Connective Tissue Part1

Connective Tissue

Part1

CONNECTIVE TISSUE

• Most diverse and abundant tissue

• Common embryonic origin – mesenchyme

• The human embryo is composed of three embryo layers called

– ectoderm, endoderm and mesoderm

• Connective tissues are composed of mesoderm layer which is located between ectoderm and endoderm.

• Embryonic mesoderma is called mesenchyme.

• Mesenchymal cells are capable of

producing various cells of connective tissues.

• It allows the body to be held together as a

whole, preserving the shape of body parts.

• These tissues are in various forms according to their location and function.

– Skeletal system, bone and cartilage are the hardest and solid tissues of the body,

– while ligaments and blood are the softer and fluid tissues.

• Components of connective tissue:

– Cells (varies according to tissue) – Matrix

• Protein fibers (varies according to tissue)

• Ground substance (varies according to tissue)

• Connective tissues occupy the most space in our body.

– They connect various structures, – provide support,

– protect, – fill gaps, – store fat,

– produce blood cells,

– protect the body against infections, and – help repair tissue damage.

• Main classes

– Connective tissue proper

– Blood – Fluid connective tissue – Cartilage

– Bone tissue Supporting connective tissues

Connective Tissue Proper - Structures

• Variety of cells, fibers & grounds substances

– Types of depend on use

• Cells found in connective tissue proper

– Fibroblasts

– Macrophages, lymphocytes (antibody producing cells) – Adipocytes (fat cells)

– Mast cells – Stem cells

• Fibers:

– Collagen – very strong & abundant, long & straight

– Elastic – branching fibers with a wavy appearance (when relaxed)

– Reticular – form a network of fibers that form a supportive framwork in soft organs (i.e. Spleen & liver)

• Ground substance:

– Along with fibers, fills the extracellular space

– Ground substance helps determine functionality of tissue

Connective Tissue Proper - Classifications

• Loose Connective Tissue

– Areolar – Reticular – Adipose

• Dense Connective Tissue

– Regular – Irregular – Elastic

Areolar Connective Tissue

• Description

– Gel-like matrix with:

• all three fiber types (collagen, reticular, elastic) for support

• Ground substance is made up by glycoproteins also made and secreted by the fibroblasts.

– Cells – fibroblasts, macrophages, mast cells, white blood cells, adipocytes

– Highly vascular tissue

• Function

– Wraps and cushions organs – Holds and conveys tissue fluid – Important role in inflammation

– Main battlefield in fight against infection

Areolar Connective Tissue

• Location

– Widely distributed under epithelia – Packages organs

– Surrounds capillaries

Adipose Tissue

• Description

– Closely packed adipocytes – Have nucleus pushed to one

side by fat droplet Function – Provides reserve food fuel – Insulates against heat loss – Supports and protects organs

• Location

– Under skin

– Around kidneys

– Behind eyeballs, within abdomen and in breasts

Reticular Connective Tissue

• Description – network of reticular fibers in loose ground substance

• Function – form a soft,

internal skeleton (stroma) – supports other cell types

• Location – lymphoid organs

– Lymph nodes, bone marrow, and spleen

Dense Irregular Connective Tissue

• Description

– Primarily irregularly arranged collagen fibers

– Some elastic fibers and fibroblasts

• Function

– Withstands tension

– Provides structural strength

• Location

– Dermis of skin

– Submucosa of digestive tract – Fibrous capsules of joints and

organs

Dense Regular Connective Tissue

• Description

– Primarily parallel collagen fibers – Fibroblasts and some elastic fibers – Poorly vascularized

• Function

– Attaches muscle to bone – Attaches bone to bone

– Withstands great stress in one direction

• Location

– Tendons and ligaments – Aponeuroses

– Fascia around muscles

Cartilage

• Characteristics:

– Firm, flexible tissue

– Contains no blood vessels or nerves

– Matrix contains up to 80%

water

– Cell type – chondrocyte

• Types:

– Hyaline – Elastic

– Fibrocartilage

Hyaline Cartilage

• Description

– Imperceptible collagen fibers (hyaline = glassy) – Chodroblasts produce matrix

– Chondrocytes lie in lacunae

• Function

– Supports and reinforces – Resilient cushion

– Resists repetitive stress

• Location

– Ends of long bones – Costal cartilage of ribs – Cartilages of nose,

trachea, and larynx Location

Elastic Cartilage

• Description

– Similar to hyaline cartilage – More elastic fibers in matrix

• Function

– Maintains shape of structure – Allows great flexibility

• Location

– Supports external ear – Epiglottis

Fibrocartilage

• Description

– Matrix similar, but less firm than hyaline cartilage

– Thick collagen fibers predominate

• Function

– Tensile strength and ability to absorb compressive

shock

• Location

– Intervertebral discs – Pubic symphysis – Discs of knee joint

Bone Tissue

• Function

– Supports and protects organs

– Provides levers and attachment site for muscles

– Stores calcium and other minerals

– Stores fat

– Marrow is site for blood cell formation

• Location

– Bones

Blood Tissue

• Description

– red and white blood cells in a fluid matrix

• Function

– transport of respiratory

gases, nutrients, and wastes

• Location

– within blood vessels

• Characteristics

– An atypical connective tissue

– Consists of cells surrounded by fluid matrix

Classes of Connective Tissue

• Components of connective tissue:

– Cells (varies according to tissue) – Matrix

• Protein fibers (varies according to tissue)

• Ground substance (varies according

to tissue)

Characteristics of CT

• Cells are spread through an extracellular fluid.

• Cells, extracellular matrixs and fibrils in the connective tissue vary from one region to another in the body.

• These units can be more or less.

• Various types can be transformed into one another by intermediate forms, or a type of connective tissue can be transformed into another type by changing conditions.

• Classification is generally dependent on

loose or dense arrangements of fibrils.

Matrix

• The most obvious difference between the epithelial tissue and the underlying tissue is the size of the intercellular space.

• Between epithelial tissue cells, less than 5% of the total volume of the tissue forms the extracellular space.

• The extracellular area in the connective tissue is about 50-70% of the total volume.

• This area is called matrix.

•Matrix is not fluid, it is in gel consistency.

•Matrixs contains a large number of fibrils and products produced by cells.

•Matrix is consists of the following elements:

- Ground substance

- The cells in the matrix,

- Fibrils, the products of cells.

GROUND SUBSTANCE

• A clear, colorless, and viscous fluid containing

glycosaminoglycans and proteoglycans to fix the body water and the collagen fibers in the intercellular

spaces.

• Ground substance slows the spread of pathogens.

• The matrix is synthesized by connective tissue cells and is the medium in which cells and fibrils are

located.

• The matrix does not have a visible structure under light microscopy, it is transparent.

• The amorphous ground substance is also called the support material.

• The supporting function of the connective tissue depends on the properties of the matrix.

• Cells receive nutrients and water which enters to matrixs with capillaries, and release waste products to the matrix

• The survival of the cells of the connective tissue is possible by continuous feeding of the matrix and renewal of the tissue fluid.

• The matrix keeps water in different amounts in different tissues

• Blood and lymphatic system- fluid,

• connective tissue-Gelatinous

• cartilage,elasticated

• Bone-solid

•The amorphous ground substance is made of various types of glycosaminoglycan molecules (GAG,

polysaccharide chains of proteoglycans).

•Glycosaminoglycans are mixed polysaccharides containing amino sugars.

•They combine to form proteoglycans (95%

polysaccharide 5% protein)

• The most important glycosaminoglycans of the matrix;

• Hyaluronic acid,

• Chondroitin sulphates,

• Dermatan sulphate,

• Keratan sulphate,

• Heparin is Heparan sulphate

• Molecular weight, chain length, and disaccharide units are different.

• Except for hyaluronic acid, glycosaminoglycans are not free in tissues; they always remain attached to the central proteins as proteoglycan components.

Hayvan hücre zarının enine kesiti (Şematik)

Hücre iskeleti filamentleri

Kolesterol

Periferal protein

İntegral

protein Sitoplazma

Glikolipit Karbohidrat

Hücre dışı matriks filamentleri

Glikoprotein

Ekstraselüler sıvı

Proteoglikan

Glikozaminoglikan Disakkarit birimleri Dokulardaki dağılımı

Hiyaluronik asit D-glukuronik asit + N-asetil-D-glukozamin Çeşitli destek dokuları, deri, kıkırdak, eklem (sinoviyal) sıvıları, vitreous sıvı Kondroitin 4-sülfat D-glukuronik asit + N-asetil-D-galaktozamin Kıkırdak,kornea,kemik, deri, atardamar Kondroitin 6-sülfat D-glukuronik asit + N-asetil-D-galaktozamin Kornea, kemik, deri ve atardamarlar Dermatan sülfat D-glukuronik asit + N-asetil-D-galaktozamin Deri, damar,epinöryum, sklera

(gözakı) veya L-Iduronik asit + N-asetil-D-galaktozamin organ kapsülü, tendon ve ligament, kalp, kalp kapakçığı

Heparan sülfat D-glukuronik asit + N-asetil-D-glukozamin Akciğer, atardamar, karaciğer, dalak, veya L-İduronik asit + N-asetil-D-glukozamin sinir endonöryumu ve hücre yüzeyi

Heparin D-glukuronik asit veya L-iduronik asit Akciğer, karaciğer, deri, mast hücreleri + N-asetil-D-glukozamin

Keratan sülfat D-galaktoz + N-asetil-D-glukozamin Kıkırdak, kornea, omurlar arası disk

GLİKOZAMİNOGLİKANLARIN (GAG) İÇERİĞİ VE DOKULARDAKİ DAĞILIMI

Hyaluronic acid

•Essential components of the vitreous humor (the translucent fluid behind the eye lens) and the synovial fluid (joint fluid)

•It is also abundant in the matrix of various tissues.

•It's a very long and heavy molecule.

• It will be about 2.5 microns when extended.

•It is highly fluid in aqueous environment.

•With this feature, it forms the consistency of the matrix.

•Because it is common and fluid, it prevents the water from flowing freely, thus creating a suitable environment for the molecules to diffuse into the cells

•With this structure, the matrix forms a wall that prevents further spread of microorganisms entering the tissue.

•Most pathogenic bacteria produce hyaluronidase enzyme.

•With this enzyme they digest hyaluronic acid and enter

•Hyaluronic acid fluidity allows bones that are encountered in the synovial fluid of joints to move in a slippery environment.

Chondroitin sulfate

•The most common glycosaminoglycan in cartilage, bone and large blood vessel proteoglycans; but also in other tissues.

Dermatan sulphate

•is found most abundantly; but also in many tissues such as lung, tendon, ligament, heart and heart valve.

Keratan sulphate,

•cornea, cartilage and discs between the vertebrae are in this structure.

Heparan sulphate

•is found in the liver, aorta and lungs.

• The type of glycosaminoglycan in the substrate of connective tissue plays an important role in

determining the type of cell that will evolve there.

• While fibroblasts synthesize and release

hyaluronic acid in a large amount, chondrocytes release relatively little.

• If the chondrocyte culture medium is loaded with free hyaluronic acid, immediate cartilage matrix production is inhibited.

Kıkırdak matriksi ile çevrili kondrosit

Fibroblast matriksi ile çevrili fibroblast

Kıkırdak matriksi ile çevrili fibroblast Fibroblast matriksi

İle çevrili kondrosit

Kondrosit olarak kalır ve kıkırdak matriksi yapmaya devam eder

Fibroblast olarak kalır ve fibroblast matriksi yapmaya devam eder

Artık kıkırdak matriksi yapmaz

Fibroblasta dönüşerek fibroblast matriksi yapar

Kondrosite dönüşerek kıkırdak matriksi yapar

Fibroblast ve kondrosit farklılaşmasına hücre dışı

ortamın etkisi

Artık fibroblast matriksi yapmaz

Classes of Connective Tissue

CELLS OF THE CT

Fixed cells

 Fibroblast

 Undifferentiated mesenchymal cells,

 adipocytes

 Reticular cells

Mobile cells

•Macrophages

•Mast cells

•Eosinophil leukocytes

•Lymphocytes

•Plasma cells

•Pigment cells

FIBROBLAST - FIBROCYTES

 The basic cell of connective tissue

 It is a young and active cell, synthesizes extracellular matrix material and fibrils

 Inactive form is called fibrocyte

 Normally, inactive fibrocytes become active in the repair of connective tissue and turn into fibroblasts for matrix and fibril synthesis

 Cells are long, with eosinophilic cytoplasma, irregular cytoplasmic extension

 They associate with neighboring fibroblasts with these extensions.

 The fibroblasts are covered with extracellular material.

 The extracellular glucosaminoglycan (GAG), collagen and elastin are the major syntheses

 Fibroblasts are more easily seen with ferric hematoxylin.

 The nucleus is oval or short cigar shaped, with one or two nuclei

 There are a couple of centrioles, a small Golgi complex

 Thin, long mitochondria are found around the nucleus, sometimes in cytoplasmic extensions.

 Cytoplasmic granules are the precursers of the GAG found in the ground substrate.

 When connective tissue repair is needed, they increase in numbers

 Fibroblasts are completely differentiated cells that do not form other cell types in the connective tissue.

 In some pathological conditions or under experimental conditions, fibroblasts can transform into cartilage and bone cells.

Kollagen teller ve aralarında fibroblastlar, Tendon ( H & E, x5.000)

Mükoz bağ dokusu ve fibroblastlar (Ok) (Göbek bağı)

Fibroblast

Fibroblast

Fibroblast (FITC, Rhodamine ve Dapi ile işaretlenmiş)

Fibroblast (FITC, Rhodamine ile işaretlenmiş)

Fibroblast (FITC, Rhodamine ve Dapi ile işaretlenmiş, DIC ile zemin görüntüsü alınmış)

Fibroblast ve kollagen teller (TEM) (x3.600)

Fibroblast (TEM)

Fibroblast (TEM)

Kollagen teller Fibroblast

Fibroblast (ince-uzun) ve Plazma hücresi (yuvarlak) (x 3.900) Tek tabakalı silindirik epitel hücrelerinin bazal kısmı

Mesenchymal stem cell

• In the adult organism, the development potential of embryonic mesenchymal cells is maintained

• It's very similar to fibroblasts, but it's smaller.

• However, they become evident when they are forced to multiply and change.

• They are located especially along the long capillary vein in loose connective tissue.

• In EM, chromatins are darker and occupy more space, few mitochondrins are present, and GER is not well-developed.

• With these features; can be distinguished from fibroblasts at EM level.

• During fetal life, differentiates in to connective tissue, blood, cartilage, bone and muscle tissue

• After birth, they become active when necessary and divide, multiply and turn into different cells of these tissues.

• For example, if the vascular wall injury suffers smooth muscle damage, it forms smooth muscle cells

• In cloning techniques these cells are used

Adipocytes, (lipocytes or fat cells)

• immobilized cells of connective tissue.

• specialized to synthesize and store lipids (fat)

• Fat accumulates in small cytoplasm of cells in small droplets.

• Then the droplets join together to form a large oil droplet

• The cytoplasm surrounds a thin ring of fat droplets.

• Golgi complex and filamentous mitochondria are distributed in the thin cytoplasmic region

• Each fat cell is surrounded by a web of fine reticular fibrils.

Active cells, use oil according to need and re-synthesize

Fat cells can be found all over the body

They are either individually or in groups.

As a result of accumulation in groups, they become a dominant volume of the tissue so they themselves form a tissue.

This is called adipose tissue or fat tissue

When groups are created, the corners are not sharp polygonal or rounded

• In the preparats, alcohol and xylol used during

dehydration dissolve oil and fat, so the oil droplets remain empty in the cytoplasm of fat cells.

• During early development, fat droplets begin to accumulate in the cell.

• A fully formed fat cell can not be divided by mitosis.

• In adolescents, new fat cells are differentiated from mesenchymal stem cells.

Adiposit kümesinin SEM görüntüsü. Destekleyici retiküler tel ağının ipliksi görünüşü. x150

Altı aylık fetüsten alınan bir yağ hücresi (Adiposit) (TEM, x1.600) Lipit damlası

Fibro blast Kollatellergen

•A reticular cell is a type of fibroblast that synthesizes

collagen alpha-1(III) and uses it to produce reticular fibers.

•The cell surrounds the fibers with its cytoplasm, isolating it from other tissue components and cells.

•Reticular cells provide structural support, since they produce and maintain the thin networks of fibres that are a framework for most lymphoid organs.

•They are found in many tissues including the spleen, lymph nodes and lymph nodules.

•They also direct B cells and T cells to specific regions within the tissue.

Reticular Cells

Retiküler

Hücre

Retiküler Hücre

Plazma Hücresi

Makrofaj Retiküler

Hücreler

Mobile cells of the CT

•Apart from fixed or immobile cells, there are also mobile cells that migrate from blood.

•These are;

•Lymphocytes (some as plasma cells),

•Monocytes (converted into macrophages),

•Eosinophils, basophils, neutrophils, and

mast cells (they use blood as a pathway)

• These cells act like amoebas and go to areas in need.

• They are found in blood circulation (except the mast cells)

• Carry out their own functions.

• They migrate from blood to connective tissue where they have functions.

• The pigment cells, which take root from the neural crest, are also among the free cells of the connective tissue.

Lymphocytes

• Are the smallest mobile cells.

• Migrate from blood and enter the CT.

• In a normal situation, their number is a very few in CT, but the number increases greatly in case of inflamation.

• They are most commonly found in the following areas:

– In the lamina of the respiratory tract (connective tissue under the epithelium)

– Loose ligaments beneath the epithelium lining the gastrointestinal tract

• Bacteria are entering the body from these regions so they are found as protective and control cells

Lenfosit

Plasma cells

•Oval, round or polygonal, about 10-20 microns in size, with basophilic cytoplasm

•There is a large Golgi complex, plenty of GER, they are protein synthesizing cells.

•Common in lymph nodes and spleen.

•They secrete antibodies (immunoglobulins) that play an important role in the humoral immunity of the organism.

•Occurs by further changes of B lymphocytes migrating from blood to tissue.

• B cells carries immunoglobulin molecules that are produced against the previously encountered antigen in the lymphocyte surface membrane.

• These form specific receptors for that antigen.

• When the antigen binds to the receptor on the surface of B lymphocyte, the antigen-antibody complex occurs and taken in to the by endocytosis

• This stimulates the conversion of B lymphocytes to lymphoblasts.

• Lymphoblast carries the same antigenic character and continuously splits and forms a B lymphocyte colony.

• Some cells of the colon differentiate into plasma cells that will synthesize specific antibodies and secrete in excess.

• The rest are circulating as B lymphocytes with the same characteristics.

• Plasma cells can not normally package the protein and store it in cytoplasmic granules.

• When necessary, it is sent in small vesicles from the Golgi complex to the cell surface and secreted at the same rate as it is produced.

•Plasma cells degenerate after a few weeks of producing antibodies.

•B lymphocytes in infection with same antigen second time or more will recognize it and form new plasma cells with the above transformation.

•Russell bodies are eosinophilic, large, homogeneous immunoglobulin-containing inclusions found in a plasma cell undergoing excessive synthesis of immunoglobulin, it occurs in the result of faulty production on the cell

• Some people have congenital plasma cell anomalies

• Hyperglobulinemia has excess plasma

cells in their tissues and intense antibodies in their blood,

• Agammaglobulinemic individuals can not

produce antibodies against the antigens,

these people do not have plasma cells

Plazma hücresi ve genişlemiş gER kanalları (x 3.200)

Plazma hücresi (TEM)

Plazma hücresi ve genişlemiş gER kanalları, TEM

Mast Cells

• Mast cells are very similar to structure and functional properties of basophil leukocytes.

• Basophils develop from the stem cell in the bone marrow, pass into the blood, then cross the

endothelium and migrate to the connective tissue.

• Mast cells also develop from the bone marrow

stem cell (hemopoietic cell); but the stem cell itself, which will form the mast cell, passes from blood to the connective tissue, here it differs to mast cell.

• Also occur by mitosis of earlier mast cells^.

 There are at least two types of mast cell populations in various connective tissues of the body.

- CT mast cells that contains mainly heparin in the granules

- mucosal mast cells with chondroitin sulphate instead of heparin in their granules

 Have round or oval nuclei.

 With EM, it is seen that there are many outcrops of cells in the form of the villus.

 When cytoplasm is stained with toluidine blue or thionine, it is filled with granules showing

methachromas due to heparin containe.

 In mast cell granules

 heparin, which inhibits clotting,

 histamine that increases vascular permeability,

 leukotrienes that cause slow muscle contraction in smooth muscle and

 ECF-A (eosinophil chemotactic factor-A), which

stimulates eosinophils to migrate into the connective tissue.

 These granules also contain various enzymes.

•Are extremely long-lived cells that detect foreign substances and initiate inflammatory response in the tissue.

•Blood serum contains IgE, apart from IgG which is effective in humoral immunity ,

•IgE is functional in allergic reactions

• There are 50 000-300 000 receptors in their membrane for binding IgE.

• When an allergic antigen is encountered, this

allergic agent binds to the receptor-bound IgE on the antigenic membrane to form a complex.

• This structure increases the membrane

permeability, causing the content of the granules to fall to envirement(connective tissue matrix).

• This content activates smooth muscles, secretory cells, small blood vessels, eosinophil leukocytes and blood flakes.

Bağ dokusunda Mast hücreleri (Aldehit fuksin, x 500)

Mast hücresi

Mast hücresi (TEM, x 10.000)

Proteoglikan Mast Hücresi

Mast hücresi

Mast hücresi

Mast hücresi (TEM) Ven

Arter Mast hücresi

Mononuclear phagocytic system (MFS)

• The mononuclear phagocytic system comprises closely related bone marrow-derived blood monocytes and tissue macrophages.

– Phagocytes on the walls of the lung alveoli, – Microglial in the central nervous system, – Kupffer cells in the liver,

– Reticular cells in bone marrow and lymph organs

• They defend the organism with their phagocytosis ability and form a system that is common throughout the body

Mononuclear phagocytic system

Stem cell

Differenciated SC Monoblastlar

Promonositlar Monositler

Monositler Makrofajlar

Bone marrow

Circulating Blood Tissues

• First Metchinikoff (1892) called the macrophage system.

• Subsequent studies have shown that some endothelial cells in bone marrow, liver and spleen sinusoids are capable of phagocytosis, and these cells also participate in this above system.

• Aschoff (1924) proposed the name reticuloendothelial system (RES).

• The opinions of the reticuloendothelial system with the contributions of cytogenetic studies have also changed considerably

• The new system of cells with high phagocytosis ability and their precursors was named mononuclear phagocytic

system by Van Furt (1969).

• This system does not include fibroblasts, endothelial cells, reticular cells and dendritic cells.

• All cells present in the mononuclear phagocytic system, originated from bone marrow and come from the same cell line.

• They migrate from the sidewalk to the tissues where they will function.

• Rich in peroxidase.

• The surface membranes have receptors for IgG and has complementary

Reticuloendothelial System

• A system that plays a role in the body's

defense against infection, formed by cells with the ability of phagocytosis which are commonly found in loose connective tissue, bone marrow, liver, lung, spleen and lymph nodes

– such as macrophages (histiocytes) in loose connective tissue,

– Kupffer cells in the liver . ;

Reticuloendothelial System

Macrophages

• The ones located in the connective tissue are mononuclear cells.

• There is no obvious shape.

• These cells digest foreign or harmful particles, bacteria and dead cells to the organism by

phagocytosis and destroy them with hydrolytic enzymes.

• Are also called phagocytes.

• Macrophages play an important role in the healthy functioning of tissues, in the repair of tissues and in the defense of the body against microorganisms.

• When morphological criteria are used, two basic classes of macrophages are

distinguished.

1) Fixed macrophages 2) Moving (free) macrophages.

• While fixed macrophages are stationary in or between collagen fibril bundles, the moving macrophages move in the connective tissue.

• Both types cames from different origins, in some

cases they are separated from one another in terms of their functions.

• Free macrophages consist of the progenitor cells in the bone marrow.

• It passes through the blood as monocytes.

• Crosses the endothelium and reaches the connective tissue.

• Here they become free macrophages.

• It is believed that fixed macrophages take root from the mesenchymal cells in the connective tissue.

• Although they are constant, they can act as free macrophages when stimulated by conditions

such as tissue damage and bacterial infection

.

• Most of the fixed macrophages in connective tissue do not show activity in normal condition, between the fibrillary structures on the tissue, they wait with their star-shaped structures.

• It is difficult to distinguish them from fibroblasts by their appearance; but its nuclei are slightly darker and smaller, separating it from fibroblasts with

vacuoles and granules at various lengths in its cytoplasm.

• Macrophages are called histocytes in

various histology books; but macrophages that are predominantly located in the

connective tissue are called histiocytes.

• In some chronic inflamation, clustered macrophages form polygonal shapes.

• In this case they are called epithelioid cells.

• Sometimes a single cell can not take a thin splitting or foreign body entering the tissue with phagocytosis.

• In this case, the macrophages combine to form a giant nucleus of giant cells.

• This is called a foreign body giant cell.

• This giant cell is capable of digesting large foreign bodies.

• Macrophages play an important role in body defense by preparing immune factors as well as

phagocytosing pathogenic m.o and other foreign bodies entering the body.

We can summarize the roles of

macrophages in the immune system and body defense as follows:

1) Macrophages enter the reaction with extracellular molecules (proteins and

polysaccharides), take them into them and metabolize them.

• These molecules can be in free form in the

liquid as well as in the bacterial structure.

2) Macrophages, which have very high secretory abilities, make a lot of biologically active substances and give them out of the cell.

Secretory products include products such as proteases,

complement proteins, growth factors such as interleukin-1 (IL-I), interleukin-6 (IL-6), tumor necrosis factors (TNFs).

All these substances have important roles in immune responses and inflammation.

3

• When a bacterium enters the body, IgG which is

previously formed against the same bacterial binds to the surface antigen of the bacteria.

The complement system derivative of plazma, C3b, is also linked to this antigen-antibody complex.

• This facilitates phagocytosis by allowing specific binding of the bacterial to the macrophage

membrane Fc receptor

• Macrophages which are stimulated by other cell products of the connective tissue most notably lymphocytes , with phagocytic and cytotoxic properties win the war between the bacteria.

4) Macrophages contain lymphokine receptors secreted by T lymphocytes.

• They are activated when they react with the lymphokines.

• Active macrophages are highly germicidal and tumor killer.

• Macrophages in critical regions of various tissues are

usually located close to the blood vessels, epithelium, and mesenchymal (mesodermal stem tissue, blood and lymph vessels).

• They are very common in spleen, lymph nodes, tonsils, liver, lung and kidney

• They are known by different names in various tissues.

• For example, macrophage or histiocyte in the connective tissue, microglia in the central

nervous system, chimeric monocytes and Kupffer cells in the liver.

Alveolar makrofaj, E.coli ve eritrosit

E.coli

Eritrosit

Alveolar makrofaj (Pembe), ince filopodyalı, E.coli (Yeşil) ve eritrosit (Kırmızı) E.coli

Serbest makrofaj. Çok sayıda sitoplazmik uzantı, hücreler arası alanda kollagen teller ve miyelinsiz

aksonlar görülüyor (TEM, x 6.000)

Akson

Akson

Serbest makrofaj

Makrofaj (TEM)