Dec 6th - MHC/antigen presentation + T cell recognition

Question 0

Learning objective 1:

What is the purpose of the invariant chain

Answer 0

To stabilize the MHCII molecules that are inside vesicles awaiting antigen.

Question 1

Learning objective 1:
Explain the MHC I antigen processing pathway
Explain the MHC II antigen processing pathway

Answer 1

MHC I pathway:
Intracellular or ‘self’ anitgens are sent to the proteosome or immunoproteosome (professional APCs), and broken into short peptides. The peptades are then brought to the ER by TAP protein, loaded onto new MHC I molecules, and transprted to the cell surface by the golgi.

MHCII: Extracellular antigens are phagocytosed and passsed into acidic endosomes, and broken down by proteases. Endosomes/lysosomes fuse with vesicles containing MHCII molecules. Inside vesicles, MHCII’s travel with invariant chain to maintain stability. CLIP protein will cleave invariant chain, leaving a small peptide is the binding site, which can be exchanged for the antigen. The exchange is facilitated by the chaperone protein DM.

Question 2

Learning objective 1

What is the purpose of the CLIP protein?

Answer 2

Cleaves invariant chain, leaving a peptide in the site of MHCII molecules to stabilize them. The peptide can be exchanged for and antigen..

Question 3

Learning objective 1

What is the purpose of the molecule DM

Answer 3

To exchange the invariant chain peptide with that of the antigen in the MHC II active site.

Question 4

Learning objective 1:

What is the purpose of transporter associated with processing molecule (TAP)

Answer 4

transports antigen fragments from the proteosome to the ER , so that mthey may complex with MHC I

Question 5

Learning objective 2
In the absence of cross presentation, the MHC I pathway uses _____ and ______ antigens, while the MHC II pathway uses ________ antigens.

Answer 5

Intracellular or self

Extracellular

Question 6

L.O. 2

Cross presentation occurs when a(n) _______ antigen is presented via the ___________ Pathway

Answer 6

Extracellular…..MHC I pathway

Question 7

LO 2

Cross presentation enables a ______ + T cell response against pathogens that ___________________________

Answer 7

CD8+ (CTL) respose against pathogens that donnt directly infect APCs

Question 8

LO3

MHC I is composed of a single polymorphic invariant chain and a small invariant chain called:

Answer 8

Beta 2 Mircoglobin

Question 9

LO3

The peptide binding cleft for an MHC I molecule can accomodate peptides:

Answer 9

~8-10 AAs long

Question 10

LO3

MHCII is composed of:

Answer 10

1 alpha and 1 beta chain, each encoded by different genes on the MHC locus.

Question 11

LO3

MHCII molecules have a binding cleft that can accomodate peptides :

Answer 11

~8-30 AAs

Question 12

LO4

What are anchor residues?

Answer 12

AA’s with specific characteristics (charge, phobocity) that reside on peptides, which provides specificity for the polymorphic variability in the MHC’s binding cleft.

Question 13

LO5

The MHC Locus on chromosome 6 encodes ______ and ______

Answer 13

MHCI and MHCII

Question 14

LO5

In humans the MHC locus is called the:

Answer 14

Human leukocyte antigen, HLA

Question 15

LO5

What is the HLA?

Answer 15

Human luekocyte antigen, this is the MHC locus

Question 16

LO5

The HLA encodes ____ MHCI molecules and _____ MHCII molecules. In total a human has ______ MHC molecules.

Answer 16

3, 3

In total we have 12 MHC moleccules, because we have onee copy of chomosome 6 from each parent.

Question 17

LO5

MHC molecule expression is ______________, meaning that APCs express ALL MHC molecules simultaneously.

Answer 17

co-dominant

Question 18

LO6

How is antigen obtained by DCs (blood borne and periph tissues)

Answer 18

for blood borne antigens, the spleen acts as a filter
in peripheral tissues, DCs indiscriminantly phagocytose material.

Pathgen-associated molecular patterns are molecular signals form pathogens that trigger maturation of the DC, causing it to lose tissue sppecific adhesion and travel to lymphatics.

Question 19

LO6

How does PAMPS facilitate DC transport to lymph nodes

Answer 19

After exposure to pathogen associated molecular patterns (PAMPS) DCs lose phagocytic capability, upregulate MHC, increase costimulator activity. For transport, they lose tissue adhesion.

Question 20

Professional APCs are those that express MHC I and MHC II constitutivley. The 3 types of professional APCs are:

Answer 20

DCs
Macropahges
B cells

Question 21

LO7

Each T cell expresses one SINGLE T cell receptor (TCR). The TCR is composed of a(n) ________ and __________

Answer 21

Alpha chain and Beta chain

Question 22

LO7
Each of the two poly peptide that make up a TCR (alpha and beta) are formed by rearrangement of Multiple regions. the four types of regions are:

Answer 22

V - variable
D - diversity
J - joining
C - constant

Question 23

LO8
the hyper-variable regions of the TCR (alpha and Beta polypeptides) interact directly with the peptide bound to the _____________ region of the MHC molecule

Answer 23

polymorphic

Question 24

LO8
After TCR binds to peptide:MHC…
CD8 co-receptors will bind the _______region of ______
and CD4 co-receptors will bind the __“_____ region of ______

Answer 24

Nonpolymorphic (constant) region

CD8 binds MHC I
CD4 binds MHC II

Question 25

LO8

Upon binding TCR to peptide/MHC, T cell signaling is induced by ______ and _____. This is known as __________

Answer 25

CD 3 and zeta chain.

Known as “signal 1”

Question 26

LO9

The “signal 2” provided by APCs to T cells is also known as:

Answer 26

Costimulation

Question 27

LO9

Costimulation is provided by interaction of _____ on APCs and ________ on T cells.

Answer 27

B7 on APCs and CD 28 on T cells.

Question 28

LO9
B7 is only exprressed on:
(Cell type + When)

Answer 28

Professional APCs after recent encounters with pathogen.

Question 29

LO9
If T cells bind pptide:MHC on a non professional APC, they recieve signal ___ without signal ___. This results in inactivation, or ________.

Answer 29

recieve signal 1 without 2.

Called ANERGY

Question 30

LO9

Anergy occurs when

Answer 30

a T cell is inactivated because it bound peptide:MHC but without any Costimulation (From B7/CD28). (I.e. signal 1 but no signal 2)

Question 31

LO12

Binding TCR-peptide:MHC releases small chemokines that result i n activation of _________

Answer 31

Integrins

Question 32

LO12
Integrins expressed on t he T cell will form tight interactions with ligand on the APC, forming what is called the _________ ________

Answer 32

Immunological synapse

Question 33

LO12

The Immunological synapse is:

Answer 33

A tight binding between T cell integrins and the APC that forms after TCR-peptide:MHC binding occurs. It helps optomize signalling between the cells.

Question 34

LO13

Define cytokine:

Answer 34

signalling molecules that are used in cellular communication, historically referring to immunological agents.

Question 35

LO13

What is the role of IL in early T cell signaling?

Answer 35

IL-2 acts in autocrine fashion or paracrine fashion
TO INDUCE T CELL PROLIFERATION.

IL 2 INDUCES T CELL PROLIFERATION. AKA CLONAL EXPANSION.

All T cells possess a low affinity IL2 receptor. Upon bindning the low affinity IL2 receptor, high affinity IL2 recepors are expressed, increasing the response.

Question 36

WHAT DOES IL-2 DO?

Answer 36

Promotes clonal expansion of T cells.

Question 37

LO14

Once activated, T cells will express the inhibitory molecule _______

Answer 37

CTLA-4

Question 38

LO14

Like CD 28, CTLA-4 binds ______, but with ______ affinity.

Answer 38

binds B7

has a higher affinity, thus CTLA-4 out competes CD28.

Question 39

LO14

Once Tcell CTLA-4 bind to B7 on APCs, they produce a(n) _____ signal, which _______

Answer 39

Inhibitory signal, which terminates T cell responses. This is a mechanism to control cell activation after infection has cleared.

Question 40

LO15

Superantigens cause _______ activation of ________

Answer 40

Non specific activation of T cells

Question 41

LO15

Superantigens interact with the variable region of the _____ chain of the TCR, leading to non-specific activation.

Answer 41

Beta

Question 42

LO15
Polyclonal activation occurs when superantigens bind all TCRs regardless of specificity, resulting in activation of ___% of totoal T cells.

Answer 42

80

Question 43

LO15

normal antigen:MHC binding might activate ____% of total tt cells

Answer 43

0.001%

Question 44

One example of a superantigen activated syndrome is:

Answer 44

Toxic Shock Syndrome.