Immunity Final
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Transcript of Immunity Final
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NATIONAL DENTAL COLLEGEAND HOSPITAL
DERA BASSI
DEPARTMENT OF PEDODONTICS
AND PREVENTIVE DENTISTRY
SEMINAR ON IMMUNITY
SUBMITTED BY:
PARVEEN BATHLA
MDS 2
st
PROF.
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CONTENTS
IMMUNITY DEFINITION AND CLASSIFICATION
INNATE IMMUNITY
ADAPTIVE IMMUNITY
Active immunity
Passive immunity
ANTIGEN
ANTIBODY/IMMUNOGLOBLIN
ARCHITECTURE OF IMMUNE SYSTEM
CELLS OF IMMUNE SYSTEM
CYTOKINES
MAJOR HISTOCOMPATIBILITY COMPLEX
IMMUNE RESPONSE
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Immunity
Resistance of host to pathogens and their toxic products.
The immune system produces antibodies or cells that can deactivate pathogens.
Immunity classified as
1) Innate immunity
2) Acquired immunity
Innate immunity
a) non specific speciesb) specific racial
individual
Innate immunity may be specific against a particular organism or non specific.
Species immunity : Total or relative immunity shown by all members by all members of a
species.
Racial immunity : Within a species, there may be marked racial differences in resistance toinfection.
Individual immunity : Different individuals in a race differ in their resistance to microbial
infections.
Factors influencing innate immunity :
1) Age : very young and very old are more suspectible to infectious diseases than persons inother old age group.
2) Hormonal influences : endocrine disorders diabetes mellitus , hypothyroidism andadrenal dysfunction more suspectible.
3) Nutritional factors: both antibody mediated and cell mediated immunity lowered inmalnutrition.
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Mechanism of innate immunity :
Mechanical barriers and surface secretions
Skin
physical barrier to microbes.
Keratin resistant to most bacterial enzymes & toxins.
Mucosa
physical barrier & produces a variety of protective chemicals.
Gastric mucosa
acidic & produces proteolytic enzymes.
Saliva contain Antimicrobial enzymes that kill bacteria.
Lysozyme
Salivary lactoperoxidase
Lactoferrin
Immunoglobulin A
Antibacterial compounds -thiocyanate, hydrogen peroxide, and secretory immunoglobulin A
Mucous
traps bacteria & moves them away from epithelial surface.
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Humoral defence mechanism
Lysozyme
Basic polypeptide
Complement
Interferon
Complement system
1890 Jules Bordet, Paul Ehrlich
Heat-labile
Augments the opsonization and killing of bacteria by antibodies (the major effector ofthe humoral branch of the immune system).
Evolved as part of the innate immune system.
The complement system comprises a group of serum proteins,many of which exist in
inactive forms.
Complement activation occurs by the classical, alternative, or lectin pathways, each
of which is initiated differently.
The three pathways converge in a common sequence of events that leads to
generation of a molecular complexthat causes cell lysis.
The classical pathway is initiated by antibody binding to acell target; reactions of
IgM and certain IgG subclassesactivate this pathway.
Activation of the alternative and lectin pathways is antibody independent.
These pathways are initiated by reaction of complement proteins with surface
molecules of microorganisms.
In addition to its key role in cell lysis, the complement system mediates opsonizationof bacteria, activation of inflammation,and clearance of immune complexes.
Interactions of complement proteins and protein fragments with receptors on cells of
the immune system control bothinnate and acquired immune responses.
Complement activation pathways
Classical pathway: requires antibodies.
Antibodies bind to target (antigen).
Complement protein C1 binds to the antibody-antigen complex (complement fixation).
Alternative pathway: complement factors interact with microorganism glycocalyx.
Both pathways lead to a cascade of protein activation, leading to activation of C3.
C3 is the start of the; Final Common Pathway .
C3 cleaves to form C3a & C3b.
C3a (& C5a) enhance inflammation by increasing histamine release, increasing vascular
permeability & stimulating chemotaxis.
C3b coats bacterial membrane supplying adhesion points (opsonization)
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C3b initiates the cascade forming the membrane attack complex (MAC).
The MAC forms a hole in the cell membrane & enhances Ca2+
influx cell lysis .
Complement also helps rid the body of antigen-antibody complexes.
Complement proteins are the culprits that cause blood vessels to become dilated and
leaky, causing redness and swelling during an inflammatory response.
Complement proteins circulate in the blood in an inactive form. The so-called
"complement cascade" is set off when the first complement molecule, C1, encounters
antibody bound to antigen in an antigen-antibody complex. Each of the complement
proteins performs its specialized job, acting, in turn, on the molecule next in line.
The end product is a cylinder that punctures the cell membrane and, by allowing fluids
and molecules to flow in and out, dooms the target cell.
Cellular Mechanism of Defence
Phagocytes
Microphages (PMNL)
Macrophages
Natural killer cells
Eosinophil
Macrophages: derived from monocytes
Free Macrophages: roam through tissues.
Fixed Macrophages: Kupffer cells (liver) & microglia (brain) .
Ingest cellular debris, foreign material, bacteria, fungi.
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Neutrophils: ingest pathogens
Eosinophils: weakly phagocytic of pathogens. Attack parasites (degranulation).
Mast Cells: phagocytic of various bacteria.
Phagocytic mechanisms:
Adherence: cell binds to invader
Aided by opsonization (a chemical process that enhances binding via
complement & antibodies).
Ingestion: formation of phagolysosomes .
Respiratory Bursts: merge phagosome with lysosome & flood phagolysosome with free
radicals (macrophage).
Defensins: proteins that crystallize out of solution & pierce pathogen membranes(neutrophils)
Natural Killer Cells:
Small population of large granular lymphocytes.
Non specific for non-self.
Not phagocytic: attack is by release of perforins that perforate the target cell
plasma membrane.
Shortly after perforation the target nucleus disintegrates.
Release chemicals that enhance the inflammatory response.
cardinal signs of inflammation
Redness
Heat
Swelling
Pain
(functional impairment Rigor)
Inflammatory response: signs are associated with vasodilation & increased vascular
permeability.
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Dilation: redness, heat
Permeability: edema, (increased pressure) pain
Pain also associated with bacterial toxins & some mediators (kinins, PGs)
Mechanisms causing vasodilation & vascular permeability
Injured cells release inflammatory mediators
Histamines
Kinins
Prostaglandins
Complement
Cytokines (also activated by receptors on macrophages in response to
microbial glycocalyx).
Edema
Dilutes harmful substances.
Provides nutrients (& O2) for repair.
Enhances entry of clotting protein.
Epithelial breaches also stimulate b-defensin release from epithelial cells.
Adaptive: responds to specific foreign substances.
Innate & adaptive mechanisms work together.
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Active immunity
Natural - clinical infection
subclinical infection
Artificial - vaccination
live and killed vaccine
Artificial active immunity
Bacterial vaccines
Live - BCG
Killed-TAB
Bacterial products
Tetanus toxoid
Diptheria toxoid
Viral vaccines
Live-sabin,MMR
Killed -salk
Passive immunity
Natural - placenta, breast milk
Artificial - immune serum ,immune cells
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Active immunity
Produced actively by hosts
immune system.
Induced by
infection/contact with
antigen.
Long lasting.
Immunity effective only
after a lag period.
Negative phase.
Not applicable in
immunodeficient.
Passive immunity
Received passively by host.
Conferred by administration
of antibodies.
Transient.
Effective immediately.
No negative phase.
Applicable.
Local immunity
Immunity at a particular site, the site of invasion and multiplication of pathogen.
Conferred by secretory IgA ab produced locally by plasma cells.
Herd immunity
Overall level of immunity in a community.
ANTIGEN
A substance, which is recognized by immune system and induces the immune response.
It comes from environment (exoantigen), or from individuals own structures
(autoantigen).
Hapten
Incomplete Ag.
Reactive, but not immunogenic.
Provokes no response by itself .
Bind to other proteins immunogenic.
Epitope
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The portion of antigen, which is recognized by the immune system (lymphocytes, Ig).
Some epitopes are on the antigens surface, others are internal.
Epitopes may be linear (amino acid sequence important), conformational (space
conformation important) Cross-reactive antigens share one or more identical or similarepitopes .
Factors affecting antigenicity
Molecular size of antigens
Molecules < 5 kDa are not able to induce immune response, the optimal molecular size
for mmune response induction is approximately 40 kDa.
Chemical nature
Proteins and polysaccharide most antigenic.
Degree of foreignness
An antigen must be foreign or alien to the host.
Autologousare found within the same individual (e.g. a skin graft from an individuals
thigh to his chest); that is, they are not foreign.
Syngeneicare found in genetically identical individuals (e.g. identical twins); that is,
they are not foreign.
Allogeneic (alloantigens) are found in genetically dissimilar members of the same
species (e.g. a kidney transplant from mother to daughter); it is foreign.
Xenogeneic (heterogeneic)are found in different species (e.g. a transplant of monkey
kidneys to human); it is foreign.
Sequestered antigens
The antigens, which are normally hidden from the immune system and thus the immune
system cannot identify them (e.g. lens, testes).
However, if these allergens are released (injury), the immune system could response to
them.
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ANTIBODY (Ab)
Described by Von Behring 1890.
Gerald M. Edelman and Rodney Porter 1972 researchers structure and chemical
nature of antibodies.
Glycoprotein molecules produced by plasma cells and can combine with the
corresponding Ag specifically .
Ig refers to all globulins that possess the activity of Ab or show a similar structure to Ab.
Therefore, All Abs are Igs, but not all Igs possess the functions of Abs.
An Antibody / immunoglobulin , is a large Y shaped protein produced in response to
antigenic stimulation.
Each tip of the "Y" of an antibody contains a paratope (a structure analogous to a lock)
that is specific for one particular epitope (similarly analogous to a key) on an antigen.
Function of immunoglobulin :
Specifically recognize and bind to a unique structural entity on microbial toxins
(antigens).
Perform a common biological function (effector function) after combining with the
antigen e.g., binding to Fc receptors on immune cells.
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BASIC STRUCTURE OF IMMUNOGLOBULINS
All Igs have the same basic structural units of 2 light chains and 2 heavy chains.
All Igs have the same basic structural units of 2 light chains and 2 heavy chains.
The heavy and light chains are joined together by interchain disulphide bonds and non-
covalent interactions. L chain - and .
The hinge region is the area of the Ig where the arms of the Abs form a Y,it is a flexible
region.
Light and heavy chains are composed of both a variable and constant region designated
VL and CL (light chains) and VH and CH1 ,CH2 and CH3 (heavy chains).
Complementarity determining regions (CDRs).
The variable regions of an Ig are also further divided into hypervariable or
complementarity determining regions (CDRs).
Hot spots .
L chains have three CDRs and the H chains have four, although only three of the four
have been associated with antibody activity.
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IMMUNOGLOBIULINS TYPES AND CLASSES.
Based on differences in the amino acid sequences in the constant region of the heavy chains there
are five classes of Igs.
IgG- gamma heavy chain
IgM-miu heavy chain
IgA- alpha heavy chain
IgD- delta heavy chain
IgE- epsilon heavy chain.
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IgG
Most abundant 75 %
IgG1 - 59%
IgG2 - 30%
IgG3 - 8%
IgG4 - 3%
major Ig in serum as well as extravascular spaces.
Only Ig that crosses the placenta.
fixes complement .
enhances phagocytosis.
IgM
It normally exists as a pen tamer in serum but can also occur as a monomer.
It has an extra domain on the mui chain (CH4) and another protein covalently bound via
S-S . called J-chain.
This chain helps it to polymerize to the pentamer form. clumping microorganisms for
eventual elimination from the body.
first Ig to be made by fetus in most species .
the 3rd most abundant Ig in serum.
good complement fixing Ig .
IgA
Serum IgA is monomeric, but IgA found in secretions is a dimer having a J chain.
Secretory IgA also contains a protein called secretory piece or T- piece, this is made in
epithelial cells and added to the IgA as it passes into secretions helping the IgA to move
across mucosa without degradation in secretions.
the second most abundant Ig in serum.
the major class of Ig in secretions- tears, saliva, colostrums, mucus,and is important in
mucosal immunity.
normally do not fix complement.
IgD
found in low levels in serum.
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found primarily on B cells surface and serves as a receptor for Ag.
does not fix complement.
IgE
the least common serum Ig, but it binds very tightly to Fc receptors on basophils andmast cells even before interacting with Ags.
involved in allergic reactions because it binds to basophils and mast cells.
Architecture of immune system
lymphoreticular system
Primary lymphoid organs:
Thymus
Bone marrow
Secondary lymphoid
organs:
lymph nodes
Spleen
Mucosa associatedlymphoid tissues
Bone marrow
Site for haemopoiesis and initial differentiation of stem cells.
Thymus
Bilobed, located in thoracic cavity and extending into the neck.
Cortex and medulla.
Major site of lymphocyte proliferation.
DiGeorge syndrome
Genetic disorder caused by the deletion of a small section of chromosome 22.
Results in a midline congenital defect including thymic aplasia, or congenital deficiency
of a thymus.
Lymph node
Small bean shaped organs.
Act as Filters.
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Humans have approximately 500-600 lymph nodes distributed throughout the body, with
clusters found in the underarms, groin, neck, chest, and abdomen.
Outer cortex and inner medulla.
Cortex consist of lymphoid follicles and medulla consists of cords of lymphocyte.
T cell concentrate in paracortex, b cell in and around germinal centre and plasma cell in
medulla.
Immune cells and foreign particles enter the lymph nodes via incoming lymphatic vessels
or the lymph nodes' tiny blood vessels.
All lymphocytes exit lymph nodes through outgoing lymphatic vessels. Once in the
bloodstream, they are transported to tissues throughout the body. They patrol everywhere
for foreign antigens, then gradually drift back into the lymphatic system to begin the
cycle all over again.
Lymphoid follicles and medullary cords contain B Lymphocyte while paracortex contains
T lymphocytes.
Spleen
The spleen, in healthy adult humans, is approximately 11 centimetres (4.3 in) in length. It
usually weighs between 150 grams
Large, encapsulated, lymphoid organ.
White pulp of cortex and red pulp of medulla. it acts primarily as a blood filter.
It removes old red blood cells and holds a reserve of blood in case of hemorrhagic
shock and also recycles iron.
As a part of the mononuclear phagocyte system it metabolizes hemoglobin removed
from senescent erythrocytes.
The spleen synthesizes antibodies in its white pulp and removes antibody-coated bacteria
and antibody-coated blood cells by way of blood and lymph node circulation. The spleen
is a center of activity of the reticuloendothelial system and can be considered analogous
to a large lymph node, as its absence causes a predisposition to infections.
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Cells of immune system
TYPE DIAGRAM APPROX % DIAMETER(um)
NEUTROPHIL 62 10-12
EOSINOPHIL 2.3 10-12
BASOPHIL .4 12-15
LYMPHOCYTE 32 7-8
12-15
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Monocyte 5.3% 12-20
Macrophage 60-80
NK cells
Plasma cells
Dendritic
B cells can be distinguished from other lymphocytes, such as T cells and natural killer
cells(NK cells), by the presence of a protein on the B cell's outer surface known as a B cell
receptor(BCR). This specialized receptor protein allows a B cell to bind to
a specific antigen.
The principal functions of B cells are to make antibodies against antigens to perform the
role of antigen-presenting cells (APCs), and to develop into memory B cells after
activation by antigen interaction.
B lymphocyte
Humoral immunity.
B cell receptor (BCR)
present on cell surface.
T lymphocytes
Cell-mediated immunity.
T-cell receptor(TCR)
present on the cell
surface.
no antigen
presenting properties
B cells work chiefly by secreting soluble substances known as antibodies. They mill
around a lymph node, waiting for a macrophage to bring an antigen or for an invader
such as a bacteria to arrive. When an antigen-specific antibody on a B cell matches up
with an antigen, a remarkable transformation occurs.
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The antigen binds to the antibody receptor, the B cell engulfs it, and, after a special
helper T cell joins the action, the B cell becomes a large plasma cell factory that produces
identical copies of specific antibody molecules at an astonishing pace--up to 10 million
copies an hour.
Activation of B Cells to Make Antibody
The B cell uses its antibody-receptor to bind a matching antigen, which it then engulfs
and processes.
This triggers the B cell to become a large plasma cell producing millions of copies of the
same specific antibody.
These antibodies then circulate in the bloodstream in search of more matching antigens.
B cell antibodies cannot themselves kill an invading organism, but they can use their
antibodies to mark invaders for destruction by other immune cells and by complement.
Functions of B cells :
make antibodies against antigens.
perform the role of antigen-presenting cells (APCs).
develop into memory B cells after activation by antigen interaction
T cells orT lymphocytes are a type of lymphocytes that play a central role in cell-mediated
immunity.
T cells subsets
Regulator cells
Helper T cells
CD4+ T cells
Help in ag specific activation of B
cell and effector T cells.
Suppressor T cells
Suppress expression of immune
response by other lymphocytes.
Effectors cells
Delayed type hypersensitivityT cells
Delayed hypersensitivity and cellmediated immune response.
Cytotoxic T cells
CD8+ T cells
destroy virally infected cells,tumor cells, and are alsoimplicatedin transplant rejection.
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They can be distinguished from other lymphocytes, such as cells and natural killer
cells (NK cells), by the presence of a T-cell receptor(TCR) on the cell surface.
They do not have antigen-presenting properties (but rather, requiring B cells or NK cells
for its antigen-presenting property).
They are called Tcells because they mature in the thymus.
There are several subsets of T cells, each with a distinct function.
T cells contribute to your immune defenses in two major ways. Some help regulate the
complex workings of the overall immune response, while others are cytotoxic and
directly contact infected cells and destroy them.
Chief among the regulatory T cells are helper T cells. They are needed to activate many
immune cells, including B cells and other T cells.
Function of T lymphocyte
regulate the complex workings of the overall immune response .
directly contact infected cells and destroy them.
activate many immune cells, including B cells responsible for the rejection of tissue and
organ grafts.
Cytotoxic T cells (sometimes called killer T cells) help rid your body of cells that have
been infected by viruses as well as cells that have been transformed by cancer but have
not yet adapted to evade the immune detection system.
They are also responsible for the rejection of tissue and organ graft.
Activation of T Cells: Helper
Helper T cells only recognize antigen in the grasp of Class II MHC markers.
An antigen-presenting cell--such as a macrophage or a dendritic cell--breaks down the
antigen it devours, then it places small pieces (peptides) on its surface along with a Class
II MHC marker.
By exhibiting its catch in this way, antigen-presenting cells enable specific receptors on
helper T cells to bind the antigen and confirm (via CD4 protein) that an invasion has
occurred.
After binding, a resting helper T cell quickly becomes an activated helper T.
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Activation of T Cells: Cytotoxic
Killer T cells only recognize antigen in the grasp of Class I MHC markers. Here a resting
cytotoxic T cell recognizes virus fragments, which are displayed by a macrophage in
combination with a Class I MHC marker.
A receptor on a circulating, resting cytotoxic T cell (and CD8 protein) recognizes the
antigen-protein complex and binds to it.
The binding process and an activated helper T cell activate the cytotoxic T cell.
Because the surfaces of other infected cells bear the same virus fragments in
combination with Class I MHC markers, the activated cytotoxic T cells can quickly
recognize, attack, and destroy the diseased cell
Cytokines
Cytokines are diverse and potent chemical messengers secreted by the cells of immune
system. They are the chief communication signals of T cells. Cytokines include
interleukins, growth factors, and interferons.
Lymphocytes, including both T cells and B cells, secrete cytokines called lymphokines,
while the cytokines of monocytes and macrophages are dubbed monokines. Many of
these cytokines are also known as interleukins because they serve as a messenger
between white cells, or leukocytes.
Interferons are naturally occurring cytokines that may boost the immune system's ability
to recognize cancer as a foreign invader.
Binding to specific receptors on target cells, cytokines recruit many other cells and
substances to the field of action. Cytokines encourage cell growth, promote cell
activation, direct cellular traffic, and destroy target cells--including cancer cells.
When cytokines attract specific cell types to an area, they are called chemokines. These
are released at the site of injury or infection and call other immune cells to the region to
help repair damage and defend against infection.
Major histocompatibility complex
MHC -cell surface glycoproteins associated with self recognition.
In humans, MHC is also called human leukocyte antigen (HLA).
HLA-A, HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-
DRA, and HLA-DRB1.
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The importance of MHC proteins is that they allow T cells to distinguish self from non-
self.
Immune response
Primary response
First exposure to antigen
Natural or artificial
IgM
Secondary response
Subsequent exposure
Much more vigorous than primary
IgG
CONCLUSION
Our Creator has indeed provided us with a wonderful defense mechanism, preventing us from
disease. The immune system is one of nature's most fascinating inventions. With ease, it protectsus against billions of bacteria, viruses, and other parasites. Immunity is a fascinating subject that
still conceals many secrets. When the immune system is fully understood, it will most likely hold
the key to ridding humankind of many of its most feared diseases.
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REFERENCES
Textbook of microbiology 5th ed. By Anantnarayan
Textbook of microbiology by Arora
Roitts essential immunology 10TH ed.
Brender, md, erin; allison burke, ma, illustrator, richard m. (2005-11-23). "spleen patient
page"(pdf). Journal of the american medical association 294 (20): 2660.
Heyman b (1996). "complement and fc-receptors in regulation of the antibody
response".immunt54 (23): 195199
Borghesi l, milcarek c (2006). "from B cell to plasma cell: regulation of v(d)j
recombination and antibody secretion". Immunol res36 (13): 2732