Re: Th1/Th2

[Guest guest]

Heres a partial account of Th2 swinging into action:

Antigen-presenting cells - macrophages, monocytes, but chiefly

dendritic cells - degrade what they ingest, and present various

epitopes (antigen pieces) to T cells of those particular clones

suited to recognize those epitopes - and those particular clones

activate, and proliferate vigorously. I forget when it is they commit

from Th0 to Th2. Regardless of when, from what Barb is saying, it

sounds like no one knows fundamentally how it is " decided " in

response to a certain stimulus that many activated Th2 cells should

be produced.

B-cells also capture and present antigen, in a cool freaking way -

they fish for it using examples of the particular kind of antibody

they are able to make, fixed onto their outer surface. When they

degrade antigen thus captured and present it to activated T cells,

they themselves recieve activation from the Ts, and start pumping out

antibodies copiously. (There are a few antigens that can make B cells

activate autonomously and and begin releasing antibody, but with most

antigens they require the activation from T-cells, as described.) So

thats how you get antibody, which of course is a big part of Th2.

This antibody often needs to get out of blood and into tissue humor

where the foe often is, which is supposed to be accomplished by

inflammation, according to Doc Ks. I am confused as to why the Th2

cytokines, which are the language of the intercell communication

essential to all these matters, are antiinflammatory. What

inflammation means, physically, is changes in vasculature which

facilitate the lavage of blood serum componants (including antibody)

and leukocytes from the vasculature into tissue, according to Doc Ks.

Doc Ks Microbio (see google) is a pretty good web source which

provided my earliest guidance in these matters - but doesnt always

agree precisely with W s Fundamental Immunology, which at 1700

pages and ~10,000 refs is naturally more nuanced and careful.

Then there are the Th2 myeloids (non-lymphocytes) like eosinophils -

and(?) basophils. I understand they beat up on helminths, but I dont

know the first thing about it. I have never seen an anti-bacterial

capacity of eosinophils discussed, and I dont know what may be the

functional distinction between eosinophil-inducing invaders and

bacteria. Strangely, the lyme histology by Nanagara (1995(?)) found

eosinophils to be by far the dominant infiltrating leukocyte in the

joints of one patient, which was suggested to possibly have to do

with immune complexes. More commonly the tissue and leukocyte

infiltrates in lyme joints look very much like RA.

I think mast cells also can have a role in Th2 responses - I think

they can figure in Th1 too. I think maybe their sole purpose is to

emit vasoactive inflammatory mediators (eg histamine) when stimulated

by cytokines. They are fixed cells but may be able to proliferate - I

dont remember.

scha wrote in part:

> What do you mean when you say that " helminths...activate Th2? " What

> exactly is it they activate, or what are the direct effects?

>

> I think it would be good to assume that question when we post. I

> don't now the answer for my own favorite use of the Th1/Th2

> dichotomy, but thought perhaps you'd know more about 'heminths'.

>

> Do they by chance leave your receptors feeling minty fresh?

>

> Cheers,

>

>

[Guest guest]

>> I think mast cells also can have a role in Th2 responses - I think

> they can figure in Th1 too. I think maybe their sole purpose is to

> emit vasoactive inflammatory mediators (eg histamine) when

stimulated

> by cytokines. They are fixed cells but may be able to proliferate -

I

> dont remember.

FWIW:

Scandinavian Journal of Immunology

Volume 59 Issue 3 Page 267 - March 2004

Regulation of Mast Cell Migration by TH1 and TH2 Cytokines:

Identification of Tumour Necrosis Factor-alpha and Interleukin-4 as

Mast Cell Chemotaxins

Mast cells act as central effector and regulatory cells in many

inflammatory disorders, including T helper 1 (TH1)-mediated

inflammations such as autoimmunity and TH2-mediated inflammations such

as allergy and parasite infections. One characteristic for mast

cell-mediated inflammations is the accumulation of mast cells in the

inflamed tissue. The factors regulating mast cell recruitment in these

inflammations are still not fully characterized. We have investigated

the potency of TH1- and TH2-secreted cytokines to mediate mast cell

migration. Supernatants from six different TH1 and TH2 clones were

tested for mast cell-chemotactic activity using the human mast cell

line (HMC-1) as a responder cell. All six clones produced factors that

induced mast cell migration. Using blocking antibodies to a broad

range of cytokines, we found that anti-tumour necrosis factor-alpha

(anti-TNF-alpha) reduced the migration of mast cells to supernatants

from TH1 clones. In contrast, the main mast cell chemoattractants

secreted by TH2 clones were found to be interleukin-4 (IL-4) and IL-8.

The potency of these cytokines to act as mast cell chemoattractants

was confirmed by using recombinant IL-4, IL-8 and TNF-alpha. Our

results suggest that TNF-alpha can be involved in the recruitment of

mast cells in TH1-mediated inflammations, whereas IL-4 and IL-8 might

play a similar role in TH2-mediated inflammations.

[Guest guest]

> Imagine that monocyctes such as macrophases are multifunctional.

Have you read this article?

J Leukoc Biol. 2004 Sep;76(3):509-13. Epub 2004 Jun 24.

Functional plasticity of macrophages: reversible adaptation to

changing microenvironments.

There has been substantial research activity in the past decade

directed at phenotyping macrophage lineages and defining macrophage

functional subsets or patterns of activity. The emphasis over the past

2-3 years has been to divide macrophage functional patterns into type

1 (Th1-driven) or type 2 (Th2-driven) functions. However, a huge array

of environmental factors (including cytokines, chemokines, pattern

recognition receptors, hormones) differentially regulates macrophage

response patterns, resulting in the display of numerous distinct,

functional phenotypes. Upon stimulation, a macrophage does not display

just a single set of functions but rather displays a progression of

functional changes in response to the progressive changes in its

microenvironment. The remarkable ability of monocytes and tissue

macrophages to adapt to changes in their microenvironment challenges

the thesis that macrophages displaying unique tissue-specific or

response-specific, functional patterns represent distinct lineages.

With the exception of mature osteoclasts and mature dendritic cells,

evidence supporting stable differentiation as the basis for macrophage

functional heterogeneity is equivocal. The concept of whether

macrophages develop into functional subsets as opposed to continuously

adapting their functional pattern in response to the changing

environment of a progressive inflammatory response is important to

resolve from the perspectives of therapeutic targeting and

understanding the role of macrophages in disease pathogenesis.