Inmunología , Tipos De Celulas

Modeling

Examples of Models

Model organisms: bacteria, Dictyostelium (amoeba), yeast,C. elegans, Drosophila, Arabidopsis thaliana (fruit fly of plants) , zebrafish, mice. A good model is something that allows you to manipulate and play with things with a lower risk. Any good theory it’s a good model. Preserves the essential logical relationships or information pertinent to the problem

The Immunoglobulin Superfamily

Genes in the immunoglobulin superfamily provide instructions for making proteins that have a certain region called an immunoglobulin-like (Ig-like) domain. The domain is described as Ig-like because it resembles regions found in molecules called antibodies (also known as immunoglobulins).

What makes a protein a family member?

1. The molecule has at least one “immunoglobulin domain.” An immunoglobulin domain consists of a pair of β-sheets linked by a disulfide bond and hydrophobic interactions. Three hypervariable loops lie at one end of the structure. Beta-Sandwich Framework with Hypervariable Loops

2. In this domain, the peptide fan-folds into a compact lump.

3. Hydrogen bonds hold these switchbacks into β pleated sheets

4. Disulfide linkages further stabilize the domain. They form by covalent joining of two cysteine R groups.

5. You can refer to the whole domain as a “bread and butter sandwich,” because the hydrophobic amino acid side chains wind up at the interior of the structure (butter) the hydrophilic at the exterior (bread) and the disulfide bond function like a toothpick in nailing everything together.

6. Often represented by a structure looking like a capital C with the ends joined by disulfide link.

7. Most of these proteins extend from the plasma membrane, nailed there by membrane-spanning regions. Antibodies are a rare exception.

Tell me a story.

1. 650 million years ago, the oceans froze solid to a depth of a mile. Liquid water remained on land around hot springs, and life also clung to the thermal vents in the depths of the ocean.

2. At this time, organisms were small and simple in structure

3. 600million years ago, the earth warmed and melted.

4. Life multiplied, spread and evolved, using these molecules to construct complex structures.

5. Animals used immunoglobulins to tag nerve cells and serve as signal receptors during development.

6. Eventually animals began using immunoglobulins to recognize not-self, which is how they came to be involved in immune responses.

The Structure of Immunoglobulin Receptors (BCR) and Antibodies

An antibody (Ab), also known as an immunoglobulin (Ig), is a large Y-shape protein produced by plasma cells that is used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, called an antigen. Each tip of the "Y" of an antibody contains a paratope (a structure analogous to a lock) that is specific for one particular epitope (similarly analogous to a key) on an antigen, allowing these two structures to bind together with precision.

Basically an Ig receptor (or B-cell receptor) is an antibody with a membrane-spanning and cytosolic domain at the end (C-terminal) . Thus the antibody is soluble and secreted from the cell and the receptor version is stuck in the cell membrane with the business end facing outside the cell.

A. Terminology

1. In the 1960s, chemists classified proteins as fibrous (silk, collagen) versus globular proteins (most proteins, actually). Globular basically meant soluble.

2. immunoglobulins: the protein fraction in the plasma involved in fighting disease.

3. Gamma (high mobility) fraction

4. Scientist purified this fraction and used it to study the structure of the antibody.

B. Analytical History – Porter and Edelman

1. Gerald Edelman - treated antibodies with mercaptoethanol

a. This treatment reduces the disulfide bond, thus breaking the covalent bond that stabilizes the antibody.

b. The antibodies separated into two peptides.

c. We now know these are the intact light and heavy chains. You can this separate them and study each in isolation. The antibody is made of at least two proteins

2. Rodney Porter -cleaved antibodies with brief exposure to proteolytic enzymes a. This treatment breaks up the peptide bonds between amino acids, targeting the most accessible bonds first.

b. Very brief treatment with pepsin: cleaves preferentially at hinge between arms and stem, separating the Fc (stem) section) from the top half, called Fab(ab')2.

c. Mix Fab(ab')2 with their antigen and they will precipitate.

d. Brief treatment with papain produces FAB fragments, which are isolated arms.

e. These can bind antigen, but will not precipitate because they cannot cross-link one antigen to two fragments.

So if I have the whole top half, I can precipitate antigen. If I have just the arms, I can't. The whole top is Fab2.The arms fab. The stem part is called an Fc domain, or fragment, or part. And this part does not bind antigen.

Treating antibodies with the proteolytic enzyme papain followed by treatment with mercaptoethanol will produce a mixture of intact light chains and heavy chains cleaved in half

C. Form and Function

1. Two light (L) chains (~25,000 MW), identical to each other, composed of 2 immunoglobulin domains, variable and constant. Chains = peptide.

2. Two heavy (H) chains (~50,000 MW), identical to each other, composed of 4 or 5 immunoglobulin domains, one variable and 3 or 4 constant.

3. The amino (NH2) end of the heavy chain joins to the light to form the Y arm.

4. The other ends (carboxyl or COOH) of the heavy chains

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