(I) Lecture 6: T cell Immunity Part I Flashcards
Where do T cells develop?
T cells start to develop in the bone marrow and finish developing in the Thymus
Types of T-cells
Cytotoxic T lymphocyte (CTL, CD8+ cells)
- kill infected “target cells” and activate macrophages
- respond to MHC Class I
T helper lymphocyte (Th1, CD4+ cells)`
- activate macrophages, B cells and other cells, and increase response
- respond to MHC Class II
APC
Antigen Presenting Cell
- ex. dendritic cells, macrophages and B cells
T-cell differentiation
- Antigen recognition (using APC cells)
- Activation (of naive CD4+/CD8+ cells)
- Clonal expansion (cytokines generate expansion)
- Differentiation
Differentiate into effector CD4+ cells or memory CD4+ cells which differentiate into effectors
- same process for CD8+ cells
T cell receptor
has an antigen binding site
each T-cell expresses a TCR with a variable region specific for ONE unique peptide (multiple receptors but all same specificity)
T-cells can only recognize/bind antigens of PROTEIN origin
Antigen vs epitope
Antigen: protein
Epitope: peptide (smaller, exposed)
T-cell antigen recognition
Epitopes recognized by TCRs are often buried
- Antigen must first be broken down into peptide fragments
- Epitope peptide binds to an MHC molecule
- TCR binds to a complex of MHC and epitope peptide (must be perfect fit to antigen and MHC)`
MHC Class I
- peptide comes from ENDOGENOUS sources (both self and not self)
- present to CD8+ T cells
- peptides are shorter than class II
- made up of one large glycoprotein heavy chain and a small protein light chain (ONLY ONE TRANSMEMBRANE DOMAIN)
MHC Class II
- peptide comes from EXOGENOUS sources
- present to CD4+ T cells
- peptides are longer
- made up of two nonidentical membrane-bound glycoprotein chains (TWO TRANSMEMBRANE DOMAINS)
MHC
Major Histocompatibility Complex
MHC-TCR interactions
- antigenic epitopes MUST be associated w/ MHC molecules to be recognized by T cells
- need right peptide and right MHC to be recognized
Co-receptors of T-cells
Mature CD4+ expresses co-receptor CD4
Mature CD8+ expresses co-receptor CD8
Co-receptors interact w/ MHC on the SIDE (NOT in the pocket)
Superantigens
- bind w/ high affinity to MHC class II on APC (small amount of superantigen = intense T-cell signalling)
- cross-link to beta T-cell receptors
- crosslinking activates both T cell and APC (constant)
- since stimulation is not specific (will work even if peptide is the wrong fit), NO adaptive immunity
- causes excessive production of cytokines (CD4)
Effect of superantigens on host
- systemic toxicity
- suppression of adaptive immune response
Double Positive stage in T-cell development
The benefit of expressing both is that it can offer T cell options as T cells will not know whether its TCR will bind MHC I and MHC II. Once the T cell finds out which MHC it can bind to, it will keep only one (CD4 or CD8) on its surface.
B and T cell development
In the bone marrow, they undergo random gene recombination to acquire a single specificity on the receptors in each B and T cell
Then, they will travel to secondary lymphatic tissues to detect pathogens.
Example of superantigen
Toxic Shock Syndrome toxin-I from Staphylococcus aureus
Menstrual Toxic Shock Syndrome
- vaginal culture will be positive for abundant S. aureus
- treated w/ IV fluids, anti-staphylococcal antibiotics, and IVIG (intravenous immunoglobulin)
Targets of T-cells
main role is against INTRACELLULAR pathogens
- intracellular viruses
- intracellular bacteria (escape phagolysosome)
T-cells and cytosolic pathogens
- degraded in cytosol
- peptides bind to MHC class I
- presented to CD8 T cells (cytotoxic)
- causes cell death
T-cells and intravesicular pathogens
- degraded in endocytic vesicles (low pH)
- peptides bind to MHC class II
- presented to CD4 T cells (helper cells)
- cause activation of macrophages to kill intravesicular bacteria and parasites
How do MHCs work?
- endogenous antigens are degraded by the proteasome into smaller peptides (MHC class I)
- exogenous antigens are engulfed into endocytic compartments and degraded by endosomal and lysosomal enzymes (MHC class II)
- antigenic peptides associate w/ MHC class I or II
- MHC-peptide complexes are then transported to the cell membrane
Where is MHC class I expressed?
Expression is found THROUGHOUT the body
- allows ongoing surveillance of internal happenings of the cell
Where is MHC class II expressed?
Expression is primarily restricted to antigen-presenting cells
- ONLY specialized leukocytes have this ability
What cells express MHC I?
- All nucleated cells express MHC I (dendritic and somatic)
- Many unique peptides are presented at same time
- not only foreign antigens are loaded, also self-peptides
MHC Class I action on cytosolic pathogens
- Virus infects cell
- Viral proteins synthesized in cytosol
- Peptide fragments of viral proteins bound by MHC class I in ER
- Bound peptides transported by MHC class I to cell surface
MHC Class II action on intravesicular pathogens
ONLY APCs can engulf extracellular pathogens and load their antigenic epitopes on MHC class II
- since they are nucleated cells, APCs can present antigens that come from intracellular locations on MHC class I as well
Memory T cells
Bulk of surviving pathogen-specific cells are memory cells
Most effector T cells have short half-lives (only 5-10% remain after pathogen is cleared)
% of circulating T cells that are memory cells increase as a person ages
- b/c they have been exposed to more pathogens and thymus shrinks, making less T cells
True or False
Antigenic epitopes recognized by T cells must be associated with MHC molecules to be recognized
True
True or False
All nucleated cells express MHC molecules
False
ONLY APC cells express MHC II
True or False
A single T cell can express multiple TCRs on its surface. All of these TCRs have different specificities
False
A single T cell can express multiple TCRs on its surface. All of these TCRs have the same specificity
