Antigen Presentation Flashcards
List the antigen presenting cells.
Mononuclear Phagocytes => macrophages
Dendritic Cells
B Cells
Where are mononuclear phagocytes/macrophages found?
blood, liver, spleen
Where are dendritic cells found?
skin, lymph tissue
Where are B Cells found?
lymph tissue, immune reaction sites
Which APCs are phagocytic?
macrophages
dendritic cells
What are Kupffer cells?
liver sinusoidal macrophages
What are microglial cells?
brain macrophages
What are Langerhans’ cells?
skin dendritic cells located between skin layers
Where are follicular dendritic cells found?
found in the B cell zone of lymph nodes
Where are interdigitating dendritic cells found?
found in the T cell zone of lymph nodes
Describe how Langerhans’ cells respond to antigen?
- phagocytose antigen in the skin
- travel to the lymph nodes via afferent lymphatic vessels
- once they enter the part of the lymph node where T cells are present, they are interdigitating cells
- interdigitate with T cells and present antigen
What happens to dendritic cells once they phagocytose the antigen?
- increased MHC expression
- increased surface area
- decreased phagocytic capabilities
- increased presentation capabilities
What are the 2 dendritic cell lineages?
- conventional
- plasmacytoid - produce anti-viral interferons
Where is MHC synthesized?
ER
Describe the mechanism of antigen processing in Class I expressing cells.
- virus enters the cell => uncoats => hijacks nucleus => production of viral proteins
- viral proteins are degraded into peptides via the proteasome
- antigen peptides enter the ER through TAP transporter proteins
- ERAAP cleaves the peptides further into 8-10 AA that will fit in the MHC Class I peptide cleft
What are the domains of the proteasome?
LMP2
LMP7
Describe MHC Class I maturation.
- nascent MHC Class 1 alpha chain is misfolded and associated with calnexin
- B2-m invariant chain then joins the misfolded alpha chain => dissociates from calnexin
- nascent MHC (alpha and beta) join chaperone proteins calreticulin and ERp57
- associates with tapasin, which brings it closer to TAP
- processed antigen enters through TAP and binds to MHC Class I
- released from ER in an endosome
- surface expression
To what T cells to Class I molecules present?
CD8+ cytotoxic T cells
What happens to Class I antigen processing and presentation under normal conditions?
old, defective, or misfolded proteins that are destined for the proteasome get degraded and are loaded on to MHC to act as self-antigens
Describe antigen processing in MHC Class II expressing cells.
- foreign antigen is phagocytosed into a phagolysosome
2. phagolysosome is acidified and antigen is degraded into peptides
Describe the mechanisms of MHC Class II maturation.
- fully synthesized MHC Class II is associated with an invariant chain the ER
- MHC:Invariant is released from the ER into an endosome
- The endosome is acidified and the invariant chain is degraded, except for CLIP that remains in the peptide cleft
Describe the mechanism of antigen loading in MHC Class II expressing cells.
- phagolysosome carrying degraded antigen peptide fuses with the endosome carrying MHC:CLIP
- HLA-DM enters the fused vesicle and unload CLIP
- loads and unloads antigen peptides until one is bound tightly enough to resist unloading
- MHC:Peptide is expressed on the surface
To what T cells do MHC Class II molecules present?
CD4+ T cells
What do MHC Class II cells express under normal conditions?
CLIP
Compare MHC maturation in Class I and Class II cells.
Class I: completed in the ER and then released
Class II: only MHC is released from the ER; loading occurs in the cytosol
Compare MHC normal condition expression in Class I and Class II cells.
Class I = self antigen
Class II = CLIP
Compare MHC antigen sources in Class I and Class II cels.
Class I = invader virus creates viral proteins inside the cell
Class II = foreign antigen found in the ECF is phagocytosed
Define MHC restriction in T cell recognition.
CD4+ T cells will only recognize antigen if it is associated with MHC Class II on an APC
What do TH1 cells do?
activate macrophages to kill the antigen that they phagocytosed
What do TH2 cells do?
activate B cells to produce antibodies
What are the signals needed for naive T cell activation?
- MHC:peptide interacts with TCR
- B7 interacts with CD28
What happens if T cells come in contact with APCs that do not express B7?
- MHC:Peptide interacts with TCR
- T cell expresses CD40L
- CD40L interacts with CD40 on APC surface
- CD40 binding stimulates APC to express B7
- B7 interacts with CD28 => second signal complete
What signals are needed for T cells to activate B cell proliferation?
- MHC:Peptide => TCR
- B7 => CD28
- CD40 => CD40L => cytokines released
Describe the zones of the immune synapse.
central zone = MHC:peptides and co-stimulatory factors
peripheral zone = adhesion molecules (T cell expresses LFA, APC expresses ICAM)
What is the purpose of adhesion molecules in the immune synapse?
allows for better interaction between MHC:peptide and TCR
