T cell mediated immunity

Question 1

Upon exposure to IL-12 a naive tcell becomes___ or___.

explain the licensing functions

Answer 1

CD4 naive Tcells can become Th1 or Th9

Th1 have a licensing function (activate other cells)

Question 2

Answer 2

Question 3

list five influencing factors influencing the polarization of Th cells

Answer 3

1. cytokine milieu determined by preceding innate immune response
2. type of APC involved in the activation of T cells
   
   1. DC vs MO cs Bcell
3. cytokines produced by the APCs
4. the abundance of specific peptide: MHC complex on the surface of APC
5. The affinity of the peptide : MHC complex for the TCR

Question 4

How do Th1 cells signal to MO ? What is the difference between inactive MO and active MO?

Answer 4

The MO activates/differentiates the Naive T cell in to a Th1.

The Th1 send cytokine (IFN-y) to MO, and CD40L interacts with MO CD40. This in turn, activates the MO.

1. activate MO
   
   1. increases CD40 expression
   2. secrete TNF-a
      
      1. inflamatory cytokine
   3. increase phagosome fusing efficiency
      
      1. leads to increase production
         
         1. ROS
         2. NOS
         3. proteases

Question 5

What are the affects of the cytokines released by the Th1, responses

Answer 5

Question 6

What itwo signals are needed to activate the MO? what happens if they are not both received/sent?

Answer 6

failure to Fully activate leads to Granuloma Formation

1. two signals : INFy, CD40 ligand, don’t make it to the MO

TB

1. The MO atack the TB and don’t listen to the Th1
2. the lack of response from MO leads to a “walling off”
3. Caseous necrosis, where the TB eats off the dead MO with in the Tcell layer

latent infection, someone has these in their lungs

reactivation is opening of granulomas

Question 7

What is the funciton of CD8 Tcells? How are they activated?

Answer 7

Major role of CD8 T cells= protection against VIRUS and TUMORS

Cross representation through the APC.

1. 2. only the DC can do this, aka professional APC

the CD8 becomes activated, proliferates and leaves to effector site

1. the CD40l/CD40 means that the T cell has been activated.
2. APC communicates through the DC to the CD8 for licensing

Question 8

CD8 cells major role. How does it perform these actions? Describe and diagram how these contents work.

Answer 8

1. major role
   
   1. protection against VIRUS and TUMORS
2. How does the Cell attack?
   
   1. CTL Fas ligand (FasL)
      
      1. binds to Fas on target cell and induces apoptosis
   2. CTL releases cytotoxins and target cell dies by necrosis
      
      1. ​contents of modified lysosomes
         
         1. perforin
            
            1. ​form pores in the cell membrane
         2. granulysin
            
            1. perturbs cell membrane integrity
         3. granzyme
            
            1. serine protease
               
               1. enters through pores, and chops up target cell proteins

Question 9

left off on slide 20

Question 10

What activates, gene is expressed, cytokines secreted, and how Th2 cells funciton?

Answer 10

naive Tc + IL-2 =Th2

this is considered the humoral response.

1. Th2 CD4+ effector cells
   
   1. activate
      
      1. B cells, ONLY they both recognize the same specific antigen
         
         1. congante interaction
            
            1. the specific epitopes recognized by the TCR and BCR can be different, but the epitope recgnized by the TCR must be part of the same physical entity bound by the BCR
      2. CD40L on the Th2 recognizes the CD40 on the B cell
      3. Th2 sends out the cytokines
         
         1. IL-4 and IL-5
            
            1. ​allow the cytokines to proliferate
         2. IL-5
            
            1. allow for the B cells to convert into
         3. IL-13
            
            1. ​plays a dominant role in regulating eosinophilic reactions
               
               1. parasites
               2. lung allergies-central mediator of allergic asthma

Question 11

two cell types act on B cells. Who are they and whay is the difference. What do they induce and what are the problems?

Answer 11

Th1 + B cells =

1. induce
   
   1. only IgG. Great for complement + opsonization
   2. poblems
      
      1. tuberculoid leprosy
         
         1. localized but the patient usually lives

Th2 + Bcells= “humoral response”

1. induce
   
   1. proliferation
   2. class switching
   3. increase antibody production
2. problems
   
   1. associated with several inflammatory conditions
      
      1. asmthma
      2. allergies
      3. lepromatous leprosy
         
         1. highly infective
         2. deformative
         3. outcome is usually fatal

Question 12

Jerry was hunting armadillo and selling the pelts. He generated a strange rash on his back. What could this be and how do the different immune cell responses play a pivitol role?

Answer 12

activation of Th1 vs Th2 will lead to different diseas outcomes

1. leprosy
   
   1. infectious disease that can live with in the macrophages
2. Th1-Tuberculoid leprosy
   
   1. activation of infected macrophages and control of bacterial growth.
   2. Patients usually survive with chronic disease
   3. Low infectivity
3. Th2-lepromatous leprosy
   
   1. `uncontrolled bacterial growth with in Macrophages
      
      1. due to lack of amcrophage actrivation.
   2. bacilli disseminate widely
   3. the outcome is usually fatal.
   4. highly infectious

Question 13

explain this figure. what is this analysis? How was this used?

Answer 13

northern blot analysis

1. what is it
   
   1. technique for identifying specific sequences of RNA in which RNA molecules are separated by electrophoresis, transferred to nitrocellulose membranes, identified with a radiolabeled complimentary nucleotide probe
2. this was used to discern the different reaction to leprosy
   
   1. the various cytokines allowed for the supportive evidence in the reactions between Th1 and Th2

Question 14

What cell is the primary response to extracellular parasites? what is an assistant?

Answer 14

Th9, Th2 assists

-both are related with inflammatory diseases and allergies. Th9 has a primary action in the process.

Question 15

What differentiates the Th9? what is the gene used, cytokines expressed, action and function? what is the positive and the negative

Answer 15

Th9

1. activated by
   
   1. IL-12
   2. INF-y
2. gene
   
   1. PU.1
3. cytokine
   
   1. IL-9
4. function
   
   1. exagerates the immune response in an area
   2. immune response to extracellular parasites
5. mechanism-good if you have a parasite…bad if you don’t
   
   1. positive
      
      1. have potent antiparasite activity
         
         1. IL-9
            
            1. enhances antibody production and increases immune cell activity in the respiratory tract
            2. increases intestinal permeability
               
               1. may enhance pro-inflammatory Th cell responses
      2. augment anti-tumor immune activity
   2. negative-all associated with IL-9
      
      1. asthma
         
         1. in the mucosal tissue
            
            1. increases Th2 cell survival
               
               1. increasing IgE
            2. increasing eosinophil reaction
      2. ulcerative colitis
         
         1. in the gut mucosal tissue, IL-9
            
            1. inhibits
               
               1. tissue repair
               2. proliferation
            2. increases permeability
               
               1. commensal infection

Question 16

Which T cell is involved in reponse against extracellular bacteria and fungi?

Answer 16

Th17

provide anti-microbial immunity at epithelial and mucosal barriers

Question 17

Which Tcell type is involved in multiple sclerosis?

Answer 17

Th17

also involved in inflammatory bowel disease

Question 18

What differentiates the Th17? what is the gene used, cytokines expressed, action and function? what is the positive and the negative

Answer 18

Th17

1. activated by
   
   1. IL-6
   2. IL-21
   3. IL-23
2. gene
   
   1. RORyT
3. cytokines expressed
   
   1. IL-17
   2. IL-6
4. action
   
   1. act against bacteria and fungus
5. function
   
   1. positive
      
      1. provide anti-microbial immunity at mucosal barriers
      2. activate tissues
      3. recruit neutrophils
      4. are an important defense against extracellular bacteria and fungus
      5. IL-6
         
         1. powerful pro-anti-inflammatory
   2. negative
      
      1. play major role in autoimmunity
         
         1. multiple sclerosis
         2. inflammatory bowel disease

Question 19

What differentiates the specialized subepithelial lymphocytes? what is the gene used, cytokines expressed, action and function?

Answer 19

specialized subepithelial lymphocytes = Th22

Th22

1. activated by
   
   1. IL-6
   2. IL-23
   3. TNF-a
2. gene
   
   1. AHR
3. cytokines
   
   1. IL-13
   2. IL-22
4. action
   
   1. IL-22
      
      1. remodeling of epidermis
      2. reinforcement of barrier function
         
         1. have things hang out in the barrier instead of going further into the tissue
5. function
   
   1. respond to plasmacytoid dedritic cells to augment an innate barrier

Question 20

What differentiates the Tfh? what is the gene used, cytokines expressed, action and function? what is the positive and the negative

Answer 20

Tfh-follicular helper cell

1. activated by
   
   1. TGF-beta
   2. IL-16
   3. IL-23
2. gene induced
   
   1. Bcl-6
      
      1. think “b cell”=Bcl
3. cytokines
   
   1. IL-21
4. action
   
   1. assist in germinal center generation
   2. give the “proliferate and survive” or “death” signal to B cells whov’e undergone
      
      1. somatic hypermutation
      2. class switching
5. funciton
   
   1. T cells tests the mutated BCR
      
      1. centrocyte presents the BCR to the FDC and Tfh
         
         1. high affinity
            
            1. proliferate via IL-22
            2. differentiate into plasma cell
         2. low affinity
            
            1. death signal

Question 21

What differentiates the Treg? what is the gene used, cytokines expressed, action and function? what is an important funciton and interesting feature about these cell?

Answer 21

T reg

1. activated by
   
   1. TGF-beta
2. gene induced
   
   1. FOXP3
3. cytokines produced
   
   1. IL-10
   2. TGF-beta
4. action
   
   1. suppress immune reponses of other cells designed to limit excessive reations and prevent autoimmunity
5. function
   
   1. two types
      
      1. ​natural
         
         1. ​graduation from thymus as nTreg
      2. induced
         
         1. ​activated from naive T cell
   2. immunosupression and tolerance
      
      1. at the end of an immune response
      2. response to self
         
         1. A-supress auto reactive T cells

the role of Tregs in supression of sutoreactive T cells requires them to interact with the same antigen-presenting cell.

1. Think about it, autoreactive cells see the self peptide. It is run away from the thymus.
2. If Treg can only supress the Tcell if it binds to the same peptide, it must also recognize self peptides.

Question 22

what are two ways to generate Thf? where are they when not needed?

what happens in their absence?

Answer 22

two ways to generate a Thf

1. Tcell graduates from thymus as nTreg
   
   1. ag stimulation into Thf
2. Dendritic cell induces naive Tcell with IL-16, IL23, TGF-b
   
   1. The Thf then travels to the germinal center in the lymphnode

Thf cells are not in the germinal centers unless needed.

W/o Thf you still get Bcells but, they are a select regime of B cells that are not very affective

Question 23

Why and how can cells relocate between naive and effector cells types?

Answer 23

effector T cells

1. 1. upregulate
      
      1. chemokine recpetors
         
         1. allow location of tissue in need of assistance
      2. adhesion molecules
         
         1. VLA-4
            
            1. integrin a4b1
            2. increases adhesion to the endothelial cells in the lumen of the blood vessels
         2. CD44
            
            1. receptor for hyaluronic acid
               
               1. tissues contiain high levels of this molecules
               2. so effector cells can be retained in these areas.
   2. down regulate
      
      1. L-selectin
         
         1. recognizes the Cd34 and Gly-CAMs inside the lymphnode
            3.

Question 24

describe and diagram the DC role in memory generation

Answer 24

T cells rely on signaling from enviornment to stay alive. When they are not needed, most of them commit to apoptosis. But, very few, move into long and short term memory. Having both is important, long term lived usually hang out in lymph node and can stay with you your whole life. Short term memory cells hangout in effector location, incase another exposure to the pathogen occus, and slowy dwindle in concentration

Dendritic cell have four signals that Tcells respond too.

1. High chemoiine signalin
   
   1. allows the generation of terminal effector cells and short term lived memory
      2.

Question 25

what is the response difference between naive and memory Band T cells?

Answer 25

Memory cells dont need second signal. They have already undergone differenciation. They can activate with signals from central APC.

this leads to a faster response.

Question 26

how do lymphoid organs and T cell lineages play a important role in memroy?

Answer 26

1. peripheal
   
   1. Tissue resident memory T cells
      
      1. ​rapid protection from tissue invading pathogens/ May be shorter lived compared to other memory populations
   2. Effector memory Tcells
      
      1. ​circulate between lymphoidorgans and tissues. Can rapidly make effector cytokines providing rapid protection
2. secondary lymphoid organs
   
   1. T stem cell memory
      
      1. ​Least differentiated, multi potent and se;f renweing
   2. Centram memory Tcells
      
      1. ​long lived backup to frontline defense. Protective against systemic infection.
   3. Follicular helper memory T. cells
      
      1. ​may be found near B cell follicles or in the blood. May require antigen to maintain photype. Provide rapid help for B cell germinal center response

Question 27

How does cell signaling play an affect on the type of cell the T cell differentiates into?

Answer 27

The affinity of the bind palys an imperative role in the generation of memory or effector.

High affinity cells tend to become memory T cells, everything else just gets better.

1. look at the chart and notice that memory cells are more sensitive because all systems have been heightend. Once the peptide is intorduced by central APC, the response begins faster

Question 28

Fill in the timeline in the immune response with respect the B&T cell memory and response

Answer 28