Introduction to Immunology Introduction to Immunology Lecture 1Lecture 1stst

Dr. Humera Kausar(PhD Molecular Biology)

What is immunology?What is immunology? Immunology is a branch of biomedical is a branch of biomedical

science that covers the study of all aspects science that covers the study of all aspects of the immune system in all organisms. It of the immune system in all organisms. It deals with the physiological functioning of deals with the physiological functioning of the immune system in states of both health the immune system in states of both health and diseases.and diseases.

Immunity is the body's ability to fight off Immunity is the body's ability to fight off harmful micro-organisms –PATHOGENS- that harmful micro-organisms –PATHOGENS- that invade it, e.g.Fungi, protozoans, bacteria, invade it, e.g.Fungi, protozoans, bacteria, and viruses are all potential pathogens.and viruses are all potential pathogens.

Edward Jenner(1749-1823)

&The Discovery of Vaccination (1796)

“Vaccinia (cowpox)” &

“human smallpox”

Eradication of smallpox (1979, WHO)

Other historic events & important findings:Other historic events & important findings:

L. Pasteur (1880s)L. Pasteur (1880s)– Vaccines against cholera, and rabiesVaccines against cholera, and rabies

R. Kock (late 19R. Kock (late 19thth century) century)– Infections caused by microorganismsInfections caused by microorganisms

P. Ehrlich et al. (1890s)P. Ehrlich et al. (1890s)– Serum factors transfer of immunitySerum factors transfer of immunity

Behring & Kitasato (1890s)Behring & Kitasato (1890s)– Antibodies in serum bound to pathogensAntibodies in serum bound to pathogens

Porter & Edelman (1960s)Porter & Edelman (1960s)– Antibody structureAntibody structure

J. Gowans (1960s)J. Gowans (1960s)– Immunological importance of lymphocytesImmunological importance of lymphocytes

Koch’s PostulatesKoch’s Postulates1.1. Pathogen must be found in the host in Pathogen must be found in the host in

every case.every case.

2.2. Pathogen must be isolated from the host Pathogen must be isolated from the host and grown in pure culture.and grown in pure culture.

3.3. When placed in a healthy host, pathogen When placed in a healthy host, pathogen produced in pure culture must cause the produced in pure culture must cause the disease in the host.disease in the host.

4.4. Pathogen must be isolated from the new Pathogen must be isolated from the new host and shown to be the original host and shown to be the original pathogen.pathogen.

The The immune systemimmune system recognizes, attacks, destroys, recognizes, attacks, destroys, and remembers each pathogen that enters the and remembers each pathogen that enters the body.body.

The Immune SystemThe Immune System includes all parts of the body includes all parts of the body that help in the recognition and destruction of that help in the recognition and destruction of foreign materials.  White blood cells, phagocytes foreign materials.  White blood cells, phagocytes and lymphocytes, bone marrow, lymph nodes, and lymphocytes, bone marrow, lymph nodes, tonsils, thymus, and your spleen are all part of tonsils, thymus, and your spleen are all part of the immune system.the immune system.

  

Immune system

  

Immune system

Organ of Immune System

Cells Of Immune System

V

Organ of Immune System

Cells Of Immune System

Types of ImmunityTypes of Immunity

Innate immunityInnate immunity– ““Innate” because shared by all animals Innate” because shared by all animals

(vertebrates and invertebrates)(vertebrates and invertebrates)– Pre-existingPre-existing– Non-specificNon-specific

Adaptive immunityAdaptive immunity– ResponsiveResponsive– SpecificSpecific

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The immune system protects organisms with

layered defenses of increasing specificity

Most simply, Most simply, 1. physical barriers1. physical barriers prevent prevent pathogens such as bacteria and viruses from pathogens such as bacteria and viruses from entering the bodyentering the body

If a pathogen breaches these barriers, the If a pathogen breaches these barriers, the 2. 2. innate immune systeminnate immune system provides an immediate, provides an immediate, but non-specific responsebut non-specific response– Innate immune systems are found in all plants and Innate immune systems are found in all plants and

animalsanimals

If pathogens successfully evade the innate If pathogens successfully evade the innate response, vertebrates possess a third layer of response, vertebrates possess a third layer of protection, the protection, the 3. adaptive immune system3. adaptive immune system

Overview of the Immune Overview of the Immune SystemSystem

Immune System

Innate(Nonspecific)

Adaptive(Specific)

CellularComponents

HumoralComponents

Cell-MediatedHumoral

(Ab)

Innate & adaptive mechanisms work together in a cohesive fashion

Innate ImmunityInnate Immunity Protection against infection that relies on Protection against infection that relies on

mechanisms that exist before infectionmechanisms that exist before infection– First line of defenseFirst line of defense

BarriersBarriers– Skin (epidermis and dermis)Skin (epidermis and dermis)– Mucous membranes: respiratory, GI, genitourinary Mucous membranes: respiratory, GI, genitourinary

tractstracts– Lacrimal apparatus: tearsLacrimal apparatus: tears– SalivaSaliva

ChemicalChemical– Sebum: acidsSebum: acids– Perspiration: lysozymePerspiration: lysozyme– Gastric juiceGastric juice– UrineUrine

Innate ImmunityInnate Immunity

Protection against infection that relies on Protection against infection that relies on mechanisms that exist before infectionmechanisms that exist before infection– Second line of defenseSecond line of defense

PhagocytosisPhagocytosis InflammationInflammation ComplementComplement IntererronIntererron

First line of defenseFirst line of defense

The SkinThe SkinServes both as mechanical and Chemical barrier.

Microorganisms normallyAssociated with skin preventPotential pathogens fromColonizing.

Sebaceous glands secrete Fatty acids and lactic acidWhich lower the skin pH(pH 4-6).

Unbroken skin is a contiguousBarrier.

Mucosal membranesMucosal membranes

Mucosal membrane consist of epithelial layerand under lying connective tissue layer.Mm of respiratory tract contains hair like projections called celia.that remove microbes inhaled through the nose and mouth.

Mucus secreted by Goblet cells prevent the microbes from associating Too closely with the cells

Mucous membrane’s microbicidal activity is owed due to the precence of Lysozyme ,Mucopeptide and Secretary immunoglobulins A. .

Lacrimal apparatus; TearLacrimal apparatus; Tear

Lacrimal apparatus is the physiologic system containing the orbital structures for tear production and drainage.

Lacrimal apparatusLacrimal apparatus

Tear mechanically remove the foreign partical and also contains,Lysozyme which constantly baths surface of the eye.(also found with egg whites and the female urogenital tract, and saliva)Lysozyme breaks the glycosidic bonds between the NAG and NAM that make up the backbone of peptidoglycan—causing bacteria to lyse.

Saliva

Saliva mechanically washes pathogens off your teeth, and reduces the # of pathogens.

Saliva contain an antibody called secretory immunoglobulin A, or “SIgA” which coats and protects every tooth from harmful bacteria that may cause decay.

Second line of defenseSecond line of defense

Phagocytosis

Phagocytosis

Inflamation causes causes

Redness - due to capillary dilation - due to capillary dilation resulting in increased blood flow resulting in increased blood flow

Heat - due to capillary dilation - due to capillary dilation resulting in increased blood flowresulting in increased blood flow

Swelling – due to passage of plasma – due to passage of plasma from the blood stream into the from the blood stream into the damaged tissuedamaged tissue

Pain – due mainly to tissue – due mainly to tissue destruction and, to a lesser extent, destruction and, to a lesser extent, swelling. swelling.

Complement system

~20 different proteins that work together to ~20 different proteins that work together to destroy invaders and recruit immune cellsdestroy invaders and recruit immune cells

Activated three different waysActivated three different ways– ““Classical” pathway: by antibodies bound to Classical” pathway: by antibodies bound to

pathogen (vertebrates only)pathogen (vertebrates only)– ““Alternative” pathway: by bacterial surfacesAlternative” pathway: by bacterial surfaces– Lectin activation pathway: by binding of Lectin activation pathway: by binding of

mannose-binding lectin (MBL) to yeast, bacteria, mannose-binding lectin (MBL) to yeast, bacteria, parasites or viruses (e.g., HIV)parasites or viruses (e.g., HIV)

Activation of complement system is tightly Activation of complement system is tightly regulated because end results can be regulated because end results can be dangerousdangerous

InterferonInterferon Interferons are proteins, immunologist Interferons are proteins, immunologist

prefer to call them cytokinesprefer to call them cytokines– They are glycosylatedThey are glycosylated

The name originates from the fact that The name originates from the fact that they interfere with viral infectionthey interfere with viral infection

Cells producing IFNsCells producing IFNs– Plasmacytoid DCs (major producers of Plasmacytoid DCs (major producers of

IFN- IFN- and IFN- and IFN- ))– Fibroblasts and epithelial cellsFibroblasts and epithelial cells– Macrophages and Th1 CellsMacrophages and Th1 Cells

Interferon Antiviral ActivityInterferon Antiviral Activity

Adaptive Immunity: Characteristics

SpecificitySpecificity: directed at specific targets: directed at specific targets

SystemicSystemic: not restricted to initial site of : not restricted to initial site of infection / invasioninfection / invasion

MemoryMemory: after initial exposure & : after initial exposure & activation, a more rapid & more vigorous activation, a more rapid & more vigorous response is made to subsequent response is made to subsequent exposures to pathogensexposures to pathogens

Adaptive Defenses: Components

Humoral ImmunityHumoral Immunity:: (antibody mediated (antibody mediated immunity) provided by antibodies floating immunity) provided by antibodies floating free in body fluidsfree in body fluids

Cell mediated immunity: Cell mediated immunity: – lymphocytes directly attack specific lymphocytes directly attack specific

invaders by lysis or indirect attack by invaders by lysis or indirect attack by initiating inflammation and/or activating initiating inflammation and/or activating other lymphocytes & macrophagesother lymphocytes & macrophages

Antigens vs AntibodiesAntigens vs Antibodies

AntigensAntigens are are macromolecules that elicit an immune

response in the body and can specifically bind with antibody.

The most common antigens are proteins and polysaccharides.

An An antibodyantibody is a “Y” shaped protein produced in response to is a “Y” shaped protein produced in response to

an antigen.an antigen.

Antigens vs ImmunogenAntigens vs Immunogen

An immunogen refers to a molecule that is

capable of eliciting an immune response,

whereas an antigen refers to a molecule

that is capable of binding to the product of

that immune response (Ab). So, an

immunogen is necessarily an antigen, but an

antigen may not necessarily be an

immunogen - The terms immunogen and

antigen are often used interchangeably but

the later is more common.

AntigensAntigens can enter the body from the can enter the body from the environment. These includeenvironment. These include

1) inhaled macromolecules (e.g., proteins on cat 1) inhaled macromolecules (e.g., proteins on cat hairs that can trigger an attack of hairs that can trigger an attack of asthma in in susceptible people)susceptible people)

2) ingested macromolecules (e.g., shellfish 2) ingested macromolecules (e.g., shellfish proteins that trigger an proteins that trigger an allergic response in in susceptible people)susceptible people)

3) molecules that are introduced beneath the skin 3) molecules that are introduced beneath the skin (e.g., on a splinter or in an injected (e.g., on a splinter or in an injected vaccine))

AntigensAntigens

Properties of Antigen Properties of Antigen

1. Antigenic Determinant

2. Foreignness

3. Complexity

4. Molecular Size

5. Charge

6. Solubility

7. Accessibility

8. Valency

Properties of Antigen Properties of Antigen

1) Antigenic Determinant:

A site on an antigen molecule to which anantibody molecule binds. Also called epitope.

Properties of Antigen Properties of Antigen

1. Antigenic Determinant:

Properties of Antigen Properties of Antigen

2. Foreignness

An antigen must be foreign or alien to the host with

which it makes contact.

The greater the phylogenetic difference, the more

Foreign something becomes.

Properties of Antigen Properties of Antigen

2) Foreignnessa. Autologous antigens are found within the same individual;

that is, they are not foreign to that individual. For example, a

skin graft from an individual's thigh to his chest is an auto graft,

and is not foreign.

b. Syngeneic antigens are found in genetically identical

individuals (e.g., individuals from an inbred strain of mice of

identical twins). A graft between members of an inbred strain is a

syngeneic graft or an isograft, and is not foreign.

c. Allogeneic antigens (alloantigens) are found in genetically

dissimilar members of the same species. For example, a kidney

transplant from mother to daughter is called an allograft or a

homograft, and it is foreign.

Properties of Antigen Properties of Antigen 3. Complexity

Just because a molecule is large, if its a polymer of a

single

amino acid or sugar it tends to lack immunogenicity.

complexity of a molecule increses its immunogenicity

Properties of Antigen Properties of Antigen 4. Molecular SizeMolecular weight greater than 10,000 daltons are excellent

Antigens. Insulin(5700 daltons) and (3600 daltons) are

immunogenic

BUT

Gelatin with molecular weight of 10,000 is poor

immunogen.Why?

5. ChargeNet surface charge of antigen has no effect. But a significant

Property b/c net surface charge of antigen determines the net

surface charge of an Antibodies.

Properties of Antigen Properties of Antigen

6. Solubility

A chemical compound exhibit a high class of antigenesity

if it is highly degradable and soluble. e.g natural

antigens. Synthetic polymers fail to initiate an immune

response.

Properties of Antigen Properties of Antigen 7. Accessibility

More accessible the antigenic determinants to the

immune cells more power full immune response will

developed.

Properties of Antigen Properties of Antigen 8. ValencyThe combining capacity of an antigen with

specific antigen binding sites of an antibody

molecule is the antigenic valency.

Chemical and physical classes of Chemical and physical classes of Antigen Antigen

(2) Chemical composition and structure (2) Chemical composition and structure Protein>polysaccharides, nucleic acids, lipidsProtein>polysaccharides, nucleic acids, lipids (Protein containing aromatic amino acid,such (Protein containing aromatic amino acid,such

as tyrosine)as tyrosine)other examplesother examples??

(3) Physical nature (3) Physical nature Polymer > MonomerPolymer > Monomer Cycle molecule >linear molecule Cycle molecule >linear molecule Particulate Ag> soluble Ag Particulate Ag> soluble Ag

ExamplesExamples??

1. Haptens are partial antigens. That is:

a.Haptens are antigenic: they can react with

immune

lymphocytes or antibodies.

b. However, haptens are not immunogenic: they

can not

by themselves cause the production of immune

lymphocytes or antibodies.

HaptensHaptens: :

Haptens:

2.Haptens are usually molecules which are too small to be immunogenic.

a.Examples? b.if a hapten of coupled to a larger carrier molecule, however, it becomes immunogenic.

Immunogens :possess both characteristics Hapten + carrier = complete antigen

(immunogens)

SuperantigensSuperantigens

Conventional Antigen

Monoclonal T cell response

Superantigen

Polyclonal T cell response

• Definition?

SuperantigensSuperantigens

ExamplesExamples– Staphylococcal enterotoxinsStaphylococcal enterotoxins– Staphylococcal toxic shock toxinStaphylococcal toxic shock toxin– Staphylococcal exfoliating toxinStaphylococcal exfoliating toxin– Streptococcal pyrogenic exotoxinsStreptococcal pyrogenic exotoxins

TD-Ag (thymus dependent Ag ) TD-AgTD-Ag stimulate B cell to produce Ab with stimulate B cell to produce Ab with the the help of T cell help of T cell

Most of TD-Ag are proteinMost of TD-Ag are protein Have many kinds of determinants Have many kinds of determinants Can induce HI and CMICan induce HI and CMI Stimulate B cell to produce :Stimulate B cell to produce :IgGIgG, IgM, , IgM, IgAIgA Have immune memoryHave immune memory ExamplesExamples

– Microbial proteinsMicrobial proteins– Non-self or altered-self proteinsNon-self or altered-self proteins

TI-Ag (thymus independent Ag)

TI-AgTI-Ag can stimulate B cells to produce Ab can stimulate B cells to produce Ab withoutwithout the help of T cell the help of T cell

Most are polysaccharideMost are polysaccharide Have more same or repeat determinantsHave more same or repeat determinants Only induce B cell to produce IgMOnly induce B cell to produce IgM Can not induce CMICan not induce CMI No immune memoryNo immune memory

• ExamplesExamples– Pneumococcal polysaccharide, LPSPneumococcal polysaccharide, LPS– FlagellaFlagella

Factors Influencing Factors Influencing ImmunogenicityImmunogenicity

Method of AdministrationMethod of Administration DoseDose RouteRoute

– Subcutaneous > Intravenous > Subcutaneous > Intravenous > IntragastricIntragastric

AdjuvantAdjuvant– Substances that enhance an immune Substances that enhance an immune

response to an Agresponse to an Ag

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