INMUNOBIOLOGÍA

• La inmunología es una rama amplia de la biología y de las ciencias biomédicas que se ocupa del estudio del sistema inmunitario en todos los organismos, entendiendo como tal al conjunto de órganos, tejidos y células que en los vertebrados tienen como función biológica el reconocer elementos extraños o ajenos dando una respuesta (respuesta inmunológica).

is widely credited as the pioneer of smallpox vaccine, and is sometimes referred to as the "Father of Immunology” 1770

Edward Jenner

Cowpox is a skin disease caused by a virus known as the Cowpox virus. The pox is related to the vaccinia virus and got its name from the distribution of the disease when dairymaids touched the udders of infected cows. The ailment manifests itself in the form of red blisters and is transmitted by touch from infected animals to humans. Cowpox is similar to but much milder than the highly contagious and sometimes deadly smallpox disease. It resembles mild smallpox, and was the basis of the first smallpox vaccines. When the patient recovers from cowpox, the person is immune to smallpox.

La viruela es una enfermedad infecciosa grave, contagiosa, causada por el Variola virus, que en algunos casos puede causar la muerte. No hay tratamiento especial para la viruela y la única forma de prevención es la vacunación. El nombre viruela proviene de la palabra latina que significa “manchado” y se refiere a los abultamientos que aparecen en la cara y en el cuerpo de una persona infectada. Según la OMS la viruela es la única enfermedad que está totalmente erradicada de todo el planeta.

Figure 25-41The principal stages in complement activation by the classical, lectin, and alternative pathways

In all three pathways, the reactions of complement activation usually take place on the surface of an invading microbe, such as a bacterium. C1–C9 and factors B and D are the reacting components of the complement system; various other components regulate the system. The early components are shown within gray arrows, while the late components are shown within a brown arrow.

Figure 25-42Assembly of the late complement components to form a membrane attack complex

When C3b is produced by any of the three activation pathways, it is immobilized on a membrane, where it causes the cleavage of the first of the late components, C5, to produce C5a (not shown) and C5b. C5b remains loosely bound to C3b (not shown) and rapidly assembles with C6 and C7 to form C567, which then binds firmly via C7 to the membrane, as illustrated. To this complex is added one molecule of C8 to form C5678. The binding of a molecule of C9 to C5678 induces a conformational change in C9 that exposes a hydrophobic region and causes C9 to insert into the lipid bilayer of the target cell. This starts a chain reaction in which the altered C9 binds a second molecule of C9, where it can bind another molecule of C9, and so on. In this way, a large transmembrane channel is formed by a chain of C9 molecules.

Scanning electron micrograph of a phagocyte (yellow, right) phagocytosing anthrax bacilli (orange, left)

• MONOCITOS• 5% de leucocitos en sangre• Producen médula ósea y liberan a la sangre• Circulan por varias semanas y después

entran a los tejidos donde se desarrollan como MACRÓFAGOS.

• Tienen núcleo en forma de herradura bilobulado y citoplasma prominente.

• Importantes contra bacterias• Abundantes en pulmones, intestino, hígado

y bazo.

Leucocitos Polimorfonucleares• Son de tres tipos

NeutrófilosCaracterística de tener un núcleo de

tres o más lóbulos

60% de leucocitos en la sangre

Son Fagocíticos

• Se producen en la médula ósea

• Abundantes en la sangre

• Vida corta

• Importantes en la inflamación, son los primeros en llegar al sitio dañado o lesión.

• BASÓFILOS Núcleo bilobulado y gránulos prominentes

• Producen médula ósea y entran a la sangre

• Al entrar a tejido sólido se desarrollan en MASTOCITOS que se concentran en el tejido conectivo de los tractos respiratorio y gastrointetinales y en la piel.

• Ambos contienen gránulos que inician la inflamación que contienen HISTAMINA, el factor Quimiotáctico de Eosinófilos.

HC=C-CH2-CH2-NH3+

N NH

C

H

Histamine

Características al MET: prolongaciones celulares cortas,gran desarrollo del A. Golgi, núcleo de bordes irregulares y numerososgránulos electrón densos.

Eosinófilos

• Son 1-2% de los leucocitos de la sangre

• Gránulos prominentes contienen:

- Proteína Básica Principal

- Proteína Catiónica de Eosinófilos

- Peroxidasa de Eosinófilo

• Tóxicos para parásitos

Células Asesinas Naturales

• 5-10% de leucocitos en la sangre

• Destruyen células infectadas por virus

• Se pegan a las células infectadas y liberan gránulos tóxicos que lisan a la célula

Fig. 11.13 Features of specific immunity (see text for details)

Each antibody binds to a specific antigen; an interaction similar to a lock and key.

Figure 23-18 Fab and F(ab')2 antibody fragments

These fragments are produced when antibody molecules are cleaved with the proteolytic enzymes papain and pepsin, respectively.

Figure 23-15Antibody-antigen interactions

Because antibodies have two identical antigen-binding sites, they can cross-link antigens. The types of antibody-antigen complexes that form depend on the number of antigenic determinants on the antigen. Here a single species of antibody (a monoclonal antibody) is shown binding to antigens containing one, two, or three copies of a single type of antigenic determinant. Antigens with two antigenic determinants can form small cyclic complexes or linear chains with antibody, while antigens with three or more antigenic determinants can form large three-dimensional lattices that readily precipitate out of solution. Most antigens have many different antigenic determinants (see Figure 23-25A) and the different antibodies that recognize these different determinants can cooperate in cross-linking the antigen (not shown).

Figure 23-16The hinge region of an antibody molecule

Because of its flexibility, the hinge region improves the efficiency of antigen binding and cross-linking.

Figure 23-19A pentameric IgM molecule

The five subunits are held together by disulfide bonds. A single J chain, which has a structure similar to that of a single Ig domain (discussed later), is disulfide-bonded between two μ heavy chains. The J chain is required for the polymerization process. The addition of each successive four-chain IgM subunit requires a J chain, which is then discarded, except for the last one, which is retained.

Figure 23-21A highly schematized diagram of a dimeric IgA molecule found in secretions

In addition to the two IgA monomers, there is a single J chain and an additional polypeptide chain called the secretory component, which is thought to protect the IgA molecules from being digested by proteolytic enzymes in the secretions.

Figure 23-20Antibody-activated phagocytosis

An IgG-antibody-coated bacterium is efficiently phagocytosed by a macrophage or neutrophil, which has cell-surface receptors able to bind the Fc region of IgG molecules. The binding of the antibody-covered bacterium to these Fc receptors activates the phagocytic process.

Figure 23-23 The role of IgE in histamine secretion by mast cells

A mast cell (or a basophil) binds IgE molecules after they are secreted by activated B cells; the soluble IgE antibodies bind to Fc receptor proteins on the mast cell surface that specifically recognize the Fc region of these antibodies. The passively acquired IgE molecules on the mast cell serve as cell-surface receptors for antigen. Thus, unlike B cells, each mast cell (and basophil) has a set of cell-surface antibodies with a wide variety of antigen-binding sites. When an antigen molecule binds to these membrane-bound IgE antibodies so as to cross-link them to their neighbors, it activates the mast cell to release its histamine by exocytosis.

Figure 1.19Transmission electron micrographs of lymphocytes at various stages of activation to effector function

Small resting lymphocytes (top panel) have not yet encountered antigen. Note the scanty cytoplasm, the absence of rough endoplasmic reticulum, and the condensed chromatin, all indicative of an inactive cell. This could be either a T cell or a B cell. Small circulating lymphocytes are trapped in lymph nodes when their receptors encounter antigen on antigen-presenting cells. Stimulation by antigen induces the lymphocyte to become an active lymphoblast (center panel). Note the large size, the nucleoli, the enlarged nucleus with diffuse chromatin, and the active cytoplasm; again, T and B lymphoblasts are similar in appearance. This cell undergoes repeated division, which is followed by differentiation to effector function. The bottom panels show effector T and B lymphocytes. Note the large amount of cytoplasm, the nucleus with prominent nucleoli, abundant mitochondria, and the presence of rough endoplasmic reticulum, all hallmarks of active cells. The rough endoplasmic reticulum is especially prominent in plasma cells (effector B cells), which are synthesizing and secreting very large amounts of protein in the form of antibody. Photographs courtesy of N. Rooney.

Figure 23-4Electron micrographs of resting and activated lymphocytes

The resting lymphocyte in (A) could be a T cell or a B cell, for these cells are difficult to distinguish morphologically until they have been activated. The activated B cell (a plasma cell) in (B) is filled with an extensive rough endoplasmic reticulum (ER), which is distended with antibody molecules. The activated T cell in (C) has relatively little rough ER but is filled with free ribosomes. Note that the three cells are shown at the same magnification. (A, courtesy of Dorothy Zucker-Franklin; B, courtesy of Carlo Grossi; A and B, from D. Zucker-Franklin et al., Atlas of Blood Cells: Function and Pathology, 2nd ed. Milan, Italy: Edi. Ermes, 1988; C, courtesy of Stefanello de Petris.)

Figure 23-6Two types of experiments that support the clonal selection theory

For simplicity, cell-surface receptors are shown only on those lymphocytes committed to respond to antigen A; in fact, however, all T and B cells have antigen-specific receptors on their surface. The experiments shown have been carried out mainly with B cells since T cells recognize an antigen only when it is bound to the surface of a host cell, as we discuss later.