Lecture 11 - T lymphocytes

Question 1

List the major T cell lineages and what they differentiate into.

Answer 1

Alpha Beta lineage

• CD4 T cell
  
  • Th1, Th2, Th17, and Treg
• CD8 T cell
  
  • Cytotoxic lymphocyte (CTL)

Gamma Delta lineage

Question 2

True or False

Th1, Th2, Th17, and Treg lymphocytes are all CD4 positive.

Answer 2

TRUE

Recall that all Th cells are from the CD4 lineage. All start out as Th0 cells, then differentiate into the different classes of T helper cells based on the cytokines and extracellular signals they receive.

Question 3

Learning Objective 1

List the different types of lymphocytes and how they recognize antigen.

Answer 3

B cell - directly recognizes intact antigen

T Cell

• Alpha Beta
  
  • CD4+ lymphocytes recognize peptides presented on MHC II molecules.
  • CD8+ lymphocytes recognize peptides presented on MHC I molecules.
• Gamma Delta lymphocytes recognize stressor signals from cells and do not require MHC. Not a lot is known about this cell type.

Question 4

How does a Th1 recognize and respond to antigens?

Answer 4

Recognizes exogenous peptides presented on MHC II.

Important in infection with intracellular pathogens.

Signature cytokines: IFNgamma, IL2, TNF.

Secrete cytokines to activate macrophages, neutrophils, NK cells, and CTLs to be better at killing. Also helps B cell to make IgG.

Question 5

How does a Th2 recognize and respond to antigens?

Answer 5

Recognizes exogenous peptides presented on MHC II.

Important in protection against parasites and IgE-mediated allergies.

Signature cytokines: IL4, IL5, IL10, IL13

Secretes cytokines to activate mast cells and eosinophils. Also helps B cell to make IgE.

Question 6

How does a Th17 recognize and respond to antigens?

Answer 6

Recognizes exogenous peptides presented on MHC II.

Important in response to extracellular bacteria and fungi.

Signature cytokines: IL17 A and F, IL22.

Attracts and activates monocytes and neutrophils.

Question 7

How does a Treg recognize and respond to antigens?

Answer 7

Recognizes exogenous peptides presented on MHC II.

Important in preventing immune reactions against self-peptides and non-dangerous antigens.

Signature cytokine: TGFbeta

Secretes cytokines to prevent other T cells from reacting against self-antigens.

If a naive T cell recognizes self antigens without the presence of danger signals, it will be induced to become a Treg.

Question 8

Learning objective 2

List the effector function, including signature cytokines, of each of the Th subtypes.

[Note: more details are on individual flashcards]

Answer 8

Th1

• (IFNgamma, IL2, TNF). Activates macrophages, NK cells, neutrophils, and CTLs to be better at killing and helps B cell with IgG secretion. Intracellular bacterial infections and viruses.

Th2

• (IL4, IL5, IL10, IL13). Activates eosinophils and helps B cell with IgE secretion. Parasitic infections.

Th17

• (IL17 A and F, IL22). Attracts and activates monocytes and neutrophils. Extracellular bacteria and fungi.

Treg

• (TGFbeta). Recognizes antigens without danger signals, suppresses other T cells from reacting against self-peptides.

Question 9

How does a Gamma Delta T cell recognize and respond to antigens?

Answer 9

Recognizes intact antigens on cell surfaces (does not require an MHC).

Responds to stress proteins on cells.

Important at mucosal surfaces.

Poorly understood.

Question 10

Learning objective 3

Compare and contrast the immune responses to extracellular pathogens/toxins, to cytosolic pathogens, intravesicular pathogens, and helminthic parasites.

[Holy crap, are you serious? This objective may as well have been written as ‘summarize the immune system.’ You know what? Fine. Bring it.]

Answer 10

Extracellular pathogen/toxin

• Endocytosed and process by APC through exogenous pathway, presented on MHCII. T cells: Th1, Th17. Results in opsonization and a neutrophil response.

Cytosolic pathogens

• Processed through the endogenous pathway and presented on MHCI. T cells: CTL. Results in apoptosis.

Intravesicular pathogens

• Processed through the exogenous pathway and presented on MHCII. T cells: TH1. Results in macrophage activation to M1 macrophage.

Helminthic pathogens

• Processed throught the exogenous pathway and presented on MHCII. T cells: Th2. Results in macrophage activation, IgE production, and eosinophil recruitment.

Question 11

Learning objective 3 in chart form

Answer 11

Question 12

Learning Objective 4

Explain what a Gamma Delta T cell is and its role in the immune response.

Answer 12

Recall that the two major T cell divisions are Alpha Beta and Gamma Delta, all classified by surface molecules.

Gamma Delta T cells are important at mucosal surfaces. Unlike Alpha Beta T cells, they can recognize intact antigens (do not use MHC). Protect against pathogens through cytokine secretion and cytotoxicity. Recognize cellular stress proteins.

Question 13

Describe the effects of IFNgamma

Answer 13

IFNgamma is a Th1 cytokine

Downstream effects to protect against intracellular pathogens and some extracellular pathogens.

Inhibits Th2 response.

Question 14

Describe the effects of IL10

Answer 14

IL10 is a Th2 cytokine.

Downstream effects to protect against parasitic infections.

Inhibits Th1 response.

Question 15

Learning objective 5

Explain how an immune response to one type of pathogen can inhibit the response to another type of pathogen and give some clinically important examples where this can play a role.

Answer 15

IFNgamma produced by Th1 inhibits the Th2 response.

IL10 produced by Th2 inhibits the Th1 response.

If an animal has parasites, its Th2 cells will be producing IL10, which inhibits the Th1 response. Vaccinating with a modified live virus may be ineffective.

Suppose an animal has allergies. If it gets a viral infection, its Th1 cells will produce large amounts of IFNgamma, inhibiting Th2. This may provide some relief from the allergies.

Question 16

Suppose you’ve got a dog that has ascarid worms and you want to give him a parvovirus vaccine. How should you proceed?

Answer 16

Treat for the parasitic infection and wait 2-3 weeks before administering the vaccine.

Recall that IL10 from the Th2 cells responding to the parasitic infection inhibit the Th1 response. Since you need Th1 cells to respond to a viral infection (or a virus vaccine), administering a vaccine while an animal has a parasitic infection could be ineffective.

Question 17

Oh shit, a B cell recognizes a viral epitope. What type of Th cell will it interact with, and which cytokines will be involed?

Answer 17

Th1

Cytokines: IFNgamma, IL2, TNF

Question 18

Can a polysaccharide stimulate a T cell?

Answer 18

No

Remember, T cells only recognize peptides presented on an MHC molecule.

Question 19

Learning Objective 6

Describe what you could do to get T cell help to B cells when B cells are responding to a polysaccharide antigen (like a bacterial capsule). Remember Th cells recognize peptide on MHC II molecules.

Answer 19

The goal here is to get B cells that recognize the polysaccharide capsule to 1) activate and proliferate and 2) class switch to an effective antibody type.

• T cells do not recognize polysaccharides, only proteins. So, we will covalently bind tetanus toxoid protein to the polysaccharide of interest. A B cell that recognizes the polysaccharide portion will internalize the molecule and present the epitopes (polysaccharide and proteins) on MHC II.
• A Th cell that recognizes the toxoid peptide will bind via its TCR and costimulatory molecule (CD40) and secrete cytokines in the space between the B and T cell. The B cell will activate and proliferate.
• Since the B cell originally recognized the polysaccharide, it will make antibodies that recognize the polysaccharide. The cytokines released by the T cell help the B cell to class switch to IgG, which will bind to the bacterial capsule.

Question 20

Suppose you have a B cell that recognizes a polysaccharide but does not interact with a Th cell. What will happen?

Answer 20

B cell will not clonally expand.

B cell will not class switch to a more effective antibody isotype.

B cell will release IgM.

Question 21

Learning objective 7

List the major signals required to get activation of a T helper cell and factors that determine the subtype of Th cell that predominates in a response.

Answer 21

3 signals are required to activate a naive T cell.

• Peptide presented on MHC II
• Co-stimulatory molecules (like CD40 ligand)
• Cytokines released by the APC

If there is only a signal detected by the TCR, the Th will become anergic (paralyzed)

The type of immune response depends on the PAMPs present, the costimulatory molecules expressed by the APC, the microenvironment, and the cytokines released by the APC>

Question 22

Why might a killed vaccine not be as effective as a modified live vaccine?

Answer 22

A killed vaccine basically acts as a foreign exogenous protein. It will be present through the exogenous pathway on MHC II. Since there is no intracellular viral replication, nothing will be presented on MHC I and there will be no cytotoxic response.

Question 23

Learning Objective 8

Use your understanding of immunologic response to describe the responses to vaccinations.

Answer 23

Let’s talk about a modified live vaccine given nasally.

APCs will phagocytose the viral particles and present them on MHC II. Based on the danger signals present, the APC will express certain costimulatory molecules. A naive Th cell will recognize viral peptides on MHC II. The APC will release cytokines to activate the Th cell. The Th cell can then influence B cells that recognize viral particles to activate and proliferate and class switch. Because the vaccine was given at a mucosal surface, they will likely class switch to IgA.

Meanwhile, some viral particles will reproduce intracellularly. They will be presented on MHC I and recognized by CD8+ CTLs. The CTLs will cause apoptosis in infected cells and will proliferate.

If an actual viral infection occurs, the animal will now have memory B cells, memory Th cells, and memory CTLs that can respond to the virus.