Slide 1: ANTIGEN I. Definition of antigen : Antigen is substance which when introduced parentally into the body stimulates the production of an antibody with which it reacts specifically and in an observable manner
Vaccine I. Definition of antigen Slide 3: 1. Immunogen: the antigen that induce specific immune response Microbes; bacteria ,virus; fungi and parasites
xenoantigenei or allogeneic tissues or organs:
grafted skin , bone marrow Slide 4: 2.Tolerogen: antigen that induce Immunologic tolerance
Immunologic tolerance is unresponsiveness to an antigen that is induced by prior exposure to that antigen. tolerogen Slide 5: 3. Allergen: antigen that induce Anaphylaxis (severe immediate hypersensitivity reaction occurring as a result of rapid generalized mast-cell granulation) Allergen: some medicine, flower powder, seafood Slide 6: 4. Vaccine: antigens that induce a protection immune response against microbes and are used to prevent diseases
Killed vaccine: Rubella virus
Attenuated vaccine: Measles
Toxoid :Tetanus Slide 7: Classification of Ag Slide 8: Complete antigen : substances with both immunogenecity and immunoreactivity
By convention , we call complete antigen as antigen.
Incomplete antigen (hapten): substances only with immunoreactivity
Hapten +carrier complete antigen (immunogens)
Hapten: Only possess immunoreactivity
Carrier: Make hapten obtain the immunogenicity Based on Immunogenicity Based on Chemical nature : Based on Chemical nature ProteinsMajority of immunogens are proteins (pure proteins or they may be glycoproteins or lipoproteins). Proteins are usually very good immunogens.
Polysaccharides Pure polysaccharides and lipopolysaccharides are good immunogens.
Nucleic AcidsNucleic acids are usually poorly immunogenic. However, they may become immunogenic when single stranded or when complexed with proteins.
LipidsIn general lipids are non-immunogenic, although they may be haptens. Slide 11: According to source of antigens
Heterophile antigen (1) Xenoantigen : (1) Xenoantigen An antigen that is found in more than one species. An antigen is something that is capable of inducing an immune response.
The prefix "xeno-" means foreign or other. It comes from the Greek "xenos" meaning stranger, guest, or host.
Pathogens: bacteria, virus , fungi, parasite
Exotoxin and toxoid
Produced by G+ bacteria
Strong antigenicity and pathogenicity
exotoxin that loses its toxicity but maintains its antigenicity under suitable conditions (low concentration of formaldehyde )
Such as tetanus toxoid , diphtheria toxoid Slide 13: HIV Pathogens Fungi bacteria Slide 14: Heterophile Ag (forssman Ag)
Common Ags shared by different species ( between human and animal or microbes, between different species of microbe)
(eg) M protein of streptococus bears common antigen determinant with basement membrane of kidney
(This common between bacteria and human being can causes poststreptococcal glomerulonephritis)
No specificity of species
Significance . immunopathology
. Diagnosis (2) Alloantigen : (2) Alloantigen Antigens of red blood cell
ABO system (blood typing)
- very important in transfusion
Rh system (Han race :>99%Rh+)----haemolytic disease of the newborn (HDNB)
HLA system (Human leukocyte antigen)
- relate to transplantation
- very important in immune regulation ABO system : ABO system Blood antigen antibody in
typing of RBC serum
A A anti-B
B B anti-A
AB A,B -
O - anti-A, anti-B (3) Autoantigen : (3) Autoantigen Release of sequestered Ag
Lens protein is released into blood to induce immune response to induce inflammation of lens
Change of molecular structure of auto-tissues
Denatured IgG becomes antigen to induce production of antibody ( rheumotoid factor)
In patient suffering from rheumotoid arthritis II. According to whether need the help of T cells when B cells produce Ab : II. According to whether need the help of T cells when B cells produce Ab TD-Ag (thymus dependent Ag )
TI-Ag (thymus independent Ag) 1.TD-Ag (thymus dependent Ag ) : 1.TD-Ag (thymus dependent Ag ) TD-Ag can stimulate B cell to produce Ab with
the help of T cell
The most of TD-Ag belong to protein
many kinds of determinants
stimulate B cell to produce :IgG, IgM, IgA
capable of inducing CMI
immune memory 2. TI-Ag (thymus independent Ag) : 2. TI-Ag (thymus independent Ag) TI-Ag can stimulate B cells to produce Ab without the help of T cell
most are polysaccharide
more ,same, repeat determinant
only induce B cell to produce IgM
can not induce CMI
no immune memory SUPERANTIGENS : SUPERANTIGENS When the immune system encounters a conventional T-dependent antigen, only a small fraction (1 in 104 -105) of the T cell population is able to recognize the antigen and become activated (monoclonal/oligoclonal response).
However, there are some antigens which polyclonally activate a large fraction of the T cells (up to 25%). These antigens are called superantigens Slide 22: Eg: Staphylococcal enterotoxins (food poisoning), Staphylococcal toxic shock toxin (toxic shock syndrome), Staphylococcal exfoliating toxins (scalded skin syndrome) and Streptococcal pyrogenic exotoxins (shock).
The diseases associated with exposure to superantigens are, in part, due to hyper activation of the immune system and subsequent release of biologically active cytokines by activated T cells. Slide 23: Tumor specific Ag ( TSA)
Only expressed on the tumor cells but normal cells
The tumor antigens encoded by genomes oncogenic virus
EB virus ---B cell lymphoma HPV-cervical carcinoma
Tumor associated Ag (TAA)
Highly expressed on tumor cells but lowly expressed on normal cells, such as AFP CEA
AFP (alpha-fetoprotein): over-expression in liver cancer
CEA (carcinoembryonic antigen): over-expression in carcinoma of colon , pancreas, stomach ,and breast Slide 24: Characteristics of Ag DEPEND ON SIZE : DEPEND ON SIZE Very high molecule haemocyanin (MW 6.75million) –highly antigenic
Low molecular weight molecule (<10,000) -non antigenic or feeble
They render antigenicity by absorbing inert particles like bentonite or kaolin Slide 26: . 1. Antigen must be foreignness to immune system:
What substances are foreignness to immune system ?
According to Burnnet’s clone selection theory , foreignness ( non-self) means substances that never contact with lymphocytes during embryo period. : What kinds of substances can be foreignness to immune system?
(1) Heterogeneous substances
Various pathogens, xenoantigeneic tissues
(2) Allogeneic substance
grafted allogeneic tissues or organs
(3)Autoantigenic components that never contact with lymphocytes during embryo period
Release of sequestered antigen------
Such as lens protein, sperm etc.
Change of molecular structure of auto-tissue
For example, denatured IgG in patient suffering from rheumatoid arthritis becomes antigen to induce production of antibody ( rheumatoid factor) 2. Two properties of immunogen : 2. Two properties of immunogen 1. Immunogenicity
An ability of antigen which can stimulate the body to evoke a specific immune response.
An ability of antigen which can combine with corresponding Ab or sensitized lymphocyte III. Specificity and cross reaction of antigen : III. Specificity and cross reaction of antigen Specificity is a cardinal feature of the adaptive immune system
Specificity is referred to that immune responses are directed toward and able to distinguish between distinct antigen or small parts of macromolecular antigens.
This fine specificity is attributed to lymphocyte antigen receptors that may bind to one molecule but not to another with only minor structural differences from the first Slide 30: Specificity of Ag Ab1 Ab2 Ab3 Slide 31: Specificity exists in both immunogenecity and immunoreactivity
Specificity is the basis of immunologic diagnosis and immunologic therapy as well as basic feature of adaptive immunity Degradability : Degradability Antigens that are easily phagocytosed are generally more immunogenic. This is because for most antigens (T-dependant antigens) the development of an immune response requires that the antigen be phagocytosed, processed and presented to helper T cells by an antigen presenting cell (APC). Slide 33: 1. Antigen determinants (epitope)
(1) The portion of antigen molecules which can be specifically recognized by antibody or antigenic receptor
Protein antigen----5-15 amino acid residues
Polysaccharide antigen----5-7 polysaccharide residues Slide 34: Chicken lysozyme bound to an antibody Three dimension figure of Angiotensin(Ag) II binding to antibody Slide 35: A change of antigenic determinant (characteristics, number and conformation) can influence the specificity of Ag.
Antigen determinant is the sites of Ag combining with Ab Slide 36: The chemical component , arrangement and conformation affect the specificity of antigen Slide 37: 2. Antigenic valence
Total number of determinants which can be bound by antibody or antigenic receptor of lymphocytes is called antigenic valence.
Most natural antigens are polyvalence antigen. 3. Classification of antigenic determinant : 3. Classification of antigenic determinant (1)According to the structure of Ag determinants
Sequential (or linear) determinants Conformational determinants : Conformational determinants Conformational determinants are formed by amino acid residues that aren’t in a sequence but become spatially juxtaposed in the folded protein. Sequential (or linear) determinants : Sequential (or linear) determinants Epitopes formed
by several adjacent
amino acid residues
are called linear
determinants. Slide 42: (2)According to types of cells recognizing antigenic determinants
T cell determinants (T cell epitopes)
B cell determinants (B cell epitopes) Difference between T cell epitope and B cell epitope : Difference between T cell epitope and B cell epitope T cell epitope B cell epitope
Receptor TCR BCR
Nature short peptide proteins, polysaccharides
Size 8-17 amino acid residues 5-15 amino acid residues
or 5-7 monosaccharides
Types linear epitope conformational epitope
or linear epitope
Position any position in antigen mostly exist on the surface of
antigen 3.Common antigen and cross reaction : 3.Common antigen and cross reaction (1) Common antigen ( common determinants in fact )
Different bacteria which possess the same epitopes are called common antigen.
(2) Cross reaction
---Existence of common determinants
Because there are some common antigen determinants existing in different microbes, so the antiserum against one kind of microbe can also react with another microbe,this called cross reaction. Slide 45: A 1 2 3 2 B Anti-typhoid
serum Anti-Ag2 Anti-Ag1 Anti-Ag2 Anti-Ag3 Anti- Paratyphoid
serum Typhoid bacillus Paratyphoid bacillus H Ag O Ag flagellum Slide 46: (3) Significance
In clinic, existence of cross reaction may lead to wrong diagnosis. Flu virus typhoid What you should know by the end of this lecture : What you should know by the end of this lecture Definition and characteristics of antigen
Definition of antigenic determinants,conformational determinants and linear determinants
Difference between T cell epitopes and B cell epitopes
Definition of common antigen and cross reaction
Difference between TD-Ag and TI-Ag