Activation of B and T Cell by Antigen Flashcards
Dendritc cells MHC II expression
- Constitutive; increases w/maturation; increase by IFN-y
Macrophagages MHC II expression
- Low or negative; inducible by IFN-y
B lymphocytes MHC II expression
- Constitutive; increased by IL-4
Dendritic cells costimulators
- Constitutive; increases w/maturation; inducible by TLR ligands, IFN-y, and T cells (CD40-CD40L interactions)
Macrophages Costimulators
- Low, inducible by TLR ligands, IFN-y, and T cells (CD40-CD40L interactions)
B-lymphocytes Costimulators
- Induced by T cells (CD40-CD40L interactions), antigen receptor cross-linking
Dendritic cells principle function
- Initiation of T cell responses to protein antigens
Macrophages principal function
- Effector phase of cell-mediated immune response
B lymphocytes principal function
- Antigen presentation to CD4+ helper T cells in humoral immune responses (cognate T cell- B cell interactions)
How antigen gets to secondary lymphoid tissue
- Dendritic cells engulf pathogens and process and present antigen
*only know function of dendritic cells is to trigger T cell responses
*migratory cells that carry their antigen load from site of infection to nearest secondary lymphoid tissue; their activation induces expression of CCR7, the receptor for chemokine CCL21
- Macrophages engul pathogens and process and present antigen
*have a range of functions in defense and repair of damaged tissue
*resident in tissue and do not migrate
*macrophages resident in lymphoid tissue can process and present antigen that is carried passively in lymph from infected tissue
T cell circlation through lymph node process
- Naive T-cells arrive at lymph nodes in arterial blood
*expressing L-selectin and CCR7 chemokine receptor; are NOT expressing E or P-selectin or receptors for chemokines from inflammatory sites
*Selectins slow them down (L-selectin on lymphocytes transiently bind to GlyCAM-1 and CD34 on HEV)
- HEV display chemokines made only in lymphoid tissue that bind CCR7
*CCR7 transduces intracellular signals that activate LFA-1
- T cells bind to endothelial cell in thin walled high endothelial venules (HEV)
*Activated LFA-1 binds tightly to ICAM-1 (immunoglobin superfamily) arresting the rolling T cells
- Squeeze through vessel wall
- Enter cortical region of lymph node
- Pass through tissue, examine APC
*see antigen: activate, proliferate, differentiate
*don’t see antigen: recirculate out
T cell activation process
- Naive T cells TCR in conjuction with its coreceptor (CD4/8) binds w/ low affinity to APCs peptide-MHC complex
*the T cells coreceptor binds to an invariant, non-polymorphic area of the MHC
- Naive T cells LFA-1 integrin upon antigen recognition goes from a low affinity state to a high one for the APC’s ICAM-1
*these adhesion molecules stabilize the T cell- APC binding until the necessary signalling threshold is achieved
- Full activation of T cells depends on the recognition of costimulators on APC’s in addition to the antigen recognition
- APCs who have encountered a microbe have increased expression of costimulators B7-1 (CD80) and B7-2 (CD86) which will bind to the T cells CD28
*CD80/86 is ONLY expressed on “professional” APC’s
*interaction b/w CD28 and CD80/86 triggers the production of the growth factor cytokine IL-2 and hight affinity IL-2 receptors that trigger autocrine and paracrine stimulation of clonal expansion of activated T cells.
*if the co-stimulatory signal is not received, this induces a state of non-responsiveness in the T cell called anergy
- Activated T cells express CD40 ligand which binds to CD40 on APCs and activates the APCs to express more costimulators and to secrete cytokines that will enhance T cell differentiation
*this interaction promotes T cell activation by making APCs better at stimulating T cells
*binding of CD40L to CD40 also activates the APC bearing the CD40
- The third signal, which triggers differentiation is largely a function of the cytokines present
T cell differentiation
- T cell differentiate based on the cytokines its exposed to from the APC
Effector T-cell migratory process to site of inflammation
- The homing of effector T-cells to a site of infection is independent of antigen recognition, but lymphocytes that recognize microbial antigens are preferentially retained and activated at the site
- Activated/effector T cells no longer express L-selectin and CCR7 receptor
- Effector T cells express high levels of E and P-selectin and the integrins LFA-1 and VLA-4
*endothelium at the site of infection are exposed to cytokines such as TNF and IL-1, which act on the endothelial cells to increase expression of E and P selectins as well as ligands for integrins, expecially ICAM-1 and VCAM-1, the ligand for VLA-4
- Effector T cells also express receptors for chemokines tha are produced by macrophages and endothelial cells at these inflammatory sites and are displayed on the surface of the endothelium
- Clonally expanded activated T cells are reactivated by any host cell displaying microbial peptides bound to MHC molecules, not just dendritic cells
B cell antigen recognition
- B cells see “native” antigen (protein, carbohydrate, lipid, nucleic acid)
*linear or conformational epitopes
- Recognized by surface immunoglobulin
*induces intracellular signalling events; Tyrosine kinase, protein kinase C, changes in gene transcription
