18

Which form of IgA are made in the sub epitheliod barrier areas?

Back 18

the dimeric version because it has to be dimeric form to interact with the poly-Ig receptor (PIG receptor). That's how you get transcytosis of IgA. IgM, remember, makes pentamers all the time nbd.

Front 19

the IgA is modified as it gets transcytosed- what is that about?

Back 19

when it interacts with the PIG R it actually gets attached to it. In order to release there's a cleavage event except that it leaves a fragment of the PIG R to the IgA and they call that the secretory component- that piece is important because it protects the Ab from cleavage of digestive enzymes

Front 20

What is one of the main jobs of IgA on the mucousal surface? (this happens in the body too though)

Back 20

virus neutralization. Viruses have trophism (attaching to our cells, like HIV for CD4). If they can't bind like during neutralization, the virus can't work.

If a bacteria binds, it colonizes which is bad.

Front 21

What are toxins (as far as we're concerned now)?

Back 21

small lightweight protein that moves away from site of infection and wreaks havoc doing bad things-- because it leaves, it's really difficult to make Ab to this. So vaccines are really really helpful for these (tetanus and diphtheria)

Front 22

IgM has low affinity for complement but they're good at fixing it

Back 22

because as a pentamer they have good avidity

Front 23

Different Ab isotypes and how they fix complement

what's another affinity they have that varies in this same pattern?

how does affinity maturation vary?

Back 23

order of expression: IgM, IgG3, IgG1, IgG2, IgG4
highest complement to lowest: same order
gene order on chromosome: same order
affinity for Fc gamma to facilitate phagocytosis: same order for IgG's

there are more somatic hypermutation rates as you go down the list so IgG3 has much less change than IgG4

Front 24

So comparatively IgG2 and IgG4 have the best affinity but don't do anything good when it comes to inflammation- why do we bother with these isotypes?

Back 24

inflammation can be really damaging, so it needs to be turned off at some point. These aren't giving B cells the signal 2 and IgG4 actually sends a signal through FcR to turn off signal 1 in b cell

Front 25

What about IgA- why is it so weak at inflammation?

Back 25

do u want your guts inflamed? You don't want these to be really sensitive because you have so much bacteria in your gut

Front 26

why for IgG3?

Back 26

IgG3 has the weakest affinity, but the super flexible hinge means avidity is not so bad but these are turned over quickly because the long hinge can be targeted?

Front 27

Fc receptors are pretty useful for stuff like

Back 27

innate cells phagocytose opsonized materials (IgG3 IgG1)

Front 28

NK- how do they work?

Back 28

IgG goes through CD16 FCgamma RIII
IgA goes through CD89 FCalpha RI

if this happens they release cytotoxins to target cell

ADDC antibody-dependent cell-mediated cytotoxicity

Front 29

What's IgE doing?

Back 29

on mast cells using Fc epsilon RI. When they have something cross-link across, mast cell activated. Supposed to be for parasites, but domestically we have more problems with pollen or mite feces