PROGRAM STUDI PENDIDIKAN DOKTER

FAKULTAS KEDOKTERAN DAN ILMU KESEHATAN

UNIVERSITAS WARMADEWA
Gartner LP, Hiatt JL : Colour Text Book of
Histology 3rd, Philadelphia, WB Saunders, 2007, pp
69-129
Lodish et all : Molecular Cell Biology, 5th ed, pp
197-201
Goodman SR : Medical Cell Biology 2nd ed, pp 195-
202.
 OUTLINE/LO
1. Cell adhesion molecules
2. Components of the extracellular
matrix
3. Cell-cell and cell-matrix adhesion
4. Structure and function of cell
junctions in tissue
5. Structure of four basic tissue
Cells often aggregate into a
tissue (cells & extracellular
matrix)

Different tissues can be

organized into an organ
Cell-Adhesion molecules (CAMs)
Cells in tissues can adhere to one another
(cell-cell adhesion) through specialized
integral membrane proteins called cell-
adhesion molecules ~ adhesion receptor
(cell-matrix junction)

Four major families of cell adhesion

molecules:
Cadherins
Ig Superfamily
Integrins
Selectins
4 major families of
CAMs
1. Cadherin
Ca2+ -dependent CAM
There are over 40 different known
cadherins, of which E-, P-, and N-
cadherins are the most widely expressed
Major role in cell-adhesion and
morphogenesis
A loss of cadherin is associated with
metastasis of cancer cells
Cadherin Structure
The cadherin molecule
consists of an N-terminal
extracellular region, a single
transmembrane spanning
segment, and a C-terminal
cytoplasmic tail
The extracellular domain
contains repeated
sequences that are sites
necessary for Ca 2+ binding
and cell-cell and the
cytoplasmic domain
adhesion, associates with
the cytoskeleton
Cadherin
Structure
2. Selectin
Ca2+ - dependent
CAM
Three major class
(P-, E-, L-selectin)
Participate in the
movement of
leukocytes circulating
in blood toward
tissues
3. Ig Superfamily
Ca2+ - independent
CAM
ICAM-1, VCAM-1,
NCAM-1, ICAM-2,
CD4, CD8
Facilitate the
transendothelial
migration of
leukocytes
4. Integrin
Ca2+ - independent CAM
Different combination of and chain are
possible, so that 22 integrins can be made from 16
and 8 chains.
Integrin can function in cell adhesion even when
dispersed on the cell surface. However, adhesion is
much weaker.
Integrin in epithelial cells concentrated in
hemidesmosomes.
Integrin Structure
Two associated and
subunits
These structure are
connected with the
cytoskeleton and
component of ECM
Cell-Cell adhesion ; Jenis2nya; Ca/Mg
dependent;interaction;cytoskeleton;junctional Cx
ECM is composed of :
1. Ground Substances
GAG
Proteoglycan
Adhesive glycoprotein

2. Fibers
Collagen
Elastic
GAG
Attracts extracellular
fluid assists in the
resistance to forces of
compression
Sulfated linked to
core protein
Non sulfated
hyaluronic acid
attached to
proteoglycan via link
protein
Proteoglycans
Protein core with
sulfated GAG
~ bottle brush
Proteoglycan +
hyaluronic acid
gel state of ECM
Have numerous
functions
Glycoprotein
Have binding sites :
Collagen
Proteoglycan
Cell
membrane(integrin)
fibronectin, laminin,
entactin, tenascin,
chondronectin,
osteonectin.
Laminin : 3 large
polypeptide chain
Collagen Fibers
Resist tensile forces
Aggregates of fibrils
Fibrils from
tropocollagen
molecules
(three polypeptide
chains)
Different collagen
types ~ chain
located in specific
region
various function
Collagen Synthesis
Elastic Fibers
Stretched one and a
half times their
resting length
Elastin core
surrounded by
microfibrils.
 SEL EPITEL

LAMINA
BASALIS
Basal lamina perlecan : proteoglycan (heparan
sulfat)..glycoprotein :laminin and entactin
 The physical nature of the ECM varies
from tissue to tissue
Very hard in bone
collagen fibrils from osteoblast that are then
mineralized (crystalline calsium and phosphate)
Gel-like properties in cartilage
predominant proteoglycan (aggrecan) assembles
with hyaluronan
Ropelike in tendon
abundance fibers and fewer cells
Fluid in blood
plasma contain 90% water , protein plasma 9%,
heparin
Extracellular matrix
The extracellular matrix consists of a large number
of different proteins. The composition of the
matrix is important for invasion because specific
integrins bind only to a particular subset of matrix
proteins.
Specific matrix structure where most cells in the
body bound is basement membrane (BM), underlies
most epithelia and surround the endothelium of
blood vessels (except for liver, no BM present,
instead a matrix rich in fibronectin)
The main component of BM are collagen type IV,
laminin and proteogylcan.
Cell-matrix adhesions
are mediated by
adhesion receptors bind
to various components
of ECM
Cell-cell adhesions are
mediated by CAMs bind
to CAMs on other cells
Its usually integral
membrane protein
domain sitosolik berikatan dengan
protein adapter. Protein adapter ini
menghubungkan CAM dengan
sitoskeleton dan intracellular
signalling pathways
Homophilic : A CAM
on one cell bind to
the same kind of
CAM on an adjacent
cell
Ig Superfamily can
form both:
homophilic (shown
here) and
heterophilic (nonself)
linkages.
Heterophilic : A
CAM on one cell
bind to a different
class of CAM on an
adjacent cell

Integrin can form

both: homophilic and
heterophilic (shown
here) linkages.
Cell-cell adhesion can be relatively weak and
transient (immune-system cells in the blood) or
can tight and long lasting (muscle cells) ?????

CAMs can be broadly distributed along the

regions of plasma membrane that contact other
cells or clustered in discrete patches or spots
called cell junctions.
cell junction merupakan bentuk stabil dari cell-cell adhesion
 3 major classes of cell
junction:
1. Occluding Junction physical barrier
Tight Junction
2. Anchoring Junction couple neighboring
cells/ECM
Zonula adherens
Macula adherens
Hemidesmosome
3. Communicating Junction transfer signal
Gap junction
Cell-cell Junction
Proteins of the Cell
Adhesion
The proteins responsible for the cell adhesion
are typically divided into three classes;
1) cell adhesion molecules/adhesion receptors
usually consist of transmembrane
glycoproteins, such as cadherin at cell-cell
contact and integrin at matrix contact,
2) the cytosol-facing domain of CAMs recruit
adapter protein/peripheral membrane
proteins, act as linkers that connect CAMs to
elements of the cytoskeleton.
3) the extracellular matrix (ECM) proteins,
large fibrillar glycoproteins like collagens
linked tightly to adhesion receptors,
 Tight Junction = Zonula
occludentes
Belt-like junction
Prevent the movement
of membrane proteins
from the apical
domain to the
basolateral domain
Prohibit water-soluble
molecules from
passing between cells
JAMs(junction adhesion molecules) merupakan

bagian dari Ig Superfamily

Zonula Adherens
Belt-like junction
Consist of :
E-Cadherin
Plaque
Actin Filament

Maintaining cell-
cell adherence
Macula Adherens =
Desmosomes
Randomly
distributed
Consist of :
E-cadherin
Plaques
Intermediate
filaments

Resist shearing
forces
Gap Junction = Nexus
Widespread
Consist of
Connexin --
connexons
Permitting the
passage of various
small molecules
pH and Ca2+
close gap
junction
Hemidesmosomes
Attach the basal
cell membrane to
basal lamina
Consist of :
Integrin
Plaque
Intermediate
filaments
Most organ contain of four main
classes of tissue :

epithelial membranes
1. Epithelial tissue as glands
2. Connective tissue
3. Muscular tissue
4. Nervous tissue
Cari organ yg tidak mengandung 4 jaringan dasar
 Functions of
Epithelia
Protection
Transcellular transport
Secretion
Absorption
Selective permeability
Detection of sensation
Contractility (myoepithelium of
glands)
Epithelial tissue :
* Epithelial cells
* Basal lamina
(extracellular
matrix)
Classification of Epithelial
Membranes
Number of cell layer

Morphology of the epithelial

cells

Specialty of free surface of the

cells
SIMPLE SQUAMOUS EP (ENDOTHEL)
 SIMPLE
CUBOIDAL
EP
SIMPLE COLUMNAR EP
PSEUDOSTRATIFIED EP
STRATIFIED SQUAMOUS (NONKERATINIZED) EP
STRATIFIED SQUAMOUS (NONKERATINIZED) EP
STRATIFIED SQUAMOUS (KERATINIZED) EP
STRATIFIED COLUMNAR EP
TRANSTITI
ONAL EP

BASAL
LAMINA
POLARITY OF EPITHELIAL
CELL
Related to cellular morphology and function.

Apical Basolateral
domain domain
 Apical Specializations of
Epithelial Cells

Microvilli
brush border in kidney and small intestine
Stereocilia
epididymis, hair cells of organon Corti
Cilia (Kinocilia)
respiratory tract, tuba palopii (oviduct)
Flagella
Spermatozoa
 SEL EPITEL

LAMINA
BASALIS
LAMINA BASALIS

LAMINA BASALIS
CLASSIFICATION OF GLANDS

1.Exocrine Gland Duct (+)

2.Endocrine Gland Duct (-)

Histology Structure of
Exocrine Glands

Parenchyme
* Acini
* Duct

Stroma
CLASSIFICATION OF EXOCRINE
GLANDS
1. Nature of their secretion
2. Mode of secretion
3. The number of cells
1. Nature of their
secretion
Serous Glands

Mucous Glands

Mixed Glands
Serous
Glands
Mucous
Glands
Mixed Glands
 SEROUS MUCOUS
SECRET Watery Viscous
NUCLEUS Round shape Flat
LUMEN Narrow Larger
H.E STAINING Redish purple Pale blue
ORGANELLE Mitochondria >> Mitochondria <<
E.R >> E.R <<
Golgi << Golgi >>
 2. Mode of Secretion

Holokrin : sebaceous gland

Merokrin : sweat glands
Apokrin : Mamma glands
3. The Number of Cells
Unicellular
Multicellular
* seromucous
* mucoserous
 SEL GOBLET

Cari sel goblet pada apa dan fungsinya

MULTICELLULAR GLANDS (Mucoserous)
MULTICELLULAR GLANDS (Seromucous)
Morphology of Multicellular Glands
Simple Tubular Glands (Fundus of
Gastric)
MYOEPITHELIAL CELL = BASKET CELL

Stellate/spindl MYOEPITHELIAL CELL

e
shaped

Base of
acinar
and duct cells Mucous
acinus

in glands

Contain
actin/myosin;
Functions of Connective
Tissue
Structural support
Medium for exchange
Defense and protection of the
body
Storage of fat
Component of Connective
Tissue
1. Cellular Components
Fixed Connective Tissue Cells
Transient Connective Tissue Cells
2. Extracellular Matrix
Ground Substances
Fibers
Cellular Components
Fixed Cells Transient cells
1. Fibroblasts 1. Plasma cells
2. Pericytes 2. Lymphocytes
3. Adipose Cells 3. Neutrophils
4. Mast Cells 4. Eosinophils
5. Fixed macrophage, 5. Basophils
kupffer cells, dust 6. Monocytes
cells, langer-hans cells 7. Transient macrophages
1. Fibroblasts
Most abundant cell type
Synthesis extracellular matrix
Fusiform cell
Active and inactive fibroblast
Myofibroblasts = characteristics similar to those
of both fibroblasts and smooth muscle cells

Myofibroblas mirip fibroblas, tapi punya banyak aktin dan myosin . Mereka bisa berkontraksi
dan terutama banyak pada wound contraction and tooth eruption
Fibroblasts
2. Pericytes : - surround endothelial cells
- Possess their own basal lamina
Baca tentang perycite hal 260
3. Adipose Cells
Function in the synthesis, storage, &
release of fat
Two types :
Unilocular fat cells
Multilocular fat cells
Adipose Cell
Multi locular Fat Cell
4. Mast Cells
Mediating the
inflammatory process
and immediate
hypersensitivity
reactions
Numerous granules
(contain mediators)
5. Macrophage
Cell surface varying, from short, blunt
projections to finger-like filopodia
Phagocytes
Antigen-presenting cells
Monocyte circulate in the blood mature
into macrophages in the connective tissue
Fixed macrophage and transient macrophage
= Kupffer cells, dust cells, Langerhans cells ~
osteoclasts and microglia
Baca bentuk osteoklas dan mikroglia
6. Plasma Cells
Derived from B
lymphocytes and
manufacture
antibodies
7. Leukocyte
Circulate in the bloodstream connective
tissue (inflammation)
Neutrophils : phagocytose & digest bacteria in
areas of acute inflammation pus
Eosinophils : allergic reaction
Basophils : control inflammatory process
Lymphocytes : small number
Classification of Connective
Tissues
1. Embryonic connective tissues
1. Mesenchymal connective tissues
2. Mucous connective tissues
2. Connective tissues proper
1. Loose connective tissues
2. Dense connective tissues
3. Reticular connective tissues
4. Adipose connective tissues
3. Specialized connective tissues
Cartilage, Bone, Blood
Embryonic Connective
tissues
Mesenchymal
Scattered throughout the embryo
do not exist in adult, except pulp of teeth

Mucous tissue
Umbilical cord and subdermal connective tissue
of the embryo
Loose (Areolar)
Connective Tissue
Loose arrangement of fibers
Dispersed cells
Abundant ground substances
Many transient cells responsible for
inflammation, allergic response, and immune
response
Loose (Areolar)
Connective
Loose arrangement ofTissue
fibers
Dispersed cells
Abundant ground
substances
Many transient cells
responsible for
inflammation, allergic
response, and immune
response
Dense
Connective
Abundance fibers Tissue
Fewer cells
Limited ground
substances
Irregular randomly
Regular parallel or
organized fashion
Dense Regular Elastic Connective Tissue
Reticular Tissue
Type III collagen
Architectural
framework of liver
sinusoids, adipose
tissue, bone marrow,
lymph nodes, spleen,
smooth muscle, and
the islets of
Langerhans
LIMPHORETICULAR
TISSUE
Adipose Tissue cari tentang sitokrom di mito karena
vaskularisasi yang banyak dan sitokrom yang banyak yang menyebabkan jar lemak coklat
berwarna coklat sampai coklat kemerahan

White Adipose Tissue

Unilocular fat cell
Single lipid droplet
Influenced by sex and
age
Brown Adipose Tissue
Multilocular fat cell
Multiple droplets
Newborn human (neck &
interscapular region)
Baca mekanisme termogenin dalam
memproduksi panas