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Prof. Marina KapitonovaProf. Marina Kapitonova
ecture:
CONNECTIVE TISSUE
for Year 1 Medical Students of UiTM
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The objectives:
1.Describe connective tissue with
regard to its classification.
2.Describe the cells and thematrix of the connective tissue
with regards to their structureand function.
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Connective tissue is a tissue of mesenchimal origin which connects,
holds and supports other bod tissue.
II. DEFINITION OF
CONNECTIVE TISSUE
fat cells
lmphocte
f ibr oblast
collagen
fiber
plasma
cell
capillar
pericte
mast cell
elastic fibers
neutrophil
histiocte
!macrophage"
capillar
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###. D#$%#&C%#'( )(*%+($ -) C-&&(C%#'( %#$$+($
1. -n the contrar to other tissues, connective tissue is composed
mostl of extracellular matrix with a limited amount of cells
scattered throughout the matrix.
2. Cells maintain their associations with the extracellular matrix bforming specialied /unctions that hold them to the surrounding
macromolecules.
0. %he extracellular matrix of connective tissue is composed of a
hdrated gellie ground substance with fibers embedded in it.
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protection against infection and other foreign material
!immunoctes"
regeneration after in/ur !fibroblasts"
IV. FUNCTIONS OF THE CONNECTIVE TISSUE
- mechanical support !fibers"
- exchange of metabolites between blood and tissue !ground
substance"
- storage of reserve energ material !adipose cells"
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ocalization
ocalization
of Epithelium
f Epithelium
& Connective
Connective
Tissue in theissue in the
Human Body
uman Body
protective
secretorabsorptive
reproductive
sensor
lubricative
excretor
epithelial
tissue
connective
tissue
bonecartilage
ligaments
tendons
loose and dense
connective tissues
adipose tissue
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CO!O"#T#O$ O% CO$$ECT#E T#""'E
1. CONNECTIVE TISSUE = CES ! E"T#$CEU$#
M$T#I"
%. E"T#$CEU$# M$T#I" = &#OUND
SU'ST$NCE ! FI'E#S
(. M$C#OMOECUES OF THE &#OUND
SU'ST$NCE = &$& ! )#OTEO&YC$NS ! $DHESIVE
&YCO)#OTEINS
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C (""#%#C(T#O$ O% CO$$ECT#E T#""'E
(""#%#C(T#O$ O% CO$$ECT#E T#""'E
Connective Tissue
Connective %issueConnective %issue
Proper Proper !fibrillar"!fibrillar"
Connective %issue
with $pecial Properties$upporting C%
*dipose*dipose
eticular
3ematopoetic !4 5M"
Pigment
Mucous
4oose
!areolar"
Dense
egular
!collagenous,
elastic"#rregular
CartilageCartilage
6one
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Classification of the
lassification of the
Connective Tissue
onnective Tissue
Cells
ells
C% cells can be characteried as
fixed or wandering.
fibroblasts and a closel relatedtpe mofibroblasts,
macrophages,
adipose cells,
mast cells,
undifferentiated mesenchimal
cells !adventitial cells, perictes".
%he cells that comprise the
wandering !transient"
lmphoctes,
plasma cells,neutrophils,
eosinophils,
basophils,
monoctes.
fat cells
fibroblastmacrophages
collagen
plasma
cells
mast cell
P
e
r
pericte
elastic
fiber
endothelial cell
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T)!E" O% CE "
#$ OO"E (*EO (* T#""'E
1. esident
fibroblasts
macrophages
mesenchmal cells
reticular cells
fat cells
mast cells
2. 'isitant
plasma cells
neutrophils
lmphoctes
leuoctes !neutrophils,
lmphoctes, etc"
pigment cells
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CO!O"#T#O$ O% +*O'$, "'B"T($CE
O!O"#T#O$ O% +*O'$, "'B"T($CE
water – mineral salts – GAG - glycoproteins 7 proteoglcans
8*8s
&onsulfated group
-Hyaluronic acid (in skin, loose connective tissue, break down with
umbilical cord, vitreous body, & synovial fluid hyaluronidase
spreading factor!
-"hondroitin (in cornea & embryonic cartilage#
$ulfated group
-"hondroitin-$-sulfate (in cornea, skin, bone & cartilage#
-"hondroitin-%-sulfate (in tendons, cartilage, umbilical cord & intervertebral disks#
-ermatan sulfate (in skin, tendons, ligaments & heart valves#-'eratan sulfate (in bone, cartilage, cornea & intervertebral disks#
Collectivel termed 9glcosaminoglcans:
8round - controls passage of pathogens
substance
functions - allows diffusion of ) & nutrients
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%his permits the rapid spread of bacteria through the
connective tissue spaces. Permeabilit ofmicrovessels ma increase under certain conditions
!inflammation, liberation of the biologicall active
substances such as histamine and bradinin".
C #$#C( CO**E (T#O$":
Man pathogenic bacteria, such as $taphlococcus
aureus, secrete haluronidase, an enme that
cleaves haluronic acid !it ma be up to 2;
micrometer long" into numerous small fragments,
thus converting gel state of extracellular matrix intoa sol state.
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%hese large structures loo lie a bottle brush, with
the protein core resembling the wire stem and the
various sulfated 8*8s pro/ecting from its surface in
threedimensional space, as do the bristles of thebrush.
!*OTEO+ )C($":
Proteoglcans constitute a famil of
macromolecules< each is composed of a protein core
to which glcosaminoglcans are covalentl bound.
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Sc*e+atic
Dia,ra+ of
$ssociation of
$,,recanMolecules -it*
Colla,en Fiers.
collagen fibres haluronic acid
molecule
haluronic
acid
lin proteincore protein
chondroitin
sulphate
proteoglcan
collagen tpe ##
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COO$
!*OTEO+ )C($"
Name Approx.Molecular Weight
Type of GAGMonomers
Approx . No. ofGAG
Chain
Distribution Function
Decorin =;,;;; Chondroitinsulfate,
dermatansulfate
1 >idedistribution in
connectivetissue
6inds tpe #collagen and
%8)
*ggrecan 21;,;;; Chondroitinsulfate,
eratan sulfate
10; Cartilage *ggregateswith
haluronan,supportive
function
Perlecan ?;;,;;; 3eparansulfate
21@ 6asal laminae )ilteringfunction
6etaglcan 0?,;;; Chondroitinsulfate,dermatan
sulfate
1 Cell surface,(xtracellularmatrix
6inds%8)
$ndecan1 02,;;; Chondroitinsulfate,heparansulfate
10 $urface offibroblast andepithelial cells
Cell adhesion,binds )8)
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%he ma/or tpes are fibronectin, laminin, entactin, tenascin,
chondronectin and osteonectin.
+ )CO!*OTE#$":
%he abilit of cells to adhere to components of the extracellular
matrix is mediated b cell adhesive glcoproteins.
%hese large molecules have several domains, at least one of
which usuall binds to cell surface protein called integrins, one
to collagen fibers, and one to proteoglcans.
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%#BE*":
1. Collagen and elastic fibers, the two ma/or fibrous proteins ofconnective tissue, have distinct biochemical and mechanical
properties as a conseAuence of their structural characteristics.
2. %he provide tensile strength and elasticit to thissubstance.
0. Classical histologists have described three tpes of fibers
although it is now nown that reticular fibers are in fact a tpe
of collagen fibers but the term reticular fibers is retained.
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SEM of Colla,en Fier 'undles in t*e E/ineuriu+. 0 %222
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Colla-en %ibrils .ith /0 nm !eriodicity of
"triations1 TE2 344244451
#n (M the collagen fibrils exhibit a banding pattern with an axial
periodicit of ?B nm. -verlapping of tropocollagen molecules is
responsible for banding pattern. %ropocollagen molecules lie
parallel to each other overlapping b of their length.
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Colla-en %ibers
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%ormation of Colla-en by %ibroblasts
Molecule of preprocollagen translated in the ( undergoesMolecule of preprocollagen translated in the ( undergoes
hdroxlation, glcoslation and formation of procollagen tripplehdroxlation, glcoslation and formation of procollagen tripple
helix in the (.helix in the (.
collagen fiber
reticular
fibers
unit fibril ofcollagen
glcine
proline
polpeptide chain
addition of
carbohdrate
tropocollagen
procollagen
peptidase
procollagen
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The "tructure of the "uperheli5 of Colla-en
he "tructure of the "uperheli5 of Colla-en
!olypeptide Chain
olypeptide Chain
.
%hese collagen molecules !whichare also called tropocollagen" self
assemble into protofilaments,
which are filaments of @ nm
diameter.
triple helix of
threepolpeptide
chains
collagen
molecule
staggered
collagen
molecules
assemble
into a fibril
fibril
banding
pattern
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Colla-en
%ibers
$chematic representation of the components of a C). %he
ordered arrangement of the tropocollagen molecules gives rise to
the gap and overlap regions, responsible for ?Bnm crossbanding of
tpe # collagen.
muscle
bundle
tendon
fiber fibril
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Types of
Colla-en
Collagen Type Location Cells ro!ucing Characteristics
%pe # !;E"!composed of twotpes of Fchain"
Dermis of sin,tendon.4oose !areolar",
dense ordinarconnective tissue,collagen fibers.Most wideldistributed tpe ofcollagen in internalorgans. 6one.
Dentin !teeth".
)ibroblasts.
eticular cells and
smooth muscle
-steoblasts
-dontoblasts
4ow hdroxlsine,low carbohdrate!broad fibrils"
%pe ## !composedof onl one tpe ofFchain"
3aline and elasticcartilage'itreous bod ofee, intervertebraldisc
Chondroctesetina cellsChondroctes
3igh hdroxlsine,high carbohdrate!thinner fibrils thantpe #"
%pe ### !composedof onl one tpe ofFchain"
4oose connectivetissue< reticularfibers, papillarlaer of dermis,!found earl indevelopment"
6lood vessels
)ibroblasts andreticular cells$mooth musclecells, endothelialcells
3ighhdroxproline, lowhdroxlsine, lowcarbohdrate
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Types of
Colla-en
Collagen Type Location Cells ro!ucing Characteristics
%pe #' !composedof two tpes of Fchain"
6asal lamina4ens capsule of ee
(pithelial andendothelial cells4ens epithelium
'er highhdroxlsine, highcarbohdrate!retains procollagenextension peptides"
%pe ' )etal membranes
!placenta"6asementmembranes6one, $moothmuscle
)ibroblasts
(pithelial cells-steoblasts$mooth musclecells
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CO (6
+E$O'"
CO$$ECT#E
T#""'E
Tendo
calcaneus
7tendon of
(chilles8
lon-itudinal
section2 H &
E2 53/91
fibrocte
nucleicollagen
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$ome individuals, especiall blacs, are predisposed
to an excessive accumulation of collagen during
healing. #n these patients the scar forms an elevated
growth nown as a eloid.
C #$#C( CO**E (T#O$":
*t the end of surger, the cut surfaces of sin are
carefull sutured< usuall a wee later the sutures
are removed. %he tensile strength of the dermis at
that point is onl about 1;E that of normal sin.
>ithin the next = wees, the tensile strength
increases to about G;E of normal, but in man cases
it never reaches 1;;E. %he initial weaness isattributed to the formation of tpe 0 collagen during
earl wound healing, whereas the later improvement
in tensile strength is due to scar maturation, when
tpe ### collagen is replaced b tpe # collagen.
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6ecause these two structures are responsible for
maintaining teeth in their socets, the smptom ofscurv include bleeding gums and loose teeth. #f the
vit * deficienc is prolonged, other sites are also
affected. %hese smptoms ma be alleviated b
eating foods rich in vitamin C.
C #$#C( CO**E (T#O$":
3droxlation of proline residues reAuires the
presence of vit C. #n individuals who suffer from a
deficienc of this vitamin, the alphachains of the
tropocollagen molecules are unable to form stable
helices, and the tropocollagen molecules are
incapable of aggregating into fibrils. %his condition,
nown as scurv, first affects C% with high turnoverof collagen, such as periodontal ligaments and
gingivae.
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Elastic (rtery2 Orcein2 5 39
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Elastic %ibers
%he are
manufactured b fibroblasts
of connective tissue and b
smooth muscle cell of blood
vessels. %he are composedof elastin, a protein rich in
glcine and lsine.
fat
cells
fibroblastmacrophages
collagen
plasma
cells
mast cell
Pe
r
pericte
elastic
fiber
endothelial cell
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E$STIC FI'E#S
In H 3 E stained tissues 4c5 elastic fiers 4E5 stand out as ,lass6
ri,*t /in78stained structures ta7in, u/ acidic d6es suc* as eosin
-it* +uc* ,reater a9idit6 t*an CF 4F firolsts5.
EF can e stained 6 s/ecial tec*ni:ues. In t*is e0a+/le EF 4E5 in
t*e der+is of t*e s7in are stained lue 6 toluidine lue 4d5 and
contrast -it* /ale8stainin, colla,en.
(
)(
C
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Elastin is a /rotein
-*ic* asse+les
into stretc*ale andresilient fiers and
s*eets 3 is t*e +ain
co+/onent of EF.
E$STIN
relaxedrelaxed !random coil"
random coil
conformation
stretched
relaxednew
random
coil
conform
ation
stretched
Elastic Fiers
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In EF ,l6co/rotein +icrofila+ents 4firillin5 surround and
or,ani;in, a core re,ion of crossed8lin7ed elastin.
Elastic Fiers
Dia8
,ra+T
E
M
elastin
core
microfibrills
M
(
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(orta2
Human2
;ei-ert<s
elastic
tissue stain
and
phlo5ine2
3/9 51
tunica intima
elastic fibers
tunica media
smooth muscle
tunica adventitia
vasa vasorum
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People who have MarfanHs sndrome are unusuall
tall, have a ver wide arm span, are prone to develop
subluxation of lens and are also prone to develop
fatal rupture of aorta. %he absence of fibrillin which
interacts with elastin in tissues provoes lens
dislocates, as its suspensor fibers normall containfibrillin. * lac of elastin recoil in aorta would weaen
the wall 5 predispose to rupture. %he growth of long
bones is somewhat constrained b the presence of
fibrillin, and hence bones grow longer in its absence.
C #$#C( CO**E (T#O$":
%he integrit of elastic fibers depends on the
presence of microfibrils. Patients with Marphan
sndrome have a defect in the gene on chromosome
1@ that codes for fibrillin< therefore their elastic fibers
do not develop normall.
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*eticular %ibers2 TE2 94244451
eticular fibers do not gather into bundles as do collagenous
fibers but tend to form delicate networs.
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*eticular %ibers
) cannot be seen in 3 5 ( sections, but can be stained b silver
impregnation methods or b P*$ reagent. #n this microphotograph, ) is
a lmph node are seen as fine blac lines, with lmphoid cells stained red in
the bacground. ', vessel.
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Connective Tissue Cells
%hefibroblasts are
the most
abundant cell
tpe in the C%.
%he are
responsible for
the snthesis
of almost all of
the extra
cellular matrix.
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Cell ines ,erived from esenchyme
Cells
%he
Mesenc*6+e cells can /otentiall6 de9elo/ into a
9ariet6 of cells -*ic* +a7e u/ different tissue t6/es.
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"chematic ,ia-ram of the Ori-ins of Cells of
Connective Tissue
+ndifferentiated
mesenchmal cell
-steoblast(ndothe
lial
cell
Mesothelial
cell)ibroblast
*dipocte
Chondroctes -steocte
Chondroblast
6 lmphocte
Plasma cell
3emapoietic
$tem cell 6C
Monocte
Macrophage
-steoclast Megaarocte
Mast cell
&eutrophil
(osinophil
6asophil
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CE " O% CO$$ECT#E T#""'E
Cells General Functions
)ibroblast Produces fibers !collagen, reticular, elastin" and amorphous /ellies !glcosaminoglcans, proteoglcans"
Macrophage Phagoctic !e.g., bacteria"*ntigen presentation$ecretor !e.g., interleuinl, interferonI"
Pericte Differentiate into fibroblasts, reticular cells, smooth musclecell in blood vessel, adipoctes
Mast cell $ecrete heparin, histamine, slowreacting substance ofanaphlaxis, eosinophilic chemotactic factor of anaphlaxis
)oreign bod giantcell
Phagoctic !larger particulate material"
eticular cell Produce reticular fibers !tpe ### collagen" for lmph nodes,
spleen, bone marrow, etc.
*dipoctes )at storage, mobiliation
Chondroblast!chondrocte"
$ecrete collagen or elastic fibers, as well as cartilageamorphous intercellular substances !glcosaminoglcan,proteoglcan", and other proteins
-steoblasts $ecrete collagen, bone matrix !proteoglcans"
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%ibroblasts and Colla-en
*
+
+
"
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%ibroblasts and Colla-en2 TE2
5942444
)ibroblasts maoccur either in active or
Auiescent state
!fibroctes".
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oose Connective Tissue Cells
oose Connective Tissue Cells
%he macrophages phagoctose foreign substances and
damaged and senescent cells as well as cellular debris< the also
assist in the initiation of the immune response.
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Macrophage,
TE2
5942444
Macrophages belong to the mononuclear phagocting
sstem and are subdivided into two groups of cells, phagoctes and
antigenpresenting cells.
$tem cells
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The
acropha-e
"ystem
*ll its members
arise from a common stem cell in
the bone marrow, possess
lsosomes, are capable of
phagoctosis, and displa
receptors for antibidies and
complement.
$tem cells
Monoblasts !in bone marrow"
Promonoctes
Monoctes !in circulating blood"
Macrophages !in tissue and organs< both free
and fixed, unless noted otherwise"
4ining lmph sinuses
J lmph nodes
4ining blood sinuses or sinusoidsJ liver !fixed Kupffer cells"
J spleen !splenoctes or
hemophages"
J bone marrow
4ining serous cavities !pericardial,
peritoneal, and pleural"
*reolar connective tissue !fixed histioctes"
4ung !alveolar macrophages or dust cells"
Circulating blood !monoctes"
Central nervous sstem !fixed mocroglia or
mesoglia"
oint cavities !tpe * snovial cell"
6one !osteoclasts"
Macrophage $stem
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p g Name of Cell Function "s# Location
Macrophage Phagoctosis,antigen presentation
4oose !areolar" connective tissue
Peritoneal or pleural
macrophages
Phagoctosis $erous cavities
Macrophage 6lood cell destruction, antigenpresentation
6one marrow, $pleen, %hmus,4mph node
*lveolar macrophage !ordust cell"
Phagoctosis *lveoli of lung
4angerhans cell *ntigen presentation (pidermis
Kuppfer cell Phagoctosis 4iver !perinsinusoidalmacrophage"
Microglia Phagoctosis,antigen presentation
Central nervous sstem
-steoclast !multinucleate" 6one resorption 6one surfaces !form from fusion ofmonoctederived macrophages"
)ibroblastderivedmacrophage
Phagoctosis #ntestinelamina propria+terusendometrium
)oreign bod giant cell!multinucleate"
Phagoctosis induced in areas of particulatematerial !e.g., talc on mesenter"
!fusion of monoctes, macrophages"
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(lveolar
acropha-es
2
"E2
/244451
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!eritoneal
acropha-es
2
"E2
34244451
Criteria for designating macrophagesL
1"avidl phagoctic
2"strong affinit for des and particulates
0"store particulates
="adhere to glass surfaces in culture@"have antibod receptor sites on cell membranes
Connective tissue cells M*$% C(44
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undifferentiaited
cell
osteoblast chondroblastendothelial
cell
mesothelial
cell fibroblast
adipocte
osteocte chondroctes
hematopoietic
stem cell
6 lmphocte
plasma cell
monocte
macrophage
osteoclastmegaarocte
mast
cell
basophil
eosinophil
neutrophil6C
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ast Cell
Human2
TE2
34244451
.
.Mast cells /ro+ote i++ediate *6/ersensiti9it6
reactions 4*a6 fe9er ast*+a ana/*6la0is5 follo-in, t*eir
release of secretor6 ,ranules -it* *e/arin and *ista+ine
-*ic* act as c*e+ical +ediators.
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ast Cell
Human2
TE2
34244451
.
.
Mast cells are a+on, t*e lar,est of fi0ed cells of t*e CT
t*e6 are %28(2 +c+ in dia+eter. T*e /resence of nu+erous,ranules in t*e c6to/las+ is t*e identif6in, c*aracteristic of
+ast cells.
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ast Cell
Human2
TE2
34244451
.
.
Mast cells /ossess *i,*8affinit6 cell8surface Fc rece/tors4Fc8e/silon#I5 for I,E. Cross8lin7in, of t*eir surface I,E
+olecules 6 anti,en causes t*eir clu+/in, and t*is tri,,eres
+ast cell de,ranulation -it* release of se9eral +ediators of
aller,ic reaction.
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ast Cells1
a8 human2 H
& E2 53/9
b8 rat2tolui6
dine blue2
53=3/
Mast cells are found
in areolar C% and
along the course of
small blood
vessels.
mast
cells
collagen
elastic
fiber
fat
cell
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'ictims of asthma attacs suffer from difficult in
breathing as a result of bronchospasm caused b
leuotriens released in the lungs.
C #$#C( CO**E (T#O$":
'ictims of ha fever attacs suffer from the effects of
histamine being released b the mast cells of the
nasal mucosa, which causes localied edema from
increased permeabilit of the small blood vessels.
%he swelling of the mucosa results in feeling 9stuffedup: and hinders breathing .
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Cells of the oose Connective Tissue
ells of the oose Connective Tissue
%he plasma cells have eccentric nucleus with spoelie
distribution of heterochromatin in the nucleus.
fat cells
fat
loose connective
tissue
fatfat cell droplets of fat
*
6
C plasma cells mast cells
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!lasma cell2 TE2 53>2444
lasma cell2 TE2 53>2444
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!lasma Cells2
amina !ropria2
?ejunum2 5/39
cartwheel
nucleus
8olgi one
lmphoctes
basophilic
ctoplasm
eosinophil
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$eutrophil2 TE2 5342444
eutrophil2 TE2 5342444
&eutrophils phagoctose and digest bacteria in areas of
acute inflammation resulting in formation of pus, an accumulation of
dead neutrophils and debris.
&
&
&
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ymphocyte2 TE2 5342444
ymphocyte2 TE2 5342444
4mphoctes are present in small numbers in most C%,4mphoctes are present in small numbers in most C%,
except at sites of chronic inflammation where the are abundant. & 7except at sites of chronic inflammation where the are abundant. & 7
nucleus of the lmphocte.nucleus of the lmphocte.
&
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*dipoctes ma be unilocular !white C%" or multilocular !brown C%".
CO$$ECT#E T#""'E CE "1 (,#!OC)TE"1
O$$ECT#E T#""'E CE "1 (,#!OC)TE"1
adipocte
fibroblast
macrophages
collagen
Plasma
cells
Mast cell
P
e
r
pericte
(lastic
fiber
endothelial cell
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De9elo/in, Fat Cell
TEM 0(222
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%(T CE 2
'nilo6
cular2
TE2
3>2444
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B*O;$ %(T
ediasti6
num2
*hesus
mon@ey2
H1 & E12
(1 3/9 5A
B1 B1 /39 51
6rown fat is an uncommon variet of human fat found in the
upper bac !interscapular region" of the bod. +nlie the more
common white fat, brown fat cells contain a number of small lipid
droplets, hence the name multilocular fat. >hite fat cells, in contrast,
contain a single lipid droplet.
lobule of
polgonal
brown
fat cells
multilocular
fat cells
lipid
droplets
capsule
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*ET#C' (*
CE "
ymph node
subcapsular
sinus1 *hesus
mon@ey2
H1 & E12 /39
51
lmphoctes
macrophage
reticular
cell
processes
capsule
reticular
cell
nucleus
reticular
cells
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E"E$6
CH)E
%etal pi-
H1 & E12
B1 >> 5A
C1 994 51
Mesenchmal cells can differentiate into most of the adult
connective tissue cell tpes, includingL !1" fibroblasts, !2"
chondroblasts, !0" osteoblasts, !=" odontoblasts, !@" reticular cells,
and !?" adipoctes.
#n this plate, note several of the mature cell tpes that have
differentiated from mesenchmal cells. (xamine the developing hair
follicles in 6.
developing
hair
follicles
*
e
s
e
nc
h
y
m
e
mesenchme
mesenchmal
cells
developing
striated
muscle
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'CO'"
CO$$ECT#
E T#""'E
'mbilical
cord2
on@ey2
H & E2
/391
fibroblasts
collagenous
connective
tissue
$#EO$# CONNECTIVE TISSUE Sucutaneous #at H3 E 0 <1%.
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elastic
fibers
lmphocte
mast
cell
fibroblasts
collagenous
fibers