Download ANTIGEN Molecule that is recognized by specific antibody or T cells

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Transcript
Fe A. Bartolome, MD, FPASMAP
Department of Microbiology
Our Lady of Fatima University
IMMUNOGENS
• Protein or carbohydrate that challenges the
immune system and that can initiate an
immune response
• Molecules that induce an immune response
• Any substance that is capable of inducing
an immune response (humoral or cellular or
both)
ANTIGEN
• Molecule that is recognized by specific
antibody or T cells
• Molecules that react with antibodies
• Substance that is recognized by a particular
immunoglobulin or T receptor and serve as
target of an immune response
ANTIGEN
PROPERTIES:
1. Foreignness
2. Chemical composition
3. Molecular size
4. Chemical complexity
5. Genetic constitution of host animal
6. Method of administration
HAPTEN
• Molecule that is not immunogenic by itself
but can react with specific antibody
• A low MW substance which by itself cannot
stimulate an immune response
• Has to be bound to a carrier molecule
• Cannot activate helper T cells  unable to
bind to MHC proteins since are not
polypeptides
• Univalent  cannot activate B cells by
themselves
EPITOPE
• Antigenic determinant
• Actual molecular structure that interacts
with a single antibody molecule or T cell
receptor
• Types:
1. Linear epitope – formed by a specific
sequence
2. Conformational epitope – formed by a 3D structure
EPITOPE
B CELL EPITOPE
• Region that is recognized by
immunoglobulins
• Size can encompass 3-20 amino acids or
sugar residues
EPITOPE
T CELL EPITOPE
• Region recognized by T cell receptor
•
recognized by T lymphocytes only after
being processed and presented in
association with an MHC protein
ADJUVANT
• Substance, which when mixed with an
antigen, enhances the magnitude and
duration of the immune response
• Functions:
1. Prolong retention of immunogen
2. Increase the effective size of the
immunogen
3. Stimulate local influx of macrophages or
immune cells to the injection site
ADJUVANT
EXAMPLES:
1. Complete Freund’s adjuvant
• Heat-killed mycobacteria in mineral oil
2. Liposomes – defined lipid complexes
3. Bacterial cell wall components
4. Polymeric surfactants
5. Cholera toxin & E. coli lymphotoxin – potent
adjuvants for IgA
MHC genes
• Human leukocyte antigens
• Chromosome 6
• Determines success of tissue and organ
transplants
• Bind peptide antigens and present them to T
cells
• Expression: co-dominant
• Polymorphic  diverse  many alleles at each
locus from each parent
• Polygenic
MHC glycoproteins
CLASS I MHC MOLECULES
• Coded for by HLA-A, HLA-B, HLA-C
• Heterodimer  polymorphic  (heavy) chain
noncovalently bound to a 2-microglobulin
(chr. 15)
• Heavy chain composed of:
1. Hypervariable region – important for
recognition of self and non-self
2. Constant region – CD8 T cell binding site
• Found on all nucleated cells and platelets
• Present endogenous peptides
CLASS II MHC MOLECULES
• Coded for by HLA-D (DP,DQ,DR)
• Heterodimer  noncovalently associated 
chain and  chain
• Composed of:
1. Hypervariable region – responsible for
polymorphism
2. Constant region – CD4 T cell binding site
3. Invariant chain (Ii) – protect the binding site
• Found on APC’s
• Present exogenous antigens
MHC glycoproteins
CLASS III MHC MOLECULES
• Between class I and class II; soluble proteins
• Contain immunologically important genes
encoding for:
1. Cytokines – TNF and lymphotoxin
2. Complement components – C2 and C4
• Does not have genes that code for
histocompatibility antigens
BIOLOGIC IMPORTANCE:
1. Antigen recognition by T cells
 CD8 T cells  class I MHC molecules
 CD4 T cells  class II MHC molecules
2. Autoimmune diseases occur in people who
carry MHC genes (e.g. HLA-B27 in ankylosing
spondylitis)
3. Success of organ transplants is determined
by compatibility of MHC genes of donor and
recipient.
Important Features of Some Human MHC Gene
Products
Class I
Genetic loci (partial HLA-A, -B, and –C
list)
Class II
HLA-DP, -DQ, and
–DR
Polypeptide
composition
MW 45,000 + 2M
(MW 12,000)
 chain,  chain,
and Ii chain
Cell distribution
All nucleated
somatic cells
Antigen-presenting
cells, activated T
cells
Present peptide
antigens to
CD8 T cells
CD4 T cells
Size of peptide
bound
8 – 11 residues
10 – 30 or more
residues
Comparison of Class I and Class II MHC Proteins
Class I
MHC
Class II
MHC
Present antigen to CD4+ T cells
No
Yes
Present antigen to CD8+ T cells
Yes
No
Found on surface of all nucleated cells
Yes
No
Found on surface of professional APCs
Yes
Yes
Encoded by genes in the HLA locus
Yes
Yes
Expression of genes is codominant
Yes
Yes
Multiple alleles at each gene locus
Yes
Yes
Composed of 2 peptides encoded in HLA
locus
No
Yes
Composed of one peptide encoded in the
HLA locus & a 2-microglobulin
Yes
No
Feature