Antigen Presentation

Question 1

List the antigen presenting cells.

Answer 1

Mononuclear Phagocytes => macrophages
Dendritic Cells
B Cells

Question 2

Where are mononuclear phagocytes/macrophages found?

Answer 2

blood, liver, spleen

Question 3

Where are dendritic cells found?

Answer 3

skin, lymph tissue

Question 4

Where are B Cells found?

Answer 4

lymph tissue, immune reaction sites

Question 5

Which APCs are phagocytic?

Answer 5

macrophages

dendritic cells

Question 6

What are Kupffer cells?

Answer 6

liver sinusoidal macrophages

Question 7

What are microglial cells?

Answer 7

brain macrophages

Question 8

What are Langerhans’ cells?

Answer 8

skin dendritic cells located between skin layers

Question 9

Where are follicular dendritic cells found?

Answer 9

found in the B cell zone of lymph nodes

Question 10

Where are interdigitating dendritic cells found?

Answer 10

found in the T cell zone of lymph nodes

Question 11

Describe how Langerhans’ cells respond to antigen?

Answer 11

• 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

Question 12

What happens to dendritic cells once they phagocytose the antigen?

Answer 12

• increased MHC expression
• increased surface area
• decreased phagocytic capabilities
• increased presentation capabilities

Question 13

What are the 2 dendritic cell lineages?

Answer 13

• conventional

- plasmacytoid - produce anti-viral interferons

Question 14

Where is MHC synthesized?

Answer 14

ER

Question 15

Describe the mechanism of antigen processing in Class I expressing cells.

Answer 15

1. virus enters the cell => uncoats => hijacks nucleus => production of viral proteins
2. viral proteins are degraded into peptides via the proteasome
3. antigen peptides enter the ER through TAP transporter proteins
4. ERAAP cleaves the peptides further into 8-10 AA that will fit in the MHC Class I peptide cleft

Question 16

What are the domains of the proteasome?

Answer 16

LMP2

LMP7

Question 17

Describe MHC Class I maturation.

Answer 17

1. nascent MHC Class 1 alpha chain is misfolded and associated with calnexin
2. B2-m invariant chain then joins the misfolded alpha chain => dissociates from calnexin
3. nascent MHC (alpha and beta) join chaperone proteins calreticulin and ERp57
4. associates with tapasin, which brings it closer to TAP
5. processed antigen enters through TAP and binds to MHC Class I
6. released from ER in an endosome
7. surface expression

Question 18

To what T cells to Class I molecules present?

Answer 18

CD8+ cytotoxic T cells

Question 19

What happens to Class I antigen processing and presentation under normal conditions?

Answer 19

old, defective, or misfolded proteins that are destined for the proteasome get degraded and are loaded on to MHC to act as self-antigens

Question 20

Describe antigen processing in MHC Class II expressing cells.

Answer 20

1. foreign antigen is phagocytosed into a phagolysosome

2. phagolysosome is acidified and antigen is degraded into peptides

Question 21

Describe the mechanisms of MHC Class II maturation.

Answer 21

1. fully synthesized MHC Class II is associated with an invariant chain the ER
2. MHC:Invariant is released from the ER into an endosome
3. The endosome is acidified and the invariant chain is degraded, except for CLIP that remains in the peptide cleft

Question 22

Describe the mechanism of antigen loading in MHC Class II expressing cells.

Answer 22

1. phagolysosome carrying degraded antigen peptide fuses with the endosome carrying MHC:CLIP
2. HLA-DM enters the fused vesicle and unload CLIP
3. loads and unloads antigen peptides until one is bound tightly enough to resist unloading
4. MHC:Peptide is expressed on the surface

Question 23

To what T cells do MHC Class II molecules present?

Answer 23

CD4+ T cells

Question 24

What do MHC Class II cells express under normal conditions?

Answer 24

CLIP

Question 25

Compare MHC maturation in Class I and Class II cells.

Answer 25

Class I: completed in the ER and then released | Class II: only MHC is released from the ER; loading occurs in the cytosol

Question 26

Compare MHC normal condition expression in Class I and Class II cells.

Answer 26

Class I = self antigen | Class II = CLIP

Question 27

Compare MHC antigen sources in Class I and Class II cels.

Answer 27

Class I = invader virus creates viral proteins inside the cell Class II = foreign antigen found in the ECF is phagocytosed

Question 28

Define MHC restriction in T cell recognition.

Answer 28

CD4+ T cells will only recognize antigen if it is associated with MHC Class II on an APC

Question 29

What do TH1 cells do?

Answer 29

activate macrophages to kill the antigen that they phagocytosed

Question 30

What do TH2 cells do?

Answer 30

activate B cells to produce antibodies

Question 31

What are the signals needed for naive T cell activation?

Answer 31

- MHC:peptide interacts with TCR | - B7 interacts with CD28

Question 32

What happens if T cells come in contact with APCs that do not express B7?

Answer 32

1. MHC:Peptide interacts with TCR 2. T cell expresses CD40L 3. CD40L interacts with CD40 on APC surface 4. CD40 binding stimulates APC to express B7 5. B7 interacts with CD28 => second signal complete

Question 33

What signals are needed for T cells to activate B cell proliferation?

Answer 33

- MHC:Peptide => TCR - B7 => CD28 - CD40 => CD40L => cytokines released

Question 34

Describe the zones of the immune synapse.

Answer 34

central zone = MHC:peptides and co-stimulatory factors | peripheral zone = adhesion molecules (T cell expresses LFA, APC expresses ICAM)

Question 35

What is the purpose of adhesion molecules in the immune synapse?

Answer 35

allows for better interaction between MHC:peptide and TCR