Hudig: Antigen Processing & Presentation

Question 1

What cells have MHC class I?

Answer 1

Every cell in the body except for RBCs

Question 2

What cells have MHC class II?

Answer 2

Only dendritic cells, macrophages, and B cells **antigen presenting cells

Question 3

When do MHC I and II systems present “self” peptides?

Answer 3

all the time, without infection

Question 4

CD8 T cells recognize foreign peptides in MHC I and become (blank)

Answer 4

cytotoxic T lymphocytes

Question 5

How can CTLs detect the virally infected cell when the virus is hidden inside an infected cell?

Answer 5

CTLs recognize antigen peptides displayed on the plasma membrane of cells in MHC I proteins

Question 6

What does the TAP (transporter of antigenic peptides) do to viral peptides?

Answer 6

It takes the peptides and brings them into the ER. This is where the peptides are loaded onto MHC class I’s. Once loaded, the peptides pass through the golgi and are expressed on the cell surface.

Question 7

What class of MHC presents the viral peptide? Is the T cell that responds to presentation of a viral peptide CD4+ or CD8+?

Answer 7

MCH I; CD8+

**self peptides can also be presented this way

Question 8

All cells, except RBCs have ~(blank) MHC I molecules and ~(blank) different peptides expressed in them

Answer 8

> 30,000; >1000

Question 9

What is this:

TCRs have dual recognition and must bind to both an antigen peptide and one MHC protein. Each CTL needs a match of the same peptide in the same MHC I to kill.

Answer 9

MHC antigen restriction

Question 10

Each naive T cell has a different (blank). What does each T cell require in order to respond and be measured?

Answer 10

TCR; each T cell receptor needs an exact match of the peptide-MHC

**this is why it is difficult to monitor CTLs for vaccine development - you would have to use target cells matching each donor individually to test a person’s T cell anti-viral immunity

Question 11

Discuss how MHC Class II proteins go about expressing antigens on their surface?

Answer 11

1. APCs (macrophages, dendritic cells) ingest bacterium, virus, or proteins into endosomes
2. Inside the endosome, all proteins are digested into peptides
3. peptides are presented to T cells by APCs via MHC II molecules on their surface

Question 12

PEPTIDE antigen presentation to T cells solves two important problems. What are they?

Answer 12

1. saves energy by only generating immunity to pathogens (not to every foreign substance - ex: there is little immunity to anything that lacks a foreign protein)
2. recognizes and presents intracellular pathogens (because there are 20 different amino acids, this allows us to recognize a very diverse subset of peptides and mark them as foreign or self)

Question 13

So what are some examples of antigen presenting cells? What do antigen presenting cells do?

Answer 13

Langerhans cells in skin, dendritic cells in lymphoid organs, macrophages; APCs have TLRs that detect PAMPS and they release cytokines in innate immunity, also they process antigens and display them with MHC II for T helper cell recognition in adaptive immunity

Question 14

What are some benefits of a live attenuated virus vs an inactivated virus for a vaccine?

Answer 14

inactivated virus: safer, stored more easily w/o refrigeration
live virus: cheaper, some viruses aren’t stopped well by antibodies so they need the live vaccine to generate a T cell response

Question 15

Give some examples of viruses that can evade MHC I antigen presentation.

Answer 15

1. HIV nef blocks MHC I synthesis
2. Human cytomegalovirus protein blocks MHC surface expression
3. Herpes simplex protein blocks TAP (transporter of antigenic peptides) activity

Question 16

To generate antibodies, what 3 cell types are needed?

Answer 16

1. T follicular helper cell (to produce IL-2 and promote T and B cell proliferation)
2. APC which presents foreign peptide to T Follicular Helper cell via MHCII
3. ThelperII cells may help B cell change its Ig type

Question 17

What is different about the antigen presented on a B cell vs a T cell?

Answer 17

The antigen that binds to Ig on B cells is NATIVE, the peptide does not have to undergo processing and be presented on MHC class II

Question 18

small proteins (~15 kD) that are secreted by leucocytes upon stimulation and that promote responses among leucocytes (white blood cells: T, B, NK, macrophages, granulocytes). E.g., IL-2.

Answer 18

interleukins

Question 19

interleukins made by lymphocytes (e.g., IFNgamma, IL-2, IL-4)

Answer 19

lymphokines

Question 20

small proteins that are secreted, by many cell types upon stimulation, and that promote responses by leucocytes and other cells. E.g., interferon alpha (IFNalpha), IL-1, IL-12, and TNFalpha from macrophages. Includes interleukins and lymphokines.

Answer 20

cytokines

Question 21

These are secreted by APCs and T cells and are essential to generating antibodies

Answer 21

cytokines

Question 22

Both B and T cells require a SECOND signal in order to respond. What is the second signal for B cells? What is the second signal for T cells? What happens without the second signal?

Answer 22

For B cells, signal 1 is antigen and signal 2 is CD40L binding to CD40
For T cells, signal 1 is antigen and signal 2 is CD28 binding to B7

• *w/o second signal, cell death or anergy
• *you also need a “third signal” or a triggering event such as infection/inflammation

Question 23

If a patient has low levels of IgM, IgG, and IgE, the patient may be deficient in what co-stimulatory signal?

Answer 23

CD40L *necessary for B cells to respond, acts as a second signal

Question 24

What are two cytokines that are essential for both T and B cells to respond to their antigens?

Answer 24

IL1 and TNFalpha

**produced by antigen presenting cells with TLRs once they bind antigen

Question 25

The lymphoid architecture is very important, meaning that there are locations w/i the lymph node and within the Peyer’s patches of the gut that are specific to T cells, resting B cells, and proliferating B cells. In what disease is this architecture compromised?

Answer 25

AIDS

Question 26

Where do T and B cells specific for the same antigen meet?

Answer 26

at T-B regional interfaces in the lymph organs