Antigen

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power point file for antigen

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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 Antigen: Immmunogen Tolerogen Allergen Vaccine I. Definition of antigen

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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

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2.Tolerogen: antigen that induce Immunologic tolerance Immunologic tolerance is unresponsiveness to an antigen that is induced by prior exposure to that antigen. tolerogen

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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

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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

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Classification of Ag

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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.

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According to source of antigens Xenoantigen Alloantigen Autoantigen 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 Exotoxin Produced by G+ bacteria Strong antigenicity and pathogenicity Toxoid : exotoxin that loses its toxicity but maintains its antigenicity under suitable conditions (low concentration of formaldehyde ) Such as tetanus toxoid , diphtheria toxoid

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HIV Pathogens Fungi bacteria

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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

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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.

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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

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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

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. 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.  2. Immunoreactivity 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

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Specificity of Ag Ab1 Ab2 Ab3

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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).

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1. Antigen determinants (epitope) (1) The portion of antigen molecules which can be specifically recognized by antibody or antigenic receptor of lymphocytes. Protein antigen----5-15 amino acid residues Polysaccharide antigen----5-7 polysaccharide residues

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Chicken lysozyme bound to an antibody Three dimension figure of Angiotensin(Ag) II binding to antibody

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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

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The chemical component , arrangement and conformation affect the specificity of antigen

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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 Conformational 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.

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(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.

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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

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(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