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 3- D 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 IClass II Genetic loci (partial list) HLA-A, -B, and –CHLA-DP, -DQ, and –DR Polypeptide composition MW 45,000 +  2 M (MW 12,000)  chain,  chain, and Ii chain Cell distributionAll nucleated somatic cells Antigen-presenting cells, activated T cells Present peptide antigens to CD8 T cellsCD4 T cells Size of peptide bound 8 – 11 residues10 – 30 or more residues

Comparison of Class I and Class II MHC Proteins Feature Class I MHC Class II MHC Present antigen to CD4+ T cellsNoYes Present antigen to CD8+ T cellsYesNo Found on surface of all nucleated cellsYesNo Found on surface of professional APCsYes Encoded by genes in the HLA locusYes Expression of genes is codominantYes Multiple alleles at each gene locusYes Composed of 2 peptides encoded in HLA locus NoYes Composed of one peptide encoded in the HLA locus & a  2-microglobulin YesNo