• selectins
• integrins
• members of Ig superfamily

• L selectin
• Function
  • mediate homing to high endothelial venules in lymph nodes and mucosal endothelium
  • bind to carbs

• β2 integrins
  • LFA-1 binding to ICAM (Ig superfamily)
• VLA-4 bind to VCAM-1 (Ig superfamily) on activated endothelium at sites of inflammation

Process of transendothelial migration of T cells into lymph node

1. L selectin promote rollling
2. stop signal via chemokines from LFA-1/ICAM
3. cell tranverses thru endothelium and enters lymph node

Explain low affinity interaction that happens in T cells with APC

• via LFA-1 and ICAM interaction, the T cell can survey the APC to see if it has the specific antigen
• the T cell probably receives low avidity signals important for survival

• express MHC II
• co-stimulatory molecules
• cytokines

• dendritic cells (primary APC)
• macrophages
• B cells

1. immature dendritic cells encounter PAMP (immature DC uptake antigen)
2. TLR signal induce CCR7 and enhance processing of antigen (mature DC process and present antigen)
3. CCR7 direct migration into lymphoid tissue and augment expression of co-stimulatory molecules of MHC molecules

• bacterial PAMP activate PRR
• promote macrophage function
  • upregulate expression of MHC and B7
  • producing cytokines

1. antigen bind to B cell
2. specific antigen efficiently internalized by receptor mediated endocytosis
3. high density of specific antigen fragments presented

Effect of T cell activation on IL-2

• promote expression of IL-2 receptor
• IL-2 production

• naive- L-selectin, CD34
• effector
  • LFA-1 and ICAM-1
  • VLA-4 and VCAM-1

Different types of Th cells

• Th1
• Th17
• Treg.
• Th2

Viruses stimulate the production of what cells? parasites stimulate the production of what cells?

• viruses- Th1
• parasites- Th2

1. dendritic cell produces IL-12
2. this cause the differentiation into Th1
3. Th1 produces IFNγ which, will continue to stimulate the production of Th1

1. dendritic cells produce IL-6, IL-23
2. TGF-β causes differentiation
3. causes differentiations into Th17 cells
4. produces IL-17

1. dendritic cells produces unknown compound to produce Treg.
2. TGF-β cause differentiation into Treg.
3. Treg produces IL-10, TGF-β

Process of Th2 cell differentiation

1. dendritic cell stimulated BY IL-25 and TSLP
2. these compounds also cause differentiation in Th2 cells
3. Th2 cells produce IL-4, IL-5

Transcription regulator most important in Th1 cell development

T-bet

T cell effector mechanisms

• cytotoxicity (granule release, FAS)
• directed lymphokine secretion
• co-stimulatory signals (CD40/CD40L)

• the IFN-γ Th1 produces cause macrophage activation
• CD40L on Th1 binds to CD40 on macrophages to cause macrophage activation

Mainly specializes in destroying viruses and cell mediated inflammation

1. lipid soluble molecule can penetrate skin and react with proteins
2. haptenated proteins (altered self) can be taken up by Langerhans cells and skill macrophages which serves as APC's to T cells in draining lymph nodes
3. built up memory T cells
4. upon subsequent exposure, Th1 cells recognize antigen and release cytokines that act on vascular endothelium
5. recruitment of phagocytosis and plasma to site of antigen invasion
6. cause visible lesion
7. enzymes are produces that degrade proteins in ECM and affect skin integrity

• Th2 cells produce IL-4 promote isotype switching to IgE
  • IgE promote mast cell and basophil activation and degranulation
    • allergic patterns of inflammation
    • immune responses to parasites
• Th2 cells produce IL-5 to recruit eosinophils that will cause asthmatic symptoms along with IL-4 effect

Major transcriptional factor of Th17

associated with human autoimmune disease

• function- secrete anti-inflam. cytokines IL-10 and TGFβ
• clinical app.- without Treg cells develop multiple autoimmune disorders

Process of cytotoxic T cells

1. before interaction, primed in lymph node
2. two options
   1. not specific- initial interaction with nonspecific adhesion molecule, but no specific interaction, so cells separate
   2. antigen specific- stable pairing and focused release of effector molecules
3. apoptosis

• granule release
• FAS/FASL interaction

1. direct cell to cell contact causes release of granule contents via exocytosis
   1. perforin- form pore in cell membrane
   2. granzyme- Ser proteases that activate apoptotic pathway

process of FasL/Fas interactions in cytotoxic T cell apoptosis function

1. FasL is upregulated on cytotoxic T cells that can bind to Fas on target cells (Fas on member on TNFR superfamily- CD40)
2. leads to activation of caspases and apoptosis