Lecture 7- Antigen Recognition: Processing and Presentation Flashcards
TCRs only recognized antigens that are:
presented by an MCH molecule on the surface of an APC
(PROCESSED and made of PROTEINS)
What are the 6 stages (?) of T-cell activation?
1 - Recognition & antigen binding
2 - Stimulation (Due to the clustering of cell surface receptors (TCRs), Polarized to one side of the cell)
3 - Clustering (Signals development inside the T cell membrane)
4 - Signal transduction (Transduction of PTKs & interaction w/ receptors)
5 - Signal is amplified (Transmitted to interior of cell)
6 - Response by T cell (Gene transcription & proliferation = clonal expansion, Production of cytokines)
Reading and Steering Cars Sometimes Seems Reasonable
What is the first signal for T-cell activation?
Antigen binding and Co-stimulation
What do co-stimulatory molecules (CD4 or CD8) do?
- Act as co-receptors
- Recognize the MHC 2 or MHC 1
- Aid to stabilize the TCR-MHC interaction → stronger binding
What do accessory molecules do, and what are some examples?
- aid in binding TCR-APC
- CD11 [or LFA-1]——CD54 [or ICAM-1]
- CD28——-B7
What are PTKs and what do they do?
protein tyrosine kinases
PTKs along with protein tyrosine phosphatases link receptors & biochemical pathways
- this happens by phosphorylation of ITAM’s and enzymes
what is the end result/goal of signaling?
- proliferation
- differentiation
- expression of cytokines
Superantigens activate T cells without ____.
attaching to the groove of MCH molecules
The attachment of superantigens is ______.
non-specific
- attaches to the variable domain of the ß chain of TCR
- Large numbers of T cells are activated
What is LFA?
Lymphocyte function-associated antigen
Activation of naive T cells leads to their proliferation & differentiation into ____ cells.
effector cells
What is the primary function of B cells?
antibody secretion & memory formation
What is the primary function of dendritic cells?
antigen presentation
Where are macrophages located?
peripherial tissues
Where are dendritic cells located?
peripherial tissues
Where are B cells found?
secondary lymphoid organs (SLO) and in circulation
Which cell can internalize antigens bound to its receptor and present them?
B cells
Which cell can phagocytose small amounts of extracellular debris for antigen presentation?
Dendritic cells (DC)
Which cells can load foreign peptides onto both MCH class molecules (1 and 2)?
Professional APCs
Which cells express MHC 1?
all somatic cells
Which cells express MHC 2?
professional APCs
What is an ICAM?
Intercellular adhesion molecules
What is an ITAM?
Intracellular adhesion molecules
The route of the antigen w/in the host determines the ________.
MCH selectivity
- Extracellular -> MHC2
- Intracellular -> MHC1
What are some features of MHC 1?
- Expressed by all somatic cells
- Cytosolic antigens
- Activates cytotoxic CD8 T cells = cell death
- Endogenous
- Both host cell & antigen within host cell → DIE
What are some features of MHC 2?
- Expressed by professional APCs
- Vesicular antigens
- Activates helper CD4 T cells
- Aids in Humoral & Cellular immune response
- Exogenous
- ONLY the antigen dies
rrrr
Why is cross-presentation by dendritic cells needed?
- Non-professional APCs do NOT migrate to lymph nodes → do NOT stimulate the immune system
- Infected DC can be compromised → unable to migrate to lymph node → do NOT stimulate the immune system
What is the function of cross-presentation by dendritic cells?
Uninfected DC able to internalize debris from killed host cells → travel to lymph node → initiate adaptive responses
How long does antigen processing take?
minutes to hours
Cross → MHC 1-exogenous antigen via Dendritic cells [an APC] INSTEAD of via somatic cell
Pathogen/antigen was exogenous = MHC 1-antigen that killed host cell = SOMATIC route
Dead host cell phagocytosed by dendritic cell = MHC 1 STILL being presented but via dendritic cell
CD8 will be activated b/c MHC 1
CD4 is NOT activated even though an APC is being used
How does antigen processing work?
- pathogens and their proteins are degraded into smaller peptides
- peptide fragments fit into/ combine with MHC 1 or MHC 2 binding grooves.
The process by which pathogens and their products are degraded to produce peptide antigens is known as ______.
Antigen processing
The MHC-peptide complex travels to the cell surface where it displays peptide fragments to T cells. This is known as _______.
Antigen presentation
Antigen presentation is only required for ________.
Activation of T cells
What happens during antigen presentation?
Generate small pieces of protein from the PATHOGEN = the epitopes i.e the antigen binding portion → can be recognized by TCR
Binds to TCRs on T cells best suited to eliminate that specific pathogen
Dictated by MHC selectivity & MHC restriction
Antigen-peptides are synthesized in the _______.
cytosol
What kind of antigens are processed on MHC 1? Explain the process.
Endogenous antigens
Intracellular antigens
Cytosol antigens
Ag-peptide attaches to MHC 1 and moves to the cell surface
Ag is recognized by cytotoxic T-cells which destroy the infected host cell
What kind of antigens are processed on MHC 2? Explain the process.
Exogenous
Vesicular antigen
Extracellular antigen
Activate humoral or cellular immune response
What do lymphocytes do once they recognize an antigen?
Proliferate
- some of the newly produced cells carry out the attack; others influence the activation and function of the attack cells
Where are lymphocytes activated?
in lymph nodes near the site of infection
What does IL-1 do?
It increases the permeability of vascular endothelium and stimulates the production of IL-6
What does IL-6 do?
It acts on the liver which leads to the production of acute phase reactants (ex: C-reactive protein), causing inflammation
What does IL-8 do?
It attracts & activates neutrophils, and increases the permeability of vascular endothelium
What does IL-12 do?
It activates NK cells and influences lymphocyte differentiation
Ubiquitin-tagged viral protein is processed via ________.
proteasome
What contributes to the recognition and binding of exogenous antigens on professional APCs?
- PRR and PAMPs
(pattern recognition receptor & pathogen-associated molecular pattern) - Mediated by various receptors
What contributes to the ingestion/phagocytosis of exogenous antigens on professional APCs?
- receptor-mediated endocytosis
- macropinocytosis by dendritic cells
destruction within the vesicles (?)
idk how to word this as a question
What does the secretion of cytokines and chemokines do?
Attracts other APCs and immune cells
What do phagolysosomes contribute to?
Degradation of antigens by lysosomal components = small peptide fragments produced
Acid hydrolases
Reactive oxygen species ROS
Nitrous oxide
What is ROS and some examples?
Reactive Oxygen Species
- Superoxide radicals
- Hypochlorite radicals
- Hydroxyl radicals
