Antigen Processing, Presentation and Co-Stimulation Flashcards
What does MHC stand for?
Major Histo-Compatibility Complex
What does APC stand for?
Antigen Presenting Cell
List the basic steps in Lymphocyte activation:
- Microbe infects host
- Microbe is taken up by APC at the site of infection
- APC enters lymph circulation toward Lymph node (LN)
- Naive T and B cells enter LN from circulation
After activation of naive lymphocytes, what happens next?
Clonal Expansion and Differentiation into effector and memory lymphocytes
Which lymphocyte will take up residence in tissues and secondary lymphoid organs?
memory lymphocytes
Which type of lymphocytes are faster at responding?
memory lymphocytes are much quicker than effector lymphocytes in the case of a future infection
Which T cells are MHC I restricted and recognize cytosolic proteins?
CD8+
Which T cells are MHC II restricted and recognize extracellular (and intravesicular) pathogens?
CD4+
______ _______ is central to the development of immune response (the bridge between antigen recognition and initiation of immune response).
Antigen Presentation
Antigen presentation enables ______-mediated killing or enables antibody production by _______.
T cell
B cells
Antigen recognition WITHOUT antigen presentation can result in _______ and a minimized chance of autoimmune activity.
tolerance
A series of molecular interactions takes place to present small fragments of ____ ________ to T cells.
Protein antigens
Antigen presentation is modulated by ________ molecules.
Co-stimulatory
Successful antigen presentation results in activation of ____.
T Cells
Which APCs are most effective for initial T cell activation (priming).
Dendritic Cells
What is “initial T cell activation” also known as?
Priming
Which APCs must be activated by phagocytosis before presenting antigens?
Macrophages
Which APCs are the major type for secondary immune response?
B Cells
All _______ cells can present endogenous antigens in association with MHC ___ molecules.
nucleated
MHC I
What are three important monocyte derivatives?
Macrophages (tissue)
Microglia (brain)
Kupffer Cells (liver)
Which two APCs are inducible for Class II expression
[negative to Positive expression]?
- Lymphocytes
2. Facultative Antigen Presenting Cells
Which APCs are inducible for Class II expression [Positive to Greatly Positive]?
Phagocytes (monocyte lineage)
What is “the process by which antigens are digested and placed on the cell surface with correct MHC molecules”?
Antigen Processing
In the two pathways for antigen presentation: Pathway 1 is used for _____ antigens, whereas Pathway 2 is used for ______antigens.
1 EXogenous
2 ENDogenous
In Pathway 1, exogenous antigens are taken into the cell and then small peptide antigens are presented to ____cells together with MHC class ____.
T Helper Cells
Class II
In Pathway 2, endogenous antigens are taken into the cell and then small peptide antigens are presented to ________ cells.
CD8+ T Cells
Cytoplasmic Proteins are broken into peptides via ______ and then the peptides are broken down into amino acids via exopeptidase.
Proteasome
Endocytic Proteins are broken into peptides via ______. Then the peptides are broken down to amino acids via exopeptidase.
Lysosome
Degradation of intracellular proteins into peptides occurs through enzymatic action.
Proteasome breaks down _________
Lysosome breaks down __________.
Pro= cytoplasmic proteins Lys= endocytic proteins
__________ breaks down peptides into amino acids.
Exopeptidase
The “Cytosolic Pathway” is used for ________ antigens.
ENDogenous
In the cytosolic pathway, proteins are tagged with _______ for breakdown into peptides.
Ubiquitin
Describe the steps in the cytosolic pathway that is used for endogenous antigens.
- Cell is infected
- Proteins are tagged with Ubiquitin for proteolysis
- Ubiquitin-Protein complex enters the proteasome
- Complex is degraded into peptides
- Peptides are transported into the lumen of the RER via transporters (TAP)
- MHC I (newly synthesized) within RER membrane binds to antigen peptide
- Antigen-MHC I Complex is released and transported to the cell surface
Which transporter molecule is associated with antigen processing and allows peptides to cross the RER membrane?
TAP
The “Endocytic Pathway” is used for ________ antigens.
EXogenous
Exogenous antigens that bind to the membrane surface will enter _______-______ vesicles. The vesicle will then un-coat and fuse to form an _______ which will then degrade the proteins.
Clathrin-Coated
Endosome
The endogenous pathway is used to present peptides on the surface of ________. The exogenous pathway is used to present peptides on _______.
Endo = MHC I Exo = MHC II
Endogenous proteins are tagged with ______for degradation; exogenous proteins are ______ and degraded.
Ubiquitin
Endocytosed
Describe the steps in the endocytic pathway that is used for exogenous antigens.
- Antigens bind to membrane receptors and are internalized within endosomes
- Digestion begins in the endosome, then continues within lysosomes
- Class II molecules are produced at RER and associated with “Invariant Chain Protein”
- Class II-Invariant Chain Protein complex moves into endocytic compartment
- Invariant Chain Protein is digested into CLIP (fragment)
- HLA-DM triggers the exchange of CLIP and antigen peptide
- Peptide Class II is released to the cell surface
The binding of Class II molecules with ________ prevents binding to endogenous antigens and initiates movement into endocytic compartments.
Invariant Chain Protein (li)
Invariant Chain Protein (li) is digested into the short fragment _______ which will be exchanged for antigen peptide in the presence of HLA-____.
CLIP
DM
HLA-____ blocks the activity of HLA-DM and therefore does not allow the exchange of CLIP for antigen peptide.
DO (off)
Class II MHC is associated with presentation of _____ antigens to _______Lymphocytes.
Extracellular
CD4+ Helper T Lymphocytes
Class I MHC is associated with presentation of _______ antigen to ________ lymphocytes.
Cytosolic
CD8+ Cytotoxic T Lymphocytes
The antigen-expressing target cell is marked for direct killing when cytosolic antigen is presented to ______.
CD8+ Cytotoxic T Lymphocytes
Antigen presentation to CD4+ helper T Lymphocytes will result in _______ ________ or ______ ________.
Macrophage Activation (on macrophage) Antibody Binding (on antigen-specific B cell)
MHC I molecules are composed of a _______ noncovalently attached to a ________. MHC II molecules are composed of a _______ noncovalently attached to a ________.
I = Polymorphic Alpha Chain + NonPolymorphic B2 microglobulin
II = Polymorphic Alpha Chain + Polymorphic Beta Chain
What are three influences of MHC (HLA) haplotype?
- How an individual responds to certain pathogens
- Susceptibility to certain diseases
- Transplant success
MHC genes (mice) are equivalent to _____ in humans.
HLA
MHC genes are highly _______ which is why it is difficult to find transplant donors.
Polymorphic
What is “MHC haplotype”?
The set of MHC alleles on an individual chromosome that determines which peptides bind and how peptides bind
T cells constantly survey for foreign antigens and _____is essential for antigen presentation to T cells.
MHC
Self MHC + Foreign Ag = ________
T Cell Response
Self MHC + Self Ag = ________
No T Cell Response
MHC molecules have a _______ specificity for peptides.
Broad
What is MHC Restriction?
A given T cell will recognize a peptide antigen only when it is bound to a host body’s own MHC molecule. This dual recognition system is critical to T Cell Function
MHC restriction prevents destruction of _______.
Self Tissue
Cell-cell adhesion is mediated by multiple ligand-receptor pairs. Molecular interaction occurs between _____ and ______. The interaction is mediated by T cell receptors, ligands (MHC), and _________.
T cells
antigen-presenting cells
intracellular adhesion molecules
MHC-peptide complex binds to ______.
TCR (T-cell Receptor)
How is the antigen-TCR interaction strengthened by CD4?
CD4 interacts with both:
MHC II on the APC
and with
TCR on the T-cell
CD8 interacts with _____ on the target cell and ______ on the T cell.
MHC I
TCR
What is the T-Cell ligand for co-stimulatory molecule B7 on APC?
CD28
Adhesion Molecule ICAM-1 on the APC binds to its T Cell ligand ______.
LFA-1
List the order of interactions at the immunological synapse.
- MHC I (APC) binds to TCR (T Cell)
- MHC I (APC) is bound by CD8 (T Cell)
- Co-Stimulatory Molecule B7 (APC) binds to CD28 (T Cell)
- Adhesion ICAM-1 (APC) binds to LFA-1 (T Cell)
At the immunolocial synapse, which molecules are involved in adhesion?
ICAM-1
LFA-1
At the immunological synapse, which molecules are involved in costimulation?
B7
CD28
What is the structure of TCR?
Membrane-anchored heterodimer consisting of the highly variable alpha (α) and beta (β) chains expressed as part of a complex with the invariant CD3 chain molecules on each side.
What are the two different forms of B7 Receptors?
Before T Cell Activation: B7–CD28 –>activation/division
At Immune Termination: B7–CTLA-4 –>inactivation
CTLA-4 will actively block signals from the TCR and CD28 when it is bound to which molecule?
B7
At the termination of the immune response, CTLA-4 replaces ________ and downregulates T cell function.
CD28
Which molecule is considered to be the main activator of T cells?
IL-2
Non-Self products will stimulate the expression of MHC, adhesion molecules, and _______ molecules which determines the modality of their responses.
Co-stimulatory
What is the difference between Th1 and Th2 in their inflammatory action?
TH1 = Pro-Inflammatory (cell mediated) TH2 = Anti-Inflammatory (humoral/antibodies)
TH1 is involved in ______ immunity.
cell-mediated
TH2 is involved in _______ immunity.
Humoral
After antigen presentation, tyrosine kinases associated with TCR/CD4(8) complex are activated. These active TK will then _______.
Phosphorylate cytoplasmic tails of the clustered receptors and initiate the kinase cascade
The kinase cascade results in the induction of ____ and ____ which will lead to cell division.
IL-2 and IL-2R
IL-2 ligation to IL-2R results in _____ _______.
Cell Division
Which receptor is essential for amplification of the T cell response?
IL-2
Interleukin-2 will act on T cells and NK cells to initiate what processes?
T Cells: clonal expansion, differentiation into effector and memory cells
T Cells: Regulate development, “Survival Sign”
NK Cells: cell proliferation, increased cytotoxic activity
TH1 and TH2 regulate each other and the interleukins driving their development are different.
IL- ____ drives TH1
IL-_____ drives TH2
IL-12 (th1)
IL-4 (th2)
TH1 cells will lead to activation of ______ in the presence of ____ and _____.
Macrophages
TNF-alpha
IFN-gamma
TH2 cells will lead to _______ in the presence of ____ and ____.
B Cells
IL-4
IL-5
Which molecules are important in regulating the complex balance of T Helper 1 and T Helper 2 cells?
Cytokines
The following are a result of which helper cell activation?
- macrophage activation
- complement binding and opsonization
- neutrophil activation
Th1
Which cytokine is extremely important for Th1 activity?
IFN-gamma
The following are a result of which helper cell activation?
- Production of neutralizing IgG antibodies (mast cells)
- Production of IgE
- Eosinophil activation
- Suppression of macrophage activation
Th2
Which cytokine is extremely important for Th2 differentiation/expansion and inhibition of Th1?
IL-4
Antigen recognition of MHC II results in ____ T Cell activation, clonal expansion via IL-___ and activation of ___ cells in peripheral tissue.
Naive CD4+
2
B
Antigen recognition of MHC I results in ____ T Cell activation, clonal expansion via IL-___ and activation of ______ in peripheral tissue.
Naive CD8+
2
macrophages
