Effector T lymphocytes Flashcards
Why do we need a cellular response?
Sometimes pathogens intracellular and hide in cells so antibody response insufficient and T cell mediated
When do T cells migrate?
once encountered dendritic cell with antigen they recognize migrate back into circulation
How do CD8/CTLs target and kill infected cell?
- When virus peptide presented on MHC Class 1 identifies and kills it
- Specific recognition of target cell by cytotoxic effectors cause polarization of cytotoxic vesicles within cell causing release of granules by T cell closer to target cell
- Induces apoptosis in target
What are 3 signals required to activate T cell?
- Antigen recognition
- DC must have MHC showing specific antigen
- Co stimulation
- To enable cells to come together
- Cytokine release
see notes
How do CTLs kill cells?
- Perforin and granzyme in cytotoxic granules: CD8 injects peforin into target cell membrane
- Allows granzyme to enter cell
- FasL on CD8 can induce cell death by interacting with Fas on target cell (contact driven approach)
- Induces apoptosis
What are the effector functions of CD4?
- Macrophage activation
- Delayed type hypersensitivity response
- B cell activation
- Regulation
- Naive CD4 can differentiate into distinct subsets after antigen encounter
- Produce restricted cytokine patterns to shape downstream response
- Also defined by what TFs they use
How many subtypes of CD4 cells are there?
6
What are the different subsets of CD4 cells?
- Th1: interferon ○ Antiviral/bacterial - Th2: produce IL4,5,13 which boost anti multicellular organism (inform eosinophils) ○ allergies - Tfh: IL21 - T17: IL17 for autoimmune disease and control of bacteria ○ Fungi and bacteria - Treg
What happens during macrophage activation?
- Activated by CD4 Th1
- increase levels of pro inflammatory molecule TNF-alpha CD40
- T cells and macrophage cross talk via cytokine
- express increased levels of CD40 and TNF-receptors, - - - secrete TNF-α which synergises with IFN-γ in the induction of antimicrobial effector mechanisms.
What happens during delayed hypersensitivity?
- Tend to be associated with allergy
- Classic allergic response has 2 waves
- Sensitivity: exposed to antigen 1st before becoming allergic to anything without being exposed to it once
- Dendritic cell takes up antigen and presents - Effector: on 2nd exposure can trigger severe response
- Independent of antibodies
- Pronounced secretions of cytokines by ThC activated by antigen in area, cytokines act as inflammatory mediators and activated macrophages to secrete potent mediators
What is the function of delayed hypersensitivity?
- Pathological and protective
- Mainly defense against intracellular pathogen
How do T-helper cells activate B cells?
- DC and B cell present same antigen on MHC2
- CD4 recognizes antigen complex becomes activated
- Tfh moves to B cell
- Tfh induced to express CD40 binding to B to secrete cytokines
- cytokines drive proliferation and differentiation of B cell to plasma cell
What is T cell exhaustion?
What is T cell exhaustion?
- over time especially chronic infection (if antigen doesn’t disappear) CD8 pool contracts
- Problem when infection not cleated e.g HIV
- Cells start exhibiting programmed death, receptors making it harder to activate T cells
What receptors do CTL express to be activated?
CD28
What receptor do B cells express to be activated by T cells?
B7
What cytokines do CTLs receive as costimulation?
IL4, IL21, IL-gamma
What is the role of TNF-β, chemokines, IFN-γ
- cytokines that affect blood vessels (TNF-β)
- recruit macrophages (chemokines)
- activate (IFN-γ) macrophages.
What is the role of CD40 ligand (CD40L) on T cells?
The T-B interactions trigger expression of CD40 ligand (CD40L) on T cells. CD40 L will
interact with CD 40 expressed by B cells;
T cells secrete cytokines and B cells express cytokine receptors
The activated B cell will differentiate into immunoglobulin (antibody) secreting
plasma cells.
