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Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt • Goldsby • Osborne
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Page 1: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

Immunology

Lecture 1

Antigens

Based onKuby IMMUNOLOGY (6ed)

Kindt • Goldsby • Osborne

Page 2: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

• Essence of immune response is to distinguish self from nonself

• Antigen can be distinguished by two properties:a) Induce an immune response

b) React specifically with what they induce

Page 3: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

• When Ag is introduced into a cell:• B-cell + Ag = Effector B cells (plasma) +

memory B cells• T-cells + Ag = Effector T cells (CTLs, TH) +

Memory T cells• Abs: Humoral response• Activated T cells: Cell mediated response

Page 4: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

• Humoral: mediated by Ag specific blood proteins called Ag

• This immunity protects against circulating extracellular Ag (bacteria, exotoxins, virus etc.)

• Cell mediated: primary effector mechanism is mediated by Ag specific T cells

• Two subpopulations (Tc –killer cells & TH-release communication molecuces, cytokines)

Page 5: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

• Substance that induces specific immune response is called an antigen immunogen

• Ability of a substance to induce humoral or cell mediated immunity is called immunogenicity

• The inducing substance is called immunogen

Page 6: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

• The ability of a substance to react with the specific Abs or activated T cells that it induces is called antigenicity.

• All immunogens are antigens; but all antigens are not immunogens

• Some small molecules called haptens are antigenic but incapable of inducing specific immune response (no Immunogenicity)

Page 7: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

• Many biological molecules can function as haptens: Drugs, peptide hormones, steroid hormones etc.

• Antihapten antibodies against hCG is used to detect pregnacy

Page 8: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.
Page 9: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

Factors that influence immunogenicity

• To protect against infectious disease, the IS must recognize bacteria, bacterial products, fungi, parasites and viruses as immunogens.

• IS recognize particular macromolecules of an infectious agent: their proteins and PS

• NA and lipids: not good immunogens unless complexed with proteins /PS

Page 10: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

• Scientists use Proteins and PS in experimental studies of humoral immunity

• For cell mediated immunity studies: only proteins and some lipids, and glycolipids serve as immunogens

• These molecules are not recognized directly• Must be processed and presented together with

MHC (proteins)/ with CD1 (Lpds and GL)

Page 11: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

Humoral (Ab mediated) Cell mediated

B cell dependent T cell dependent

Can recognise Ag without support molecules (Not MHC restricted)

Recognise Ag in asosication with MHC

Produce Effector B cells (plasma) + memory B cells

Produce memory T cells and Effector T cells

Page 12: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

Molecualr weight of some common experimetnal Ags used in immunology

Antoigen Mol Mass (Da)

Bovine gamma globulin 150,000

BSA 69,000

Flagellin (monomer) 40,000

Hen eggw white lysozyme 15,000

Ovalbumin 44,000

Sperm whale myoglobin 17,000

Tetanus toxoid 150,000

Page 13: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

Characteristics of immunogen

• Foreignness• Recognise as non self• Unresponsiveness to self antigens: during

lymphocyte development• Ag not exposed to immature lymphocyres

will eb recognised as nonself• Degree of immunogencity depends on

degree of foreignness

Page 14: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

• Greater phylogenietic distance between two sepcies

• BSA in Cow! Vs BSA in rabbit• BSA in chicken is more immunogenci than

in sheep• MHC-I is a good immunogen even in same

species (HLA typing)• Conserved proteins (Collagen/ Cyt c)• Sequested proteins (corneal tissue, sperm)

act as immunoigen in same animal

Page 15: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

Molecular Size

• Minmum 100 KDs• Less than 10Kd: poor immunogen• Less than 1Kd not immunogenic• Buildiign block of macromoleuces

(aa,nt,fa,ms) not immunogenic

Page 16: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

Chemical composition

• Must not be inorganic in nature• Kidney stones• Biggest thread to integrity of an organism is

organic molecules

Page 17: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

• Large synthetic homopolymers: X• Collagen (many tyrosine residues), nylon,

polyacralamide, teflon• Polypeptides of D-aa is as immunogenic as L-aa?• Will Abs against D-a.a react with L-a.a

polypeptide?• Aromatic more immunogenic than nonaromatic

amino acids• Four levels of protein organisation: more

complexity

Page 18: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.
Page 19: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

• Pure lipids: not immunogenic• But mix with proteins (cardiolipin in

Wasseman test)• Specific Abs are raised agiant sterids, fat

soluble vitamins like E, complex lipids (LT)• Level of leukotriene is determined using Abs

(evaluating asthma)• Anti-lipid Abs used in transplnataion assays• Lipid antigens in recognising Mycobacterium

tuberculosis and Mycobacterium leprae

Page 20: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

• Pure NA vs nucleoproteins• Abs to NA appear in serum of patients with

SLE• Penicillin-Protein conjugate

– Drugs become allergen (sulfadrugs)

Page 21: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

Biodegradability

• Intact Ag must be broken down • APC degrade Ag (antigen processing)• Large insoluble macromolecules better than

small soluble molecules• Large molecules are readily phagocytosed

and processed

Page 22: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

Charge

• Molecules need not to be charged to function as immunogens

• Excessive high charge depress immune response

Page 23: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

Conformation

• Denatured molecules can be immunogenic• Native molecules are better as all antigenic

determinants are intact

Page 24: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

Role of biological system

• Genotype of the recipient– Hereditary absence of the lymphocyte receptor

recognizing a particular Ag– Failure of an Ag to be presented by a given

MHC

Page 25: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

Dosage

• Insufficient dose will not stimulate IR– Failure to activate lymphocytes– Immunological tolerance

• High dose also induce tolerance• Booster dose require for clonal proliferation

of B and T cells

Page 26: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

Route of Administration

• Intravenous (into vein): moves to spleen• Intradermal (into the skin): lymph nodes• Subcutaneous (beneath the skin): moves to

lymph cells/local lymph nodes• Intramuscular (into a muscle): lymph nodes• Intraperitoneal (into the peritoneal cavity):

spleen

Page 27: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

Adjuvants

• Substances that enhances immunogenicity of Ag– When Ag has low immunogenicity– When small amount of Ag is available

• It works by:– Ag persistence is prolonged– Co-stimulatory signals are enhanced (B7 of

Macrophages and CD28 of TH cells)– Local inflammation is increased– The nonspecific proliferation of lymphocytes is

stimulated

Page 28: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

• Aluminum potassium sulphate• Freund’s incomplete adjuvants (Ag in aqueous

solution, mineral oil, mannide monooleate)• Freund’s complete adjuvants (heat killed

mycobacteria for muramysl dipeptide, Ag in aqueous solution, mineral oil, mannide monooleate)

• Mycobacterium tuberculosis• Bordetella pertusus• Bacterial lipopolysachharide• Synthetic polynucleotides (poly IC, AU)

Page 29: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

Epitopes• Whole Ag is not immunogenic• Ag has two regions: Hapten and carrier• Haptens are antigenic, but not immunogenic• Hapten portion is called AD• Ag advertise its foreignness through epitopes• Can purified AD induce IR?• At least one AD make a molecule

immunogenic

Page 30: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

• It is at least 6 sugars or 15-22 a.a • Dextran (homopolymer of glc) is a good Ag• It must be accessible to Abs

– On surface/ hydrophilic

• It can be continuous or discontinuous• Mb (16.7Kd) has 5 AD of 6-10aa• Rich in basic amino acid: Ab binding is

through hydrophilic interaction

Page 31: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

Egg white lysozyme: discontinuous epitopes

Page 32: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

129aaDiscontinuous1-12 and 122-129

Page 33: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.
Page 34: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

• Some residues are more important (immuno dominant)

• Lysozyme: 60-83

Page 35: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

• B cells and T cell recognize different epitopes on the same antigenic molecule

• Human Glucagon (29aa): B cells of mice identify the amino terminal portion and T cells identify the carboxy terminal portion

Page 36: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

Ag recognition by T and B lymphocytes (qualitative differences)Based on the studies of PGH Gell and Baruj Benaceraff (1959)

Primary Immunization

Secondary immunization

Secondary immune response

Ab Production Cell mediated T Response

Native Protein Native Protein + +

Native Protein Denatured Proteins

- +

Page 37: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.
Page 38: Immunology Lecture 1 Antigens Based on Kuby IMMUNOLOGY (6ed) Kindt Goldsby Osborne.

Check your leraning

• Write down the characteristics of ADs