Antigen-Specific Immune Responses Flashcards
Antigen specific immune responses
- Expand the host protection provided by innate immune responses
Antigen specific immune responses are provided by
- T cells
- Antibodies
Almost any molecule has the potential to
- Initiate an immune response
Features of antigen specific immune responses
- Randomly generated
- Regulated response
- Inducible response
- Ignores “self” proteins
Central immune tolerance
- During fetal growth the body develops “tolerance” towards self-antigens
Peripheral tolerance
- Develops later in life
- Tolerance to other proteins to prevent uncontrolled or autoimmune responses
Class I MHC antigens
- Expressed on the surface of all nucleated cells
Class II MHC antigens
- Expressed by antigen-presenting cells (APCs)
- Dendritic cells , macrophages and B lymphocytes
Immunogen
- A protein or carbohydrate that challenges the immune system
- Induces an immune response
- May contain more than one antigen
Antigens
- A molecule that is recognized by a specific antibody or a by a T cell antigen receptor (TCR)
Epitope
- Actual molecular structure that interacts with a single antibody molecule or TCR
- Also called the “antigenic determinant”
Monoclonal antibody recognizes
- A single epitope
Immunogen performance
- Not all molecules are immunogens
- Proteins = best
- Carbohydrates = weaker
- Lipids and nucleic acids = poor
The type of immune response initiated by an immunogen depends on the molecular structure
- Rapid antibody response initiated towards bacterial polysaccharides, peptidoglycan, or flagellin
- Due to repetitive structure of these molecules
T-independent antigens
- Large repetitive structures
- Polysaccharides, peptidoglycan, LPS
T-independent antigens primitive response
- Fails to stimulate an anamnestic response (production of an antibody due to previous stimulation by the same antigen)
T-dependent antigens (proteins)
- Must be presented to T and B cells for antibody production
- Able to stimulate all 5 classes of immunoglobulins
- Elicit an anamnestic response
T-cell help needed to stimulate
- Response with memory
Adaptive immune response initiated when
- Receptors of lymphocytes recognize antigens
B cells antigen receptors
- Antibodies that can recognize a wide variety of molecules (proteins, polysaccharides, lipids, nucleic acids)
T cells
- “See” only peptide fragments of protein antigens
- Can only “see” when peptides are presented by specialized peptide display molecules on host cells
Antigens recognized by T cells
- Recognize peptide antigens that are bound to and displayed by major histocompatibility complex (MHC) molecules of antigen-presenting cells (APCs)
Major histocompatibility complex (MHC)
- A genetic locus whose principal products function as the peptide display molecules of the immune system
MHC restriction
- In every individual, different clones of T cells can see peptides only when these peptides are displayed by that individual’s MHC molecules
How do the rare lymphocytes specific for any microbial antigen find that microbe?
How does the immune system produce the effector cells and molecules best able to eradicate a particular infection?
- The immune system has developed a highly specialized system for capturing and displaying antigens to lymphocytes
Distinguishing surface markers of T cells
- TCR – T cell receptor
- CD2
- CD3
- CD4 or CD8
Antigens recognized by T cells
- T cell receptor (TCR) recognizes some residues of a peptide antigen
- TCR recognizes residues of the MHC molecule that is displaying that peptide
How T cell receptor recognizes peptide antigen
- Dual specificity
- MHC on antigen-presenting cells display peptides derived from protein antigens
- Peptides bind to the MHC molecules
- TCR of every T cell recognizes some residues of the peptide and some residues of the MHC molecule
Antigen-presenting cells
- Specialized cells that capture microbial antigens and display them for recognition by T lymphocytes
Naive T lymphocytes need to see protein antigens presented by
- Dendritic cells: the most effective “professional” APCs to initiate clonal expansion and effector cell differentiation
Differentiated effector T cells again need to see antigens, presented by various APCs, to activate
- Effector functions of the T cells in humoral and cell-mediated immune responses
T cell development
- Thymus: genetic events generate numerous TCRs
- Each TCR expressed on a different T cell clone
- Those that cannot interact with MHC do not grow
- Those that react with host are signaled for apoptosis
T cells are distinguished by
- Type of T-cell antigen receptor they express
- Either consisting of γ and δ chains or α and β chains
- Further distinguished by the cytokines they produce
Distinguishing factor of α/β T cells
- Presence of CD4 or CD8 co-receptors
Specificity of the TCR determines
- Antigenic response of the T cell
Each TCR molecule
- Each made up of two different polypeptide chains (α and β)
- Each chain has a constant region and a variable region (like antibody)
TCR chains are anchored in
- Plasma membrane
TCRs are not produced in
- Secreted form
TCR repertoire
- Very large
- Identify a large number of antigenic specificities
- Estimated to recognize 10^15 separate epitopes
- TCRs bind antigen presented with the MHC molecules
Structure of T cell receptor gene
- Genetic mechanisms for the development of the diversity is similar to those for antibody
TCR gene composition
- Multiple V (V1V2V3 … Vn), D, and J segments
- Only cells with functional TCRs will survive
- Each T-cell clone expresses a unique TCR
