3° Teórico Conectivo 2020 - Puyó

Tejido Conectivo: Estructura y Clasificación

Introducción al Tejido Conectivo

• El tejido conectivo se encuentra justo debajo de los epitelios, a diferencia del tejido epitelial que carece de sustancia extracelular entre las células.

• Este tipo de tejido contiene una gran cantidad de células rodeadas por una matriz extracelular abundante.

Componentes de la Matriz Extracelular

• La matriz extracelular está compuesta principalmente por fibras (colágenas, elásticas y reticulares) y una sustancia fundamental formada por glucoproteínas, glucosaminoglucanos y proteoglicanos.

Origen Embriológico del Tejido Conectivo

• Se desarrolla a partir del mesodermo, una de las tres capas del disco trilaminar embrionario; excepto en el caso del tejido conectivo en la cabeza que proviene de la cresta neural.

• El tejido conectivo embrionario se denomina mesénquima, que es crucial para el desarrollo celular posterior.

Clasificación del Tejido Conectivo

• Se clasifica en:

• Tejido conectivo embrionario: incluye mesénquima y mucosa.

• Tejido conectivo adulto: puede ser laxo o denso.

• Tejidos conectivos especializados: como adiposo, cartilaginoso, hemopoyético, linfático, óseo y sanguíneo.

Detalles sobre el Tejido Conectivo Embrionario

• El mesénquima tiene células uniformes con prolongaciones interconectadas mediante uniones de hendidura; contiene fibras reticulares finas y pocas fibras colágenas.

• La gelatina de Burton en el cordón umbilical presenta grandes espacios intercelulares con colágeno fino.

Características del Tejido Conectivo Adulto

• Se clasifica según la cantidad relativa de células y fibras:

• Laxo: alta cantidad de células y baja cantidad de fibras.

• Denso: alta cantidad de fibras y baja cantidad de células; subdividido en modelado (fibras paralelas) y no modelado.

Ejemplos de Tejidos Especializados

• Incluyen:

• Adiposo (almacenamiento energético).

• Cartilaginoso (soporte estructural).

• Hemopoyético (producción celular sanguínea).

• Linfático (defensa inmunológica).

• Óseo (estructura ósea).

• Sanguíneo (transporte).

Observaciones Morfológicas

• Las imágenes muestran diferencias morfológicas entre tipos diferentes de tejido conectivo embrionario; el mesénquima es homogéneo mientras que la gelatina ocupa grandes espacios intercelulares.

Preparación Histológica

• Un preparado histológico muestra características clave del tejido conectivo laxo con predominancia celular sobre las fibras; fibroblastos son las principales células observadas junto a mastocitos que contienen gránulos rojos.

Overview of Blood and Connective Tissue

Components of Peripheral Blood

• The transcript discusses various components of peripheral blood, including eosinophils (located at the bottom left), neutrophils (center), and lymphocytes (smallest cells in the air).

• Adipocytes are identified as large cells with yellow droplets in their center, found isolated within connective tissue.

Vascular Structures

• A distinction is made between arteries and veins: arteries transport oxygenated blood and are conventionally colored pink, while veins carry deoxygenated blood and are typically blue.

Dense Connective Tissue Types

• The right image shows dense regular connective tissue resembling a tendon, characterized by parallel fiber arrangements that provide strength.

• In contrast, the left image depicts non-modelled dense connective tissue from mammary glands, stained with trichrome to highlight its structure.

Types of Fibers in Connective Tissue

Fiber Classification

• Three main types of fibers in connective tissue are identified: collagen fibers, reticular fibers, and elastic fibers.

Collagen Fibers

• Collagen fibers have complex structures visible under optical microscopy; they consist of numerous fibrils only seen through electron microscopy.

• There are 28 types of collagen; type I is the most abundant, followed by type II (found in cartilage), type III (forms reticular fibers), and type IV (present in basal laminae).

Reticular Fibers

• Reticular fibers form a network rather than linear structures like collagen; primarily composed of type III collagen.

Elastic Fibers

• Elastic fibers consist of different proteins: microfibrils made from fibrillin surround a central core of elastin.

Collagen Structure Insights

Molecular Composition

• Collagen molecules feature triple helices formed by three polypeptide chains called alpha chains. Variations exist based on amino acid composition.

Specific Amino Acids

• Type I collagen contains two alpha 1 chains and one alpha 2 chain arranged in a triple helix. Unique amino acids like hydroxyproline contribute to its structure.

Fibril Formation

• These helices self-associate into fibrils which further assemble into larger collagen fibers. This results in alternating light and dark zones observable under microscopy.

Advanced Imaging Techniques for Collagen

Microscopy Observations

• An atomic force microscope image reveals the three-dimensional structure of dense regular connective tissue's collagen fibers with cross-linking patterns every 68 nanometers.

Types of Collagen Identified

• Common fibrillar collagens include types I, II, III, V, and XI characterized by repeating sequences rich in glycine and proline.

Specialized Collagens

• Other types include FACIT collagens associated with fibril surfaces (types IX, XII), hexagonal network-forming collagens (types VIII & X), transmembrane collagens involved in cell adhesion (types XIII & XVII), as well as multiplexins with multiple interruptions.

Overview of Collagen Types and Their Functions

Key Types of Collagen

• The most abundant collagen type is Type I, constituting over 90% of total collagen. Other significant types include Type II (found in cartilage), Type III (reticular fibers), and Type IV (a major component of basal membranes).

• Type I collagen interacts with other collagen types, including small amounts of Types II, III, V, and XI, which assist in the assembly of Type I fibers.

Interactions Between Collagen Types

• A diagram illustrates the relationship between fibrillar (Type II) and non-fibrillar collagens. Type II is part of the extracellular matrix in cartilage and associates with Type IX collagen.

• These interactions provide links between collagen fibrils and glycosaminoglycans like chondroitin sulfate.

Biosynthesis of Collagen

Cellular Synthesis Process

• Collagen synthesis primarily occurs in connective tissue cells such as fibroblasts and chondrocytes. The process begins with transcription in the nucleus to form mRNA.

• The mRNA moves to the rough endoplasmic reticulum where alpha chains are synthesized along with a signal peptide.

Importance of Vitamin C

• Vitamin C is crucial for hydroxylation during collagen synthesis; its deficiency leads to scurvy, resulting in defective collagen production.

Post-Synthesis Modifications

• Following synthesis, pro-collagen undergoes modifications including glycosylation and formation of hydrogen bonds before being packaged into vesicles by the Golgi apparatus for extracellular processing.

Degradation Mechanisms of Collagen

Extracellular vs Intracellular Degradation

• Collagen degradation occurs through two main processes: extracellular via proteolytic enzymes produced by fibroblasts (e.g., matrix metalloproteinases or MMPs), and intracellular via phagocytosis by macrophages or fibroblasts.

Enzymatic Breakdown

• MMP enzymes have specific roles in degrading denatured collagen while macrophages can engulf aged or damaged collagen for further breakdown.

Structure and Assembly of Basal Lamina

Composition of Type IV Collagen

• The structure includes an amino-terminal domain that connects with other molecules forming lateral associations essential for basal lamina integrity.

Visual Representation

• Electron microscopy reveals a network formed by Type IV collagen contributing to the structural framework known as reticular lamina.

Reticular Fibers in Lymphatic Structures

Characteristics of Reticular Fibers

• Reticular fibers consist mainly of Type III collagen; they form networks that support various organs, particularly lymphatic tissues like lymph nodes.

Staining Techniques

• Specific staining methods highlight these fibers due to their carbohydrate content; techniques include periodic acid-Schiff reaction which enhances visibility under optical microscopy.

Elastic Fibers and Connective Tissue Components

Structure of Elastic Fibers

• Elastic fibers are highlighted in the image, showing fine elastic fibers intercrossed with thicker collagen fibers. Unlike collagen, elastic fibers are composed of elastin.

• Elastin has an affinity for certain dyes like orcein and fuchsin but does not stain well with eosin. The structure of elastic fibers is depicted, emphasizing the role of desmosine in their formation.

• Desmosine forms cross-links between elastin molecules through covalent bonds mediated by a unique large amino acid, which is exclusive to elastin.

Functionality Under Stress

• When relaxed without applied force, elastic fibers exhibit a relaxed structure; upon stretching, they reveal a different molecular arrangement that allows for elasticity.

Fundamental Substance in Connective Tissue

• The fundamental substance or amorphous matrix of connective tissue is gelatinous and contains cells and fibers. It consists mainly of water and salts.

• This gelatinous component includes polysaccharides such as glucosaminoglycans (GAGs), which are made up of disaccharide units combined with organic acids.

Proteoglycans and Their Role

• Proteoglycans are high molecular weight molecules with a protein core to which GAGs are covalently attached. They play crucial roles in connective tissue structure.

• Multiadhesive glycoproteins like fibronectin and osteopontin facilitate connections within the extracellular matrix (ECM).

Complex Structures of Glycosaminoglycans

• Various types of GAG structures are illustrated; for instance, hyaluronic acid consists of approximately 25,000 disaccharide units while chondroitin sulfate has around 250 units.

Proteoglycan Aggregates

Composition and Structure

• A proteoglycan aggregate features a central protein core (colored blue), surrounded by GAG chains resembling brush bristles. These aggregates connect to hyaluronic acid via binding proteins.

Microscopy Insights

• Electron microscopy reveals large proteoglycan aggregates intertwined with collagen fibrils type I, showcasing their structural complexity.

Variability Among Proteoglycans

Diversity in Structure

• Different proteoglycans vary significantly; some may contain only one GAG unit while others can have over 200 units. For example, decorin has one unit whereas aggrecan can have many more.

Functional Implications

• The ability to bind proteins found in the cytosol with the ECM highlights the functional diversity among proteoglycans.

Multiadhesive Glycoproteins: Key Players

Stabilization Functions

• Multiadhesive glycoproteins stabilize the ECM and link it to cell surfaces. Fibronectin is noted as the most abundant glycoprotein in connective tissue, featuring two polypeptide chains linked by disulfide bridges at their carboxyl ends.

Overview of Multi-Adhesive Proteins in the Extracellular Matrix

Structure and Function of Poly-Peptide Chains

• The central figure illustrates poly-peptide chains with specific domains for binding various elements found in the extracellular matrix, including sulfates and fibrin for collagen types 1, 2, and 3.

• Multi-adhesive proteins like fibrin play a crucial role in linking different components within the extracellular matrix.

Types of Multi-Adhesive Proteins

• The lamina is highlighted as a multi-adhesive protein that forms part of basal laminae in epithelial tissues and muscle tissue; it consists of heavy alpha chains and beta chains forming a cross-like structure.

• Tenascin-C is identified as a high molecular weight protein with six polypeptide chains, primarily active during embryonic development but can reactivate during wound healing or malignancies.

Osteopontin: A Key Protein in Bone Matrix

• Osteopontin is described as a single polypeptide chain with an alpha helix shape, featuring binding sites for heparin, hydroxyapatite (the mineral component of bone), calcium, and integrins on osteoclast cells involved in bone resorption.

Interaction Between Components in the Basal Lamina

• Entactin (nidogen), depicted in yellow, is a glycoprotein that connects to laminins and collagen type IV within the basal lamina.

• An illustration shows various elements composing the amorphous substance of the basal lamina, including entactin molecules (yellow), perlecan (green spheres), collagen type IV (red circles), and integrins (green).

Cellular Components of Connective Tissue

• Fibronectin interacts with integrins at focal adhesions linked to actin filaments inside cells; this connection facilitates communication between internal cytoskeleton structures and external cellular environments.

Resident vs. Free Cells in Connective Tissue

• Two categories of connective tissue cells are discussed: resident cells (fixed within tissue such as fibroblasts, macrophages, mast cells) versus free or wandering cells (like lymphocytes that can migrate).

Role of Fibroblasts

• Fibroblasts are emphasized as vital resident cells responsible for synthesizing all components of the extracellular matrix including collagen fibers, elastic fibers, reticular fibers, glycosaminoglycans, and multi-adhesive glycoproteins.

Overview of Connective Tissue and Cell Types

Fibroblasts and Their Functions

• A colored image of connective tissue shows only the nuclei of fibroblasts, which are elongated oval structures. The cytoplasm is difficult to observe with this staining technique.

• Activated fibroblasts are highlighted, showing active synthesis of extracellular matrix components during processes like wound healing. These cells exhibit a more prominent cytoplasm.

• Transmission electron microscopy reveals enlarged rough endoplasmic reticulum and Golgi apparatus in activated fibroblasts, indicating active collagen fiber synthesis.

Lymphatic Organs and Reticular Cells

• In lymphatic organs, reticular cells perform functions similar to fibroblasts by synthesizing fibers that form the organ's cytoskeleton and reticular matrix.

• An argentaffin staining technique illustrates dense connective tissue capsules surrounding lymphatic organs, highlighting the abundance of reticular fibers.

Macrophages: Key Players in Immune Response

• Macrophages originate from peripheral blood monocytes and primarily function in phagocytosis while also presenting antigens to T lymphocytes.

• Upon ingesting foreign cells or bacteria, macrophages display antigens on their surface, facilitating T cell activation. They also produce nitric oxide and cytokines involved in inflammation.

• Two types of macrophages are identified: M1 (pro-inflammatory) and M2 (anti-inflammatory), each playing distinct roles in immune responses.

Microscopy Insights into Macrophage Structure

• Transmission electron microscopy shows a macrophage nucleus with an indentation; it contains various phagocytic components such as lysosomes.

• Scanning electron microscopy displays macrophage extensions capable of capturing bacteria, emphasizing their role in immune defense.

Mast Cells: Mediators of Allergic Reactions

• Mast cells play crucial roles in allergic reactions; two main types exist: connective tissue mast cells (CTMC) and mucosal mast cells (MMC).

• Staining with toluidine blue reveals mast cell granules that mediate inflammation; these granules contain substances like heparin and histamine.

Adipose Tissue Overview

• Adipocytes store lipids primarily as triglycerides for energy reserves. There are two types: white adipose tissue (dominant in adults) and brown adipose tissue (more common during embryonic development).

Histological Techniques and Adipose Tissue Development

Histological Analysis of Lipid Droplets

• The histological technique reveals empty lipid droplets within cells, characterized by a small nucleus and fine cytoplasm surrounding a large lipid droplet. This is illustrated in slide 38, showing the formation of different types of adipose tissue.

Formation of White Adipose Tissue

• White adipose tissue originates from a stem cell located in the vascular zone, stimulated by a nuclear component called PPAR-gamma, transforming it into a pre-adipocyte or early lipoblast. Over time, these cells accumulate lipids.

Development Stages of Lipoblasts

• As lipid accumulation progresses, an intermediate lipoblast forms with multiple lipid droplets that merge into one large droplet, leading to the mature white adipocyte where both cytoplasm and nucleus are pushed to the cell's periphery.

Brown Adipose Tissue Formation

• Brown adipose tissue arises from myogenic progenitor cells under different stimulation conditions, resulting in early lipoblasts that develop into mature brown adipocytes characterized by numerous small lipid droplets instead of one large droplet.

Endocrine Functions of Adipose Tissue

• Both types of adipose tissues synthesize various hormones; leptin is crucial for appetite regulation via hypothalamic receptors. Other hormones include angiotensinogen (linked to blood pressure), adiponectin, resistin, and several inflammatory cytokines.

Plasma Cells and Their Characteristics

Overview of Plasma Cells

• Plasma cells are common in loose connective tissue and derive from B lymphocytes; they are spherical with eccentrically located nuclei containing heterochromatin clusters visible under staining techniques like EMMA stain.

Antibody Synthesis Mechanism

• These cells primarily synthesize antibodies (immunoglobulins) necessitating extensive rough endoplasmic reticulum development for protein exportation alongside well-developed Golgi apparatuses due to their secretory function.

Pericytes: Role in Angiogenesis

Functionality of Pericytes

• Pericytes surround capillaries and play a role in angiogenesis; they can differentiate into vascular wall-repairing cells when blood vessels are damaged (e.g., due to injury). They share characteristics with endothelial cells but have larger nuclei.

Fibroblasts and Myofibroblasts

Myofibroblast Characteristics

• Myofibroblasts resemble fibroblasts but exhibit features akin to smooth muscle cells including actin bundles and junctional connections known as fibronexus which enable contraction during wound healing processes.

Mesenchymal Stem Cells

Potentiality of Mesenchymal Cells

• Mesenchymal stem cells found within connective tissue possess the ability to differentiate into various connective tissue cell types such as fibroblasts or chondrocytes contributing significantly to tissue repair mechanisms.

Lymphocytes: Immune Response Mediators

Morphology and Types

• Lymphocytes are among the smallest immune response mediators found in connective tissues; they feature round nuclei with indentations surrounded by minimal cytoplasm containing few organelles like mitochondria or Golgi apparatuses observed through microscopy techniques.

Types of Circulating Lymphocytes

• There are three main types: T lymphocytes which play critical roles in adaptive immunity; further details on their specific functions were not provided within this segment but will be explored later on in the transcript.

Overview of Immune Cell Types and Functions

T-Cells, B-Cells, and Natural Killer Cells

• The transcript discusses membrane receptors known as TRC (T-cell receptors), which are crucial for T-cell mediated immunity.

• B-cells can transform into plasma cells, playing a significant role in antibody-mediated immunity.

• Natural killer (NK) cells are highlighted for their ability to destroy virus-infected and tumor cells through cytotoxic effects.

Neutrophils: First Responders in Infection

• Neutrophils are the most abundant leukocytes in peripheral blood and connective tissues, characterized by a multi-lobed nucleus (3 to 5 lobes).

• These cells possess numerous granules with neutral staining properties; they are primarily phagocytic and act quickly during infections.

• Neutrophils can bind immunoglobulins of type C and complement receptors, enhancing their immune response capabilities.

Eosinophils: Role in Allergies and Parasitic Infections

• Eosinophils participate in allergic reactions; they have a bi-lobed nucleus visible under optical microscopy.

• Their granules appear large with darker centers when viewed under an electron microscope, indicating their specific functions.

• While not highly phagocytic, eosinophils are abundant in asthmatic individuals and play a role against parasitic infections.

Monocytes: Transitioning to Macrophages

• Monocytes originate from bone marrow, circulate briefly in peripheral blood before migrating into connective tissue where they differentiate into macrophages.

• Under transmission electron microscopy, monocytes show many non-specific granules along with Golgi apparatus, mitochondria, and visible centrosomes.

• Their nuclei typically have a horseshoe shape or similar morphology.