1. local DC process antigen and takes to draining LN
2. Lymphocytes activated will stay and proliferate
3. if not activated lymphocytes cont to recirculate through hymph and blood

1. Enter LN through HEV by expressing CCR7
2. attracted to primary follicle by CSCL13

IL-12 from Dendritic Cell, Vitamin D

Bind to CCR4, CLA, CCR10

The form a dimer bound by a J-Chain that also has a receptor for epithelial cells allowing the dimer to be transcytosed across the epithelial layer into the gut lumen to neutralize microbes and toxins.

After IgA is bound, M-Cells bring it all back in through endosomes to be brought to DC

B-cell orientation to isotype subclasses

recruit eosinophils - PARASITES

1. cytokines like IL-1beta, or TNFalpha are very destructive-cause apoptosis
2. constant exposure of microbes, like in gut, keeps cells partially activated, but you don't want them to get out of control

Eliminate pathogen, having short lived plasma cells and antibodies, suppress T cells

T-cell regulation is most important bc they are the most potent and can keep getting activated and live for a long time

1. AICD
2. suppression of co-stimulatory molecules
3. regulatory T-cells

After T-cell activation by TCR and CD28 binding B7 CTLA-4 is upregulated which competes with higer affinity than for CD28 for B7, so the T cell is activated less.

Also, when CTLA-4 is bound to B7 it induces transcription of genes that will inhibit activation of T-cell

CD8-Reg T cell

Th3

Treg1

-naive T cells that are 'induced' by DC from persistent presentation of microbes in local tissues

Dec. MHC and B7

Dec. APC function

Dec. inflammatory cytokines

Dec proliferation

dec IL-4

Dec IFN-gamma

1. inhibitory cytokines
2. Cytolysis (CD8-Reg)
3. Targeting DC to disturb maturation so it can't activate T-cells
4. Metabolic Disturbance-capture IL-2 in environment (through CD25)-depriving T-cell, which causes death

1. Knock out RAG1/2 genes so mice won't have their own T-cells
2. Isolate naive (CD62) T-cells from spleen of good mouse
3. Introduce to no T-cell mouse

With just T-cells caused massive inflammation of gut when exposed to antigen

But with Treg cells also, it suppressed disease

After txt with anti-IL10 and anti-TGFbeta suppressive effect decreased

To show that Treg cells leave a minimum amount of infection to persist without damage in order to have time to acquire long term immunity.

-w/o Treg cells infection is cured quickly without est. long term immunity

L.major inf, Treg cells isolated and put with DC with L.major on MHC and with another microbe and IL-10 was only released for DC w/L.major antigen.

-TCR specific for particular antigen

Babies have the biggest thymus which undergoes involution with age (replaced by fat).

little T-cell development with age

IL-7 is secreted by thymic epithelial cells in the cortex which inc. the expression of Notch1L on their surface to bind Notch1 on Thymocyte-

When Notch1 is bound it intracellularly cleaves portion to act as a maturation transcription factor

Cortical Epithelial Cells of the thymus expressing MHC class I and II bind TCR to test if it is attracted to self MHC, if it is it proliferates-if not it dies.

The type of MHC it binds to determines if it will be CD8 or CD4

What is the process of Heavy chain rearrangement and what if a successful H-chain doesn't arise?

What kind of B cell is this happening in?

Both chromosomes rearrange until one produces a successful which arrests rearrangement of the other chromosome and a preBCR is created.

If niether are good the cell dies.

A pro-Bcell

it is the heavy chain coupled to a surrogate light(vprebeta and delta5) and Igalpha and Igbeta chain internally to see if it has the ability to bind to a light chain.

Only if the heavy chain successfully binds can the light chains start to rearrange

1. with preBCR to see if H-chain binds surrogate

2. to see if the light chain rearrangements were successful

-death if not successful-

if the IgM in BM binds self peptide it stays in the BM and undergoes Receptor Editing of light chain to fix the problem, if still binds self peptide it dies

If it doesn't bind self peptide it leave BM to blood and upregulates IgD