Immunity Final

7/30/2019 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

Immunity Final

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