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

2. Essence of immune response is to distinguish self from nonself
Antigen can be distinguished by two properties:
Induce an immune response
React specifically with what they induce

3. 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

4. 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)

5. 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

6. 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)

7. Many biological molecules can function as haptens: Drugs, peptide hormones, steroid hormones etc.
Antihapten antibodies against hCG is used to detect pregnacy

9. 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

10. 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)

11. 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

12. 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

13. 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

14. 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

15. 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

16. Chemical composition Must not be inorganic in nature Kidney stones
Biggest thread to integrity of an organism is organic molecules

17. 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

19. 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

20. Pure NA vs nucleoproteins
Abs to NA appear in serum of patients with SLE
Penicillin-Protein conjugate
Drugs become allergen (sulfadrugs)

21. 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

22. Charge Molecules need not to be charged to function as immunogens
Excessive high charge depress immune response

23. Conformation Denatured molecules can be immunogenic
Native molecules are better as all antigenic determinants are intact

24. 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

25. 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

26. 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

27. Adjuvants Substances that enhances immunogenicity of Ag It works by:
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

28. 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)

29. 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

30. 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

31. Egg white lysozyme: discontinuous epitopes

32. 129aa
Discontinuous
1-12 and

34. Some residues are more important (immuno dominant)
Lysozyme: 60-83

35. 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

36. 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 +
Denatured Proteins -

38. Check your leraning
Write down the characteristics of ADs