医学免疫学课件：2 antigen

1、Antigen（Ag）,Chapter ,Antigen,1. Concept 2. Immunogenicity and specificity 3. Requirements for immunogenicity 4. Types of antigens 5. Superantigen and adjuvants,KNOWLEDGE POINTS,Concept,1. 抗原Antigen (Ag) the substances that are recognized by TCR/BCR or antibody and induce a specific immune response.

2、蛋白质、多糖、脂类、核酸,Antigen,2.Properties of Ag -immunogenicity -immunoreactivity (react with the products of a specific immune response),-substances that induce specific immune response.,Complete Ags（完全抗原）：have the properties of immunogenicity and immunoreactivity. Hapten（半抗原）：have the property of immunore

3、activity but not immunogenicity . - A substance that is non-immunogenic but which can react with the products of a specific immune response.,Antigen,Haptens are small molecules which could never induce an immune response when administered by themselves but which can when coupled to a carrier molecul

4、e. hapten + carrier complete Ag,Antigen,抗原特异性Antigen specificity,induce a specific immune response, react with the products of a specific immune response,Antigenic specificity 抗原特异性 1. epitope (antigenic determinant ) 抗原决定簇（基），表位 - the portion of the antigen that binds specifically with the binding

5、site of an antibody or a receptor on a lymphocyte. - the size of an epitope is approximately equivalent to 5-15 amino acids. 抗原结合价antigenic valence,Antigen,Epitope表位,Antigen,description,example,One epitope,haptens,Many epitopes of the same specificity,Many polysaccharides, homopolymers,Many epitopes

6、 of different specificity,proteins,Representation of some possible antigenic structures,2. the types of epitope conformational epitope构象表位: Some epitopes form only when the critical residues are brought together in space through folding of the polypeptide or polysaccharide chain into its normal thre

7、e-dimensional conformation. sequential epitope顺序或线性表位: All of the amino acid or sugar residues that form a given epitope are positioned sequentially in the linear sequence of a protein or polysaccharide antigen.,Antigen,构象表位 线性表位, B cell epitope T cell epitope,Antigen,Antigen,T cell epitope B cell e

8、pitope Receptor TCR BCR APC,MHC necessary unnecessary Character linear short natural polypeptide peptide polysaccharides linear determinant conformational determinant ; linear determinant Size 8-10aa (CD4+T) 5-15aa 2,9 anchor residue 13-17aa(CD8+T) Location Ag surface of Ag,Antigen,3. hapten-carrier

9、 effect半抗原载体效应,Antigen,Antigen,common epitope and cross-reaction（交叉反应） cross antigen,Factors influencing immunogenicity,Contribution of the antigen 1. Foreignnessy异物性 - The immune system normally discriminates between self and non-self such that only foreign molecules are immunogenic.,Antigen,Factor

10、s influencing immunogenicity,2.chemical Composition protein polysaccharide nuclear acid 3. size - There is not absolute size above which a substance will be immunogenic. In general, the larger the molecule the more immunogenic it is likely to be.,Antigen,4.chemical complexity- In general, the more c

11、omplex the substance is chemically the more immunogenic it will be. An increase in the chemical complexity of a compound is accompanied by an increase in its immunogenicity 5.conformation 化学基团的性质、数目、位置和空间构象 6. accessibility 7. physical form - In general particulate antigens are more immunogenic than

12、 soluble ones.,Antigen,Antigen,B. Contribution of the host 1. Genetic Factors - Some substances are immunogenic in one species but not in another. Similarly, some substances are immunogenic in one individual but not in others (i.e.responders and non-responders). 2. Age，gender - Age can also influenc

13、e immunogenicity. Usually the very young and the very old have a diminished ability to mount and immune response in response to an immunogen.,Antigen,C. Method of Administration 1. Dose - The dose of administration of an immunogen can influence its immunogenicity. 2. Route - Generally the subcutaneo

14、us route is better than the intravenous or intragastric routes. The route of antigen administration can also alter the nature of the response 3. Adjuvants,Antigen,Types of antigens抗原的种类,Th: Thymus-dependent antigen(TD-Ag) Thymus-independent antigen(TI-Ag) Relative: Xenogenic antigen Allogenic antige

15、n Autoantigen Heterophilic antigen Idiotypic antigen,Antigen,TD-Ag胸腺依赖性抗原 Thymus -dependent antigens are those that do not directly stimulate the production of antibody without the help of T cells. B cell epitope T cell epitope Humoral immunity and cellular immunity Antibody: five types Immune memor

16、y Proteins are thymus -dependent antigens.,Antigen,TI-Ag胸腺非依赖性抗原 Thymus -independent antigens are antigens which can directly stimulate the B cells to produce antibody without the requirement for T cell help In general. only B cell epitope Humoral immunity Antibody :IgM No Immune memory polysacchari

17、des are TI- antigens.,Antigen,TI-Ag Thymus-independent antigens can be subdivided into Type 1 and Type 2 based on their ability to polyclonally activate B cells. Type 1 TI-Ag(LPS) are polyclonal activators while Type 2 are not.,Antigen,异嗜性抗原 Heterophilic Ag (Forssman antigen) -A cross-reacting antig

18、en that appears in widely ranging species such as humans and bacteria. Postinfectious glomerulonephritis: group A Streptococcus glomerular basement membrane,Antigen,Types of antigens,Forssman antigen,Heterophilic Ag (Forssman antigen),Xenogenic Ag异种抗原 -An antigen found in more than one species. Allo

19、genic Ag同种异型抗原 -individuals of a species differ in alleles (are allogeneic) and the antigenic differences will cause an immune response to allografts. The antigens concerned are often of the MHC and are referred to as alloantigens.,Antigen,Autoantigen自身抗原 -The antigens of an organisms own cells and

20、cell products are self antigens to the immune system of that organism. - Clones of immune cells reactive with self antigens are normally eliminated.,Antigen,Types of antigens,idiotypic Ag独特型抗原 - The combined antigenic determinants (idiotopes) found on antibodies of an individual that are directed at

21、 a particular antigen; such antigenic determinants are found only in the variable region.,Antigen,Endogenous antigen内源性 Exogenous antigen外源性,Tolerogen, allergen,耐受原Tolerogen: an antigen that induces a state of specific immunological unresponsiveness 变应原Allergen: a substance capable of inducing aller

22、gy or specific hypersensitivity. pollens, dust, drugs, and foods,Stimulator(superantigen, adjuvant, mitogen),超抗原Superantigen (SAg) - When the immune system encounters a conventional TD-Ag, only a small fraction (1 in 104 -106) of the T cell population is able to recognize the antigen and become acti

23、vated (monoclonal/oligoclonal response). However, there are some antigens which polyclonally activate some subtypes of the T cells (up to 20%). These antigens are called superantigens. 外源性：SE(AE)T cell SPAB cell 内源性：小鼠乳腺肿瘤病毒蛋白,Antigen,超抗原激活T细胞与普通抗原不同,佐剂Adjuvant it is a substance which, when mixed wi

24、th an antigen, enhances the immune response against the antigen. The use of adjuvants, however, is often hampered by undesirable side effects such as fever and inflammation. 生物性佐剂；无机化合物；人工合成物；有机物；脂质体 FCA（弗氏完全佐剂）, FIA （弗氏不完全佐剂）, BCG, CP, LPS, CpG。,丝裂原Mitogen 淋巴细胞多克隆激活剂 ConA PhA PWM,Antigen,Some Key Points,An antigen is defined by any molecule which is recognized