26.07.2013 Views

Untitled - D Ank Unlimited

Untitled - D Ank Unlimited

Untitled - D Ank Unlimited

SHOW MORE
SHOW LESS

You also want an ePaper? Increase the reach of your titles

YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.

Calmette, Albert (1863–1933) 131 Campylobacter immunity<br />

Endoplasmic reticulum<br />

Cytosol<br />

TAP<br />

transporter<br />

Peptides<br />

Peptides are transported into the endoplasmic reticulum.<br />

Once the peptide binds, MHC class I<br />

folding is complete and calnexin is<br />

released.<br />

Calmette, Albert (1863–1933)<br />

French physician who was subdirector of the Institut<br />

Pasteur in Paris. In a popular book published in 1920 titled<br />

Bacillary Infection and Tuberculosis, he emphasized the<br />

necessity of separating tuberculin reactivity from anaphylaxis.<br />

With Guérin, he perfected the BCG (bacille<br />

Calmette–Guérin) vaccine and also investigated snake<br />

venom and plague serum.<br />

calnexin<br />

An 88-kDa membrane molecule that combines with<br />

newly formed α chains that also interact with nascent<br />

β 2-microglobulin. Calnexin maintains partial folding of<br />

major histocompatibility complex (MHC) class I molecules<br />

in the endoplasmic reticulum. It also interacts with MHC<br />

class II molecules, T cell receptors, and immunoglobulins<br />

that are partially folded.<br />

calreticulin<br />

A calnexin structurally-related soluble protein present in the<br />

endoplasmic reticulum that facilitates proper folding of major<br />

histocompatibility complex (MHC) molecules and other<br />

glycoproteins; a molecular chaperone that binds to MHC class<br />

I and class II, as well as other immunoglobulin-like domains<br />

containing proteins, including antigen receptors for both T<br />

and B cells. Calreticulin resembles calnexin structurally and<br />

functionally.<br />

CAM (cell adhesion molecule)<br />

Cell-selective proteins that promote adhesion of cells to one<br />

another and are calcium-independent. They are believed to<br />

help direct migration of cells during embryogenesis. The<br />

majority of lymphocytes and monocytes express this antigen,<br />

which is not found on other cells. The “humanized” antibodies<br />

specific for this epitope are termed Campath-1H. Refer to<br />

CD52.<br />

campath-1 (CD52) CAMPATH-1M<br />

A rat immunoglobulin M (IgM) monoclonal antibody<br />

against the CD52 antigen. It is able to lyse cells using<br />

human complement, making no other manipulation necessary<br />

to deplete T cells other than to add donor serum.<br />

This antibody has been used to deplete T cells to prevent<br />

MHC class I Calnexin<br />

The folded molecule is exported<br />

to the Golgi apparatus.<br />

Calnexin.<br />

Calnexin is bound to partially folded MHC class I.<br />

Peptide approaches MHC class I.<br />

MHC class I transports the bound<br />

peptide to the surface of the cell.<br />

graft-vs.-host disease. It is a lipid-anchored glycoprotein<br />

with a very small peptide constituent. Anti-CD52 antibodies<br />

are potent lytic agents, killing cells in vitro with human<br />

complement as well as in vivo. These antibodies have been<br />

used for therapy of leukemia, bone marrow transplantation,<br />

organ transplantation, rheumatoid arthritis, vasculitis,<br />

and multiple sclerosis. Campath-1H (human IgG 1) was the<br />

first monoclonal antibody to be humanized. It was formed<br />

by transplanting complementarity-determining regions of<br />

campath-1G into human heavy and light chain genes. Even<br />

though initial binding affinity was decreased, this was corrected<br />

by modifying framework residues. Patients receiving<br />

this humanized antibody developed very low antiglobulin<br />

responses compared with the original rat antibodies. The<br />

CD52 antigen is a glycoprotein with only 12 amino acids. It<br />

is a complex carbohydrate consisting of sialylated polylactosamine<br />

units with fucosylated mannose cores. It is<br />

attached to Asn3 at the C terminus as a glycosylphosphatidylinositol<br />

(GPI) anchor. The campath-1 epitope is comprised<br />

of the C terminal amino acids and part of the GPI<br />

anchor, which means that the antibodies bind near the cell<br />

membrane, facilitating cell lysis. The antigen is expressed<br />

abundantly on all lymphocytes except plasma cells and<br />

also on monocytes, macrophages, and eosinophils. It is not<br />

found on any other tissues except the male reproductive<br />

tract, where it is strongly expressed on epithelial cells lining<br />

the epididymis, vas deferens, and seminal vesicle. The<br />

CD52 antigen is a principal membrane protein of sperm.<br />

Campylobacter immunity<br />

Circulating antibodies develop rapidly in patients with<br />

Campylobacter enteritis. These antibodies fix complement,<br />

are bactericidal, and agglutinate. Following an initial but<br />

short-lived immunoglobulin M (IgM) response, a rapid<br />

IgA response peaks 14 days after onset of symptoms but<br />

declines by the fifth week. IgG antibodies appear by the<br />

tenth day after infection and are present for several months.<br />

Antibodies are believed to limit the infection. Serologic<br />

tests for diagnosis depend on an acid-extractable surface<br />

antigen that consists mainly of flagellin, which is the<br />

C

Hooray! Your file is uploaded and ready to be published.

Saved successfully!

Ooh no, something went wrong!