lymph node development and T cell migration

What chemokine is produced by lymph node stromal cells, starting the process of cellular recruitment into the lymph node?

CCL21

Where do we find the follicular dendric cells?

follicle

Diapedesis is the process of the T cell moving between the endothelial cells. This process is mediated by

chemokine gradient

Naive T cells enter lymph nodes via endothelial cells call HEVs. The first stage of entry is "rolling" along the HEVs. What on the surface of the T cell stimulates the "rolling?"

selectins

What chemical in the blood attracts T cells out of the lymph node?

S1P

What chemokine receptor is expressed on activated dendritic cells that causes them to migrate to the lymph node?

CCR7

When do dendritic cells (DC) express the most B7 on the surface of their cells?

Activated DCs in the lymph node

When do dendritic cells (DC) express the most phagocytic receptors like dectin-1 and DC-SIGN?

resting DCs in the tissue

Lymphnodes organize around gradients of...

chemokines

This cell is the fist to enter a lymph node.  It produces CCL21, creating the gradient that stimulates the chemotaxis of the other cells that make up the mature lymph node.

stromal cells

Immature dendritic cells are attracted to tissue because they express tissue specific chemokine receptors like…

CCR 1,2,5, or 6

Activated dendritic cells are attracted to lymph nodes because they express the lymph node specific chemokine receptor…

CCR7

Naïve T cells, expressing CD28, engage with activated Dendritic cells via the TCR/MHC and CD28

B7

How many different types of T cells inspect MHC class I restricted antigens?

1 (cytotoxic T cells)

How many different types of T cells inspect MHC class II restricted antigens.

5

Which type(s) of T cells are responsible for directing infections of the following types.

Bacteria and fungi infection of mucosal tissue: TH17, TH1

Viruses: TFH

Bacteria that persist in macrophage vesicles: TFH, TH1

Parasite and helminths: TH2

What type(s) of cytokines are released by TH1 T cells and what do these cytokines do?

cytokines released: IFN-gamma

activates macrophage causing them to fuse endosomes with lysosome, primary and secondary granules

What type(s) of cytokines are released by TH2 cells and what do these cytokines do?

cytokines released: IL-4, IL-5, IL-13

stimulate B cells to isotype switch to IgE, increase mucus production and increase differentiation of mast cells, basophils and eosinophils

What type(s) of cytokines are release by Treg cells and what do these cytokines do?

cytokines released: IL-10 and TGF-beta

decease inflammation and suppress the activity of the other T cell types

Describe the mechanism of polarization observed in TH1 vs TH2 cells

TH1 cell release IFN-g that suppresses the development of TH17 and TH2.

TH2 release IL-4 that suppresses the development of TH1 and TH17

You are setting up an experiment to study T cell polarization. You inject mice with antibodies to remove IL-4 from mice. The mice were then infect with the parasitic blood fluke Schistosoma mansoni. The parasite is usually controlled by basophils and eosinophils. What would you predict would happen in your experiment? Explain.

the mice die

What are the two human diseases caused by Mycobacterium leprae

tuberculoid leprosy and lepromatous leprosy 

Describe the clinical presentation of Tuberculoid leprosy.

organisms present at low undetectable levels, low infectivity, granulomas and local inflammation, peripheral nerve damage, normal serum Ig levels, normal T-cell responsiveness, specific response to M. leprae antigens

Describe the clinical presentation of Lepromatous leprosy.

organisms show florid growth in macrophages, high infectivity, disseminated infection, bone cartilage and diffuse nerve damage, hypergammaglobulinemia, low or absent T-cell responsiveness, no response to M. leprae antigens

Which cytokines are found in Tuberculoid leprosy lesions?

IL-2, IFN-gamma, LT, IL-4

Which cytokines are found in Lepromatous leprosy lesions?

IL-4, IL-5, IL-10

What type of T cell polarization do you think happens in Tuberculoid leprosy?

TH1

What type of T cell polarization do you think happens in Lepromatous leprosy?

TH2

Case Study #46 is about Ursula Iguaran who is diagnosed with lepromatous leprosy. List her primary clinical signs and symptoms observed by her primary care physician

loss of eyebrows/eyelashes, recurrent nosebleeds, loss of sensation on back of hands, hyper-pigmented lesions on both arms

Which test done to Ursula’s dermatologist was suggestive of a Mycobacterium leprae infection?

biopsy on arm lesions which revealed acid-fast bacilli in clumps 

How was Ursula treated? Was the treatment successful?

She was placed on a drug regime: dapsone, clofazamine, rifampin (which are antibotics that kill M. leprae) and her lesions gradually flattened

What type of T cell response do you suspect happed in Ursula’s body?

TH2

An alternate treatment for Ursula could have been injection of cytokine specific antibodies. What cytokines, if removed, could change the progression of Ursula’s disease?

IL-4