T-Cell Mediated Immunity Flashcards
(44 cards)
Cell-mediated immunity=?
What does it respond to?
T cell immunity
Responds to intracellular microbes
What must we do to clear infection?
Must clear all microbial reservoirs (natural source of a microbe: which cells infected? Must get rid of), including our own infected cells
Which microbes require CMI control?
Intracellular microbes
How do we get from initial exposure to effector cells?
Dendritic cell comes in and activates CD8 (does NOT result in death of dendritic cell). FIRST interaction is about ACTIVATION, then rest of recognition is death to the cell w/ the antigen: can only replicate inside of cells
Cells activate, leave lymph, travel to site of infection, helpers tell others what to do, CD8s target and destroy infected cells
What do CD8s Vs CD4s talk to?
CD8s work am non phagocytic cells and kill infected ones
CD4s talk with phagocytic
Define clonal deletion
Recognizing self-reactive cells (negative selection) and telling them to die (clone refers to single cell
Explain T cell activation and what T cell activation results in
TCR complex engages MHC and peptide (key1)
Full activation requires co-stimulation (key2) (think double keys for nuclear launch)
Activation results in:
- stimulation of innate and adaptive responses
- cytokine production and release
- inflammation
- CTL activity
- b cell regulation
What are the characteristics of a naive T cell?
Mature, but never been activated, has survived maturation process
Overview of T cell activation
1) antigen and co stimulation –> IL-2R (cytokine) activation and differentiation
2) cell secretes IL-2 and creates more (+ feedback loop)
3) IL-2: made for T cells for T cells= forces them to divide
4) after divided: leaves and is now called effector cell (in peripheral tissues)
5) small proportion differentiate into memory cells (long lived, keep populations up)
IL-2R versus IL-2
IL-2R is a cytokine, for activation and differentiation
IL-2 is positive feedback loop that forces T cells to divide
Effector cells, memory cells
Effector: activated and now doing work
Memory: previously activated cells (both b and T cells make them)
What are the 3 signals that a T cell receives during activation
1: TCR complex with MHC and antigen interaction (key1) must recognize both MHC and antigen
2: co-stimulation signal between CD28 (t cell surface) and B7 (surface of APC) (key2)
3: cytokines released by APC, signal tells helper T cells what form of helper t to become (1,2,17)
List T cell activation ligand-receptor pairs
T cell: APC
CD4/8 : MHC class 2/1 (signal transduction)
TCR (a/B chains) : peptide/antigen&MHC
(Antigen recognition)
CD3 : no ligand
(Signal transduction)
Zeta chains : no ligand
(Signal transduction)
CD28 : B7
(Costimulation)
Adhesion : ICAM-1
What is costimulation and why is it important for T cell activation? What happens if costimulation doesn’t occur?
B7 (APC) with CD28 (t cell)
AND MHC with TCR
Both needed to activate T cell
If costimulation doesn’t happen–> no response or tolerance, cell is turned off
(APCs only make B7 when they have engaged right receptors: been activated by binding TLR, so no costim= prob no microbial antigen, presenting with costim only happens when APC recognizes foreign)
If it does: activates and secreted cytokines
Central tolerance?
Positive and negative selection during maturation
Another later of tolerance, presenting with costim only happens when dendritic cell recognizes something foreign
How are CTLs activated?
Cell is infected with microbe
Phagocytosis by host APC (dendritic present MHC 1&2, can activate both)
TCR recognized MHC and antigen AND costimulation
Activation
*note: CD4 activation can lead to secretion of cytokines that help activate CD8
For activation of T cells: always need TCR:MHC&antigen recognition AND costim
What happens after T cell activation?
T cells talk to macrophages and B cells via cytokines
B cells --> class switch and antibody secretion Macrophage activation: destruction of phagocytosed antigen
CD8s: seek out infected cells w/ same antigen as they were activated with once activated
Killing of infected cells
What is the function of IL-2?
IL-2 is secreted after T cell activation by antigen and costim
IL-2 receptors are also made
Sole purpose of IL-2 is for the CELL to DIVIDE
Positive feedback loop that drives more division
IL-2= proliferation
T cell expansion and decline
Clonal expansion, contraction, only memory cells left behind (non memory cells die)
Vaccines
Live-atenuated: robust response probs
Flu: shot is dead inactivated, intranasal is live attenuated and stays in upper respiratory tract, doesn’t make it to lungs
Intranasal: get serum and mucosal protection, better memory
Shot dead inactive is only serum protection
Helper T cell subtypes?
TH1: activates macrophages and B cells, standard pro-inflammatory response, works back&forth with innate
TH2: anti-inflammatory, antagonistic to TH1 (prevent each other) because cytokines inhibit each other’s pathway
TH17: similar to TH1, mediate neutrophil response, guide them to sit and for their action, pro-inflammatory
1&17 can work together (pro-inflammatory and activate innate cells
T1&T2 are mutually exclusive in the same region
What dictates what type of helper T cell it will become?
Cytokines
Cytokines secreted by APC and resulting TH cell. What they secrete, and pro-anti inflammatory
IL-12 and IFN-y –> TH1 –> secretes IFN-y–> macrophage activation, proinflammatory
IL-4 –> TH2 –> secretes IL-4 (leads t B cell class switch to IgE: mast cell de granulation and allergies) and IL-5 (eosinophils activation), anti inflammatory.
TGF-B & IL-6 –> TH17–> secretes IL-17–> proinflammatory and increased neutrophil response
What do T cell secreted cytokines tell B cells to do?
Class switch (antibodies). Tells them what to class switch to
Antibodies if B cells have effector functions. Not the B cells themselves!!
