Module 33 - Cooperation in Immune Responses Flashcards
Describe dendritic cells’ characteristics in an immature state.
- highly efficient at capturing antigen in tissue, but poor stimulators of naive T cells
- active sampling
- macro-pinocytosis
- mannose receptors
- FcR
- migration to lymph nodes is restricted
- low levels of MHC II on plasma membrane
- secrete TGF-beta (suppress immune response)
Describe the maturation process of dendritic cells.
Initiated by binding PAMPs to dendritic cell PRR and induces:
- Migration of DC to lymphoid tissue
- Increased antigen processing
- Increased surface expression of MHC I and II,
- Increased surface expression of adhesion molecules
- Expression of costimulatory molecules (CD80, CD86)
- Secretion of cytokines (eg. TGF-β, IL-6, IL-12)
- Maturing DC’s loose capacity to capture antigen.
Describe the activation mechanism of naive CD4+ T cells by interaction with dendritic cells.
3 signals are required for the activation of naive T cells.
Signal 1 - binding of the TCR to the MHC-peptide.
Signal 2 :
- upregulation of adhesion expression (eg. ICAM-1) and
- ligation of CD28 (T-cell) and CD80, CD86 (DC): provides signals to induce activation and proliferation of the naive antigen-specific T cell
Signal 3:
- The activated T cell now expresses CD40 L as well as expression of IL-2R and secretion of IL-2 (autocrine) - proliferation
- several cytokines (secreted by DC) allow for T cell differentiation => perform effector function
Mention several possible pathways for CD4+ T cell differentiation in response to various cytokines (Signal 3).
- IL-12 & IFN-γ => TH1 => IFN-γ & TNF => M1 macrophage activation, IgG (inflammation)
- IL-4 => TH2 => IL-4, IL-5, IL-13 => IgE production (for parasites), M2 activation, help for B cells for antibody production
- TGF-β, IL-6 => TH17 => neutrophil recruitment (early in infection)
- TGF-β => T<strong>REG</strong> => TGF-β, IL-10 => suppress T cell response
How does T cell activation assist B cell? Which type of T cell is it?
After the three signals are received by the CD4+ T cell from APC, it becomes activated. Features include induction of CD40L in the membrane of the helper T cell as well as production/secretion of IL-4 (TH2).
Activated B cells (acting as APC) then bind to the helper T cell (TH2) as CD40L is recognised by CD40R in the B cell membrane as well as the antigen-specific interaction of MHC II-TCR. IL-4, 5 then acts on the B cell stimulating:
- proliferation,
- affinity maturation,
- isotype switching,
- antibody secretion
- memory
How does T cell activation assist Macrophages? Which type of T cell is it?
T cell activation leads to the differentiation to TH1 (by IL-12, IFN-γ). TH1 which is antigen-specific to macrophages’ MHC II-peptide (alongside the expression of co-stimulatory signals) will induce IFN-γ and activate tissue macrophages.
Describe how activated CD8 cells kill virus-infected target cells.
CD8+ T cell migrates to the infected site and interacts with infected cell. It undergoes MHC II-antigen-TCR interaction, as well as the binding of the FASL and FAS. This induces the release of perforin and granzymes which lyses the infected cell.
Briefly describe the interaction and cooperation between the innate and adaptive immune system.
Lymphoid follicles mainly consist of _________, while paracortex mainly have _________.
B cells, T cells
Describe the mechanism of activation of CD8+ T cells by activated APC.
Similar to activation of CD4+ T cells by APCs, other than the fact that CD8+ have CD8 co-receptors
Why can’t B cell activate naive T cells?
Because it lacks the co-stimulatory molecules (CD80, CD86) which is one of the signals required for naive T cell activation.
What isotype of antibody attaches to the bacterial capsule?
IgM
Isotype switching requires the help of effector helper T cell (TH2), which only recognises peptide antigens displayed in the MHC-II of the B cell. Since the bacterial capsule is polysaccharide-based, it is not recognised by the TH2.