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DEPARTMENT OF IMMUNOBIOLOGY
Antigens (Ag)Antigens (Ag)
Xiaowu Hong
Department of ImmunologyShanghai Medical College of Fudan University
I Definition and characteristics of antigenI Definition and characteristics of antigen
II Properties of Ag: Foreignness and specificity II Properties of Ag: Foreignness and specificity
III Factors that influence immunogenicity III Factors that influence immunogenicity
IV Classification of antigenIV Classification of antigen
V Nonspecific stimuli for immune responseV Nonspecific stimuli for immune response
antigen
Antigen (Ag)
Chapter 1 Definition of antigenChapter 1 Definition of antigen
Substances that combine combine specificallyspecifically
with a B or T cell’s antigen-binding rece
ptors can then induceinduce an immune respo
nse are called antigens.
Antigen (Ag)
Antigen binding causes cytotoxic T cells
Memory T cell
Activated cytotoxic T cell
Antigen binding triggers release of antibodies
Memory B cell
Activated B cell
Antibodies
Chapter 2 Characteristics of antigen
( 1 ) immunogenicit
y
( 2 ) antigenicity
The antigen molecule generally pose The antigen molecule generally pose two natures, that is two natures, that is
(1) Immunogenicity
Immunogenicity is t
he ability to induce a humoral and / or cell mediated immune response, including induce production of antibody and effector lymphocytes.
Activated B cell
antibody
Activated CTL
(2) antigenicity
Antigenicity is the ability to combincombine specificallye specifically with the final products of the above responses (i.e., antibody and /or cell-surface receptors).
antigenicity
immuogenicity
T
TT
Ag
1 SpecificitySpecificity of antigen The characteristic that antigen only binds the antibody and sensitized lymphocyte specifically, is called specificity of antigen ( Specificity )
Antigenic determinants or epitopes are the i
mmunologically active regions of an immuno
gen that bind to antigen-specific membrane r
eceptors on lymphocytes (TCR/BCR) or to se
creted antibodies.
(1) Antigenic determinants or epitopes
Epitope or An
tigenic Deter
minant
antigen
antigen antigen
1 Conformational epitope
Nonsequential polypeptides or polysaccharide on the sursur
faceface of the molecules,
Native conformationNative conformation,
2 liner epitopeA sequential amino acid fragment,
Linear determinantLinear determinant,
InsideInside of the antigen molecule
Structure of epitopes
Conformational and Linear Epitope
T cell Epitope and B cell EpitopeIn immune response, the epitopes that TCR and BCR recognize is different, and are called T cell epitope and B cell epitope, separately.
( 1 ) human pancreatic glucagon was inoculated into the mouse
12 3 4 5
67
89
1011
1213
14 1516
17
18NH3
1920
2122
2324
2526
2728
29 COOH
( 2 ) Production of specific antibody and T effector cell.
antibody : aim directly at 1~17 amino acids in the N terminal
T effector cell :aim directly at 18~29 amino acids in the C terminal
No epitope was found to be recognized by T cell and B cell simultaneously.
*natural,
*on the surface of the molecule
* conformational or sequential determinant
* tertiary structure of the molecule
COOH
12 3 4 5
67
89
1011
1213
14 1516
17
18
NH3
1920
2122
2324
2526
2728
29
* Antigenic peptide presented by APC* linear determinant
T cell Epitope and B cell Epitope
T cell Epitope
T cell EpitopeB cell Epitope
Digested
**on surface of molecule antigen
antibodyCDR3
epitope
B cell epitope
is recognized by BCR and antibody
** conformational determinants
(i) B cell epitope
(ii) T cell epitope The peptide that is presented by MHC molecule a
nd recognized by TCR is called T cell epitope .
TCR
MHC
HIV peptide
TCR recognize MHC/antigenic peptide
TCR
Antigenic peptide
MHC-II
T cell
APC
Ep1 Ep2 Ep3
T Cell epitope
Antigenic peptides recognized by T cell form
trimolecular complexes with a TCR and an MHC molecule
Depend on the amino acid sequence of the peptide
Relevant to the expression of MHC molecule of the host
(2) Common antigen and cross-reaction Each B cell determinant induces production of a
specific antibody. Thereby a complicated antigen can
induce production of multiply antibodies.
complicated antigen
A same or similar antigenic determinant
that exists between the two different antigens
is called common antigen .
The reaction that antibody reacts with same or
similar antigenic determinant between the
different antigens is called cross-reaction.
Cowpox vaccineVA
CC
INE Smallpox virus
Bm cell
Immunological memory
ABcowpoxDE
Anti-Cowpox antibody
cowpox Bm cell
Anti- Cowpox antibody against Smallpox
Smallpox Bm cellcowpox Bm cell
days
First response to antigen Cowpox
Antigen Cowpox immunity
Antigen SmallpoxAntigen B immunity
Ant
ibod
y co
ncen
trat
ion First response
to antigen B
Secondary response to antigen Smallpox
Foreignness is the centre of immunogen .
The greater of the phylogenitic distance between two species, the greater the structural disparity between them.
**Various pathogens ,animal protein
**homologuous
**Self-molecule that has not been exposed to immature
lymphocytes during lymphocyte development may be later
recognized as nonself, or foreign,by the immune system.
2 Foreignness
Chapter 3 Factors influencing
immunogenicity
1 Physicochemical nature of antigens
(1) chemical nature glycoprotein, lipoprotein 、 polysaccharide 、 LPS
DNA , chromosome 、 histone in the activated lymphocyte
Auto-antibody for self-DNA, histone
Antinuclear antibody (ANA)
Autoimmune diseases
(2) molecule size
>10kD
>100kD
<10kD
immunogens
Strong immunogens
Poor immunogens
The higher is the molecule weight
The more are antigenic determinants
The more complex is the antigenic structure
Not be degradated easilier
Stimulating immune cell continuously
High immune response
(3) complicated chemical structure
Glutin MW>100kD )
Straight chain amino acid Add Aromatic amino acid ( 2% tyrosine )
( poor immunogenicity ) ( better immunogenicity )
(4) conformation and accessibility of the molecule
+++ ± +++
Tyrosine poly-alanine Glutan poly-lysine
immunogenicity
(1) Genetic characteristics of the host
Genetic control of immune responsiven
ess, largely confined to genes within the MH
C.
(2) Age, sex, and state of healthInfection, use of immune inhibitor
2 Effect of host
Chapter 4 Classification of antigens1. Depend on whether need the Th for producing the antibody
** thymus dependent antigen, TD-Ag **thymus independent antigen, TI-Ag
TI and TD antigen
1
2
CD40/CD40L
B cell B cell Th cell
TI- antigen TD antigen
CD4
1 2
(1) Thymus dependent antigen, TD-AgT-dependent Antigens - do not directly stimulate the production of antibody without the help of T cells.
Proteins . Structurally characterized by a few copies of many different antigenic determinants
(2) Thymus independent antigen, TI-AgT-independent Antigens - directly stimulate the B cells to produce antibody without the requirement for T cell help Polysaccharides
Characterized by the same antigenic determinant repeated many times
2 Depend on the relationship with host
(1) Xenogenic Ag : The antigen from diffe
rent species is called xenogenic antigen.Microorganism Animal immune serum for therapy : horse serum (antitoxin)
Horse serum antitoxins posses dual natures :
(i). Specific antibody ---- neutralization of toxin(ii). Xenogenic antigen---stimulate production of antibody against horse serum
toxoidtoxin
Horse serum
antitoxin
hypersensitivity
antibody
antigen
(2) Allogenic Ag :The antigens from different individuals of the
same species are called allogenic antigen.
Human allogenic Ag : blood type ( RBC ) antigen Histocompatibility (transplantation) antigens
Blood type : ABO and Rh
A B O AB
antigen
antibody
A B - A,B
Anti-B anti-A anti-A,anti-B -
Blood type
RBC
+
RBC
complement
RBC
RBC
Type A
A antigen
Type B
Anti-A antibody
Anti-A antibody
transfusion reactiontransfusion reaction
RBC
Autoimmune hemolytic anemia
drug
RBC
Auto-antibody
RBCAg-Ab complex
Activate complement
Membrane of RBC
C9C8
C5b
6 7
(3) AutoantigenInfection, wound and medicine use make the
covercover antigen release or auto-antigen changed or modified, which induce response for auto-antigen.
(4) Hetorophilic antigen, or Forssam antigen
Hemolytic streptococcus B C antigen M antigen
Streptococcus infection
Acute Glomerulonephritis
Glycoprotein of Cardiac valve heart muscle
Rheumatic fever
Streptococcus A
Glomerular basement membra
ne
The hetorophilic antigens are common antigen, which are irrelevant to s
pecies and exist in human, animal, plant and microorganism.
Ⅵ Superantigen, SAg
1 conception:Exceed low dose(1 ~ 10ng/ml) of superantigen is needed to a
ctive 2 %~ 20 % of T cell clones to initiate very strong immune response.
2 category:Exogenous superantigen eg.Staphylococcus aureus enterotoxin A-
E
Endogenous superantigen eg. mouse mammary tumor virus protei
n
3 difference with common antigen :1 ) low dose, but strong response2 ) not constraint by MHC3 ) recognition is not specific , and procession and presentation is not required4 ) induce a lot of cytokines releasing, resulting in severe pathologic disease
Ⅶ MitogensSubstances which can active a cluster of lymphocytes including a lot of clones.
Such as ConA, PHA,PWM, LPS and so on.
Nonspecific stimuli for immune responseNonspecific stimuli for immune response
Ⅷ adjuvant1 conceptionAdjuvants (from Latin adjuvare, to help) are substances that, when mixed with an antigen and injected with it, enhance the immunogenicity of that antigen.
2 category
Biological agents: BCG
Inorganic compound:Al(OH)3
Synthesis: cytidine monophosphate(CMP ), liposome
immunostimulating complex ( ISCOM )CpG et al which is neotype of adjuvant
Freund‘s complete adjuvant (CFA) and Freund’s non-complete adjuvant (IFA) are co
mmonly used
3 mechanism of actionn Prolong antigen persistencen Enhance co-stimulatory signalsn Induce granuloma formationn Stimulate lymphocyte proliferation nonspecifically
1.Master the concept , characteristic of the antigen, and the factors influencing immunogenicity ( chemical nature, molecule size, foreignness, and genetic characteristics of the host ).2. Master antigenic determinant, common antigen.3.Understand antigen category.4.know superantigen5.Understand the important antigen in medicine.
School of Medicine
Fudan University