HM

1. AntigenAntigen
Initiator of the immune response

2. The function of immune systemThe function of immune system
 Protect us from infections disease.(immune
defence)
pathogens: Viruses, Bacteria, Fungi, Worms, Parasites
 Removes abnormal cells including cancer
cells （ immune surveillance ）
 Promote normal functioning of the body （ immune
homeostasis ）
Tissue cleanup, wound repair
 But the immune system can also cause disease
when it does function improperly.
Allergies, Immunodeficiency Disease, Autoimmunity,

3. The player of the immune systemThe player of the immune system
 lymphoid organs:lymphoid organs:
Thymus, Bone marrow——primaryThymus, Bone marrow——primary
Lymph nodes, Spleen——secondaryLymph nodes, Spleen——secondary
 Immune cellsImmune cells
neutrophil, monocyte, macrophage, dendritic cells, NKneutrophil, monocyte, macrophage, dendritic cells, NK
cells, mast cellscells, mast cells
T cells, B cellsT cells, B cells
 Immune moleculesImmune molecules
Antibodies, Cytokines, Complements, MHCAntibodies, Cytokines, Complements, MHC

4.  Innate immunityInnate immunity
 Consists of the defenses against infection that areConsists of the defenses against infection that are
ready for immediate activation prior to attack by aready for immediate activation prior to attack by a
pathogen.pathogen.
 predeployed before an infection and poised topredeployed before an infection and poised to
prevent or eliminate it.prevent or eliminate it.
 allow a rapid response to infectionallow a rapid response to infection
 is the first line of defense against pathogensis the first line of defense against pathogens
 is not specificis not specific
 neutrophil, monocyte, macrophage, dendriticneutrophil, monocyte, macrophage, dendritic
cells, NK cells, mast cellscells, NK cells, mast cells
Two categories of Immune respone

5. Develops in response to infection and adapts to recognize,
eliminate and then remember the invading pathogens.
T and B cells
Become more powerful following repeated encounters with
the same antigen.
- highly antigenic specificity: distinguish subtle differences
among antigens.
- Immunologic memory: a second encounter with the same
antigen induces a heightened state of immune reactivity.
- self-nonself recognition: immune system normally
responds only to foreign antigen.
Adaptive immunity

6.  Humoral immune responseHumoral immune response
 Cellular immune responseCellular immune response
AgAg
TT
BB
EffectorEffector
T cellsT cells
PlasmaPlasma
cellscells
antibodyantibody
Adaptive immunity

7. The content ofThe content of antigenantigen chapterchapter
 The concept and properties of antigenThe concept and properties of antigen
 The molecule features of antigens thatThe molecule features of antigens that
influence in immunogenicity of antigeninfluence in immunogenicity of antigen
 The concept and the types of epitopeThe concept and the types of epitope
 The types of the antigenThe types of the antigen
 The important antigen in medicineThe important antigen in medicine

8. Antigen ：
Substances (molecules) that can induce anan
immune response and can react specifically with
products of immune response (antibodies or effector
T cells) in vivo or in vitro..
T
B
Effector
T cell
plasma
Antibody
Ag

9. How does T/B cell recognize the antigen?
BCR and TCR
BCR
TCR
DC or Mφ
MHC
Antigen

10. Antigens are also defined specifically asAntigens are also defined specifically as
molecules that interact with B cells receptor (BCR) ormolecules that interact with B cells receptor (BCR) or
with the T cell receptor(TCR) when complexed withwith the T cell receptor(TCR) when complexed with
MHC.MHC.
T/BT/BT/B
Ag1 Ag2 Ag3
Ab1Ab2 Ab3

11. Antigens possess two immunologic properties:
Immunogenicity: Ability to induce a humoral and/or
cell-mediated immune response.
Ability to bind specifically with the final products of the
immune response. i.e. secreted antibodies and effector
T cells.
Antigenicity

12. All Antigens that have the property of immunogenicityAll Antigens that have the property of immunogenicity
also have the property of antigenicity.also have the property of antigenicity.
Is the reverse true?Is the reverse true?

13. HaptenHapten
Concept
Small molecules that can react with specific
antibody, but are incapable by themselves of inducing a
specific immune response.
Include: drugs, peptide hormones, steroid hormones
CarrierHapten Conjugate＋
Large protein

14. Haptens are valuable research and diagnostic tools
HCG( human chorionic gonadotropin): a sign of pregnancy

16. Properties of the antigen contribute toProperties of the antigen contribute to
immunogenicityimmunogenicity
 ForeignnessForeignness
 Molecular SizeMolecular Size
 Chemical composition and complexityChemical composition and complexity
 Ability to be processed and presented by APCsAbility to be processed and presented by APCs

17. 1. Foreignness
 Antigen must be recognized as non-self by the
biological system.
 Intensity of the immune response depends on the
phylogenetic distance.
BSA
inject
Cow -
Goat +
Rabbit ++
Chicken ++
Immunogenicity
(Bovine serume albumin)
 Some molecules are too well conserved: collagen.
 Some self components can be served as immunogens
Exception:

18. 100 kDa Size is
optimal for antigens
2. Molecular size
MW 100,000≻MW 100,000≻ daltons (Da)daltons (Da)
strongstrong immunogenicityimmunogenicity
MW 4000-10000 DaMW 4000-10000 Da
weak immunogenicityweak immunogenicity
MW 4000 Da≺MW 4000 Da≺
poor immumogenspoor immumogens
There is a correlation between the size of a molecule and its
immunogenicity

19. 3. Chemical Composition
 Synthetic homopolymers tend to lack immunogenicity
regardless of their size
 heteropolymers are usually more immunogenic than
homopolymers
Chemical complexity contributes to immunogenicity

20. Antibody Reactivity to Lipid Molecules

21.  Antigen must be processed and presented by APCs
before is recognized by T cells.
 Large, insoluble and aggregated Ags are best since
they can be phagocytized and processed
4. Susceptibility to antigen processed and
presentation

22. What molecules generate the best
immune response ?
Proteins > Carbohydrates > Lipids and Nucleic acids

23. Specificity of the antigenSpecificity of the antigen
T/BT/BT/B
Ag1 Ag2 Ag3
Ab1Ab2 Ab3
Antigen can only bind with corresponding antibody orAntigen can only bind with corresponding antibody or
receptors on B or T cells.receptors on B or T cells.
Antigen→specific lymphocyte→responseAntigen→specific lymphocyte→response
BCR/TCR
Specificity of the antigen determine the specificity of
adaptive immune respose
Specificity of the antigen is determined by epitopes
of the antigen

24. Antibodies or T cells and B
cells do not react with an entire
antigenic molecule, Instead
they react only with discrete
sites on the molecule, called
an epitope or antigenic
determinant.
How does the antigen bind with the antibody or T/B
cell ?
Computer simulation of an interaction
between antibody and influenza virus
antigen

25. Epitope (Antigenic determinant)Epitope (Antigenic determinant)
Epitopes are the immunologically
active regions of an antigen that
bind to antigen-specific membrane
receptors on lymphocytes (TCR or
BCR) or to secreted antibodies.

26. Four Levels of Protein Organization
An epitope on a protein antigen may involve elements of
the primary, secondary, tertiary ,even quaternary structure
of the protein.

27. ·· linear / sequential epitopeslinear / sequential epitopes
Contain several contiguous amino acids inContain several contiguous amino acids in
a polypeptide chaina polypeptide chain
·· conformational / non-sequentialconformational / non-sequential
epitopesepitopes
The residues that constitute theseThe residues that constitute these
epitopes are far apart in the primary aminoepitopes are far apart in the primary amino
acid sequence but close together in theacid sequence but close together in the
tertiary structure of the antigen.tertiary structure of the antigen.
The types of epitopeThe types of epitope

29. B-cell epitope
• Be reconizied by B cell, it binds with BCR directly
• BCR and antibodies react with intact, soluble molecules. so B cell
epitopes must be highly accessible sites on the exposed surface of
the antigen.
• B-cell epitopes are usually made up of hydrophilic amino acids on the
surface of the molecule
• both linear epitope and conformational epitope can acted as B-cell
epitopes.
B cell epitope and T cell epitope

30. T cell epitope
• be recognized by T cell, it binds with TCR in the form of MHC-
polypeptide complex
• linear epitopes
• distributing in any part of antigen molecule. T- cell epitopes are
often hidden within the interior of a protein and consist of
predominantly hydrophobic amino acids.

32. The types of antigenThe types of antigen
 Immunogen, Hapten, allergen, tolerogenImmunogen, Hapten, allergen, tolerogen
 Protein, polysaccharide, nucleic acid, lipid, etcProtein, polysaccharide, nucleic acid, lipid, etc
 Thymus-dependent antigen(TD-Ag) and Thymus-Thymus-dependent antigen(TD-Ag) and Thymus-
independent antigen(TI-Ag)independent antigen(TI-Ag)
 Xenoantigen, alloantigen, autoantigenXenoantigen, alloantigen, autoantigen

33. 1. Thymus-dependent1. Thymus-dependent
antigen(TD-Ag)antigen(TD-Ag)
An antigen that requires TAn antigen that requires T
cell and B cellcell and B cell
cooperation to inducecooperation to induce
specific antibodyspecific antibody
formation.formation.

34. TD-Ag Include: cells, blood cells, serum proteins,TD-Ag Include: cells, blood cells, serum proteins,
bacteria and almost all the proteins.bacteria and almost all the proteins.
The structure of TD-Ag is more complex.The structure of TD-Ag is more complex.
Features: (1) require T cells activationFeatures: (1) require T cells activation
(2) induce cellular immunity and(2) induce cellular immunity and
humoral immunityhumoral immunity
(3) antibody types: IgM, IgG, etc(3) antibody types: IgM, IgG, etc
(4) apparent immune memory(4) apparent immune memory

35. 2. Thymus-independent antigens(TI-Ag)2. Thymus-independent antigens(TI-Ag)
TI-Ag: An antigen that can be recognized by B cells,TI-Ag: An antigen that can be recognized by B cells,
does not require T cells assisting in thedoes not require T cells assisting in the
production of antibody.production of antibody.
Include: Lipopolysaccharides (LPS),Include: Lipopolysaccharides (LPS),
polymeric bacterial flagellin.polymeric bacterial flagellin.

36. FeaturesFeatures ：： (1) not require T cell activation(1) not require T cell activation
(2) only induce humoral immunity, not(2) only induce humoral immunity, not
cellular immunitycellular immunity
(3) antibody type: IgM(3) antibody type: IgM
(4) no apparent memory(4) no apparent memory

37. 1. Xenoantigen1. Xenoantigen
(1) pathogenic microorganisms(1) pathogenic microorganisms::
Important Antigens in MedicineImportant Antigens in Medicine
—— 208 viruses208 viruses
—— 538 bacteria538 bacteria
—— 57 parasite57 parasite
—— 317 fungi317 fungi
—— 287 worms287 worms

38. exotoxin: is a toxin secreted by bacteria .
An exotoxin can cause damage to the host by destroying cells
or disrupting normal cellular metabolism.
Such as: tetanus-toxin 、 diphtheria toxin
toxoid: is a bacterial toxin (usually an exotoxin) whose toxicity
has been inactivated or suppressed either by chemical or
heat treatment, while other properties, typically
immunogenicity, are maintained.
Such as: tetanus-toxoid 、 diphtheria-toxoid
(2) Exotoxin and toxoid

39. (3) animal immune serum /antiserum
contain specific antibodies.
such as: tetanus-antitoxin, diphtheria-antitoxin
Horse
serum
hypersensitivity
Antiserum
exotoxin Toxoid
Preparation of antiserum

40. 2. Alloantigen
An antigen present
in different member of
the same species.
(1) ABO blood group(1) ABO blood group
antigens system.antigens system.
(2) Rh antigen(2) Rh antigen
(3) HLA (human leukocyte(3) HLA (human leukocyte
antigen)antigen)

41. 3. Heterophile antigen (Forssman antigen)3. Heterophile antigen (Forssman antigen)
Heterophile antigens are the shared antigens thatHeterophile antigens are the shared antigens that
present in many species, such as human, animal, plantpresent in many species, such as human, animal, plant
as well as microorganisms, without species specificity.as well as microorganisms, without species specificity.
streptococcus kidneystreptococcus kidney 、、 heartheart
Nephritis

42. 4.4. AutoantigensAutoantigens
RA (Rheumatoid arthritis), Multiple sclerosis, LupusRA (Rheumatoid arthritis), Multiple sclerosis, Lupus
erythematosis.erythematosis.
(1) releasing of sequestered antigen(1) releasing of sequestered antigen
such as: brain, protein of the lens of eye, sperm,such as: brain, protein of the lens of eye, sperm,
thyroid globulin normally sequestered fromthyroid globulin normally sequestered from
the circulationthe circulation
(2) modified self tissue.(2) modified self tissue.
drugsdrugs
radiation self tissue autoantigensradiation self tissue autoantigens
infectioninfection

43. 5. Tumor antigens: antigens on tumor cells5. Tumor antigens: antigens on tumor cells
(1) tumor specific antigen (TSA)(1) tumor specific antigen (TSA)
are unique to tumor cells and do not occur onare unique to tumor cells and do not occur on
normal cells in the bodynormal cells in the body
(2) tumor associated antigen (TAA)(2) tumor associated antigen (TAA)
are not unique to tumor cells, may be proteins that areare not unique to tumor cells, may be proteins that are
expressed on normal cells during fetal development, notexpressed on normal cells during fetal development, not
expressed in the adult normally. But expressed increasely onexpressed in the adult normally. But expressed increasely on
tumor cells. embryon antigentumor cells. embryon antigen
such as AFP alpha-fetoproteinsuch as AFP alpha-fetoprotein
CEA carcinoembryonic antigenCEA carcinoembryonic antigen
(3) tumor antigens may be induced by virus: virus antigens(3) tumor antigens may be induced by virus: virus antigens
such as EBV—Burkitt tumorsuch as EBV—Burkitt tumor
nasopharynx cancernasopharynx cancer
HBV—liver cancerHBV—liver cancer
HPV—cervical cancerHPV—cervical cancer

44. Non-specific stimulatorNon-specific stimulator
Superantigen are viral or bacterial proteins that bind
simultaneously to the Vβ domain of a T-cell receptor and
to α chain of class II MHC molecule.
Superantigen (SAg)

45. Type of SAgType of SAg
 Exogenous SAg:Exogenous SAg:
soluble proteinssoluble proteins secretedsecreted by bacteria.by bacteria. (exotoxin)(exotoxin)
 Endogenous SAg:Endogenous SAg:
cell membrane protein encoded by certain viruscell membrane protein encoded by certain virus

46.  Cross-linkage of a T-cell receptor and class II MHCCross-linkage of a T-cell receptor and class II MHC
molecule by either type of SAg produces anmolecule by either type of SAg produces an
activating signal that induces T –cell activation andactivating signal that induces T –cell activation and
prolieration.prolieration.
 MMassive immune response that caused by SAgs isassive immune response that caused by SAgs is
not specific to any particular epitope on the SAg.not specific to any particular epitope on the SAg.
Normal antigen: 0.001-0.0001% of T-cell
SAg: up to 20% T-cells.

48. Mitogens ( polyclonal T/B activator)
The most commonly used mitogens in clinical laboratory medicine
 The chemical substance that encourages a cell to
commence cell division, triggering mitosis.
 are able to activate all members of T/B cells regardless
of their antigenic specificity.
 Mitogens are often used to stimulate lymphocytes and
therefore assess immune function.

49. The endThe end