1.3.1 Antigen Capture and Presentation

Question 1

What are the 3 states of activation of T cells?

Answer 1

Naive, Memory, Effector

Question 2

What the two locations that memory T cells tend to reside?

Answer 2

Lymph node (waiting for Ag presentation via an APC), Tissues (surveilling for that particular Ag)

Question 3

What APC is best for naive T cells?

Answer 3

DCs

Question 4

What are some APCs that can activate effector T cells?

Answer 4

Macrophages, B cells, DCs

Question 5

Describe these features of classical DCs: surface markers, major location, expression of toll-like receptors, major cytokines produced, and postulated major function.

Answer 5

surface markers: CD11c, CD11b (complement proteins) major location: tissues expression of toll-like receptors: TLR 3, 4, 5, 8 high major cytokines produced: TNF, IL-6, IL-12, IL-23 postulated major function: Induction of T cell response against most Ag

Question 6

How do most naive T cells enter the lymph nodes?

Answer 6

High endothelial venule (HEV)

Question 7

Where within the lymph node do T cells and DCs interact w/ one another?

Answer 7

Paracortex

Question 8

Where within the lymph node are naive B cells most commonly aggregated?

Answer 8

Follicles of the cortex

Question 9

Via what vessel do DCs enter the lymph node? exit?

Answer 9

Enter: Afferent lymphatic vessel Exit: Efferent lymphatic vessel

Question 10

Where are plasma cells primarily located within the lymph node?

Answer 10

Primarily medula, also been indicated to reside in the paracortex

Question 11

Describe the process a DC must go through from when it encounters an Ag in the epithelia and goes on to present that Ag to T cells in the lymph node.

Answer 11

1) Ag capture (epithelia) 2) Activation of the DC 3) Migration of the DC 4) Maturation of the migrating DC 5) Mature DC presentation to naive T cell (paracortex of lymph)

Question 12

Where are blood borne Ag’s most often found by DCs?

Answer 12

The spleen

Question 13

Which of the following does a patient have a higher risk of after a splenectomy? A) Autoimmunity B) Periodic fever syndrome C) Sepsis D) Uncontrolled viral infection

Answer 13

Sepsis It isn’t D because viral infections require host cells, the host cells would be encountered by DCs then the viral Ag’s could be presented to the naive T cells within the lymph nodes

Question 14

What is the term for T cells only being able to recognize peptide Ag in the MHC molecule?

Answer 14

MHC restriction

Question 15

What is the name of the genomic section that codes for the MHC complex? Draw it and its components.

Answer 15

Human leukocyte antigens (HLA)

Question 16

Are MHC genes highly conserved or highly polymorphic? Why?

Answer 16

highly polymorphic, allows for greater repertoire of recognition of adaptive immune system, ensures at least some members of the population will be able to present a particular microbial protein Ag

Question 17

What do the polymorphic residues of the MHC genes determine?

Answer 17

Which Ag peptide is presented by which MHC

Question 18

Describe the expression of MHC?

Answer 18

Codominantly expressed - alleles inherited from both parents expressed equally

Question 19

How many haplotypes of MHC do all heterozygous individuals have?

Answer 19

2 HLA

Question 20

Describe the Class I MHC.

Answer 20

alpha 1 and 2 (polymorphic) form the peptide binding cleft alpha 3 (constant): CD8 binding site 1 TM region

Question 21

Describe the Class II MHC

Answer 21

Alpha 1 and Beta 1 (polymorphic): peptide binding cleft beta 2 (constant): CD4 binding site

Question 22

What length of peptide is suitable for class I MHC? class II MHC?

Answer 22

Class I: 8-11 Class II: 10-30

Question 23

What is the name of the phenomenon that MHC is capable of presenting many different peptides?

Answer 23

Promiscuity

Question 24

For an functioning MHC molecule to be expressed on the surface, what must occur?

Answer 24

Acquire peptide during assembly inside cells

Question 25

Do MHC molecules display self peptides?

Answer 25

Yes, expression of MHC I is crucial for survival of self cells. The trick is that the within healthy individuals the cells only respond to foreign Ag

Question 26

What type of cells expressed MHC class I?

Answer 26

All nucleated cells

Question 27

What type of cells express MHC class II?

Answer 27

APCs (DC, ME, B cells), thymus, induced on other cells by IFN-gamma

Question 28

Describe the process of MHC II peptide loading.

Answer 28

1) Uptake of extracellular proteins into vesicular compartments of APC 2) Processing of internalized proteins in endosomal/lysosomal vesicles 3) Biosynthesis and transport of class II MHC molecules to endosomes 4) Association of processed peptides w/ class II MHC molecules in vesicles 5) Expression of peptide-MHC complexes on cell surface

Question 29

What prevents the Class II MHC from binding self peptides while it resides in the ER?

Answer 29

Invariant chain

Question 30

The invariant chain that block binding of self Ag’s while in the ER is cleaved into CLIP while in endosomes. What removes CLIP to allow the Ag peptide to be loaded?

Answer 30

HLA-DM

Question 31

Describe the process of MHC I peptide loading.

Answer 31

1) Cytosolic proteins are degraded by the proteasome IFN-g increases efficiency 2) Peptides are transported into the ER by the TAP complex (TAP: transporter associated with antigen processing)—TAP1/TAP2 3) Chaperones-calreticulin and calnexin bind immature, unstable class I 4) Passed off to chaperone tapasin, which mediates the interaction between TAP and MHC class I 5) MHC class I loaded with peptide 6) Stable MHC/peptide complex goes to cell surface

Question 32

What is cross presentation? What cells are capable of it?

Answer 32

It is the process in which cells infected with intracellular microbes, such as viruses, are ingested (captured) by professional APCs, and the antigens of the infectious microbes are broken down and presented in association with the major histocompatibility complex (MHC) molecules of the APCs; a subset of DC

Question 33

How do immune reactions to superantigens differ from immune reactions of standard antigens?

Answer 33

Polyclonal; Since Sag doesn’t need to fit within the peptide binding groove because it can cause association of TCT and MHC w/out doing so, it is able to activate many types of T cells. Polyclonal activation leads to a cytokine storm

Question 34

What type of Ag’s are recognized by alpha/beta T cells?

Answer 34

Peptide

Question 35

Of what chemical moiety are the Ag’s that are bound by B cells?

Answer 35

Proteins, polysaccharides, lipids, small chemicals

Question 36

What is the special type of cell used to display Ag to B cells w/in LN?

Answer 36

Follicular Dendritic Cells (FDCs)

Question 37

What the Ags on FDCs coated w/?

Answer 37

Ab’s or complement byproducts

Question 38

NKT cells have what type of receptor? What does it bind?

Answer 38

Invariant TCR, Lipids expressed on CD1d

Question 39

What type of Ag’s do gamma/delta T cells bind?

Answer 39

Variety of Ags

Question 40

A mutation in TAP1, TAP2 or tapasin expression would lead to what type of deficiency?

Answer 40

Bare lymphocyte syndrome Type I: HLA class I deficiency; no MHC I expression

Question 41

A mutation in 1 of the 4 genes that encode txn factors that regulate MHC II expression (CIITA, RFX5, RFXAP, or RFXANK) will lead to what type of deficiency?

Answer 41

Bare lymphocyte syndrome Type II: HLA class II deficiency; no MHC II expression

Question 42

What type of Ag’s are involved with MHC Class II peptide loading? MHC Class I?

Answer 42

MHC Class II: extracellular Ag (Ag cleaved in endosome) MHC Class I: intracellular Ag (cleaved by proteasome in cytosol)

Question 43

Where do naive, memory, and effector T cells reside?

Answer 43

Naive and Memory: Lymph node Effector: Skin, Mucosa

Question 44

What is this an image of?

Answer 44

MHC class I

Question 45

What is this an image of?

Answer 45

MHC class II