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HUMAN HISTOLOGY

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LECTURE TRANSES

HISTOLOGY UNIT 1: INTRODUCTION TO HISTOLOGY


degrees Celsius until it becomes completely
Outline infiltrated with this substance.
I. Histology ▪ After infiltration, the paraffin-infiltrated tissue is
a. Two interacting components of tissue placed in a small mold with melted paraffin and
II. Preparation of tissues for study allowed to harden, a process called embedding.
a. Basic steps in tissue preparation ▪ The resulting paraffin block is then trimmed to
i. Light microscopy expose the tissue for sectioning on a microtome.
ii. Transmission electron microscopy o Staining
(TEM) ▪ This step allows tissues to be studied
III. Basic principles of cell structure and function microscopically since most cells and extracellular
a. Cell shape materials are colorless.
b. Cytoplasm features ▪ Anionic components (nucleic acid with a negative
c. Nucleus features charge) have an affinity for basic dyes and are
d. Cell size termed basophilic. 8D dyes
blue negative -

✓ Examples of basophilic dyes are toluidine


blue, alcian blue, and methylene blue.
✓ These components ionize and react with
WHAT IS HISTOLOGY?
basic dyes because of deoxyribonucleic
● It is the study of the tissues of the body and how these
acid (DNA), ribonucleic acid (RNA), and
tissues are arranged to constitute organs.
glycosaminoglycans.
● It involves all aspects of tissue biology, with the focus on
▪ Cationic components (nucleic acid with a positive
how cells’ structure and arrangement optimize functions
charge) stain more readily with acidic dyes and are
specific to each organ.
termed acidophilic. red dyes positive -

TWO INTERACTING COMPONENTS OF TISSUE ✓ Examples of acidic dyes are eosin,


● Extracellular matrix (ECM) zn contains fluidthe for
transport cell

orange G, and acid fuchsin


o It supports the cell and contains the fluid responsible ✓ Acidic dyes stain the acidophilic
for transporting nutrients to the cells and carrying components of the cell, like the
away waste and secretory products. mitochondria, secretory granules, and
● Cells collagen.
o They produce the ECM and are strongly influenced
by matrix molecules. Table 1. Basic steps in tissue preparation
Basic steps in tissue preparation
PREPARATION OF TISSUES FOR STUDY
● This is the most common procedure used is histologic
procedure, which can be visually examined with Transmission Electron
Light Microscopy
transmitted light. us iixation Of tissues FOR M A 1 D E H Y D E
Microscopy (TEM)
G 1 U T A R Al D E H Y D E

o Fixation
▪ Small pieces of tissue are placed in solutions of ● Fixation: Small pieces ● The steps for TEM are
chemicals that cross-link proteins and inactivate of tissue are placed in similar to light
degradative enzymes, which preserves cell and solutions of chemicals microscopy, except the
preserves tissues by preventing
tissue structure. A enzyme degradation
.
that cross-link proteins fixative used is
▪ This step preserves tissue structure and prevents and inactivate glutaraldehyde and the
degradation caused by enzymes released from degradative enzymes, blocks are cut at less
cells or microorganisms. which preserves cell and than 1 μm thick. The
▪ Tissues are cut into small fragments to allow tissue structure. section is then placed on
penetration and diffusion of fixative through the ● Dehydration: The tissue a metal grid for staining
tissues to preserve cells. is transferred through a and examination.
▪ Fixatives are used in this step, which are series of increasingly metal grid 115 glass slide

solutions of stabilizing or cross-linking compounds concentrated alcohol glitter aldehyde vs formaldehyde


thick
▪ Formalin is a buffered solution of 37% solutions, ending in less than 1hm vs 1mm

formaldehyde that is a widely used fixative for light 100%, which removes all
microscopy. les most used buffering solution 37% formaldehyde
-

,
water.
o Embedding and Sectioning dehydration yoconcentration
increasing
● Clearing: Alcohol is
▪ Dehydration is done first before infiltration where removed in organic
the tissue is transferred through a series of solvents in which both
increasingly concentrated alcohol solutions, alcohol and paraffin are
ending in 100%, which removes all water. miscible.
▪ The ethanol is then removed in organic solvents in ● Infiltration: The tissue is
which both alcohol and paraffin are miscible, a then placed in melted
process called clearing. paraffin until it becomes
▪ Infiltration is a process wherein the tissue is then completely infiltrated
placed in melted paraffin in an oven at 52 to 60 with this substance.

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HUMAN HISTOLOGY LECTURE: Unit 1

● Embedding: The
paraffin-infiltrated tissue
is placed in a small mold
with melted paraffin and
allowed to harden.
● Trimming: The resulting
paraffin block is trimmed
to expose the tissue for
sectioning (slicing) on a
microtome. The block is
cut at 3-10 μm thickness,
and the section is placed round

on a glass slide. ● Spherical/Ovoid yn


o The cell is round
to oval shaped
BASIC PRINCIPLES OF CELL STRUCTURE AND like a ball or an
FUNCTION egg.

Table 2. Descriptive terms for normal cells in terms of cell


shape
Cell Shape
scaly
● Squamous yr
o This is an
epithelial cell with
a flattened,
“squamous”
shape. ● Fusiform te
o It is usually o These cells are
visioned as thin, elongated and
flat, and scaly tapering at two
since it is usually ends, almost
cut edgewise. thread-like.

same length &


yn
● Cuboidal width

o This is an ● Polyhedral I
epithelial cell with o The cells show a
equal height and shape of
width, as the polygons due to
name suggests, it the multiple
looks like a cube flattened
or squarish- surfaces.
looking.

end is

● Polarized different
jn one
from other the

● Columnar height / width o These cells have


o This is an a distinct
epithelial cell with orientation with
the height one end of the cell
distinctly greater being different
than the width, or from the other.
simply, it is taller
than it is wide.

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HUMAN HISTOLOGY LECTURE: Unit 1

stained
pliantly stained yr darkly
Table 3. Descriptive terms for normal cells in terms of
cytoplasm features ● Euchromatic S ● Heterochromatic
o Dispersed, U o Condensed,
Cytoplasm features lightly stained, S darkly stained,
on blue / Purple →
RER red 1 pink D mitochondria accessible to inactive
pp
● Basophilia ● Acidophilia transcription
o In a o In a H&E-stained
hematoxylin section,
and eosin acidophilic
(H&E)- components stain
stained pink-red.
section, o The pinkish stain
basophilic maybe a result
components V from a
stain blue- E concentration of
purple. R mitochondria. ● Simple Segmented
o The bluish S o A simple o A segmented
stain maybe a U nucleus nucleus appears
result from a S appears to in sections as two
concentration have a single or more distinct
of rough structure that parts, which is
endoplasmic can have commonly seen
reticulum various in some types of
shapes white blood cells.
(round, oval,
indented,
fusiform,
irregular).
on active nucleolus RER
● Granules ● Nucleoli prominent ten protein synthesis jnactire

o The retention of some of the granules’ contents ● The presence of an obvious nucleolus/nucleoli
results in the staining of the vesicle. indicates that the cell has an active ribosomal and
o The stain can either show large or small granules protein synthesis.
on the cytoplasm.
● Mitotic nucleus
● Vacuolated cytoplasm ● When a cell divides, the nuclear envelope dissolves,
o This type of cytoplasm contains what appear to be and the chromosomes are dark, condensed
empty holes, which usually can either be lipid particles.
droplets or vesicles.
Table 5. Descriptive terms for normal cells in terms of cell size
● Abundant ● Scant
o There is a ● There is only a Cell size
substantial slight amount of
amount cytoplasm ● Large versus Small
(volume) of V surrounding the o The total spectrum of cell sizes is broad, however,
cytoplasm E nucleus. most cells have diameters falling in the range of 10
surrounding R to 20 μm.
the nucleus. S
U
S REFERENCES:
Cui, D. (2011). Atlas of Histology with Functional
and Clinical Correlations. Philadelphia:
Lippincott Williams & Wilkins, a Wolters Kluwer
business.
Mescher, A. L. (2018). Junqueira's Basic
Table 4. Descriptive terms for normal cells in terms of nucleus Histology Text & Atlas 15th Edition. Indiana:
features McGraw-Hill Education.

Nucleus features Saint Louis University Baguio. (2021). Human


Histology Lecture Module 1.
● Large V ● Small
o Cell shows a E o Cell shows a
large nucleus. R small nucleus.

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HUMAN HISTOLOGY You don’t drown by falling
in the water; you drown by
staying there. –Ed Cole
LECTURE TRANSES

HISTOLOGY UNIT 2: THE CELL


directs protein synthesis
µ
NUCLEUS
OUTLINE ● Largest organelle of the cell on main DNA on cytoplasm
I Nucleus ● Includes the nuclear envelope, nucleolus, nucleoplasm,
II Nuclear Envelope ten covering

i Outer Nuclear Membrane


and chromatin
ii Inner Nuclear Membrane ● Contains genetic material encoded in the
iii Perinuclear Cisterna deoxyribonucleic acid (DNA) of chromosomes
iv Nuclear Pores ● Function:
v Nuclear Pre-Complexes o Directs protein synthesis in the cytoplasm via
III Nucleolus ribosomal ribonucleic acid (rRNA), messenger
IV Nucleoplasm RNS (mRNA) and transfer RNA (tRNA)
i Nuclear Matrix o Also synthesizes regulatory RNAs (noncoding
ii Nuclear Particles
V Chromatin
RNAs)
i Heterochromatin
ii Euchromatin NUCLEAR ENVELOPE
VI Chromosomes ● Surrounds the nuclear material
i Extended Chromatin ● Consists of two parallel membranes separated from each
ii Condensed Chromatin other by a narrow perinuclear cisterna on membrane
divides the nuclear

VII DNA
o These membranes fuse at intervals, forming
VIII RNA
i mRNA openings called nuclear pores
her membranes fuse
where

ii tRNA on tacet cytoplasm


iii rRNA OUTER NUCLEAR MEMBRANE
iv Regulatory RNAs ● About 6 nanometers thick
IX Stages of Meiosis ● Faces the cytoplasm and is continuous at certain sites with
i. Reductional division (meiosis I) the rough endoplasmic reticulum
ii. Equatorial division (meiosis II)
● Surrounded by vimentin on its cytoplasmic aspect
X Cytoplasm
XI Organelles o A loosely arranged mesh of intermediate filaments
i Ribosome ● Studded by ribosomes on its cytoplasmic surface
ii Polyribosome o Synthesizes proteins that enter the perinuclear
iii Rough endoplasmic reticulum (RER) cisterna
iv Golgi complex princes nuclear material
v Secretory vesicle INNER NUCLEAR MEMBRANE
vi Lysosome
vii Other types of membrane-delimited vesicles
● About 6 nanometers thick
viii Smooth endoplasmic reticulum (SER) ● Faces the nuclear material but is separated and supported
supports nuclear
ix Mitochondrion on its inner surface by the nuclear lamina yn lamina

XII Peroxisomes o Composed primarily of lamins A, B1, B2, and C


i. Inclusions
NUCLEAR ENVELOPE
▪ Forms orthogonal trellis that binds to
a. Glycogen 1) Outer NM transmembrane receptor molecules (emerin
b. Lipid droplet ten faces cytoplasm
vimentin ( fibers )
• and lamina-associated polypeptides)
c. Lipofuscin studded w/ ribosomes

traversing the inner nuclear membrane


d. centrosome a) Peri nuclear cisterna
ii. Cytoskeleton bln outer and inner mem
→ . ▪ Assists in organizing the nuclear envelope,
a. Microtubules
nuclear pores

directing the formation of nuclear pore
b. Actin filaments 3) Inner Membrane
complexes, and in organizing the perinuclear
c. Intermediate filaments faces the nuclear material
• chromatin.
XIII Cell Membranes NUCLEAR LAMINA
Essential in mitotic events
:
supported by
is

↳ tannins A. BI B2 if ▪
i Lipid Bilayer
,

FOR ASSEMBLY OF Nnc ENVELOPE


* ▪ Responsible for the ordered disassembly and
ii Proteins
.

phosphorylation assemble
reassembly of the nuclear envelope
-
-

iii Cell Surface Dephosphorylation disassemble


Phosphorylation – disassembly
-


XIV Interactions among organelles
i Uptake and release of materials by cells Dephosphorylation – reassembly
ii Protein digestion Synthesis
iii Intracellular digestion PERINUCLEAR CISTERNA
XV Extracellular matrix ● Between the inner and outer nuclear membrane
i Structure ● 20 to 40 nanometers wide
ii Function ● Continuous with the cisterna of the RER
XVI Ground Substance ● Perforated by nuclear pores at various locations
i GAGs
ii Proteoglycans NUCLEAR PORES
iii Glycoproteins
iv Fibronectin receptors
● 80 nm in diameter
XVII Fibers ● Dozens to thousands depending on metabolic activity
i Collagen ● Associated with the nuclear pore complexes (NPC)
ii Elastic Fibers o Aided in communicating with each other by the
XVIII Clinical Correlations nuclear lamina

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HUMAN HISTOLOGY LABORATORY: Unit 2

● Formed by fusion of the inner and outer membranes ● Some of these transmembrane
● Permits passage of certain molecules between the nucleus proteins also project into the
and cytoplasm via a 9-nm channel opening perinuclear cistern
Transporter/c ● In the center of the luminal ring
rgnnncieoporins ( proteins )
entral plug (hourglass shaped)
NUCLEAR PORE COMPLEXES ● Ribosomes/protein complexes that
● Protein subunits surrounding the nuclear pore are being transported through the
● Composed of nearly 100 proteins (nucleoporins) NPC
o Some are arranged in eightfold symmetry around
NUCLEAR PORE COMPLEX
the margin of the pore •
proteins that surround the
complex To 100 proteins
● Nucleoplasmic side: exhibits a nuclear basket -
nncieoporins
2 sides
● Cytoplasmic side: displays fibers extending into the

11 nucleoplasm ic basket like


- -

2) cytoplasmic extq fibers


cytoplasm
-


TRANSPORT PROTEINS
→ transport via receptor-mediated
cytoplasmic
● A transport protein is located in the central core • NUCLEAR LOCALIZED SEGMENTS
→ amino acid transport signal

o Responsible for transporting proteins into and out -


mediated by RAN
EXPORT IN -

export
of the nucleus via receptor-mediated transport •
IMPORT IN -
import

o Proteins have clusters of certain amino acids


known as nuclear localized segments that act as nucleoplasm ic
↳ amino acid transport signal
signals for transport
● Permits passive movement across the nuclear envelope via
a 9 to 11 nm open channel for simple diffusion
● Transport mechanisms involve a group of transporter
proteins, exportins and importins
o Function of these proteins is regulated by Ran
▪ a group of GTP-binding proteins export

o Recognizes polypeptide sequences on the Figure 1. The nuclear pore complex


proteins that are to be transported in one direction
observed in INTERPHASE cells
or the other zn ; gone in prophase phase

o Exportins NUCLEOLUS
▪ Recognizes polypeptide sequences known as ● Nuclear inclusion that is not surrounded by a membrane
nuclear export sequences ● Observed in interphase cells that are actively synthesizing
▪ Exports molecules into the cytoplasm proteins
o Importins ● Can be more than one is present in the nucleus
▪ Recognizes nuclear localization ● Contains mostly rRNA, proteins (nucleostemin, nucleolin,
sequences fibrillarin), and a modest amount to DNA
▪ Facilitates import into nucleus ● Possesses nucleolar organizer regions (NORs) and
▪ Transport signals of this type are called portions of the chromosomes where rRNA genes are
nucleoplasmic shuttling signals located (chromosome 13,14,15,21,22)
o Involved in reconstituting the nucleolus during the
Table 1.1 Parts of the nuclear pore complex G1 phase of the cell cycle
PART FUNCTION ● Involved in the synthesis of rRNA and its preliminary
Cytoplasmic ● Around the cytoplasmic margin of the assembly into ribosome subunit precursors as well as in the
ring nuclear pore primary processing of micro RNAs
ten staging area ● Composed of 8 subunits, each ● Sequesters certain nucleolar proteins (nucleostemin) that
→ subunits
8
possessing a cytoplasmic filament function as cell cycle checkpoint signaling proteins
composed of a Ran-binding protein o Signaling proteins remain sequestered in the
(guanosine triphosphate [GTP]- nucleolus until their release is required
binding protein) ● Disintegrates after prophase of the cell cycle because the
● May serve as a staging area prior to NORs of chromosomes 13,14,15,21, and 22 are
protein transport unavailable for transcription
Nucleoplasmi ● Around the nucleoplasmic margin of ● Reconstitutes when NORs unwind
c ring the nuclear pore
↳ nucleoplasm
● Composed of 8 subunits
basket Table 2. Distinct regions of the nucleolus
→ DISTAL RINGexport
:

● Extending from this ring into the PART FUNCTION


nucleoplasm is a basket-like structure, Fibrillar centers ● Composed of the NORs of the 5
the nuclear basket chromosomes, the
● Attached at the distal end of the ribonucleoprotein (RNP) signal
nuclear basket is the distal ring which recognition particle, and RNA
assists in the export of RNA into the polymerase I (enzyme required
cytoplasm for the transcription of rRNA)
Luminal ring ● Between the cytoplasmic and Pars fibrosa ● Composed of 5-nm fibrils
nucleoplasmic ring surrounding the fibrillar centers
● Eight transmembrane proteins project ● Contains transcriptionally
into the lumen of the nuclear pore, active DNA, ribosomal genes,
anchoring the complex into the pore and a substantial amount of rRNA
rim ● Also contains RNP fibrillarin and
● The lumen may be a gated channel the phosphoproteins nucleolin
that impedes passive diffusion which participate in the

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HUMAN HISTOLOGY LABORATORY: Unit 2

processing of the rRNA • Increases in liver cells if exposed to


precursors to form mature rRNA carcinogens or temperature above
Pars granulosa ● Composed of 15-nm maturing 37°C
ribosomal precursor particles hnRNP • Complexes of precursor mRNA
where 18S rRNA and 28S rRNA particles (pre-mRNA) and proteins
subunits are assembled • Involved in the processing of pre-
● Ribosomal proteins are combined mRNA
with rRNA to form the small and Small nuclear • Complexes of proteins and small
large ribosomal subunits that are RNPs(snRNPs) RNAs
then individually exported into the • Involved in hnRNP splicing or in
cytoplasm where ribosomal cleavage reactions
assembly is completed functions related to DNA
go
● Also contains nucleostemin, a
CHROMATIN
protein that resembles guanine
• Consists of DNA double helix complexed with histones and
nucleotide-binding protein
nonhistone proteins
o Large quantities of this
protein are present in cancer • Resides within the nucleus as heterochromatin and
and stem cells euchromatin
o Regulated the cell cycle and o Higher in malignant cells than in normal cells
has a direct influence on cell • Folds the DNA strand into small enough volume to be able
differentiation to contain it within the nucleus
Nucleolar matrix • Fiber network participating in the • Protects the DNA from physical damage and between cell
organization of the nucleolus division
• Controls the activity of DNA (permitting or preventing
transcription)
NUCLEOPLASM • Controls precise duplication of the DNA in preparation for
cell division
• Protoplasm within the nuclear envelope
• Facilitates and repairs DNA in case of replication error or
• Where chromosomes and nucleoli are embedded
physical or chemical insult
• A viscous matrix composed mostly of water ✗ transcribed min active ; female
on condensed i

• Ordered by the presence of a cytoskeletal-lie framework HETEROCHROMATIN


known as nuclear matrix • Condensed because it is not transcribed
• Comprises approximately 90% of the total chromatin in the
NUCLEAR MATRIX
cell
• Includes fibrillar elements, nuclear pore-nuclear lamina
• Formed from euchromatin that is folded into 30-nm thick
complex, residual nucleoli, and a residual RNP network
filaments
• Involved in the transcription and processing of mRNA and
• Appears as basophilic clumps of nucleoprotein when
rRNA, steroid receptor-binding sites, carcinogen-binding
examined under a light microscope
sites, heat shock proteins, DNA viruses, viral proteins (T
• Although transcriptionally inactive, it functions in
antigen), etc.
maintaining the integrity of chromosomal centromeres and
• Nucleoplasmic reticulum is continuous with the
telomeres and has roles in interchromosomal interactions
endoplasmic reticulum of the cytoplasm and nuclear
and chromosomal segregation during meiosis
envelope
• Corresponds to one or two X chromosomes and is
o Contains nuclear calcium functioning within the
present in nearly all somatic cells of female mammals
nucleus
o During interphase, the inactive X chromosome
o Possesses receptors for inositol 1,4,5-
(Barr body/sex chromatin) is visible as a dark-
triphosphate, regulating calcium signals within
staining body within the nucleus
compartments of the nucleus related to gene
transcription, protein transports, etc.
EUCHROMATIN
NUCLEAR PARTICLES • Constitutes approximately 10% of the total chromatin
• Transcriptionally active
Table 3. Nuclear particles • Appears as a lightly stained region of the nucleus when
PART FUNCTION viewed under light micrographs
Interchromatin • Clusters of irregularly distributed • Appears as electron-lucent regions among
granules particles heterochromatins when viewed with transmission electron
• 20-25 nm microscope (TEM)
• Contains RNP and enzymes • Composed of 10-nm strings of nucleosomes
Perichromatin • Single dense granules
granules CHROMOSOMES
• 30-50 nm
• Consists of chromatin extensively folded into loops
ten
• Surrounded by a less dense halo
increases in liver cells

o Conformation is maintained by DNA-binding


• Located at the periphery of
proteins
heterochromatin and exhibits a
• Each chromosome contains a long DNA molecule and
structure of 3-nm packed fibrils
associated proteins, assembled into nucleosomes
• Contains 4.75 RNA and 2 peptides
o Structural unit of chromatin packaging
• May represent messenger RNPs o Each nucleosome has a core of eight histones
(mRNPs) (histone octamers) and DNA double helix

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HUMAN HISTOLOGY LABORATORY: Unit 2

(wrapped around the histone octamers which


makes two spiral turns)
o DNA double helix between adjacent histone
octamers is not associated with histones and
appears as if it were a string that connects
neighboring histone octamers to each other
▪ Connecting regions of DNA double helix
are known as linker DNA
• Visible under light microscope (LM) only during mitosis and
meiosis when their chromatin condenses
• G-banding is observed in chromosomes during mitosis
after staining with Giemsa (specific for DNA sequences
which is adenine (A) and thymine (T)
o Represents folded DNA loops
o Characteristic for each species and is used to
identify particular chromosomes and
Figure 2. The packaging of chromatin into the condensed
chromosomal anomalies
metaphase chromosome
• Karyotype
o Number and morphology of chromosomes
DNA
o Characteristic for each species
• A long double-stranded helical linear molecule composed
o Haploid number (n)
of multiple nucleotide sequences
▪ Number of chromosomes in germ cells
(23 in humans) • Stores genetic information of an individual and acts as a
o Diploid number (2n) template for the synthesis of RNA
▪ Number of chromosomes in somatic cells
(46 in humans) Table 4. Composition of DNA
• Where the total genetic complement of an individual is PART FUNCTION
stored Nucleotides • Composed of a base (purine or
o In humans, the genome consists of 22 pairs of pyrimidine), a deoxyribose sugar,
autosomes and 1 pair of sex chromosome (XX and a phosphate group
or XY), totaling 23 homologous pairs, or 46 • Purines – adenine (A) and
chromosomes guanine (G)
• Each chromosome is composed of two chromatids joined • Pyrimidines – cytosine (C) and
together at a small point called the centromere thymine (T)
DNA double helix • Consists of two complementary
DNA strands held together by
EXTENDED CHROMATIN hydrogen bonds between the
• Formed by adjacent nucleosomes base pairs A-T and G-C
o Each nucleosome core is around which the DNA Exons • Regions of the DNA molecule
double helix is wrapped two full turns code
that code for specific RNAs
▪ Nucleosome core consists of two copies Introns • Regions of the DNA molecule,
each of histones H2A, H2B, H3, and H4 does not code between exons, that do not code
o Nucleosomes are spaced at intervals of 200 base for RNAs
pairs A codon • A sequence of three bases in the
o Nucleosomes support DNA and regulate its DNA molecule that codes for a
accessibility for replication and transcription as single amino acid
well for its repair A gene • A segment of the DNA molecule,
• Resemble beads on a string when viewed with TEM located in a specific region of a
o The beads represent nucleosomes and the string chromosome
represent linker DNA • Responsible not only for the
formation of a single RNA
CONDENSED CHROMATIN molecule but also for the
• Contains an additional histone, H1 regulatory sequences that control
o Wraps around groups of nucleosomes, thus the expression of a particular trait
forming 30-nm diameter filaments of helical coils • In certain viruses, a gene may be
of six nucleosomes per turn composed of RNA rather than
DNA
A genome • Complete set of hereditary
information that an individual
possesses
• Classified into genes and
noncoding segments
• Only 2% of the genome is
composed of genes (which code
for proteins/polypeptides),
whereas most of the remainder is
noncoding segments

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HUMAN HISTOLOGY LABORATORY: Unit 2

tRNA
RNA • Folded into cloverleaf shape
• A linear molecule similar to DNA • Contains approximately 80 nucleotides, terminating in
• Single stranded and contains riboses instead of adenylic acid (where amino acids attach)
deoxyribose sugar and uracil (U) instead of thymine • Each tRNA combines with a specific amino acid that has
• Synthesized by transcription of DNA rRNA
I been activated by an enzyme
o Catalyzed by three RNA polymerases
▪ I for rRNA ☒
II

III tRNA
mRNA
• One end of the tRNA possesses an anticodon, a triplet of
nucleotide that recognizes the complementary codon in
▪ II for mRNA mRNA. If recognition occurs, the anticodon ensures that the
▪ III for tRNA tRNA transfers its activated amino acid molecule in the
• Some of the noncoding segments of DNA are transcribed proper sequence to the growing polypeptide chain
to form tRNA, rRNA, as well as regulatory RNAs
• Other RNAs can act as enzymes (ex. ribozymes – catalyzes rRNA
the formation of peptide bonds during protein synthesis) • Associates with many different proteins (including
enzymes) to form ribosomes
mRNA • Associates with mRNA and tRNA during protein synthesis
• Carries the genetic code to the cytoplasm to direct protein • rRNA synthesis takes place in the nucleolus and is
synthesis catalyzed by RNA polymerase I
• Single stranded molecules o A single 45S precursor rRNA (pre-rRNA) is formed
• Consists of hundreds to thousands of nucleotides and processed to form ribosomes
• Contains codons that are complementary to the DNA o Pre-rRNA associates with ribosomal proteins and is
codons from which it was transcribed cleaved into three sized (28S, 18S, 5.8S) of rRNAs
o 1 start codon (AUG) – initiates protein synthesis present in ribosomes
o 1 of the three stop codons (UAA, UAG, or UGA) o The RNP containing 28S and 5.8S rRNA then
– terminates protein synthesis combines with 5S rRNA (synthesized outside the
• Synthesis of mRNA: nucleolus) to form the large subunit of the ribosome
o RNA polymerase II recognizes a promoter on a o The RNP containing 18S rRNA forms the small
single strand of the DNA molecule and binds tightly subunit of the ribosome
to it
o The DNA helix unwinds about two turns, separating
the DNA strand and exposing the codons that act
as the template for synthesis of the complementary
RNA molecule
o RNA polymerase II recognizes a chain terminator
(stop codons) on the DNA molecule, it terminated
its association with the DNA and is released to
repeat transcription
o Pre-mRNA (primary transcript) associates with
proteins to form hnRNP
o Exons are spliced through several steps, involving
spliceosomes producing an mRNP
o Proteins are removed as the mRNP enters the
cytoplasm, resulting in functional mRNA
o RNA segments remaining from the transcription Figure 4. Formation of rRNA and its processing into ribosomal subunits
process becomes modified to perform regulatory
functions that parallel regulatory proteins related to Regulatory RNAs
development, gene expression, and evolution
MICRORNAS (MIRNAS)
• Very small segments of single-stranded RNA molecules of
only 19 to 25 nucleotides in length
• Regulates gene expression
• Transcribed from DNA
• Noncoding and are not translated into proteins
• Diverse population of more than 1,000 human miRNAs
regulate developmental and physiological processes
• Some miRNAs methylate specific regions of the DNA, thus
preventing transcription from taking place
• May influence most genetic pathways since each miRNA
can control hundreds of gene targets
• Also acts as “central switchboards” of signaling networks
that control stem cell homeostasis as well as various
diseases processes (fibrosis, metastasis, biology of
malignant cells)
• Represses certain cancer-related genes and are known to
Figure 3. Transcription of genetic information encoded in DNA into depress angiogenesis, which may become useful in
mRNA clinically restricting cancer growth

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HUMAN HISTOLOGY LABORATORY: Unit 2

• Other miRNAs appear to regulate differentiation (repressing REDUCTIONAL DIVISION (MEIOSIS I)


adipocyte formation) ● without DNA replication.
● sister chromatids are portioned out among the two daughter
LARGE INTERGENIC NONCODING RNAS cells, divide, resulting in the distribution of chromosomes
• More than 200 nucleotides in length into four daughter cells; containing its own unique
• Functions in gene regulation recombined genetic material (1CDNA;n)
● more rapidly than mitosis.
• Since each cell of a female possesses two X chromosomes,
one of the X chromosomes is transcribed to form lincRNAs
o lincRNAs specifically coat that particular X
chromosome and prevents the transcription of
genes
o other lincRNAs prevent the transcription of various
genes on different chromosomes
o Other lincRNAs complete with certain mRNAs for
miRNAs, thereby acting as decoys that protect the
mRNAs from the inhibitory actions of miRNAs and
facilitating the translation of the mRNA to
synthesize a particular protein

SMALL INTERFERING RNAS (SIRNAS)


• Similar to miRNAs
• 19 to 25 nucleotides in length
• Frequently arise from the genome of RNA viruses that infect
a cell
• Resembles miRNAs in their mode of action
o They also methylate specific regions of the DNA
and thus interfere with the process of transcription

STAGES OF MEIOSIS
CYTOPLASM
REDUCTIONAL DIVISION (MEIOSIS I) ● organelles, inclusions, and the cytoskeleton.
• chromosome number (46) remains unchanged, giving the ● Cytosol = fluid component
cell a 4CDNA content ● Functions: uptake and release of material by the cell,
protein synthesis, and intracellular digestion.
PROPHASE I
• Five stages: leptotene, zygotene, pachytene, diplotene, and ORGANELLES
diakinesis ● plasma membrane - which envelops the cell and forms a
o Chromatin condenses, two chromatids joined at the boundary between it and adjacent structures
centromere.
o synaptonemal complex- Homologous maternal and RIBOSOME
paternal chromosomes pair forming a tetrad. ● Structure: 12 nanometers (nm) wide and 25 nm long, small
Chiasmata- where exchange of genes occurs, thus and a large subunit.
increasing genetic diversity. ● Ribosomes may be free in the cytosol - constitute a single
o nucleolus and nuclear envelope disappear. interchangeable population.
METAPHASE I ● polyribosome (polysome) - cluster of ribosomes along a
• Homologous pairs of chromosomes align on the equatorial single strand of mRNA
plate = genetic mixing. ● Function:
• Spindle fibers from either pole attach to the kinetochore = o mRNA is translated into protein
genetic mixing o small ribosomal subunit binds mRNA and activated
transfer ribonucleic acids (tRNAs); the codons of the
ANAPHASE I mRNA then base-pair with the corresponding
anticodons of the tRNAs.
● similar to anaphase in mitosis except that each o tRNA recognizes the start codon (AUG) on the mRNA.
● chromosome consists of two chromatids that remain held o large ribosomal subunit then binds to the complex
together. o chain-terminating codon (UAA, UAG, or UGA) causes
● Chromosomes migrate to the poles. release of the polypeptide from the ribosome

TELOPHASE I POLYRIBOSOME
● nuclear envelope is reestablished and two daughter cells ● formed by the alignment of several ribosomes along the
are formed via cytokinesis. length of an mRNA molecule.
● 23 chromosomes (n) and 2CDNA content (the diploid ● When an mRNA for a cytosolic or mitochondrial protein is
amount) being translated, the polyribosome is not associated with
● composed of two similar sister chromatids endoplasmic reticulum, but rather it is suspended in the
cytosol as a free polyribosome.

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HUMAN HISTOLOGY LABORATORY: Unit 2

ROUGH ENDOPLASMIC RETICULUM (RER) ▪ contain both lysosomal hydrolases and lysosomal
membrane proteins
● Structure:
o Types of Lysosomes
O flattened membrane-delimited cisternae that are
studded with ribosomes ▪ Multivesicular bodies - formed by fusion of an early
o interior region of RER is called the cisterna, or the endosome
lumen ▪ Phagolysosomes - fusion of a phagocytic vacuole
o receptors (ribophorins) in its membrane to which with a late endosome or a lysosome.
the large ribosomal subunit binds. ▪ Auto phagolysosomes - formed by fusion of an
● RER is abundant in cells synthesizing secretory proteins autophagic vacuole with a late endosome or
lysosome.
● transitional element - gives rise to buds free of ribosomes
that form vesicles -formed when cell components targeted for
destruction become enveloped by smooth areas of
● FUNCTION:
membranes derived from the RER.
o membrane-packaged proteins are synthesized
▪ Residual bodies - expended their capacity to
o monitors the assembly, retention, and even
degradation of certain proteins. degrade material.

GOLGI COMPLEX
OTHER TYPES OF MEMBRANE-DELIMITED
- consists of a stack of flattened membranous saccules
- receives polypeptides from the RER, modifies them, and
VESICLES
sorts and packages - other than the secretory products of secretory granules
● STRUCTURE: - Coated vesicles are characterized by a visible cytoplasmic
o Cisternae are disk-shaped and slightly curved surface coat.
o distinct polarity exists across the Golgi stack
● REGIONS: ● CLATHRIN-COATED VESICLES
o cis face of the Golgi apparatus typically lies deep o Structure:
in the cell toward the nucleus next to the RER. ▪ coated with clathrin
o vesicular–tubular clusters (VTC) - network of ▪ three large and three small polypeptide chains that
interconnected tubes and vesicles, form a triskelion
● FUNCTIONS: ▪ Proteins called adaptins are also part of clathrin-
o processes membrane-packaged proteins coated vesicles.
o recycles and redistributes membranes ▪ Dynamin - (GTP)– binding protein called dynamin
forms a ring around the neck of a budding vesicle
o Function:
SECRETORY VESICLE
▪ Clathrin-coated vesicles are formed during
● membrane-delimited packages of secretory products receptor-mediated uptake (endocytosis)
● stored in the cytoplasm or immediately secreted by exocytosis ▪ signal-directed (regulated) transport of proteins
of the vesicle from the TGN either to the secretory granule
pathway or to the late endosome–lysosome
LYSOSOME pathway
- characterized by its low pH and the content of a variety of
hydrolases ● COATOMER-COATED VESICLES
- digest proteins, lipids, and polysaccharides o Structure:
- function both in the turnover of intrinsic cellular components ▪ consisting of coatomer
and in the breakdown of the material ingested by endocytosis. ▪ large protein complex formed by individual coat
● STRUCTURE: protein subunits called COPs
o dense membrane-bound organelles ▪ coatomer depends on the protein ADP-
o identified in sections of tissue by cytochemical staining ribosylation factor (ARF) -
for acid phosphatase o Function:
o 50 acid hydrolases, which are synthesized in the RER. ▪ mediate the continuous constitutive protein
ATP- powered proton pumps in the lysosome transport within the cell.
membrane maintain an acid pH ▪ SNARES - GTP-binding proteins are present at
● FORMATION each step of vesicle budding and fusion, and
o Early endosomes proteins
▪ irregular vesicles- form part of the pathway for ▪ transport proteins from the RER to the VTC to the
receptor-mediated endocytosis and contain Golgi apparatus
receptor–ligand complexes. ✓ anterograde transport - transports
▪ CURL - compartment for uncoupling of receptors molecules forward from the RER to the
and ligands VTC [COP II]
▪ acidic interiors (pH 6) - maintained by ATP-driven ✓ retrograde transport - might move
proton pumps. forward between Golgi regions to the
o Late endosomes TGN [COP I]
▪ key role in various lysosomal pathways -
intermediate compartment
▪ irregular vesicles (pH 5.5)- receive ligands via
microtubular transport of vesicles from early
endosomes

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HUMAN HISTOLOGY LABORATORY: Unit 2

● CAVEOLIN-COATED VESICLES ▪ present in brown fat cells, which produce heat


-less common and less well understood ▪ swell in response to calcium, phosphate, and
o Structure: thyroxine, which induce an increase in water
▪ Caveolae - invaginations of the plasma uptake and an uncoupling of phosphorylation
membrane, possess a distinct coat formed by the o Annulate lamellae
protein caveolin. ▪ Structure:
o Function: ✓ parallel stacks of membranes (usually 6 to
▪ cell signaling 10)
▪ transport ✓ arranged with their annuli (pores) in register
▪ processes, such as transcytosis and endocytosis and are frequently continuous with the
RER.
SMOOTH ENDOPLASMIC RETICULUM (SER) ▪ Function:
● membrane delimited labyrinth ✓ function and significance remain unknown.
● form of tubules
● appears as branching, anastomosing tubules, or vesicles, PEROXISOMES
whose membranes do not contain ribophorins. ● also known as microbodies
● prominent in cells synthesizing steroids, triglycerides, and ● Peroxisomes may contain a nucleoid but the human
cholesterol. peroxisome lacks a nucleoid
● Structure: ● originate from preexisting peroxisomes
o irregular network of membrane-bounded ● life span of approximately 5 to 6 days.
o lacks ribosomes ● STRUCTURES:
● Function: o membrane-bound, spherical, or ovoid
o synthesis of membrane phospholipids organelles that may be identified in cells by a
o degradation of some hormones and toxic substances cytochemical reaction for catalase.
o synthesis of steroid hormones, ● FUNCTIONS:
o sequestration of calcium stores o oxidation of long-chain fatty acids
o synthesis of cholesterol
MITOCHONDRION o detoxification of substances such as ethanol.
● Structure:
INCLUSIONS
o double-membrane organelle
● not metabolically active
o rod-shaped organelles that are 0.2 _m wide and up to
● present temporarily
7 _m long
o subdivided into an intermembrane compartment
between the two membranes and an inner matrix GLYCOGEN
compartment. ● Structure:
o Cations: Mg2_ and Ca2_ o small clusters of electron-dense 20- to 30-nm _-
● Functions: particles
o generates adenosine triphosphate (ATP) o not bound by a membrane
o specialized synthetic pathways such as that for steroid o close to the SER
hormones. ● Functions:
● Enzymes and genetic apparatus. o stored energy source that can be degraded to glucose,
o Contains: which enters the bloodstream to elevate blood sugar
▪ All of the enzymes of the Krebs (tricarboxylic acid levels
[TCA]) cycle LIPID DROPLETS
▪ Adenosine triphosphate (ATP) synthase ● Structure:
▪ head portion and a transmembrane H_ carrier and o vary markedly in size and appearance
is involved in coupling oxidation to o not bound by a membrane
phosphorylation of adenosine diphosphate (ADP) ● Functions:
to form ATP. o storage forms of
o Origin and proliferation o triglycerides (an energy source) and cholesterol (used
▪ originated as symbionts (intracellular parasites) in the synthesis of steroids and
▪ proliferate by division (fission) of preexisting o membranes).
mitochondria
▪ 10-day life span LIPOFUSCIN
o Mitochondrial ATP synthesis
● called age pigment
▪ synthesize ATP via the Krebs cycle
● Structure:
▪ produces ATP by oxidation of fatty acids, amino
o membrane-bound, electron-dense granular
acids, and glucose
o varying greatly in size and often containing lipid
▪ synthesized via a chemiosmotic coupling
droplets
mechanism
● Functions:
o Condensed mitochondria
o represents a residue of undigested material present in
▪ conformational change
residual bodies.
▪ in response to an uncoupling of oxidation from
● Location:
phosphorylation.
o nondividing cells (e.g.,cardiac muscle cells, neurons)
▪ size of the inner compartment is decreased
but also is found in hepatocytes.
▪ matrix density is increased
▪ intermembrane compartment is enlarged

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HUMAN HISTOLOGY LABORATORY: Unit 2

CENTROSOME INTERMEDIATE FILAMENTS


● self-duplicate in the S phase ● Structure:
● form basal bodies, which give rise to the axonemes of cilia o 8 to 10 nm in diameter
and flagella o population of
● Structure: o heterogeneous filaments that includes keratin,
o composed of a pair of centrioles embedded in vimentin, desmin, glial fibrillary acidic protein (GFAP),
amorphous material lamins, and neurofilament
o composed of nine triplet ● Functions:
o sets of microtubules o provide mechanical strength
o located near the nucleus.
● Functions: CELL MEMBRANES
o organizing the array of microtubules in the cell’s ● Composed of phospholipids and proteins
cytoplasm
o developing the spindle apparatus during cell division LIPID BILAYER
o major microtubule-organizing center
o maintain the organization of the centrosome PHOSPHOLIPIDS
CYTOSKELETON ● Contains glycerol backbone
● structural framework within the cytosol ● Hydrophilic head
● maintaining cell shape, stabilizing cell attachments, ● Hydrophobic (two fatty-acid) tail
facilitating endocytosis and exocytosis, and promoting cell ● Hydrophobic tails face each other and form a bilayer
movement
LIPID-SOLUBLE SUBSTANCES
MICROTUBULES ● Can cross cell membranes
● Structure: ● Can dissolve in hydrophobic lipid bilayer
o 25 nm in diameter ● e.g. O2, CO2, steroid hormones
o rigid wall composed of 13 protofilaments
o polar WATER-SOLUBLE SUBSTANCES
o microtubule-associated proteins (MAPs) - stabilize ● Cannot cross cell membranes
them and bind them to other cytoskeletal components ● Can cross water-filled channels, pores, or may be
and organelles transported by carriers
o kinesin and cytoplasmic dynein ● e.g. Na , Cl−, glucose, H2O
▪ two force-generating proteins
▪ motor for movement PROTEINS
▪ kinesin (outward)
▪ dynein (inward) INTEGRAL PROTEINS
● Functions:
● Imbedded in the cell membrane through hydrophobic
o tracks for movement of materials within the cytoplasm.
reactions
o maintain cell shape
● Span the cell membrane
o aid in the transport of macromolecules within the
● E.g. ion channels, transport proteins, receptors, and
cytosol
guanosine 5′-triphosphate (GTP)–binding proteins (G
o assemble into the mitotic spindle during mitosis and
proteins)
ensure the correct distribution of chromosomes to
daughter cells
o assist in the formation of cell PERIPHERAL PROTEINS
● Not imbedded and loosely attached in the cell membrane
ACTIN FILAMENTS/MICROFILAMENTS through electrostatic interaction
● In contractile cells, actin filaments interact with myosin ● Not covalently bound to membrane components
● (thick) filaments.
● Structure: CELL SURFACE
o thin (6 nm) filaments
o beneath the plasmalemma of many cells Table 1. Components of the Cell Surface
o 7 nm in diameter and are composed of globular actin PART FUNCTION
monomers (G actin) linked into a double helix (F actin). Cilia - thickness: 200 nm
They are thin, flexible, and abundant in cells - length: 5 to 10 μm
o display polarity - extensions that are capable of moving
o Actin filaments are abundant at the periphery of the Microvilli - diameter: 80 nm
cell, where they are anchored to the plasma membrane - length: 1 μm
● Functions: - extensions that are not capable of
o Establishing focal contacts between the cell and the moving
extracellular matrix Zonula - tight junction
o locomotion of non-muscle cells occludens - site of fusion that separate the lumen
o formation of the contractile ring (in dividing cells) from underlying connective tissue
o folding of epithelia into tubes during development. - intercellular pathways
- “tight” impermeable
- “leaky” permeable

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HUMAN HISTOLOGY LABORATORY: Unit 2

Zonula - site of mechanical adhesion between ▪ The tRNA anticodon sites base-pair with
adherens adjacent epithelial cells complementary codon sites in the mRNA
-bands ▪ The is codon is recognized
- Actin filaments ▪ The mRNA moves a distance of one codon (three
Macula - desmosomes nucleotides) through the small subunit, and the
adherence - site of mechanical adhesion between “spent” initiator tRNA moves to the E site and is
cells ejected leaving the A site empty so that a new
- spots aminoacyl tRNA can bind
- Intermediate filaments o Transport of the newly formed peptide into the RER
Gap Junctions - nexus junctions cisterna
- allow free flow of small ions to ensure ▪ Signal hypothesis
that cells are electrically coupled ▪ mRNAs for secretory, membrane, and lysosomal
Basolateral - increases the surface area of the cell proteins contain codons that encode a signal
folds that help in extensive traffic of sequence.
substances ▪ When the signal sequence is formed on the
- remove water and ions from a lumen ribosome, a signal recognition particle (SRP)
- contributes mechanical strength to cell ▪ in the cytosol binds to it.
layer ▪ Synthesis of the growing chain stops until the SRP
Basal Lamina - characteristic of the basal surfaces of facilitates the relocation of the polysome to SRP
epithelia, but not restricted to epithelia. receptors in the RER membrane.
▪ The large subunits of the ribosomes interact with
ribosome receptor proteins, which bind them to the
INTERACTIONS AMONG ORGANELLES RER membrane.
● Interactions provide the basis for a functional approach to o Posttranslational modification in the RER
examine some dynamics of cell biology ▪ After the newly formed polypeptide enters the
cisterna, a signal peptidase cleaves the signal
UPTAKE AND RELEASE OF MATERIAL BY CELLS sequence from it.
▪ The polypeptide is glycosylated.
ENDOCYTOSIS ▪ Disulfide bonds form, converting the linear
polypeptide into a globular form.
● uptake (internalization) of material by cells.
o Protein transport from the RER to the cis Golgi
o Pinocytosis (“cell drinking”)
▪ Transitional elements of the RER give rise to
▪ nonspecific (random) uptake
COP-II coatomer–coated vesicles containing
o Receptor-mediated endocytosis
newly synthesized protein.
▪ specific uptake of a substance
▪ These vesicles move to the VTC where they
o Phagocytosis (“cell eating”)
deliver the protein.
▪ uptake of microorganisms and particulate matter
▪ The VTC appears to be the first way station for the
▪ degrade proteins and cellular debris
segregation of anterograde versus retrograde
transport in the secretory pathway. Either proteins
EXOCYTOSIS move forward toward the cis
● release of material from the cell ▪ Golgi, or if they are RER-resident proteins that
o Regulated escaped from the RER, they are captured by
▪ (signal directed) ▪ a specific membrane receptor protein and
▪ secretion is the release in response to an returned in COP-I coatomer-coated vesicles to
extracellular signal ▪ the RER along a microtubuleguided pathway.
o Constitutive secretion o Anterograde transport from the VTC to the cis
▪ (default pathway) Golgi is via COP-II coatomer–coated vesicles.
▪ less continuous release of material o Movement of material anterograde among the
▪ extracellular signal is not required Golgi subcompartments
▪ e.g. collagen and plasma proteins ▪ Cisternae containing proteins may change in
biochemical composition as they move intact
MEMBRANE RECYCLING across the stack.
▪ COP-II–coated vesicles may bud off one cisterna
● Maintains a relatively constant plasma membrane surface
and fuse with the dilated rim of another cisterna.
area
▪ Although both mechanisms have been observed,
● Secretory granule membrane is retrieved through
the precise way that anterograde transport occurs
endocytosis via clathrin coated vesicles. This membrane is
across the Golgi stack of cisternae is unresolved.
returned to the TGN via early endosomes for further
▪ Retrograde vesicular transport occurs between
recycling.
Golgi cisternae and between the Golgi and the
VTC or RER via COP-I–coated vesicles.
PROTEIN SYNTHESIS
o Protein processing in the Golgi complex
▪ Proteins targeted for lysosomes are tagged with
SYNTHESIS OF MEMBRANE-PACKAGED PROTEINS mannose 6-phosphate in the cis cisterna.
● Involves translation and transport ▪ Mannose residues are removed in cis and medial
o A three-step process translates mRNA as follows: cisternae.
▪ mRNA binds to the small subunit of a ribosome ▪ Some proteins undergo terminal glycosylation with
that has three binding sites (A, P, and E) for tRNA sialic acid residues and galactose.
molecules

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HUMAN HISTOLOGY LABORATORY: Unit 2

▪ Sulfation and phosphorylation of amino acid ● linked into core protein


residues take place. ● resists compression
▪ A membrane similar in composition and thickness ● Four main groups
to the plasma membrane is acquired. o Hyaluronic acid
o Sorting of proteins in TGN o Chondroitin Sulfate
▪ Regulated secretory proteins are sorted from o Dermatan Sulfate
membrane and lysosomal proteins and delivered o Heparin
via clathrin-coated vesicles to condensin o Heparan Sulfate
vacuoles, in which removal of water via ionic o Keratan Sulfate
exchanges yields secretory granules.
▪ Lysosomal proteins are sorted into clathrin- PROTEOGLYCANS
coated regions of the TGN that have receptors for ● consist of a core protein from which many GAGs extend
mannose 6-phosphate and are delivered to late ● show marked heterogeneity
endosomes via clathrin-coated vesicles. ● binding sites for growth factors
▪ Plasma membrane proteins are sorted into ● attributes to the extracellular matrix in certain locations
coatomer-coated regions of the TGN and
delivered to the plasma membrane in COP-II
GLYCOPROTEINS
coatomer–coated vesicles.
SYNTHESIS OF TRANSMEMBRANE PROTEINS ● promotes adhesion between the cell and the matrix.
● takes place on polyribosomes PART FUNCTION
● rather than entering the lumen, the transfer process is halted
Fibronectin - binds with collagen, heparin, various
(by a stoptransfer sequence), and the transmembrane
cell-surface receptors,
protein becomes anchored in the RER membrane.
and cell adhesion molecules (CAMs).
● The ultimate destination of this protein will be the RER
- mediates cell adhesion to the
membrane
extracellular matrix by binding to
fibronectin receptors on the cell surface.
SYNTHESIS OF CYTOSOLIC PROTEINS
● takes place on polyribosomes lying free in the cytosol and is Laminin - mediates interaction between epithelial
directed by mRNAs that lack signal codons. cells and the extracellular
matrix by anchoring the cell surface to the
INTRACELLULAR DIGESTION basal lamina

NONLYSOSOMAL DIGESTION Entactin - links laminin with type IV collagen in the


● degradation of cytosolic constituents by mechanisms outside lamina densa.
of the vacuolar lysosomal pathway in proteosome.
Tenascin - promotes cell–matrix adhesion and
LYSOSOMAL DIGESTION thus plays a role in cell migration.
● degradation of material within various types of lysosomes by
Chondronectin - plays a role in the development and
lysosomal enzymes.
maintenance of cartilage.
o Heterophagy
▪ ingestion and degradation of foreign material by
Osteonectin - plays a role in bone formation and
receptor-mediated endocytosis or phagocytosis.
remodeling and in maintaining
▪ digestion of endocytosed ligands occurs in
bone mass by influencing calcification.
multivesicular bodies.
▪ digestion of phagocytosed microorganisms and
foreign particles begins and may be completed in
phagolysosomes. FIBRONECTIN RECEPTORS
o Autophagy ● transmembrane proteins with two polypeptide chains from
▪ segregation of an organelle integrin family of receptors
o Crinophagy ● link fibronectin outside the cell to cytoskeletal components
▪ remove excess numbers of secretory granules (e.g., actin) inside the cell and may activate cell-signaling
from the cell pathways which determine the cell’s behavior

EXTRACELLULAR MATRIX FIBERS


● Composed of ground substance and fibers
● Alter the cells and influence their shape, migration, division, COLLAGEN FIBERS
and differentiation ● Intracellular events in collagen synthesis
o Preprocollagen synthesis occurs at the rough
GROUND SUBSTANCE endoplasmic reticulum (RER) directed by
messenger ribonucleic acid (mRNAs) that encode
GAGS the different types of chains to be synthesized.
● repeating identical disaccharide units o Hydroxylation of specific proline and lysine
● sulfated residues of the forming polypeptide chain occurs
● possess a uronic acid sugar within the RER. The reaction is catalyzed by
● has a strong negative charge because of its carboxyl group specific hydroxylases that require vitamin C as a
in the repeating disaccharide unit cofactor.

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o Glycosylation to specific hydroxylysine residues Defective Gs - leads to mental retardation, diminished


also occurs within the RER. proteins growth and sexual
o Procollagen triple-helix formation takes place in development, and decreased responses to
the RER and is precisely regulated by propeptides certain hormones.
(extra nonhelical amino acid sequences) at both Hereditary - fragile, misshapen red blood
ends of each chain. spherocytosi cells, or spherocytes; destruction of these
o Addition of carbohydrates occurs in the Golgi s spherocytes in the spleen leads to anemia.
complex, to which procollagen is transported via
transfer vesicles. With the addition of NUCLEUS
carbohydrates, the oligosaccharide side chains Oncogenes -inhibit cell proliferation and
are completed. development
o Secretion of procollagen occurs by exocytosis Aneuploidy -abnormal number of chromosomes
after secretory vesicles from the trans-Golgi -includes down syndrome, turner’s
network are guided to the cell surface along syndrome, and klinefelter syndrome.
microtubules. CYTOPLASM
● Extracellular events in collagen synthesis Flaccid -transmission and contraction of
o Cleavage of procollagen is catalyzed by paralysis of the neuromuscular is prevented by Botox
procollagen peptidases, which remove most of postsynaptic (botulinum neurotoxin A) cleaves
the propeptide sequences at the ends of each muscle. SNAP-25
chain, yielding tropocollagen or simply collagen. PEROXISOMAL
o Self-assembly of tropocollagen occurs as
Zellweger - absence of normal peroxisomes
insoluble tropocollagen molecules aggregate near
syndrome
the cell surface.
Adrenoleukody - caused by the inability of peroxisomes
o Fibrils characteristic of types I, II, III, V, and VII
strophy to metabolize fatty
collagen are produced.
acids.
o These fibrils have a transverse banding
periodicity of 67 nm in types I, II, and III collagen;
the periodicity varies in other types of collagen. FILAMENT
o Covalent bond formation (cross-linking) gives Tumor diagnosis - the type of intermediate filament
great tensile strength to collagen present identifies the tissue from
o Formation of lysine- and hydroxylysine-derived which the metastatic cancer cells
aldehydes. originated.
Familial - elevated level of cholesterol in the
ELASTIC FIBERS hypercholesterole bloodstream.
mia
● Components: LYSOSOME
o Elastin
Tay-Sachs disease - characterized by glycolipids
▪ mostly made from 90% elastic fibers
(namely, GM2 gangliosides)
▪ imparts remarkable elasticity to the extracellular accumulating in the lysosomes of
▪ matrix neurons as a result of a deficiency
o Fibrillin of the enzyme hexosaminidase A.
▪ organizes elastin into fibers and is the main
Hallmark of Hurler - glycosaminoglycans (GAGs) and
component of the peripheral microfibrils of elastic
syndrome mucopolysaccharides accumulate in
fibers.
the different organs of the body
● SYNTHESIS OF ELASTIC FIBERS
Glycogen storage - disease involving the synthesis or
o Elaboration of fibrillin microfibrils that appear near the
diseases the degradation of glycogen. As a
surface of the cell.
result, glycogen accumulates
o Formation of elastin among the bundles of microfibrils.
most often in the liver, skeletal
muscle, and the heart, but the major
CLINICAL CORRELATIONS FOR:
organ involvement depends on the
particular enzymatic defect.
PLASMA MEMBRANE
Cystinuria -abnormal carrier proteins that are
unable to remove cystine from the urine,
resulting in the formation of kidney stones. REFERENCES
Graves -production of antibodies that specifically Notes from the discussion by (Dr. Vinluan)
disease bind Gartner, L.P. & Hiatt J.L. (2011). BRS Cell Biology &
(hyperthyroi to and activate certain plasma membrane Histology (7th ed.)
dism) receptors. Main Reference:
Cholera - alters Gs protein so that it is unable to Mescher, A. (2013). Junqueira’s Basic Histology Text and
toxin hydrolyze its GTP molecule. As a result,
Atlas (13th Edition). McGraw-Hill
cAMP levels increase in
the surface-absorptive cells of the intestine, Education
leading to excessive loss of electrolytes and Saint Louis University Baguio. (2021). Human Histology
water and severe diarrhea. Laboratory Module 1.
Pertussis -accumulation of the inactive form of G
toxin proteins resulting in irritation of the mucosa
of the bronchial passages.

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