Chapter 2 Flashcards
Immunogen
macromolecules capbale of triggering an adaptive immune response by inducing the formation of antibodies or sensitized T cells in an immunocompetent host
can specifically react with antibodies or sensitized T cells
Antigen
a substance that reacts with an antibody or sensitized T cells but may not be able to evoke an immune response in the first place
Relationship of immunogen to antigen
Immunogen = antigen; antigen =/= immunogen
Immunogen is basically a type of antigen; angiten is a broader term
Biological properties of an individual that influence the immune response
age (middle aged = best) overall health (nourishment/fatigue/stress) dose (quantity of immunogen) route of inoculation (IV, ID, SubQ, oral) genetic capacity (MHC)
Immunogenicity
the ability of an immunogen to stimulate a host response
depends on macromolecular size, foreigness, chemical composition/molecular complexity, ability to be processed and presented with MHC molecules
Immunogenicity characteristics
molecular weight - the bigger the beter (response)
foreigness - allows distinguishing self from nonself
chemical composition/chemical complexcity - longer/larger chains of proteins/amino acids (more complex shapes)
ability to be processed - must be degraded and presented to MHC to create a response
Epitope
key portion of the immunogen (determinant site)
molecular shapes or configurations that are recognized by B/T cells
Linear/conformational epitope
LE - (sequential) amino acids following one another on a single chain
CE - One+ chains folded to make linear and conformational epitopes
Antigen-presenting cell (APC)
cell that degrades and presents immunogens for immune response
Haptens
nonimmunogenic materials that, when combines with a carrier, create new antigenic determinants
small substances that cannot create a rxn on their own
categorized as antigens (not immunogens)
hapten + carrier = precipitation and agglutination reaction
Examples of haptens
Catechols (H) (poison ivy) + tissue proteins of skin -> rxn of skin
Penicillin (Normal body proteins + hapten)
Adjuvant
a substance administered with an immunogen that increases the immunce response in order to provide immunity to a particular disease help make immunization more effective protect immunogens from degradation + allow a longer response time (larger immune response)
Autoantigens
antigens that belong to the host do not evoke an immune response under normal circumstances
Autoimmune Disease
when autoantigens become self reactive to the body
Alloantigens
antigens from other members of the host’s species and are capable of eliciting an immune response important to tissue transplantation and blood transfusions
Heteroantigens
antigens from other species (other animals, plants, or microbes)
Heterophile anitgens
heteroantigens that exist in urelated plants or animals but are either identical or closely related in structure so that antibody to one will cross-react with antigen of the other
(blood group A/B antigens and bacterial polysaccharides)
SRBCs
Sheep red blood cells important to the development/study of heterophile antigens
MHC location and function
- located on all nucleated cells in the body
- function in determining self/non-self, can function as antigens, activate T cells
- once called HLA - Human Leukocyte antigens
MHC system
- most polymorphic system found in humans
- code for proteins immune recognition/ diverse immunogens
MHC gene coding
- found on short arm of chromosome 6
- 3 categories/ classes
MHC class 1
- found at 3 loci; A,B,C
- only one gene coding for each particular molecule
MHC Class 2
- found in the D region
- loci are DR,DQ, DP
- one gene codes for alpha chain; 1+ gene(s) code for beta chain
MHC Class 3
- Found between Class 1 and class 2 regions on chromosome 6
- codes for C4A, C4B, C2, and B complement proteins, Cytokines and tumor necrosis factor
Roles of MHC classes
MHC class 1 and 2 - involved in antigen recognition (influence the antigens Tcells respond to)
MHC class 3 - secreted proteins that have an immune function (not expressed on cell surfaces
Alleles
alternate forms of a gene that code for slightly different varieties of the same product
Polymorphic system (MHC)
many possilbe alleles at each location at each loci
(HLA-A) 2,013
(HLA-B) 2,605
(HLA-C) 1,551
Low probability that 2 individuals will express the same MHC molecules
characteristics of MHC genes
- codominant (all alleles expressed)
- Haplotype inheritance (closely linked, genes inherited together)
- each inherited chromosomal region has a package of genes for A,B,C,DR,DP,DQ
- One haplotype inherited from each parent
expression of MHC class 1
- on all nucleated cells
- highest on lymphocytes and myeloid cells
- low/undetectable on liver hepatocytes, neural cells, muscle cells and sperm
Structure of Class 1 MHC molecules
Glycoprotein dimer of two noncovalently linked polypeptide chains
alpha chain (heavier), folded into 3 domains, inserted in the cell membrane, hydrophobic
Beta 2- microglobulin (lighter) encoded by one gene on chromosome 15 (not polymorphic)
(this is the same in every Class 1 molecule, essential for folding of alpha chain, no cell membrane penetration
expression of MHC class 2
found on APCs (B lymphocytes, monocytes, macrophages, dendritic cells, thymic epithelium)
Structure of Class 2 MHC molecules
DP,DQ,DR - 2 noncovalently bound polypeptide chains (heterodimers)
DR expressed the most (accounts for 1/2 of all Class 2 molecules)
DR beta - most highly polymorphic
Antigen presentation
process by which degraded peptides within cells are transported to the plasma membrane where T cells can then recognize them
MHC classes present to which T cells
Class 1 molecules peptides synthesized withine the cell to CD8 T cells (viral, tumor, parasitic antigens)
Class 2 molecule present exogenous antigen to CD4 T cells (bacterial infections, extracellualr pathogens)
Class 1 MHC-peptide interaction
Endogenous pathway of antigen presentation
synthesized in ER and bind peptides from where they are bound on the ER
forms a complex and moves to the cell surface where it can be recognized by T cells
CD8+ T cells produce cytokines that cause lysis of the entire cell
Proteasomes
large cytoplasmic complexes of the proteases
cleave peptides for delivery to class 1 molecules
Transporters associated with antigen processing
proteins responsible for ATP-dependent transport of peptides to class 1 molecules
most efficient with 8-16 amino acids in size
Class 2 MHC - peptide interaction
synthesized in ER (+invariant chain), transported to endosomal compartment where they can bind to peptides
binds to peptides of 13-18 amino acid residues
once bound, molecule is transported to cell surface for recognition by T cells
CD4+ recruits and triggers B-cell response
Clinical importance of MHC molecules
Ankylosing spondylitis Celiac disease Rheumatoid arthritis Type 1 diabetes (autoimmune diseases) Vaccine sensitivity
