T-Cell Immunity II Flashcards
Describe the characteristics of Th2 response.
Included any infection or antigenic stimulus that causes dominant production of what type of interleuken?
What type of pathogens might elicit this response?
When will this occur?
Describe inducer cytokine, transcription factor and signature cytokines.
Any infection or antigenic stimulus that causes dominant production of IL4 by the activated T cells: - Soluble antigen - Bacteria - Multi-cellular parasites
This will occur when:
- TLR signaling does not result in the production of IL12
- There are TLRs that induce DCs to produce IL4 instead of IL12
- Naive T cells engage in antigen recognition presented by B cells
For the Th2 response:
Describe inducer cytokine, transcription factor and signature cytokines.
Inducer cytokine: IL4
Transcription factor: GATA3
Signature cytokines: IL4, IL5, IL10, IL13
How do B and T cells activate each other?
BCRs on B cells bind antigens, which are then processed and presented by MHC II
molecules. Interaction between B cells and T cells results in activation of both parties
through expression of co-stimulatory molecules (CD40L on T cells) and cytokines. Activated Th2 cells produce cytokines like IL4, IL5 and IL6 which act on B cells and
maintain B cell activation.
Figure p 14
- Antigen-specific B cell binds antigen
- Specific antigen efficiently internalized by receptor-mediated endocytosis
- High density of specific antigen fragments presented
- Antigen recognition induces expression of effector molecules by the T cell, whic activates the B cell
- B-cell activation by antigen and helper T cells
What are initial exogenous IL4 sources?
mast cells
basophils
eosinophils
TCR-gamma/delta
What are Th2 signature cytokines?
IL4
IL5
IL10
IL13
The key for Th2 response is to induce high expression of GATA3 and maintains its
expression at high level. Describe the stages of this process.
This occurs in several stages: The initial interaction between TCR and peptide/MHC II, together with co-stimulatory molecules (CD28- CD80/86, CD40L- CD40) induces the initial expression of a low level of GATA3.
This interaction also induces
expression of the high affinity IL2R-alpha subunit and IL2. IL2 signal further induces expression of GATA3.
The increase in expression of GATA3 then induces expression of IL4 by the T cells which augments GATA3 expression.
IL4 can also come from other cells beside T cells like mast cells, basophils, eosinophils and
TCRgamma/delta T cells.
How does Th2 response affect B cells?
Enhance B cell function and ultimately antibody production:
- Make pathogens more attractive to Macs and Polys
- Bind toxins
- Target mutant/viral infected cells for killing
See figure p 16
- Antigen recognition induces expression of effector molecules by the T cell, which activates the B cell
- B cell proliferation
- Differentiation to resting memory cells and antibody-secreting plasma cells
Summarize the functions of the Th2 cytokine IL4
- IL4 initiates and is an absolute requirement for a Th2 response
- IL4 is the growth factor for Th2 cells; it is also produced by Th2 cells
- On B cells, IL4 promotes B cell growth and induces B cells to differentiate into antibody-producing plasma cells. May play a role in pathogenic autoantibodies
- IL4 also induces Ig class switching from IgG1 to IgE, thus plays a role in allergies
- On T cells, IL4 inhibits the development of Th1, even with high concentration of IFNgamma
- IL4 also inhibits Th1-mediated macrophage activation, thus functions as antiinflammatory
cytokine
Describe the functions of other Th2 cytokines: IL5, IL 10, IL13.
- IL5 plays a critical role in eosinophil maturation and recruiting of mature eosinophils
- IL10 is the major drivers of B cell differentiation and isotype switching-major source
is Th2 cells; other cells that make IL10 are iTreg and Thf - IL10 also inhibits Th1 differentiation and dendritic cell function: inhibits production of
pro-inflammatory cytokines IL1, IL12, TNFalpha - Both IL5 and IL13 are capable of driving allergic type inflammatory response and
promoting pathology of Th2-mediated immune diseases such as asthma
Which cells make IL10?
Th2, iTreg, Thf
What are the inducers, transcription factor, and signature cytokines for the Th17 response?
Inducers: TGFbeta, IL1, IL6, IL21, IL23
Transcription factor: ROR-gamma-t
Signature cytokines: IL17, IL21, IL22
Describe Th17 cell functions:
What kinds of pathogens do they target?
What types of diseases?
What is the most prominent interleuken they produce?
Extracellular bacteria, fungi, eukaryotic pathogens
Organ specific autoimmune diseases: MS, type I diabetes, inflammatory bowel
disease (IBD), airway inflammatory disease
- The Th17 cell produces multiple types of IL-17 (6 different a-f); the prominent are
IL17a, f
What do IL17, IL21 and IL22 do?
(Th17 response)
IL17:
- Recruitment of and activation of neutrophils and monocytes
- Induce expression of pro-inflammatory cytokines IL6, IL8
- IL21: enhances B cell function; contributes to antibody mediated pathology such as
hyper IgE syndrome. These patients face recurrent staphylococcus and fungal
infection
- IL22: functions in protective immunity of the gut by restricting commensal bacteria to their niches, induce expression of antimicrobial peptides
What are the inducer, transcription factor, and signature cytokines of Thf T cells?
Inducer: IL6
Transcription factor: BCL6
Signature cytokines: IL6, IL10, IL21
Describe T follicular Helper T Cells (Thf).
What type of immune response to they facilitate and how?
Where are they found?
Where are fully mature Thf found?
What transcription factors are critical for the development of Thf cells?
- Thf cells facilitate humoral immune responses by assisting B-lymphocytes with the production of pathogen-neutralizing antibodies
- Found in the B cell zone of the secondary lymphoid organ i.e. lymph nodes
- Recruitment into the B cell zone is mediated by the chemokine receptor CXCR5.
This induces further migration in to germinal center of the follicle - Fully mature Tfh are found in germinal center upon interacting with B cells
- The transcription BCL6, IL6 and IL21 are critical for the development of Thf cells