Ch. 5 Cell-Mediated Immune Response (T-cells) Flashcards
- Connections btw naive T-cell and APC cell for activation + function of each
- TCR - recognizes the non-self antigen and the self- MHC
- CD4/CD8 - recognizes MHC-II and MHC-1 respecitvely, signal transduction
- CD28 - on T-cell recognizes the B7 on APC and leads to co-simulation when microbe is present
- CD3 - Signal transduction when TCR is activated
- LFA-1 - Binds I-CAM on APC to hold the cells together
LFA-1 Affinity
- LFA-1 integrin on T-cells binds to ICAM-1 on the APC cells
- LFA-1 has low affinity for ICAM-1 when on an inactive T-cell
- Affinity is increased by:
- Activation of T-cell by antigen
- Chemokines released by the innate immune system during an infection
CD40L
CD40L on T-cells
- expression is increased when T-cells activated by antigen
- The CD40L binds to CD40 on macrophages, DCs, and B-cells.
- This activates these cells, and increases co-stimulator production
- positive feedback loop
Types of Memory Cells
Central Memory cells
- in lymphoid organs
- lead the rapid clonal expansion upon re-exposure
Effector Memory cells
- Mucosa
- rapid effector function when re-exposed to antigen
Types of CD4 Helper Cells
Th1 - Cell mediated
Th2 - Eosinophil mediated
Th17 - ?
Th1
Th1 CD4 Helper Cells work in cell-mediated immunity (phagocytic)
- Differentiate into Th1 when APC cells secrete IL-12
- They then produce INF-gamma:
- Macrophages activated
- increase MHC-II, and co-stim production on APC (+ feedback/amplification)
- induce B-cells to make antibodies that will bind to Fc receptors and increase phagocytosis
- increase phagocytosis and complement
Th2
Th2 Helper CD4 cells stimulate eosinophilic immunity (Helminthic)
- form by the lack of IL-12
- produce IL-4 - stimulates IgE production - IgE activates mast cells and binds eosinophils
- Produce IL-5 - activate eosinophil
- IL-4, IL3 - increases mucous secretion (epithelial barrier)
- IL-4, IL-10, IL-13 inhibit macrophages and suppress Th1
- designed against helminthic parasites
T-cell Signal Transduction
- Lck on CD4/CD8 phos. ITAMS on CD3 and zeta
- Zap70 binds to ITAMs, is phos, then phos adaptor protein
- NFAT
- Phospholipase C- PIP- IP3 DAG - increase Ca+
- Ca+ , calmodulin -> Calcinuerin (cyclosporin, drug, prevent calcinuerin - graft reject)
- Calcinuerin phos. NFAT
- NFAT - transcribes IL-2 genes
- Ras/Rac
- Ras-GTP - ERK, JNK (MAPK)
- c-Fos + c-Jun = AP-1
- NF-kB
- Pip- IP3 + DAG - Protein Kinase C -
- PKC - destroys IkB, frees NF-kB
- Inflammation
- NFAT
IL-7
needed for lymphocyte proliferation and surivial
IL-15
needed for NK cells
G-CSF
needed for neutrophil survival
EPO
needed for RBC development and survival
IL-2 receptor development
- IL-2 is a growth factor for activated T-cells
- Naive T-cells have an IL-2 receptor, but only the Beta and Gamma chain.
- this receptor is a very low affinity
- but when Naive T-cells get activated by MHC and their TCR they begin expressing the IL-2R alpha chain.
- This creates the three chains together that has an extremely high affinity for IL-2 and therefore binds it.
- (gamma chain is in a lot of IL receptors and it is what is damaged in X-linked SCIDs)
IL-17
bridges innate and adaptive immunity
- induces typical innate response - neutrophils, acute phase response,
- elevated in autoimmune disease
- produced by Th17 cells
Th1 cells - cytokine that causes their development, what they produce, and what they do
- Th1 development is stimulated by IL-12 (from macrophages/ DC cells)
- Th1 cells produce INF-gamma which activates macrophages and B-cell Ig production
- Main immune function is to fight intracellular organisms
