Third Lecture Immuno 2013 2003

7/28/2019 Third Lecture Immuno 2013 2003

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T-cell Receptor

• Can only recognize a foreign antigen if it is

presented as a complex with an MHC molecule.

• This is a different kind of antigen recognition from

that involving the B-cell antigen receptor, whichbinds directly to the antigen.



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B-cell and T-cell Antigen Receptors Differ in : • B-cell antigen receptors can interact directly with

antigen

• T-cell antigen receptors only recognize antigen when

it is presented to them on the surface of another cell

by MHC molecules

T-cell Receptor

• Contacts residues on the foreign peptide and the

MHC molecule.

• This is a different kind of antigen recognition from

the the B-cell antigen receptor

• The dual recognition requirement distinguishes T-

cell receptor molecules from B-cell receptor molecules.



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Diversity Mechanisms of (MHC) Compared withImmunoglobulin (Ig) and T-cell receptors (TCR)

Unlike B-cell or T-cell receptors, which differ in every lymphocyte in anindividual

All of the MHC alleles are the same in an individual, but they

are different between individuals

Two Separate Properties of the MHC Make it Difficultfor Pathogens to Evade (avoid) Immune Responses:

• First, the MHC is polygenic: it contains several

different MHC class I and MHC class II genes,

• So that every individual possesses a set of MHC

molecules with different ranges of peptide-binding

specificities.

• Second, the MHC is highly polymorphic; that is,

there are multiple variants of each gene within the

population as a whole.

• The MHC genes are, in fact, the most polymorphic

genes known.





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GENETIC POLYMORPHISM

• Polymorphism is the occurrence in a populationof two or more genetically determined forms

(alleles, sequence variants)

• A difference in DNA sequence among

individuals, groups, or populations that gives

rise to different forms

The genes of the MHC are the most variable.

Major Histocompatibility Complex (MHC) –

Encoded Molecules Govern Immune Responses :

• By presenting antigenic peptides to T cells.

• The extensive polymorphism of genes encoding

these molecules

• Is believed to enhance immune defense byexpanding the array of antigenic peptides available

for T cell recognition



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Antigens and Antibody Structure

Objectives:

• 1. Compare antigenicity and immunogenicity

• 2. Define antigen, antibody, antigenic determinant, epitope, and

hapten

• 3. Basic structure of the immunoglobulin molecule,

indicating the location of the major structural

• 4. Fragments of immunoglobulin may be produced by

proteolytic digestion

• 5. The structural features and biologic properties of the differentantibodies (immunoglobulin)

• 6. Define monoclonality and polyclonality with respect to antibodies

• 7. Exploring the nature of antibody-antigen interaction

Antigens and Antibodies



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The Antigens That Enter Our Body are of

Diverse Structure

• The higher their molecular weight, the higher the chancethat they can induce an immune response.

• When an antigen enters the body,

• It stimulates the immune system( body's natural defensesystem) to produce antibodies.

• The antibodies attach, or bind, themselves to the antigenand inactivate it.

Antibodies (Abs)

Also called immunoglobulins

Are proteins manufactured by the body that help

fight against foreign substances called antigens.

A specific protein which is produced in response to an

immunogen and reacts with an antigen.



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• Are the antigen-specific proteins produced by B cells in

response to contact with antigen.

• Circulate in the blood and lymph as plasma components.

• Each individual has the capacity to synthesize a high number

of different antibody molecules.

• Each antibody is capable of specifically interacting with an

antigen

Antibodies

5 Classes of AntibodiesHuman Immunoglobulin Classes

• Each one of those has a different biological

outcome

• Its structure determines its function



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5 Classes of Antibodies- Human Immunoglobulin Classes

5 Classes of Antibodies-Human Immunoglobulin Classes



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Antibodies

5 Classes of Human Antibodies • Immunoglobulin G (IgG),

• Immunoglobulin M (IgM),

• Immunoglobulin A (IgA),

• Immunoglobulin D (IgD),

• Immunoglobulin E (IgE).



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Immunity Results From:• The production of antibodies specific to a given antigen

(antibody-generators, located on the surface of an invader).

• Antibodies bind to the antigens on invaders and kill or

inactivate them in several ways.

• Antigens can be any molecule that causes antibody production.

Antibody Secretion • Antibodies are immunoglobulins that react

specifically with the antigens that stimulated their production

• B Cell Differentiation into Plasma Cell

• It gives rise to many large plasma cells

• Every plasma cell is essentially a factory for producing antibody.



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Lymphocytes produce antibodies as a

result of antigens

• Each antigen will only stimulate the production of one specific antibody that will fit into its receptor

area (natural active induced immunity).

•

• It is protection gained against a particular pathogen

by the production of specific antibodies after the

antigen on the pathogen has been detected.

Antibodies act in many ways: • a. Some bind to the antigens on the

surface on the pathogens. This prevents

the pathogen from entering the host cell.

• b. Some cause the pathogens to clump

together. Phagocytes then engulf the

clumped pathogens.

• c. Some activate the complement system

which then acts to burst the pathogen.



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Antibodies function in many ways:

Antigen • Foreign substance that, when introduced into the body, is

capable of stimulating an immune response

• Specifically activating lymphocytes, which are the body’s

infection-fighting white blood cells.

• Any large foreign molecule can act as an antigen, including

those contained in:

• Bacteria, viruses, protozoa, helminths, foods, snake venoms,egg white, serum components, red blood cells, and other cells

and tissues of various species, including humans.



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Antigens

Compounds capable of being bound by:

• Immunologic receptors (B-cell receptors [BCR]

• T-cell receptors [TCR]

• Major histocompatibility complex [MHC])

• They do not necessarily elicit an immune response

by themselves.

Antigens and Immunogens

Antigens:

Foreign (non-self) molecules which by themselves may or may notcause an immune response.

Molecule bind to components of the immune response

Bind with varying degrees of specificity to immune receptors

(antibodies on B cells; T cell receptor on T cells)

Any agent (molecule) that binds to components of the immuneresponse (lymphocytes and their receptors) antibodies and the TCR

Any substance that binds specifically to an antibody or a T-cellreceptor



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Antigens and Immunogens

Immunogens:

Stimulus that produces a humoral or cell-mediated immuneresponse

Always cause an immune response by itself (e.g., production of

an antibody )- the inducer of specific antibody formation.

Agent capable of inducing an immune response

An antigen that induces an immune response—i.e., stimulates the

lymphocytes to produce antibody or to attack the antigen directly

Capable of binding immune receptors and inducing an immune

response by B cells or T cells

Immunogens - Antigens

All substances which are immunogenic are also

antigenic; not the reverse

All Immunogens are Antigens But All Antigens Are Not

Immunogens

Although all molecules that have the property of

immunogenicity also have the property of antigenicity,

the reverse is not true



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Antigenicity

Ability to combine specifically with Ab and/or cell-surface Ig/TCR

Ability to combine specifically with the final products of the above responses(i.e.,antibodies and/or cell-surface receptors).

Binding specifically with the final product of Ab or T cell without causing immuneresponse- Ability to combine specifically w/ products of immune responses

Ability to combine with the final products of the response (antibodies and/or T cellreceptor

Immunogenicity:

The ability to induce a humoral and/or cell-mediated immuneresponse

Binding leads to an immune response

Ability to induce an antibody and/or cell-mediated immuneresponse

The ability of a particular substance, such as an antigen or epitope,to provoke an immune response in the body of a human or animal.

The ability to induce an immune response.

Provoking an immune response or the degree to which it provokesa response



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Antigenicity.

Immunogenicity

The Property of Antigenicity is Different FromImmunogenicity Ability of an antigen to induce immune response is knownas antigenicity.

Ability of immunogens to induce immune response isknown as immunogenicity.

Antigenicity refers to recognition by the effector components of an immune response

Immunogenicity is the ability to elicit such a response.

Contribution of the immunogen to immunogenicity:

Factors That Influence Immunogenicity

• The Nature of Immunogens is determined by 4

properties:

- Degree of Foreignness

- Molecular size

- Chemical structure + heterogeneity

- Ability to be processed and presented by anAPC (Susceptibility to antigen processing

and presentation)



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Effective Immunogens

- Foreign to the host

- Fairly large (molecular weight greater than ≈ 6000)

- Chemically complex

• Factors influencing immunogenicity

• Foreigness

• Molecular Size

•Chemical composition and complexity

HaptensSmall molecules have the property of antigenicity but areincapable, by themselves, of inducing a specific immuneresponse. they lack immunogenicity

Become immunogenic only upon chemical conjugation to larger proteins, which function as carriers.

Can elicit an immune response only when attached to alarge carrier such as a protein

Poorly reactive antigens and more antigenic whenconjugated to carrier proteins

React with the products of a specific immune response.



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Haptens

• Small molecules which could never induce an immune

response when administered by themselves

• Have the property of antigenicity but not immunogenicity

• When coupled to a carrier molecule.

• Turn to be immunogenic.

Haptens

Low molecular weight- Non-immunogenic alone- Coupling tocarrier proteins makes it immunogenic

Incomplete antigens or partial antigens because they are unable toelicit immune response by itself

But they can gain this ability when bind with carrier molecule

– Haptens are antigenic: they can react with immune

lymphocytes or antibodies.

– Haptens are not immunogenic: they can not by themselvescause the production of immune lymphocytes or antibodies.

.

Generally, only large molecules, infectious agents, or insolubleforeign matter can elicit an immune response in the body



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For example, a relatively simple chemical compound,

such as penicillin, cannot by itself induce an antibodyresponse.

These simple molecules are known as haptens.

If the hapten is coupled to a macromolecule (e.g., a

protein)

Antibodies can be generated that bind very

specifically to the hapten

Hapten-Carrier Conjugate

Hapten-Carrier Conjugate



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Haptens are partial antigens (Incomplete)

– Haptens are usually molecules which are too small to beimmunogenic.

– Examples of haptens are antibiotics, analgesics (painkillers), and other low-molecular weight compounds

• Penicillin, for example, a clinically important hapten,

– If a hapten of coupled to a larger carrier molecule,however, it becomes immunogenic.

- The carrier molecules may be albumins, globulins, or

synthetic polypeptides.

Epitopes

• Are the sites either on or within the antigen with whichantibodies react.

• Epitopes are very small

• Epitopes and haptens are similar

• An epitope, also known as antigenic determinant

• The part of an antigen that is recognized by theimmune system, specifically by antibodies, B cells, or T cells.



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Epitope (Antigenic Determinant)

• The part of an antigen that is recognized by the

immune system, specifically by antibodies, B cells,

or T cells

• The surface portion of an antigen capable of eliciting

an immune response and of combining with the

antibody produced to counter that response

• That portion of an antigen that combines with the

products of a specific immune response

Epitope (Antigenic Determinant)



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Physical Properties of Epitopes

The epitopes on an antigen can be:

Linear (i.e., continuous within the amino acid sequence of molecule)

A linear epitope is formed by a continuous sequence of amino acids from the antigen

• Or

Conformational (i.e., containing amino acids that end up inthe same area on the surface of the protein but are notadjacent in the peptide chain)

Conformationa is composed of discontinuous sections of the antigen's amino acid sequence

Epitopes (the Binding Sites on the Protein) can be Dividedinto Linear and Conformational Discontinuous

• Linear epitopes are formed by a continuous

sequence of amino acids in a protein,

• Continuous or linear epitopes, which are contiguous

areas of sequence (e.g., amino acids 12-22 in apolypeptide chain)



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Discontinuous or Conformational Epitopes Resulting from bringing together amino acid residues from non-

continuous areas of the polypeptide chain into a three-dimensional (3D) shape

Composed of amino acids that are discontinuous in the protein

sequence but are brought together upon three-dimensional

protein folding.

Sequence of subunits (usually, amino acids) composing an

antigen that come in direct contact with a receptor of the

immune system

In general: Most epitopes are conformational

Epitopes and Antibody Specificity

Epitopes determine the specificity of the antigen

molecule and are what induce the antibody response.

Antibodies are specific for epitopes.

Antibodies can recognize both types of epitope



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Linear and Conformational Discontinuous Epitopes

Linear (epitopes 1 and 2)

Conformational (epitopes 3-5)

Linear and Discontinuous Epitopes



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Epitope and Paratope• The part of an antibody that recognizes the epitope is called

a paratope.

• Epitopes interact with the paratope based on the 3-Dsurface features and shape or tertiary structure of theantigen

• Linear epitopes interact with the paratope based on their primary structure.

• The epitopes of protein antigens are divided into twocategories, conformational epitopes and linear epitopes

• Based on their structure and interaction with the paratope.

IgG, IgA, IgM, IgD, IgE - Antibodies (immunoglobulins) are gamma globulin proteins

- They make up approximately 20% of the plasma proteins and

were initially detected by analytic techniques (electrophoresis),

- In the "gamma globulin" fraction of serum



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Gamma Globulin Fraction Where it Contains

Most of the Immunoglobulins

• The serum protein components into five

classifications by size and electrical charge:

• Serum albumin, alpha-1 globulins, alpha-2 globulins,

beta globulins, and gamma globulins

• Gamma portion of electrophoresis where the

immunoglobulins present

The gamma globulin fraction band of serum usually containsat least 3 of the 5 Immunoglobulin proteins which migrate

together

Gamma-A globulin: IMMUNOGLOBULIN A.

Gamma-D globulin: IMMUNOGLOBULIN D.

Gamma-E globulin: IMMUNOGLOBULIN E.

Gamma-G globulin: IMMUNOGLOBULIN G.Gamma-M globulin: IMMUNOGLOBULIN M.



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Electrophoresis pattern of human serumproteins

• Serum proteins can be resolved into 5 or 6 bands by

electrophoresis• More than half of total human serum protein content

can be accounted for by the immunoglobulin

(gamma globulin) fraction

Electrophoresis of Total Human Serum



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Serum • Is the liquid phase that is separated from clotted blood.

• It differs from plasma (the liquid phase that may beseparated when blood is drawn and prevented fromclotting) in that it is lacking the protein fibrinogen

• Serum is (Blood plasma with the fibrinogens removed).

• (The fluid portion of the blood after the blood has clotted)

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Third Lecture Immuno 2013 2003

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