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PRESENTED BY:-
GANESH NAIR
PG First Yr
CELL
GUIDED BY:-
Dr. Anita Panchal
Dr. Hardik Mehta
Dr. Sachin K.
Dr. Bhaumik
Nanavati
INDEX:-
•INTRODUCTION
•THE CELL THEORY
•ORGANIZATION OF CELL
•PHYSICAL STRUCTURE OF THE CELL
•CYTOPLASM AND ITS ORGANELLES
•INTER CELLULAR JUNCTIONS
•NUCLEUS
•FUNCTIONAL SYSTEM OF THE CELL
•REGRESSION OF CELL AND AUTOLYSIS
OF CELL
•FUNCTION OF MITOCHONDRIA
 CELLS OF IMMUNITY AND
INFLAMMATION
 TRANSENDOTHELEAL MIGRATION
 LEUKOCYTE FUNCTIONS
 ANTIGEN PROCESSING AND
PRESENTATION
 SPECIFIC IMMUNE RESPONSE
INTRODUCTION
 Cell is the structural and functional
unit of life.
 Robert Hook, an English scientist,
observed a thin slice of cork under the
microscope in 1665, he described
small spaces surrounded by wall and
named them cells. Later Robert Brown
discovered the nucleus of the cell.
THE CELL THEORY
 The cell theory put forth by two scientists
Matthias Scheiden and Theodore
Schwann. The theory is as follows(with
modification by Rudolf Virchow in 1855):-
 All living organism are made up of cell
and their products.
 Cell is the structural and functional unit
of organism.
 New cells are formed by division of the
pre existing cell.
cell
eukaryotes prokaryotes
ORGANIZATION OF THE CELL
 Cell has two major parts the nucleus
and the cytoplasm. The nucleus is
separated from the cytoplasm by
nuclear membrane, and the cytoplasm
is separated from the surrounding
fluids by the cell membrane, also
called the plasma membrane
 The basic constituents of the cytoplasm are as
follows ;-
 Water:- the principle fluid medium of the cell is
water, which is present in most of the cell, except for
the fat cells, in a concentration of 70-85%.
 Ions :- the most important ions for the cell are
potassium, magnesium, phosphate, sulphate,
bicarbonate and small quantities of sodium, chloride
and calcium.
 Proteins:- after water, the most abundant
substances in most of the cell are protiens, which
normally constitute 10-20% of the cell mass. These
can be divided into two types: structural protiens
and functional protiens.
 Lipids :- the especially important lipids are
phospholipids and cholesterol, which constitute 2%
of the total cell mass. In addition phospholipids and
cholesterol, some cells contain large quantities of
triglycerides, also called neutral fat.
 Carbohydrates:- they have little structural function in
the cell except as a parts of glycoprotien molecules,
but play a major role in nutrition of the cell. It
accounts to 1% of the total cell mass.
PHYSICAL STRUCTURE OF
THE CELL
 Cell membrane:- the cell membrane envelops
the cell in a thin, pliable, elastic structure only
7.5-10nm in thickness. It is composed mainly of
protiens and lipids.
 The approximate concentration are as follows:-
 Proteins 55%
 Phospholipids 25%
 Cholesterol 13%
 Other lipids 4%
 Carbohydrates 3%
 Membrane carbohydrates:- carbohydrates mostly
occur in the form of glycoprotein and glycolipid,
many other carbohydrate compounds are called
proteoglycans. The entire outside surface of the cell
has a loose carbohydrate coat called the glycocalyx.
 The function of these carbohydrate moieties are:-
 Many of them electrically negative charge which
gives the overall cell a negative charge that repel
other negative substances.
 Helps in attachment with other cell by glyocalyx –
glycocalyx attachment.
 Many of them act as receptor substances for
binding hormones.
 Some of the enter into immune reactions.
CYTOPLASM AND ITS
ORGANELLES
 The cytoplasm is filled with both minute
and large dispersed particles and
organelles. The clear fluid portion of the
cytoplasm is called cytosol.
 There are 5 major organelles:
 Endoplasmic reticulum
 Golgi apparatus
 Mitochondria
 Nucleus
 Lysosome
Endoplasmic reticulum
 Granular endoplasmic reticulum:- there are
several minute granular particles called the
ribosomes. The ribosomes are composed of
RNA and proteins, and they function to produce
new proteins in the cell.
 Smooth or agranular endoplasmic reticulum:- it
functions for production lipid substances.
Golgi apparatus
 This apparatus prominent in secretory cells, where it
is located on the side of cell from which secretory
substances are extruded.
 Apparatus works in association with the
endoplasmic reticulum. The substances produced in
the endoplasmic reticulum are transported to the
golgi apparatus via the transport vesicles or the ER
vesicles.
 The transported substances are then processed by
the golgi apparatus to form lysosomes, secretory
vesicles, and other cytoplasmic components.
SPECIFIC FUNCTION OF THE
GOLGI APPARATUS :-
 It has the capability of producing certain
carbohydrates that are not produce by the
endoplasmic reticulum. This especially include
the production of hyaluronic acid and chondroitin
sulphate.
 Few functions of hyaluronic acid and chondroitin
sulphates are as follows:-
 They are major components of proteoglycans
secreted in mucus and other glandular
secretions.
 They are major components of the ground
substances outside the cell and interstitial
spaces acting as a filler between collagen fibers
and cell.
 They are the principal components of the organic
matrix of the bone and cartilage.
Lysosomes
 They serve as intracellular digestive system that
allows the cell to digest:-
 Damaged cellular substances.
 Food particles that have been ingested by the cell.
 Unwanted matter such as bacteria.
 The lysosomes are usually 250 to 750 nm in
diameter. It is surrounded by a lipid bilayer
membrane and is filled with large no. small granules
5-8 nm in diameter, which are protein aggregates of
as many as 40 different hydrolase enzymes.
Peroxisomes &Secretory
vesicles
 PEROXISOMES:- they are similar to lysomes but
are different in two different aspects. First, they are
believed to be formed by self replication by budding
off from smooth endoplasmic reticulum. Second,
they contain oxidases rather than hydrolases.
 SECRETORY VESICLES:- almost all the secretory
substances are forms by the endoplasmic reticulum-
golgi apparatus system and are then released from
the golgi apparatus in to the cytoplasm in the form
of storage vesicles called secretory vesicles or
secretory granules.
Mitochondria
 The powerhouse of the cell.
 It is composed of two lipid bilayer-protein
membranes – the inner and outer membrane. Many
infolding in the inner membrane form shelves onto
which oxidative enzymes are attached.
 The inner cavity is filled with a matrix that contains
large quantities of dissolved enzymes that is
necessary for extracting energy from the nutrients.
 The released energy is used to synthesize high
energy substance called adenosine triphosphate
(ATP).
Filament and other tubular
structures of the cell
 the fibrillar portions of cell are usually
organized into filaments or tubules. A special
type of stiff filament composed of polymerized
tubulin molecules is used in a cell to construct
a very strong tubular structure called
microtubule. The primary function of the
microtubule is to act as a cytoskeleton,
providing rigid physical structures for certain
parts of cell.
Centrosome and centrioles
 Centrosome is a round and dense mass of
cytoplasm present near the nucleus. Within the
centrosome lies a pair of centrioles. The
individual centrioles are so arranged that they
look likeT. Each centriole consists of 9
microtubules
 During cell division, the centriole divides into
two and the two centrioles appear at two
different poles of the nucleus. Further, these
two centrioles are connected by spindles.
 The spindles subsequently contract and the
two halves of the nucleus now separate from
each other and the mitosis is completed. Cell
division is not possible without centrioles
 Nerve cell bodies do not have centriole and are
not capable of cell division..
NUCLEUS:
 The nucleus contains large quantities of DNA,
which are the genes. the genes determine the
characteristics of cell’s proteins, including the
structural protein as well as the intracellular
enzymes that determine the cytoplasmic and
nuclear activities.
 The genes also control the rate of reproduction of
the cell. The membrane covering the nucleus is
Nuclear membrane also known as nuclear envelop.
 Nucleoli and formation of ribosomes:- the nuclei of
most cells contain one or more highly staining
structures called the nucleoli. It is simply an
accumulation of large amount of RNA and protein of
the type found in the ribosome.
 When cells come into contact with one another, and sometimes
with the extracellular matrix, specialized junctions may form at
specific sites on the contacting cell membranes. These
specialized junctions may be classified as:
1. Occluding (tight) junctions (zonula occludens)
2. Adhesive junctions
a. Cell-to-cell
i. Zonula adherens
ii. Macula adherens (desmosorne)
b. Cell-to-matrix
i. Focal adhesions
ii. Hemidesmosomes
3. Communicating (gap) junctions
Intercellular junctions:-
 The term zonula describes a junction that encircles the
cell; macula indicates a junction that is more
circumscribed in extent (e.g., spot like).
 Junctions may occur in certain combinations.
 On the molecular level, intercellular junctions typically
consist of three components:
A transmembrane adhesive protein,
A cytoplasmic adapter protein, and
A cytoskeletal filament.
 These three components differ depending on the type of
junction.
 In occluding, or tight junctions the opposing cell
membranes are held in close contact by the presence of
transmembrane adhesive proteins arranged in
anastomosing strands that encircle the cell.
 The intercellular space essentially is obliterated at the
tight junction. The transmembrane adhesive proteins,
which include occludin, members of the claudin family,
and in some tissues, junctional adhesion molecule
(JAM), interact homotypically with the same proteins on
 Tight junction
 Hold cells together or anchor cells to the extracellular matrix. In
contrast to tight junction the intercellular space in cell-cell
adhesive junction is maintained at approximately 20 nm.
 Adhesive junctions are also important in cellular signaling. Their
cytoplasmic components may interact with the cytoskeleton
triggering changes in cell shape or motility, or with certain tumor
suppressor molecules or they may act as nuclear transcription
factors or co-activators.
 In some instances, the loss of cell-cell or cell-matrix contact
may lead to apoptosis (programmed cell death), whereas in
others, loss of contact may lead to loss of cell polarity and
differentiation or unregulated cell proliferation.
Adhesive junctions
 ADHERING JUNCTION
 In the Desmosome the cadherins are desmoglein and
desmocollin. The interaction of these transmembrane proteins
with those from the adjacent cell results in a dense line in the
middle of the intercellular space at the desmosome.
 The catenins are desmoplakin and plakoglobin, which form an
electron- dense plaque on the cytoplasmic side of the
desmosome. This plaque serves as an attachment site for the
cytoskeletal components, which in the case of the desmosome
are intermediate filaments.
DESMOSOME
 Have a structural organization similar to that of cell-cell
adhesive junctions, but they use different molecular
components and attach the cell to the extracellular matrix.
 In focal adhesions the transmembrane component is a member
of the integrin family of adhesion molecules.
 Integrins are heterodimers of different alpha and beta subunits
with specificity for various extracellular matrix molecules.
 Eighteen known alpha subunits and 8 beta subunits occur in 24
different combinations.
CELL MATRIX JUNCTIONS:-
 The cytoplasmic adapter proteins, which include the actin-
binding proteins alpha-actinin, vinculin, and talin, link the
transmembrane integrins to the actin cytoskeleton.
 Binding of the integrin to collagen, laminin, fibronectin, and
other extracellular matrix proteins results in recruitment and
remodeling of the actin cytoskeleton.
 The transmembrane adhesive molecules present in
hemidesmosome are the integrin alpha 6, beta 4, which binds
specifically to the basal lamina glycoprotein laminin, and
collagen XVII (also identified as BPI8O).
 Hemidesmosomes link the cell to the basal lamina, and through
additional extracellular molecules, to the rest of the
extracellular matrix.
 Are plaque like regions of the cell membrane where the
intercellular space narrows to 2 to 3 nm and transmembrane
proteins of the connexin family form aqueous channels
between the cytoplasm of adjacent cells.
 Six connexin molecules form a connexon, which has a central
channel approximately 2nm diameter.
 The connexons in one cell pair with connexons in the adjacent
cell to create a patent channel. Small molecules such as ions
and signaling molecules can move readily from one cell to
another.
 The connexin family includes more than a dozen different
proteins that have specific tissue and cellular distributions and
confer differing permeability properties to the gap junctions.
GAP JUNCTIONS:-
GAP JUNCTION
INGESTION BY THE CELL
 Endocytosis:-
 Very large particles enter the cell by
specialised function of the cell called the
endocytosis. The principle form of endocytosis
are pinocytosis and phagocytosis
Pinocytosis:-
 It is a means of ingesting small particles that form
vesicles of extracellular fluid and particulate
constituents in the cell cytoplasm.
 Pinocytosis is the only means by which most large
macromolecules, such as most proteins
molecules.
 These molecules attach to specific receptor on the
surface of the membrane that are specific type of
protein that is to be absorbed.
 These receptors are usually located on the small
pits on the outer surface of the cell membrane
called as the coated pits. On the inside of the cell
membrane beneath these pits is a lattice work of
fibrillar proteins called clathrin.
Phagocytosis:-
 It is the means of ingestion of large particles such
as bacteria, whole cells, or portions of degenerating
tissue.
 Phagocytosis occurs in the same as pinocytosis,
except that it involves large particles rather than
molecules.
 Phagocytosis occurs in the following steps:-
 The cell membrane receptor attaches to the surface
ligand of the particles.
 The edges of the membrane around the points of
attachment evaginate outward within a fraction of
second to surround the entire particle;
 then progressively more and more membrane
receptors attach to the particle ligands. All this
suddenly occurs in a zipper like fashion to form a
phagocytic vesicle.
 Actin and other contractile fibrils in the cytoplasm
surround the phagocytic vesicle and contract around
the outer edge, pushing the vesicle in the interior.
 The contractile proteins then pinch the stem of the
vesicle so the vesicle is completely separated from
the cell membrane, leaving the vesicle in the cell
interior in the same way the pinocyte vesicle is
formed.
DIGESTION OF PINOCYTOTIC
AND
PHAGOCYTIC FOREIGN
SUBSTANCE:
 Almost immediately after a pinocytotic or phagocytic
vesicle appears inside a cell, one or more
lysosomes become attached to the vesicles and
empty their acid hydrolases to the inside the vesicle.
 Thus a digestive vesicle is formed inside the cell
cytoplasm in which the vesicular hydrolases begin
hydrolyzing the proteins, carbohydrate, lipids, and
other substances in the vesicle
 The product of the digestion are small
molecules of amino acids, glucose and
phosphates that diffuse through the vesicle into
the cytoplasm.
 The left off products that are indigestible are
still in the vesicle and the vesicle called as the
residual body.
 The residual body products are excreted by the
cell by the process called exocytosis which is
the opposite of endocytosis. Hence pinoctotic
and phagocytic vesicles are the digestive
organs of the cell.
REGRESSION OF TISSUE AND
AUTOLYSIS OF CELL
 Lysosomes also help in removal of damaged
cells and portion of tissues, the cell can get
damaged by heat, cold, trauma, chemicals and
other factors. The lysosomes burst in these
cases and releases hydrolases which in turn
digest the surrounding organic substances.
 In case of slight injury only that portion of
the cell is removed in case of severe
damage entire cell is digested this is called
as autolysis
 The lysosomes contain bactericidal agents that
kills the phagocytised bacteria like:-
 Lysozyme which dissolve the bacterial cell
membrane.
 Lysoferrin which binds to the iron and other
substances before they can promote bacterial
growth.
 Acid at the pH 5.0 which activates the
hydrolases and inactivates bacterial metabolic
systems.
FUNCTION OF THE
MITOCHONDRIA:-
 The principal substances from which the cell
extracts energy are foodstuff that reacts with
oxygen--- carbohydrates, proteins and fat.
Essentially all carbohydrates are converted to
glucose, the proteins are converted into amino
acids, fats into fatty acids.
 All the converted substances are transferred to the
mitochondria which converts then into high energy
molecules known as ATP. Them ATP is to energize
all the metabolic activity of the cell.
 When ATP releases it energy, phosphoric acid
radical splits away, and adenine diphosphate is
formed.
 This released energy is used for various
cellular functions such as synthesis of
substances and muscle contraction.
 ADP is reacted with phosphoric acid to form
ATP again. Hence ATP is called the energy
currency of a cell because its spent and
remade continuously.
CHEMICAL PROCESS IN THE
FORMATION OF ATP- Role of
Mitochondria
 On entry into cell, glucose is subjected to enzymes
in the cytoplasm that convert it into pyruvic acid(a
process called glycolysis). A small amount amount
of ADP is changed into ATP by the energy released
during this conversion, but this amounts to only 5 %
of the total ATP production.
 The rest 95% is produced in the mitochondria. The
pryruvic acid derived from carbohydrates, fatty acid,
from lipids, and amino acids from proteins are
eventually converted into a compound called the
acetyl-CoA in the matrix of mitochondria.
 Acetyl CoA reacts with other series of enzymes
in the mitochondria matrix undergoes a series
of chemical reaction known as the citric acid
cycle or the KREBS cycle.
 The citric acid cycle releases carbon dioxide
and hydrogen atoms. The carbon dioxide
diffuses out of the mitochondria and is excreted
by the cell and eventually from the body by the
lungs.
 The reaction is catalysed using the enzyme
ATP synthetase, that protrude from the shelves
of the mitochondria where the reaction
between hydrogen and oxygen takes place.
 Uses of ATP for cellular function :-
 Transport of substances through multiple
membranes in the cell.
 Synthesis of chemical compounds throughout
the cell.
 Mechanical work.
 Inflammation is an observable alteration in the
tissue associated with changes in the vascular
permeability and dilation, often with infiltration of
leukocyte into the affected tissues. Inflammation is
divided into three stages:- immediate, acute and
chronic. All these stages are controlled by
leucocytes.
immunity
Innate
acquired
MAST CELLS
 They posses receptor for the complement
system as well as the Fc portion of antibody
molecules immunoglobulin E (IgE) and
immunoglobulin G(IgG) FcϵR and FcɣR.
More recently the mast cells are shown to
express toll like receptors.
 These receptor allow the innate immune
system to adapt class II molecules (MHC).
The stimulation of these receptor can lead to
activation and secretion of vasoactive
substances that increase vascular
permeability and dilation, two important
features of anaphylaxis.
 Mast cells prominent features include the
presence of large no. of lysosomes., which
store inflammatory mediators like histamine,
eosinophil chemotactic factor, neutrophil
chemotactic factor, and heparin.
 Mast cells are synthesized de novo other
inflammatory mediators are slow reacting
substances anaphylaxis(SRS-A), tumor
necrosis factor(TNF–α), interleukin-6(IL-6),
and leukotrine C4.
DERMAL DENTROCYTES
 or histiocytes are widely distributed and form a
large system of collagen associated with
dendritic cells of myeloid origin.
 These are distributed near the blood vessels
and posses receptor for the complement
system, by which it participate in immediate
inflammation.
 It has been shown that histiocytes express
matrix metalloprotineses (MMPs) in reponse to
bacterial challenge and thus potentially
contribute directly to periodontal tissue
destruction.
PERIPHERAL DENDRITIC
CELLS
 (DCs) are leucocyte with cytoplasmic
projections or dendrites. Langerhan cells are
DCs that reside in the suprabasilar portions of
squamous epithelium.
 DC ingest antigen and transport the antigen to
lymph node through afferent lymphatics. DCs
express high level of MHC class II and CD1, as
well as cell adhesion molecules (intercellular
adhesion molecule -1[Icam-1]) and co
stimulatory factors.
NEUTROPHILS AND
MONOCYTES/
MACROPHAGES
 They are closely related phagocytic leucocyte. The
fundamental difference between the two is that
neutrophils differentiate completely within the bone
marrow whereas monocytes exit the bone marrow
within 2 days in a relatively immature state and may
differentiate in the tissue.
 Because neutrophil do not to differentiate
substantially to function, they are suited for rapid
response. Neutrophils posses receptor for
metabolites of the complement molecule C3,
designated completent receptors 1,3,4 and C5 .
they also posses receptor for IgG antibody(FcɣR).
 By convention, monocytes are reffered to as
macrophages when they leave blood. Because
macrophages, differentiate and live in the local
tissues, they are suited for communicating with
lymphocytes and other surrounding cells.
 Together lymphocytes and macrophages
orchestrate the chronic immune response.
Monocytes posses CR1, CR4, CR3, and C5aR,
several classes of Fcɣ receptors and molecules
important for antigen presentation.
LYMPHOCYTES
 The three main type of lymphocytes are divided on
the basis of their receptors for antigen : T cell, B
cells and natural killer (NK).
 T cells: - they recognize antigen using a low affinity
transmembranous complex T cell antigen receptor
(TCR). T cells are divided further on the basis of co
receptors present into CD8 and CD4.
 B cells:- they help control extracellular antigen such
as bacteria, fungal yeast and virions. B cells
recognize diverse antigen using a high affinity
antigen receptor called as B cell antigen
receptor(BCR).
 Before antigen presentation, B cell express
immunoglobulin M(IgM) as a part of BCR. After
exposure the B cells differentiate to form plasma
cells dedicated to the production and secretion of
IgM isotype.
 NATURAL KILLER(NK):- these cells identify and kill
certain tumor and virally infected cells. The natural
killer posses several classes of antigen receptors,
including killer inhibitory response (KIR) and killer
activating receptor (KAR).
 Normal cells posses MHC class I molecules that
present antigen recognised as ‘self’ these interact
with KIR’s and protect the cell for NK cell mediated
killing.
 KAR activation can override the KIR inhibition and
TRANSENDOTHELEAL
MIGRATION
 It is referred to the movement of leukocytes from the
blood to the local tissue in the central region of
inflammation. Defects in transendothelial migration
are seen in aggressive periodontits, reflecting the
importance of this process in periodontal disease.
 Neutrophils and monocytes spend less than 12 hrs
in the circulation. B cells and T cells stay in the
blood for about 30 min. They constantly exit the
blood vessel pass through the lymphatics and
secondary lymphoid organs, and re enter the blood
circulation in a perpetual process known as
lymphocyte recirculation.
LEUKOCYTE FUNCTIONS
 CHEMOTAXIS:- once the leukocyte enters the
connective tissue , it must be able to locate and
migrate to the site of insult. This is a accomplished
by chemotaxis, which depends on the leukocyte
ability to sense a chemical gradient across its cell
body and migrate to the direction of increasing
concentration.
 The receptor for chemotaxis belong to the family of
G-protein coupled family. The only class of
chemotaxin derived directly from bacteria are
formyl-methionyl peptide. To migrate toward a
target, leucocytes assume a asymmetric polarized
shape rather than rounded morphology evident in
PHAGOCYTOSIS
 Neutrophils and monocytes/macrophages are the
only cells efficient enough at phagocytosis to be
considered “professional phagocytes”.
 The immune system has evolved mechanism of
coating the pathogen with a few recognizable
ligands, which enable the phagocyte to bind and
ingest the pathogen. This is referred to as
opsonisation. Phagocyte kill bacteria by two broad
categories of killing mechanisms oxidative and non-
oxidative.
 Non oxidative killing requires phagosome-
lysosome fusion. The process involves the
movement toward and consequent membrane
fusion of the lysosome with the phagosome
called the phagolysosome. This is result of
secretion of lysosomal components into the
phagolysosome.
 Each neutrophil posses three main type of
lysosome:
GRANULE CLASS GRANULE COMPONENTS
Primary/ azurophilic Cathepsin G, BPI, lysozyme,
elastase, MPO, α-defensins
Secondary/specific Flavocytochrome b558 , LL-
37,lysozyme, lactoferrin, CD11
Tertiary/ gelatinase Flavocytochrome b558 ,
lysozyme, gelatinase
 Less than 30 seconds after phagocytosis,
neutrophils secrete specific granules contain
several microbiocidal components, including
lysozyme and lactoferrin.
 Lysozyme is an enzyme which possesses
enzyme dependent bactericidal activity and
fungicidal activity. Lactoferrin is a bacteriostatic
component.
 Neutrophils secrete azurophilic granules into
the phagolysosome minutes after secretion of
specific granules. Among the microcidal
components are small antimicrobial peptides
known as the α-defensin, serposidins,
 These are non oxidative mechanism of
neutrophil killing may be of particular
importance in periodontal disease because of
highly anaerobic conditions in the subgingival
environment.
 In the presence of oxygen, phagocyte
additionally posses mechanism of oxidative
killing. In particular neutrophils exert intense
microbiocidal activity by performing toxic,
reduced oxygen metabolites such as
superoxide anion (O2
- ) using NADPH oxidase
system
 The super oxide contributes in the formation of
hydrogen peroxide, which is capable of diffusing
across the membrane. Inside the cell the hydrogen
peroxide further reduced into hydroxyl radicals,
which can cause DNA damage. More importanatly
H2O2 is a substrate for myeloperoxidase (MPO).In
the presence of H2O2 and chloride, MPO catalyzes
the formation of hypochlorous acid (HOCl).
 In summary, phagocytosis is of primary importance
in the ability of the host to resist and combat
infection. Because of highly anaerobic environment
in the periodontium, non oxidative mechanism of
killing are more prevalent.
ANTIGEN PROCESSING AND
PRESENTATION
 the major histocompatibilty complex(MHC) is a
locus on the short arm of the chromosome 6 that
encodes a no. of molecules, which are involved in
antigen uptake, processing and presentation.
 MHC I :- present the intracellular antigen to the
CD8+ T cells and NK cells.
 MHC II :-presents extracellular antigens presented
by APC.
 MHC III :- include complement factors.
 Externally derived antigens are processed by
phagocytosis, and the resulting pepdtide molecules
are associated with the MHC class II molecules.
 Molecules of the MHC classes I, II, III are among
the most pleomorphic molecules in humans.
 Enabling the APC to present antigen to the T cell
with the second stimulation called as co-stimulation.
Co-stimulation reaffirms the T cell that it has
recognised an undesirable antigen.
 Co-stimulation performs three functions:-
 Makes T cell resistant to apoptosis.
 Upregulates the growth factor receptors on the T
cell, there by stimulating proliferation.
 Decrease the amount of time required to trigger T
cell.(referred to as amplification)
 A receptor molecule named “toll” first identified
in fruit flies was shown to be in response to
certain injury and infection.
 The human toll like receptor(TLRs) are
stimulated by highly conserved bacterial
components such as lipopolysaccharides(LPS)
and are important in dictating the adaptations
found in the innate immune system
SPECIFIC IMMUNE
RESPONSE
 Chronic inflammation, if protracted can result in an
adaptation called the specific immune response.
 Four phases are involved in the generation of
specific immunity:-
 Clonal selection: the selection of lymphocytes that
bear receptors recognizing the specific antigen.
 Clonal expansion: the proliferation those
lymphocytes. (In the expansion phase it leads to
the increase in 100-5000 folds increase in these
cells. )
 Clonal contraction: the death of effector
lymphocytes
 Memory: the maintenance of the expanded clone
of cells that bear the specific receptor recognising
the antigen.
 The increase in the antibody titer or antigen-specific
T cells resulting in exposure of a host to an antigen
for the first time is referred to as primary respone.
The secondary response occurs after subsequent
exposure to the same antigen.
 The primary response takes slightly more than 1
week (8-14 days) to become measurable and
biologically or clinically useful. Secondary
responses are measurable within 1-3 days and are
so effective that the individual may not be aware of
the infection.
 Vaccination is the development of immunity, or
resistance to infections, after secondary response
that is adequate to consider the individual immune
to subsequent infections.
T CELL RESPONSES
 T cells may express 3000-5000 TCRs on the
surface. Antigen presented to the TCR by MHC
class I or class II molecules on the APC.
 The TCR peptide binding is more specific than
that of MHC peptide complex, which is based
on recognition of a smaller no. of discontinuous
amino acids.
 Thus the T cell may recognise fewer antigen
than those presented by the MHC.
 The low affinity of the TCR enables the T cells
to bind to the APCs reversibly, which occurs
with multiple TCRs and one or more antigen at
the over time.
 This time dependent interaction of many TCRs
with a few antigen is referred as scanning.
 Scanning leads to T cell activation known as
serial triggering.
 To fully activate a T cell, multiple TCR
engagement must be sustained for 2-20 hrs.
B CELL RESPONSE AND
ANTIBODIES
 B cell produces immunoglobulin. The
immunoglobulin that binds to the antigen is called as
antibody. Humans posses 9 genetically distinct
immunoglobulin IgM, IgD, IgG1, IgG2, IgG3, IgG4,
IgA1, IgA2 and IgE. When B cell exit the bone
marrow it posses only receptor fro IgM.
 The ability of B cell to respond to antigen depends
on the BCR. The BCR is formed partly by
immunoglobulin molecules on the B cell surface.
 B cells are capable of responding to certain antigen
in the absence of T cells this feature is called as T
cell independent B cell antibody response.
 But, for a B cell to enter the memory pathway it has
to interact with the T cell thus the memory pathway
is considered to be T cell dependent.
REFERENCES:-
 Chapter 2, Eleventh Edition, Textbook of
Clinical Physiology, Guyton and Hall.
 Chapter 12, Tenth Edition, Textbook of Clinical
Periodontology, Carranza, Takei, Newmann,
Klokkevold.
 Orban’s Oral Histology
Cell

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Cell

  • 1.
  • 2. PRESENTED BY:- GANESH NAIR PG First Yr CELL GUIDED BY:- Dr. Anita Panchal Dr. Hardik Mehta Dr. Sachin K. Dr. Bhaumik Nanavati
  • 3. INDEX:- •INTRODUCTION •THE CELL THEORY •ORGANIZATION OF CELL •PHYSICAL STRUCTURE OF THE CELL •CYTOPLASM AND ITS ORGANELLES •INTER CELLULAR JUNCTIONS •NUCLEUS •FUNCTIONAL SYSTEM OF THE CELL •REGRESSION OF CELL AND AUTOLYSIS OF CELL •FUNCTION OF MITOCHONDRIA
  • 4.  CELLS OF IMMUNITY AND INFLAMMATION  TRANSENDOTHELEAL MIGRATION  LEUKOCYTE FUNCTIONS  ANTIGEN PROCESSING AND PRESENTATION  SPECIFIC IMMUNE RESPONSE
  • 5. INTRODUCTION  Cell is the structural and functional unit of life.  Robert Hook, an English scientist, observed a thin slice of cork under the microscope in 1665, he described small spaces surrounded by wall and named them cells. Later Robert Brown discovered the nucleus of the cell.
  • 6.
  • 7. THE CELL THEORY  The cell theory put forth by two scientists Matthias Scheiden and Theodore Schwann. The theory is as follows(with modification by Rudolf Virchow in 1855):-  All living organism are made up of cell and their products.  Cell is the structural and functional unit of organism.  New cells are formed by division of the pre existing cell.
  • 9. ORGANIZATION OF THE CELL  Cell has two major parts the nucleus and the cytoplasm. The nucleus is separated from the cytoplasm by nuclear membrane, and the cytoplasm is separated from the surrounding fluids by the cell membrane, also called the plasma membrane
  • 10.  The basic constituents of the cytoplasm are as follows ;-  Water:- the principle fluid medium of the cell is water, which is present in most of the cell, except for the fat cells, in a concentration of 70-85%.  Ions :- the most important ions for the cell are potassium, magnesium, phosphate, sulphate, bicarbonate and small quantities of sodium, chloride and calcium.  Proteins:- after water, the most abundant substances in most of the cell are protiens, which normally constitute 10-20% of the cell mass. These can be divided into two types: structural protiens and functional protiens.
  • 11.  Lipids :- the especially important lipids are phospholipids and cholesterol, which constitute 2% of the total cell mass. In addition phospholipids and cholesterol, some cells contain large quantities of triglycerides, also called neutral fat.  Carbohydrates:- they have little structural function in the cell except as a parts of glycoprotien molecules, but play a major role in nutrition of the cell. It accounts to 1% of the total cell mass.
  • 12. PHYSICAL STRUCTURE OF THE CELL  Cell membrane:- the cell membrane envelops the cell in a thin, pliable, elastic structure only 7.5-10nm in thickness. It is composed mainly of protiens and lipids.  The approximate concentration are as follows:-  Proteins 55%  Phospholipids 25%  Cholesterol 13%  Other lipids 4%  Carbohydrates 3%
  • 13.
  • 14.  Membrane carbohydrates:- carbohydrates mostly occur in the form of glycoprotein and glycolipid, many other carbohydrate compounds are called proteoglycans. The entire outside surface of the cell has a loose carbohydrate coat called the glycocalyx.  The function of these carbohydrate moieties are:-  Many of them electrically negative charge which gives the overall cell a negative charge that repel other negative substances.  Helps in attachment with other cell by glyocalyx – glycocalyx attachment.  Many of them act as receptor substances for binding hormones.  Some of the enter into immune reactions.
  • 15. CYTOPLASM AND ITS ORGANELLES  The cytoplasm is filled with both minute and large dispersed particles and organelles. The clear fluid portion of the cytoplasm is called cytosol.  There are 5 major organelles:  Endoplasmic reticulum  Golgi apparatus  Mitochondria  Nucleus  Lysosome
  • 16. Endoplasmic reticulum  Granular endoplasmic reticulum:- there are several minute granular particles called the ribosomes. The ribosomes are composed of RNA and proteins, and they function to produce new proteins in the cell.  Smooth or agranular endoplasmic reticulum:- it functions for production lipid substances.
  • 17.
  • 18. Golgi apparatus  This apparatus prominent in secretory cells, where it is located on the side of cell from which secretory substances are extruded.  Apparatus works in association with the endoplasmic reticulum. The substances produced in the endoplasmic reticulum are transported to the golgi apparatus via the transport vesicles or the ER vesicles.  The transported substances are then processed by the golgi apparatus to form lysosomes, secretory vesicles, and other cytoplasmic components.
  • 19. SPECIFIC FUNCTION OF THE GOLGI APPARATUS :-  It has the capability of producing certain carbohydrates that are not produce by the endoplasmic reticulum. This especially include the production of hyaluronic acid and chondroitin sulphate.  Few functions of hyaluronic acid and chondroitin sulphates are as follows:-  They are major components of proteoglycans secreted in mucus and other glandular secretions.  They are major components of the ground substances outside the cell and interstitial spaces acting as a filler between collagen fibers and cell.  They are the principal components of the organic matrix of the bone and cartilage.
  • 20. Lysosomes  They serve as intracellular digestive system that allows the cell to digest:-  Damaged cellular substances.  Food particles that have been ingested by the cell.  Unwanted matter such as bacteria.  The lysosomes are usually 250 to 750 nm in diameter. It is surrounded by a lipid bilayer membrane and is filled with large no. small granules 5-8 nm in diameter, which are protein aggregates of as many as 40 different hydrolase enzymes.
  • 21. Peroxisomes &Secretory vesicles  PEROXISOMES:- they are similar to lysomes but are different in two different aspects. First, they are believed to be formed by self replication by budding off from smooth endoplasmic reticulum. Second, they contain oxidases rather than hydrolases.  SECRETORY VESICLES:- almost all the secretory substances are forms by the endoplasmic reticulum- golgi apparatus system and are then released from the golgi apparatus in to the cytoplasm in the form of storage vesicles called secretory vesicles or secretory granules.
  • 22. Mitochondria  The powerhouse of the cell.  It is composed of two lipid bilayer-protein membranes – the inner and outer membrane. Many infolding in the inner membrane form shelves onto which oxidative enzymes are attached.  The inner cavity is filled with a matrix that contains large quantities of dissolved enzymes that is necessary for extracting energy from the nutrients.  The released energy is used to synthesize high energy substance called adenosine triphosphate (ATP).
  • 23.
  • 24. Filament and other tubular structures of the cell  the fibrillar portions of cell are usually organized into filaments or tubules. A special type of stiff filament composed of polymerized tubulin molecules is used in a cell to construct a very strong tubular structure called microtubule. The primary function of the microtubule is to act as a cytoskeleton, providing rigid physical structures for certain parts of cell.
  • 25. Centrosome and centrioles  Centrosome is a round and dense mass of cytoplasm present near the nucleus. Within the centrosome lies a pair of centrioles. The individual centrioles are so arranged that they look likeT. Each centriole consists of 9 microtubules  During cell division, the centriole divides into two and the two centrioles appear at two different poles of the nucleus. Further, these two centrioles are connected by spindles.
  • 26.  The spindles subsequently contract and the two halves of the nucleus now separate from each other and the mitosis is completed. Cell division is not possible without centrioles  Nerve cell bodies do not have centriole and are not capable of cell division..
  • 27. NUCLEUS:  The nucleus contains large quantities of DNA, which are the genes. the genes determine the characteristics of cell’s proteins, including the structural protein as well as the intracellular enzymes that determine the cytoplasmic and nuclear activities.  The genes also control the rate of reproduction of the cell. The membrane covering the nucleus is Nuclear membrane also known as nuclear envelop.  Nucleoli and formation of ribosomes:- the nuclei of most cells contain one or more highly staining structures called the nucleoli. It is simply an accumulation of large amount of RNA and protein of the type found in the ribosome.
  • 28.  When cells come into contact with one another, and sometimes with the extracellular matrix, specialized junctions may form at specific sites on the contacting cell membranes. These specialized junctions may be classified as: 1. Occluding (tight) junctions (zonula occludens) 2. Adhesive junctions a. Cell-to-cell i. Zonula adherens ii. Macula adherens (desmosorne) b. Cell-to-matrix i. Focal adhesions ii. Hemidesmosomes 3. Communicating (gap) junctions Intercellular junctions:-
  • 29.  The term zonula describes a junction that encircles the cell; macula indicates a junction that is more circumscribed in extent (e.g., spot like).  Junctions may occur in certain combinations.  On the molecular level, intercellular junctions typically consist of three components: A transmembrane adhesive protein, A cytoplasmic adapter protein, and A cytoskeletal filament.
  • 30.  These three components differ depending on the type of junction.  In occluding, or tight junctions the opposing cell membranes are held in close contact by the presence of transmembrane adhesive proteins arranged in anastomosing strands that encircle the cell.  The intercellular space essentially is obliterated at the tight junction. The transmembrane adhesive proteins, which include occludin, members of the claudin family, and in some tissues, junctional adhesion molecule (JAM), interact homotypically with the same proteins on
  • 32.  Hold cells together or anchor cells to the extracellular matrix. In contrast to tight junction the intercellular space in cell-cell adhesive junction is maintained at approximately 20 nm.  Adhesive junctions are also important in cellular signaling. Their cytoplasmic components may interact with the cytoskeleton triggering changes in cell shape or motility, or with certain tumor suppressor molecules or they may act as nuclear transcription factors or co-activators.  In some instances, the loss of cell-cell or cell-matrix contact may lead to apoptosis (programmed cell death), whereas in others, loss of contact may lead to loss of cell polarity and differentiation or unregulated cell proliferation. Adhesive junctions
  • 34.  In the Desmosome the cadherins are desmoglein and desmocollin. The interaction of these transmembrane proteins with those from the adjacent cell results in a dense line in the middle of the intercellular space at the desmosome.  The catenins are desmoplakin and plakoglobin, which form an electron- dense plaque on the cytoplasmic side of the desmosome. This plaque serves as an attachment site for the cytoskeletal components, which in the case of the desmosome are intermediate filaments.
  • 36.  Have a structural organization similar to that of cell-cell adhesive junctions, but they use different molecular components and attach the cell to the extracellular matrix.  In focal adhesions the transmembrane component is a member of the integrin family of adhesion molecules.  Integrins are heterodimers of different alpha and beta subunits with specificity for various extracellular matrix molecules.  Eighteen known alpha subunits and 8 beta subunits occur in 24 different combinations. CELL MATRIX JUNCTIONS:-
  • 37.  The cytoplasmic adapter proteins, which include the actin- binding proteins alpha-actinin, vinculin, and talin, link the transmembrane integrins to the actin cytoskeleton.  Binding of the integrin to collagen, laminin, fibronectin, and other extracellular matrix proteins results in recruitment and remodeling of the actin cytoskeleton.  The transmembrane adhesive molecules present in hemidesmosome are the integrin alpha 6, beta 4, which binds specifically to the basal lamina glycoprotein laminin, and collagen XVII (also identified as BPI8O).  Hemidesmosomes link the cell to the basal lamina, and through additional extracellular molecules, to the rest of the extracellular matrix.
  • 38.
  • 39.  Are plaque like regions of the cell membrane where the intercellular space narrows to 2 to 3 nm and transmembrane proteins of the connexin family form aqueous channels between the cytoplasm of adjacent cells.  Six connexin molecules form a connexon, which has a central channel approximately 2nm diameter.  The connexons in one cell pair with connexons in the adjacent cell to create a patent channel. Small molecules such as ions and signaling molecules can move readily from one cell to another.  The connexin family includes more than a dozen different proteins that have specific tissue and cellular distributions and confer differing permeability properties to the gap junctions. GAP JUNCTIONS:-
  • 41.
  • 42. INGESTION BY THE CELL  Endocytosis:-  Very large particles enter the cell by specialised function of the cell called the endocytosis. The principle form of endocytosis are pinocytosis and phagocytosis
  • 43. Pinocytosis:-  It is a means of ingesting small particles that form vesicles of extracellular fluid and particulate constituents in the cell cytoplasm.  Pinocytosis is the only means by which most large macromolecules, such as most proteins molecules.  These molecules attach to specific receptor on the surface of the membrane that are specific type of protein that is to be absorbed.  These receptors are usually located on the small pits on the outer surface of the cell membrane called as the coated pits. On the inside of the cell membrane beneath these pits is a lattice work of fibrillar proteins called clathrin.
  • 44.
  • 45. Phagocytosis:-  It is the means of ingestion of large particles such as bacteria, whole cells, or portions of degenerating tissue.  Phagocytosis occurs in the same as pinocytosis, except that it involves large particles rather than molecules.  Phagocytosis occurs in the following steps:-  The cell membrane receptor attaches to the surface ligand of the particles.  The edges of the membrane around the points of attachment evaginate outward within a fraction of second to surround the entire particle;
  • 46.  then progressively more and more membrane receptors attach to the particle ligands. All this suddenly occurs in a zipper like fashion to form a phagocytic vesicle.  Actin and other contractile fibrils in the cytoplasm surround the phagocytic vesicle and contract around the outer edge, pushing the vesicle in the interior.  The contractile proteins then pinch the stem of the vesicle so the vesicle is completely separated from the cell membrane, leaving the vesicle in the cell interior in the same way the pinocyte vesicle is formed.
  • 47. DIGESTION OF PINOCYTOTIC AND PHAGOCYTIC FOREIGN SUBSTANCE:  Almost immediately after a pinocytotic or phagocytic vesicle appears inside a cell, one or more lysosomes become attached to the vesicles and empty their acid hydrolases to the inside the vesicle.  Thus a digestive vesicle is formed inside the cell cytoplasm in which the vesicular hydrolases begin hydrolyzing the proteins, carbohydrate, lipids, and other substances in the vesicle
  • 48.  The product of the digestion are small molecules of amino acids, glucose and phosphates that diffuse through the vesicle into the cytoplasm.  The left off products that are indigestible are still in the vesicle and the vesicle called as the residual body.  The residual body products are excreted by the cell by the process called exocytosis which is the opposite of endocytosis. Hence pinoctotic and phagocytic vesicles are the digestive organs of the cell.
  • 49.
  • 50. REGRESSION OF TISSUE AND AUTOLYSIS OF CELL  Lysosomes also help in removal of damaged cells and portion of tissues, the cell can get damaged by heat, cold, trauma, chemicals and other factors. The lysosomes burst in these cases and releases hydrolases which in turn digest the surrounding organic substances.  In case of slight injury only that portion of the cell is removed in case of severe damage entire cell is digested this is called as autolysis
  • 51.  The lysosomes contain bactericidal agents that kills the phagocytised bacteria like:-  Lysozyme which dissolve the bacterial cell membrane.  Lysoferrin which binds to the iron and other substances before they can promote bacterial growth.  Acid at the pH 5.0 which activates the hydrolases and inactivates bacterial metabolic systems.
  • 52. FUNCTION OF THE MITOCHONDRIA:-  The principal substances from which the cell extracts energy are foodstuff that reacts with oxygen--- carbohydrates, proteins and fat. Essentially all carbohydrates are converted to glucose, the proteins are converted into amino acids, fats into fatty acids.  All the converted substances are transferred to the mitochondria which converts then into high energy molecules known as ATP. Them ATP is to energize all the metabolic activity of the cell.
  • 53.
  • 54.  When ATP releases it energy, phosphoric acid radical splits away, and adenine diphosphate is formed.  This released energy is used for various cellular functions such as synthesis of substances and muscle contraction.  ADP is reacted with phosphoric acid to form ATP again. Hence ATP is called the energy currency of a cell because its spent and remade continuously.
  • 55. CHEMICAL PROCESS IN THE FORMATION OF ATP- Role of Mitochondria  On entry into cell, glucose is subjected to enzymes in the cytoplasm that convert it into pyruvic acid(a process called glycolysis). A small amount amount of ADP is changed into ATP by the energy released during this conversion, but this amounts to only 5 % of the total ATP production.  The rest 95% is produced in the mitochondria. The pryruvic acid derived from carbohydrates, fatty acid, from lipids, and amino acids from proteins are eventually converted into a compound called the acetyl-CoA in the matrix of mitochondria.
  • 56.  Acetyl CoA reacts with other series of enzymes in the mitochondria matrix undergoes a series of chemical reaction known as the citric acid cycle or the KREBS cycle.  The citric acid cycle releases carbon dioxide and hydrogen atoms. The carbon dioxide diffuses out of the mitochondria and is excreted by the cell and eventually from the body by the lungs.  The reaction is catalysed using the enzyme ATP synthetase, that protrude from the shelves of the mitochondria where the reaction between hydrogen and oxygen takes place.
  • 57.
  • 58.  Uses of ATP for cellular function :-  Transport of substances through multiple membranes in the cell.  Synthesis of chemical compounds throughout the cell.  Mechanical work.
  • 59.
  • 60.  Inflammation is an observable alteration in the tissue associated with changes in the vascular permeability and dilation, often with infiltration of leukocyte into the affected tissues. Inflammation is divided into three stages:- immediate, acute and chronic. All these stages are controlled by leucocytes. immunity Innate acquired
  • 61.
  • 62. MAST CELLS  They posses receptor for the complement system as well as the Fc portion of antibody molecules immunoglobulin E (IgE) and immunoglobulin G(IgG) FcϵR and FcɣR. More recently the mast cells are shown to express toll like receptors.  These receptor allow the innate immune system to adapt class II molecules (MHC). The stimulation of these receptor can lead to activation and secretion of vasoactive substances that increase vascular permeability and dilation, two important features of anaphylaxis.
  • 63.  Mast cells prominent features include the presence of large no. of lysosomes., which store inflammatory mediators like histamine, eosinophil chemotactic factor, neutrophil chemotactic factor, and heparin.  Mast cells are synthesized de novo other inflammatory mediators are slow reacting substances anaphylaxis(SRS-A), tumor necrosis factor(TNF–α), interleukin-6(IL-6), and leukotrine C4.
  • 64. DERMAL DENTROCYTES  or histiocytes are widely distributed and form a large system of collagen associated with dendritic cells of myeloid origin.  These are distributed near the blood vessels and posses receptor for the complement system, by which it participate in immediate inflammation.  It has been shown that histiocytes express matrix metalloprotineses (MMPs) in reponse to bacterial challenge and thus potentially contribute directly to periodontal tissue destruction.
  • 65. PERIPHERAL DENDRITIC CELLS  (DCs) are leucocyte with cytoplasmic projections or dendrites. Langerhan cells are DCs that reside in the suprabasilar portions of squamous epithelium.  DC ingest antigen and transport the antigen to lymph node through afferent lymphatics. DCs express high level of MHC class II and CD1, as well as cell adhesion molecules (intercellular adhesion molecule -1[Icam-1]) and co stimulatory factors.
  • 66. NEUTROPHILS AND MONOCYTES/ MACROPHAGES  They are closely related phagocytic leucocyte. The fundamental difference between the two is that neutrophils differentiate completely within the bone marrow whereas monocytes exit the bone marrow within 2 days in a relatively immature state and may differentiate in the tissue.  Because neutrophil do not to differentiate substantially to function, they are suited for rapid response. Neutrophils posses receptor for metabolites of the complement molecule C3, designated completent receptors 1,3,4 and C5 . they also posses receptor for IgG antibody(FcɣR).
  • 67.  By convention, monocytes are reffered to as macrophages when they leave blood. Because macrophages, differentiate and live in the local tissues, they are suited for communicating with lymphocytes and other surrounding cells.  Together lymphocytes and macrophages orchestrate the chronic immune response. Monocytes posses CR1, CR4, CR3, and C5aR, several classes of Fcɣ receptors and molecules important for antigen presentation.
  • 68. LYMPHOCYTES  The three main type of lymphocytes are divided on the basis of their receptors for antigen : T cell, B cells and natural killer (NK).  T cells: - they recognize antigen using a low affinity transmembranous complex T cell antigen receptor (TCR). T cells are divided further on the basis of co receptors present into CD8 and CD4.  B cells:- they help control extracellular antigen such as bacteria, fungal yeast and virions. B cells recognize diverse antigen using a high affinity antigen receptor called as B cell antigen receptor(BCR).
  • 69.  Before antigen presentation, B cell express immunoglobulin M(IgM) as a part of BCR. After exposure the B cells differentiate to form plasma cells dedicated to the production and secretion of IgM isotype.  NATURAL KILLER(NK):- these cells identify and kill certain tumor and virally infected cells. The natural killer posses several classes of antigen receptors, including killer inhibitory response (KIR) and killer activating receptor (KAR).  Normal cells posses MHC class I molecules that present antigen recognised as ‘self’ these interact with KIR’s and protect the cell for NK cell mediated killing.  KAR activation can override the KIR inhibition and
  • 70. TRANSENDOTHELEAL MIGRATION  It is referred to the movement of leukocytes from the blood to the local tissue in the central region of inflammation. Defects in transendothelial migration are seen in aggressive periodontits, reflecting the importance of this process in periodontal disease.  Neutrophils and monocytes spend less than 12 hrs in the circulation. B cells and T cells stay in the blood for about 30 min. They constantly exit the blood vessel pass through the lymphatics and secondary lymphoid organs, and re enter the blood circulation in a perpetual process known as lymphocyte recirculation.
  • 71.
  • 72. LEUKOCYTE FUNCTIONS  CHEMOTAXIS:- once the leukocyte enters the connective tissue , it must be able to locate and migrate to the site of insult. This is a accomplished by chemotaxis, which depends on the leukocyte ability to sense a chemical gradient across its cell body and migrate to the direction of increasing concentration.  The receptor for chemotaxis belong to the family of G-protein coupled family. The only class of chemotaxin derived directly from bacteria are formyl-methionyl peptide. To migrate toward a target, leucocytes assume a asymmetric polarized shape rather than rounded morphology evident in
  • 73. PHAGOCYTOSIS  Neutrophils and monocytes/macrophages are the only cells efficient enough at phagocytosis to be considered “professional phagocytes”.  The immune system has evolved mechanism of coating the pathogen with a few recognizable ligands, which enable the phagocyte to bind and ingest the pathogen. This is referred to as opsonisation. Phagocyte kill bacteria by two broad categories of killing mechanisms oxidative and non- oxidative.
  • 74.
  • 75.  Non oxidative killing requires phagosome- lysosome fusion. The process involves the movement toward and consequent membrane fusion of the lysosome with the phagosome called the phagolysosome. This is result of secretion of lysosomal components into the phagolysosome.  Each neutrophil posses three main type of lysosome: GRANULE CLASS GRANULE COMPONENTS Primary/ azurophilic Cathepsin G, BPI, lysozyme, elastase, MPO, α-defensins Secondary/specific Flavocytochrome b558 , LL- 37,lysozyme, lactoferrin, CD11 Tertiary/ gelatinase Flavocytochrome b558 , lysozyme, gelatinase
  • 76.  Less than 30 seconds after phagocytosis, neutrophils secrete specific granules contain several microbiocidal components, including lysozyme and lactoferrin.  Lysozyme is an enzyme which possesses enzyme dependent bactericidal activity and fungicidal activity. Lactoferrin is a bacteriostatic component.  Neutrophils secrete azurophilic granules into the phagolysosome minutes after secretion of specific granules. Among the microcidal components are small antimicrobial peptides known as the α-defensin, serposidins,
  • 77.  These are non oxidative mechanism of neutrophil killing may be of particular importance in periodontal disease because of highly anaerobic conditions in the subgingival environment.  In the presence of oxygen, phagocyte additionally posses mechanism of oxidative killing. In particular neutrophils exert intense microbiocidal activity by performing toxic, reduced oxygen metabolites such as superoxide anion (O2 - ) using NADPH oxidase system
  • 78.  The super oxide contributes in the formation of hydrogen peroxide, which is capable of diffusing across the membrane. Inside the cell the hydrogen peroxide further reduced into hydroxyl radicals, which can cause DNA damage. More importanatly H2O2 is a substrate for myeloperoxidase (MPO).In the presence of H2O2 and chloride, MPO catalyzes the formation of hypochlorous acid (HOCl).  In summary, phagocytosis is of primary importance in the ability of the host to resist and combat infection. Because of highly anaerobic environment in the periodontium, non oxidative mechanism of killing are more prevalent.
  • 79.
  • 80. ANTIGEN PROCESSING AND PRESENTATION  the major histocompatibilty complex(MHC) is a locus on the short arm of the chromosome 6 that encodes a no. of molecules, which are involved in antigen uptake, processing and presentation.  MHC I :- present the intracellular antigen to the CD8+ T cells and NK cells.  MHC II :-presents extracellular antigens presented by APC.  MHC III :- include complement factors.  Externally derived antigens are processed by phagocytosis, and the resulting pepdtide molecules are associated with the MHC class II molecules.  Molecules of the MHC classes I, II, III are among the most pleomorphic molecules in humans.
  • 81.  Enabling the APC to present antigen to the T cell with the second stimulation called as co-stimulation. Co-stimulation reaffirms the T cell that it has recognised an undesirable antigen.  Co-stimulation performs three functions:-  Makes T cell resistant to apoptosis.  Upregulates the growth factor receptors on the T cell, there by stimulating proliferation.  Decrease the amount of time required to trigger T cell.(referred to as amplification)
  • 82.  A receptor molecule named “toll” first identified in fruit flies was shown to be in response to certain injury and infection.  The human toll like receptor(TLRs) are stimulated by highly conserved bacterial components such as lipopolysaccharides(LPS) and are important in dictating the adaptations found in the innate immune system
  • 83. SPECIFIC IMMUNE RESPONSE  Chronic inflammation, if protracted can result in an adaptation called the specific immune response.  Four phases are involved in the generation of specific immunity:-  Clonal selection: the selection of lymphocytes that bear receptors recognizing the specific antigen.  Clonal expansion: the proliferation those lymphocytes. (In the expansion phase it leads to the increase in 100-5000 folds increase in these cells. )  Clonal contraction: the death of effector lymphocytes  Memory: the maintenance of the expanded clone of cells that bear the specific receptor recognising the antigen.
  • 84.
  • 85.  The increase in the antibody titer or antigen-specific T cells resulting in exposure of a host to an antigen for the first time is referred to as primary respone. The secondary response occurs after subsequent exposure to the same antigen.  The primary response takes slightly more than 1 week (8-14 days) to become measurable and biologically or clinically useful. Secondary responses are measurable within 1-3 days and are so effective that the individual may not be aware of the infection.  Vaccination is the development of immunity, or resistance to infections, after secondary response that is adequate to consider the individual immune to subsequent infections.
  • 86. T CELL RESPONSES  T cells may express 3000-5000 TCRs on the surface. Antigen presented to the TCR by MHC class I or class II molecules on the APC.  The TCR peptide binding is more specific than that of MHC peptide complex, which is based on recognition of a smaller no. of discontinuous amino acids.  Thus the T cell may recognise fewer antigen than those presented by the MHC.
  • 87.  The low affinity of the TCR enables the T cells to bind to the APCs reversibly, which occurs with multiple TCRs and one or more antigen at the over time.  This time dependent interaction of many TCRs with a few antigen is referred as scanning.  Scanning leads to T cell activation known as serial triggering.  To fully activate a T cell, multiple TCR engagement must be sustained for 2-20 hrs.
  • 88. B CELL RESPONSE AND ANTIBODIES  B cell produces immunoglobulin. The immunoglobulin that binds to the antigen is called as antibody. Humans posses 9 genetically distinct immunoglobulin IgM, IgD, IgG1, IgG2, IgG3, IgG4, IgA1, IgA2 and IgE. When B cell exit the bone marrow it posses only receptor fro IgM.  The ability of B cell to respond to antigen depends on the BCR. The BCR is formed partly by immunoglobulin molecules on the B cell surface.
  • 89.  B cells are capable of responding to certain antigen in the absence of T cells this feature is called as T cell independent B cell antibody response.  But, for a B cell to enter the memory pathway it has to interact with the T cell thus the memory pathway is considered to be T cell dependent.
  • 90. REFERENCES:-  Chapter 2, Eleventh Edition, Textbook of Clinical Physiology, Guyton and Hall.  Chapter 12, Tenth Edition, Textbook of Clinical Periodontology, Carranza, Takei, Newmann, Klokkevold.  Orban’s Oral Histology