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Antigen Structure and Immunogenicity

Updated: September 16, 2014

Folder Title: Antigens(NoTP)(Without TP Slides)

Antigen Recognition by the Specific Immune System:

Recognition by B-cell and T-cell Receptors Antigen (Ag): Binds specifically to an antibody

binding site (Ab), or to a T-cell receptor (TCR)*• (* When the antigen is being presented to the TCR on a

specific set of cell-membrane proteins called MHC)

Immunogen: Binds specifically to an antibody binding site or to a T-cell receptor*,

and generates a humoral or cellular immune response.

All immunogens must be antigens, Not all antigens can generate a response.

Haptens and Epitopes Haptens: Small organic molecule

(e.g. 1-Fluoro-2,4-dinitrobenzene)

Not Immunogenic by themselves

Can be immunogenic when attached to an immunogenic macromolecular carrier

The Anti-hapten antibody so generated will bind the Hapten

Epitope: A region of a macromolecular antigen that is actually an antigenic determinant,

a molecular sub-region that is actually recognized and bound by an Antibody or T-Cell Receptor

Fig.4-6bKuby3rd Ed

AgAb

Sep

Influenza Virus AntigenAntibody Heavy ChainVariable Region

Antibody Light Chain Variable Region

Antigen-Antibody Complementarity

Antigen - Antibody BindingAntibody Light Chain

Variable Region

Fig.

4-6a

Kuby

3rd Ed

AgAb

KissInfluenza Virus Antigen

Antibody Heavy Chain

Variable Region

Prot2nd

Primary sequential epitopes in

sperm whale myoglobin

(Epitopes are antigenic determinants inMacromolecules)

Conformational (non-sequential) Epitope in Hen

Egg White Lysozyme.

(Colors show amino acid side chains

contacting the two different chains of the

antibody, or contacting both

chains. Antibody structure to be covered later)

Myoglobin Single Polypeptide

17,000 MW (Tertiary Structure)

About 7 secondary domains. One bound Heme in hydrophobic

pocket

Hemoglobin: a2b2 Tetramer64,000 MWOne heme per subunit

What Determines Immunogenicity of an Antigen?

1.Properties of the immunogen(See detailed breakdown next slide)

2.Properties of the Host (Slides 12 and 18)

a. Geneticb. Physiological

3. Mode of Antigen Exposure

ImGenFx1

ImGenFx2

Called “H2” in Mice; “HLA” in HumanHLA = Human Leucocyte-associated Antigens

Immunogenicity of Antigens and the MHC Gene Collection:MHC = Major Histocompatibility ComplexHaplotype = a set of closely linked genes controlling the immune response. Haplotype is usually transferred to progeny as a linked set

Antigen #1 Antigen #2

Ag&MHCbAg 1 Ag 2

Two different antigens

Ag&MHCcAg 1 Ag 2

Two different antigens

Ag&MHCdAg 1 Ag 2

Two different antigens

Ag&MHCAg 1 Ag 2

Two different antigens

ImGenFx3

ImAdmin

Conformational Properties of Epitopes for Antibodies

64

80

Hen Egg-White Lysozyme: Conformations of Sequence 62 to 80

Anti-hapten Antibodies

AbHaptenSee Figure 4-1p. 77Kuby, 6th Edition

To Here Sept. 11

AgByB&Ta

AgByB&Tb

AgByB&T

Conformational (non-sequential) Epitope in

Hen Egg White Lysozyme.

Antigens in Immunologically-Based Clinical Diagnosis and Pathology

Cancer Antigens in Diagnosis of Cancer

Carcino-Embryonic Antigen (CEA)

Prostate Specific Antigen (PSA)

Ovarian Cancer Antigen (CA 125)

Whole-body Imaging of Metastatic Colon Carcinoma

A33 Antigen

Anti-Human Chorionic Gonadotropin Pregnancy Test(Early Home Pregnancy Test)

Type II Allergic Hypersensitivity

Blood Group Antigens in Transfusions

Hemolytic Disease of New-Borns: Rh Antigen incompatibility

Super-Antigens in Toxic Shock Syndrome

Antigens in Immunologically-BasedTreatment of Cancers and Other Pathologies:

(Specifics Later)

Cancer Antigens as Targets for Therapy

Radioactively-labeled Antibodies

Cytolytic Antibodies

Specifically Activated Antigen-presenting Cells.

Imaging with Antibodies Carrying “Reporter Groups”

Radioactive IsotopesFluorescent Groups (“Chromophores”)Metals

Antigen-Antibody Interactions in Research and Clinical Medicine

e.g. Radioactively labeled monoclonal antibody reacting with tumor cell antigens in detection of metastatic colon cancer

SeeMets

Arm

Head

Imaging on Metastatic Colon Carcinoma with Radioactive-Iodine-Labelled Monoclonal Ab to A33 AgLloyd Old, Scientific American, August, 1996, p. 138)

Antihapten Antibodies in the Detection and Measurement of Small Molecules

For example: Anti-HCG (Human chorionic gonadotrophin) antibody in the detection of soluble HCG in urine

AntiHCGWhat will happen when concentration of Anti-HCG-Ab is about equal to Hapten-carrier conjugate?

What will happen when you put excess soluble hapten in the way of the anti-HCG-Ab?

PregTest

Antibodies in Blood Transfusions

Antibodies to A, B, O Blood Group Antigens

Pre-existing Antibodies to Non-tolerated (Unmatched) Blood Group Antigens : “Isohemagglutinins”

ABOTypes

Pre-existing serum antibodies from exposure to bacterial antigens that mimic antigens on red blood cells

ABO Blood Group Genotypes, Phenotypes, Antigens andSerum Antibodies Present

ABOSugar

See Figure 15-13 (a), p. 389,

Kuby, 6th EditionGalactose

Not a hexasaccharide(No terminal sugar)

Antibodies in Hemolytic Disease of the New-born (HDNB)

(Rh-Factor Sensitization)

Rh-Factor positive baby – Rh Negative Mother

HDNB

See Figure 15-14p. 390, Kuby6th Edition

HDNBPhoto

AntiRhAb

Following are three Turning Point short answer questions.

Please put all notes on the floor.Do not have any electronic devices other than your NXT transmitter.No consulting with other students.

If you have a problem with your device, I can provide you with a loaner NXT device.

If you have a problem using your NXT device, please ask Elisabeth for help.

It is imperative that the integrity of these in-class Turning Point quizzes be maintained at the same level as we will do with the three written exams.

Immunopathology of Bacterial Septic Shock Caused by Gram Negative Bacterial Endotoxins:Examples -E. coliPseudomonas aeruginosaNeisseria meningitidisMeningococcus

70,000 Deaths per yearDiarrhea, Fever, Blood Clotting, Blood Pressure Drop

Macrophage Activation by Endotoxin:Generates systemic cytokine production -IL1 and TNF-alpha (Tumor necrosis factor)

Immunopathology of Bacterial Toxic Shock Exotoxins Secreted or Presented Membrane Bound:Act as "Superantigens"Examples -Staphylococcus aureus: TSST1 (Toxic Shock Syndrome Toxin)Streptococcus pyrogenes - Rheumatic fever and shockStaphylococcus enterotoxins: Food poisoning

Superantigens cross-link TCR with Antigen-presenting Cell MHC Class II Proteins

Generates systemic cytokine production - IL1 and TNF-alpha (Tumor necrosis factor)

SuperAg

See Figure 11-67th Edition p. 367

Staphylococcal enterotoxins (food poisoning)Streptococcal pyrogenes exotoxins (rheumatic fever, toxic shock)See Table 11-2, p. 367, 7th Edition

Mitogens and Lectins

Mitogens: Stimulate mitosis and cell division non-specifically(non-specific therefore stimulate polyclonally)

Lectins: Proteins that bind to carbohydrate in glycoproteins(Can be potent mitogens)

Glycoproteins: Conjugated protein with covalently attached carbohydrate residues

Examples of Mitogens

Concanavalin A (Con A) : Non-specific T-cell mitogen

Phytohemaglutinin (PHA): Non-specific T-cell mitogen

Pokeweed Mitogen (PWM): Non-specific T- and B-cell Mitogen

Lipopolysaccharide (LPS): Gram negative bacterial cell wall component

Potent Polyclonal (non-specific) B-Cell Mitogen

Immune Adjuvants and the Immunogenicity of Vaccines(See Scientific American, October, 2009)

Boosting Vaccine Power, pp 72 to 79

Activating Antigen-presentation by Cells of the Innate Natural Immune Response

e.g. Purified derivatives of bacterial lipo-polysaccharidesBacterial DNA derivativesBacterial flagellin protein

Specific Activation of Antigen-presenting Cells Extra-corporeally (outside of the body)

Dendritic Cell VaccinesSee Dendreon

Innate Natural Immunity and Systemic Sepsis:NOVA Video on Meningitis (Meningococcal

Meningitis, Endotoxin, and Systemic Sepsis)

http://www.pbs.org/wgbh/nova/meningitis/

Has video links to steps in meningococcal sepsis

“Amy’s Story”and related NOVA Stories

tpfondy.mysite.syr.edu

The Story of the Oakwood Children

See “Song of the Oakwood Children” as a self-running presentation

Following are two Turning Point short answer questions.

Please put all notes on the floor.Do not have any electronic devices other than your NXT transmitter.No consulting with other students.

If you have a problem with your device, I can provide you with a loaner NXT device.

If you have a problem using your NXT device, please ask Elisabeth for help.

It is imperative that the integrity of these in-class Turning Point quizzes be maintained at the same level as we will do with the three written exams.

5. No problem. Please get moving!4. Maybe a bit too fast, but mostly OK.

3. I’m following OK, I can catch up with what I miss.4. I’m struggling to keep up. It’s too much too fast.

5. I’m lost(This slide is anonymous. I won’t know who you are)

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Duration: 0 Seconds

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