CELL AS A UNIT OF HEALTH

AND DISEASE
Dr. Ashish Jawarkar
MD
OBJECTIVES

CELL
GENOME,
PLASMA MEMBRANE,
ORGANELLES,
CELLULAR ACTIVATION,
EXTRACELLULAR MATRIX,
CELL DIVISION,
STEM CELLS
CELL

Pathology patho suffering, logos study

Cellular pathology Virchow study of cellular abnormalities
GENOME
GENOME

Human genome contain roughly 3.2 billion DNA base pairs, only 1.5%
(20,000) of which code for proteins (coding genes), remaining are non
coding genes
This coding genome is similar across species, and the diversity lies in the non
coding genome
As the complexity of organism increases so does the proportion of non
coding genome
WE ARE 99.9% SIMILAR

ANY TWO INDIVIDUALS 99.9

HUMAN AND CHIMPS 99.5
HUMAN AND CAT - 90
HUMAN AND CHICKEN 60

DIFFERENCE IS DUE TO VARIATIONS IN

GENOMES CALLED
SNP SINGLE NUCLEOTIDE POLYMORPHISM
CNV COPY NUMBER VARIATION
EPIGENETICS

Even though virtually all cells in the body contain the same genetic
material, terminally differentiated cells have distinct structures and
functions.
Clearly, different cell types are distinguished by lineage-specific programs
of gene expression and not by genetic differences
Study of such cell type-specific differences in DNA transcription and
translation is known as EPIGENETICS
EPIGENETIC FACTORS

HISTONES
DNA in cell is wound around these proteins
Not uniformly wound Heterochromatin and Euchromatin
Histone acetylation and methylation can cause neoplasia
NON CODING RNAs microRNAs and longRNAs
miRNA

Primarily involved in gene silencing, if doesnt work, can lead to neoplasia

That means its a tumor suppressor
Long non coding RNA (lncRNA)
ORGANELLES
ORGANELLES

PLASMA MEMBRANE
GOLGI BODIES AND ENDOPLASMIC RETICULUM
LYSOSOMES
MITOCHONDRIA
CELLULAR HOUSEKEEPING

A cell can survive only if the following house keeping functions are
performed on a regular basis
protection from the environment,
nutrient acquisition,
communication,
movement,
renewal of senescent molecules,
Molecular catabolism,
energy generation.
1. PLASMA MEMBRANE
Functions of plasma membrane

(1) ion and metabolite transport

(2) fluid-phase and receptor mediated uptake of macromolecules, and
(3) cell-ligand, cell-matrix, and cell-cell interactions.
 Passive diffusion
Active transport
Oxygen
Carbondioxide
Steroid based
estradiol, Vit D

Water
Ethanol
Urea

transferrin
and low-
density
lipoprotein
(LDL)
2. CYTOSKELETON

The ability of cells to adopt a particular shape,

Maintain polarity,
organize the relationship of intracellular organelles,
and move about
Depends on the intracellular scaffolding of proteins called the cytoskeleton
3. ENDOPLASMIC RETICULUM
GOLGI APPARATUS
(Biosynthetic Machinery)
The structural proteins and enzymes of the cell are constantly renewed by
ongoing synthesis tightly balanced with intracellular degradation.
The endoplasmic reticulum (ER) is the site for synthesis of all the
transmembrane proteins and lipids for plasma membrane and cellular
organelles, including ER itself.
It is also the initial site for the synthesis of all molecules destined for export
out of the cell.
GOLGI APPARATUS
4. LYSOSOMES AND PROTEASOMES

Lysosomes are membrane-bound organelles containing roughly 40

different acid hydrolases
Functions
Autophagy senescent organelles
Heterophagy (Macrophages and leucocytes) destroy pathogens
PROTEASOMES

Proteasomes play an important role in degrading cytosolic proteins these

include denatured or misfolded proteins
any other macromolecule whose lifespan needs to be regulated (e.g.,
transcription factors)
Proteasomes digest proteins into small (6 to 12 amino acids) fragments that
can subsequently be degraded to their constituent amino acids and
recycled.
5. MITOCHONDRIA

Mitochondria provide the enzymatic machinery for oxidative

phosphorylation (and thus the relatively efficient generation of energy from
glucose and fatty acid substrates).
They also play a fundamental role in regulating programmed cell death, so-
called apoptosis
CELLULAR COMMUNICATION
CELLULAR COMMUNICATION

Extra cellular communication - extracellular signals determine whether a

cell lives or dies, or whether it remains quiescent or is stimulated to perform
its specific function.
Intercellular signaling
clearly important in the developing embryo,
that tissues respond in an adaptive and effective fashion to various threats, such
as local tissue trauma or a systemic infection.
Loss of cellular communication can variously lead to growth (cancer) or an
ineffective response to extrinsic stress (as in shock).
Stages of cellular communication

1. Signalling
2. Signal Transduction
3. Cellular activation or deactivation
SIGNAL TRANSDUCTION

Binding of a ligand to a cell surface receptor mediates signaling

Cellular receptors are grouped into several types based on the signaling
mechanisms
CELLULAR ACTIVATION
(/DEACTIVATION)
Enzyme activation (or inactivation)
Transcription factor activation (or inactivation)

Most signal transduction pathways ultimately influence cellular function by

modulating gene transcription
GROWTH FACTORS
GROWTH FACTORS

role of growth factors is to stimulate

the activity of genes that are
required for cell growth and cell
division
EXTRACELLULAR MATRIX

Extracellular matrix (ECM) is a network of interstitial proteins

CELL CYCLE
CELL CYCLE

The sequence of events

that results in cell division is
called the cell cycle
CELL CYCLE contd.

The cell cycle is regulated by activators and inhibitors.

Cell cycle progression is driven by proteins called cyclins and cyclin-
associated enzyme called cyclin dependent kinases (CDKs)
Enforcing the cell cycle checkpoints is the job of CDK inhibitors (CDKIs)
STEM CELLS
STEM CELLS

During development, stem cells give rise to all the

various differentiated tissues
In the adult organism, stem cells replace damaged or
senescent cells
Stem cells are characterized by two important
properties:
Self-renewal, which permits stem cells to maintain their
numbers.
Asymmetric division, in which one daughter cell enters a
differentiation pathway and gives rise to mature cells,
while the other remains undifferentiated and retains its
self-renewal capacity.
Types of stem cells

Embryonic stem cells - Totipotent

Adult stem cells
Hematopoietic stem cells

Hematopoietic stem cells may be isolated directly from bone marrow, as

well as from the peripheral blood
These stem cells can be used to repopulate marrows depleted after
chemotherapy (e.g., for leukaemia), or to provide normal precursors to
correct various blood cell defects e.g. sickle cell disease
Besides hematopoietic stem cells, the bone marrow (and notably, other
tissues such as fat) also contains a population of mesenchymal stem cells.
These are multipotent cells that can differentiate into a variety of stromal
cells including chondrocytes (cartilage), osteocytes (bone), adipocytes
(fat), and myocytes (muscle).
they may represent a ready means of manufacturing the stromal cellular
scaffolding for tissue regeneration.
 Regenerative medicine

identify, isolate, expand, and transplant stem cells

a handful of genes have been identified whose
products canremarkablyreprogram somatic
cells to achieve the stem-ness of ES cells
Eg. insulin-secreting -cells in a patient with
diabetes
Summary

CELL GENOME, PLASMA MEMBRANE,

ORGANELLES, CELLULAR ACTIVATION,
EXTRACELLULAR MATRIX, CELL DIVISION,STEM CELLS
This survey of selected topics in cell biology will serve as a basis for our later
discussions of pathology and we will refer back to it throughout the book
References

Robbins 8/e
Google