Lecture 23: Effector Mechanisms in Cell-mediated (T cell) Responses Flashcards
Describe the immune response to a viral infection.
- virus infects and replicates within the epithelium
- DC activation
- T and B cell priming in the lymph node
- adaptive immunity
What happens if a patient lacks RAG genes?
there will be a lack of pathogen control
How do DCs initiate T cell responses?
antigen presentation -> T cell priming
T cell priming = activation -> clonal expansion and differentiation
What are the specific instructions DCs provide to T cells?
TCR activation, co-stimulation and cytokines
What is the role of cytokines secreted by DCs onto T cells?
migration imprinting and functional polarisation (T cell responses are tailored to distinct pathogens)
What happens when a skin-resident dendritic cell engages with a T cell and vitamin D is present?
results in upregulation of particular ligands which equips the T cell in the lymph node to home back to the skin
What happens when a skin-resident dendritic cell engages with a T cell and retinoic acid is present (converted to retinoic acid from vitamin A)?
upregulates integrins such as a4b7 and certain chemokine receptors such as CCR9 on the T cell
What is homing potential programmed by?
tissue-specific cues
TCR stimulation strength
inflammation in SLOs and peripheral tissues
What do cytotoxic T cells target?
viruses
What do Th1, Th17 and Th2 cells target?
Th1: intracellular bacteria and viruses
Th17: extracellular bacteria and fungi
Th2: parasites
How do CD8+ T cells kill infected cells?
cytokines release, granule release and FasL / Fas interactions (death receptors)
What is the process of CD8+ T cell cytotoxicity?
non-specific adhesion -> specific recognition and cytoskeletal changes -> granule release
What is the role of perforin?
forms pores in target cell membrane and aids delivery of granzymes into target cell cytoplasm
What are granzymes?
family of serine proteases
What is the role of granzymes?
initiates apoptotic cell death in target cells
What is the role of granulsyin?
antimicrobial actions
initiates apoptotic cell death in target cells
What is the role of serglycin?
scaffold
forms complex with perforin and granzymes
What are characteristics of apoptotic cell death?
immunologically silent, no inflammation, pathogen containment
What are cytotoxic CD8+ T cells associated with?
IFNy production
Which cytokines are secreted by Tc1 CD8+ T cells?
IFNy and TNFa
What do “exhausted” CD8 T cells exhibit?
reduced functionality (reduced secretion of cytokines)
What does persistent antigen exposure and chronic TCR stimulation lead to?
T cell dysfunction
What is T-bet?
the major regulator that is upregulated in either a Tc1 or Th1 and is linked to the production of IFNy
What are the effector functions of Th1 cells?
macrophage activation, killing, proliferation, hematopoiesis, endothelial activation and chemotaxis
What is the role of RORyt?
regulates the development of Th17 cells
What are the effector functions of Th17 cells?
epithelial protection, epithelial turnover, neutrophil production and chemotaxis
What is the role of GATA-3?
regulates the development of Th2 cells
