Cell Mediated Immunity I Flashcards
describe the cells and the functions involved in cell-mediated immunity
- cell involved:
- antigen specific: T helper CD4 and T cytotoxic CD8
- antigen non-specific: NK cells, macrophages, neutrophils and eosinophils
- functions:
- response to intracellular pathogens
- activation of M1 macrophages
- induce B cells (INF-γ) to class switch (IgG) to opsonize
- direct killing (Tc)
describe the function of TH1, TH2 and TH17 cells
describe the phases of T cell response
- Naive T lymphocytes recognize antigen presented by dendritic cells in peripheral lymphoid organs
- production of cytokines (e.g. IL-2) and its receptors
- autocrine pathway of cell proliferatoin and differentiation
- memory cells
- effector cells
- some activated CD4 T cells remain in the lymph node, migrate into follicles and help B cells
- migration of effector T cells to sites of antigen
- T cell effectors
- CD4 T cells recruit and activate phagocytes
- CD8 cytotoxic T cells (CTLs) kill infected cells
- elimination of infection results in elimination of stimuli and death of clones, only memory cells remain
describe the selected receptors/ligands part of T-cell activation
summarize the selected receptors/ligands involved in T-cell activation
describe signal 1 (recognition of MHC-associated peptides)
- digested protein antigens by phagocytes: Class II MHC
- recognized by CD4 T cells
- protein antigens in cytosol: Class I MHC
- recognized by CD8 T cells
- coreceptor need to be engaged simulataneously
- TCR recognizes antigen but can not signal on its own
- TCR noncovalently associated with CD3
describe polyclonal activators and superantigens
- antibodies for the TCR or CD3
- carbohydrate-binding proteins (e.g. phytohemagglutinin)
- superantigens:
- cause pathology through massive load of cytokines (toxic shock syndrome)
- crosslinks VBTCR domain with non-polymorphic region MHCII on APC
- T cell mitogens: induce cell proliferation
- examples: staphylococcal entertoxins, staphylococcal toxic shock toxin, staphylococcal exfoliating toxin, streptococcal pyrogenic exotoxins
describe the adhesion molecules (CAMs)
- CAMs: selectins, mucins, integrins and immunoglobulin superfamily
- function: stabilization of binding between ligand on APCs and T-cells
- overcome moderate affinity between TCR and peptide/MHC
- most important of adhesion molecules are the integrins:
- leukocyte function-associated antigen (LFA-1)
- affinity increases when T cell is activated
- ligand on APCs: intercellular adhesion molecule I (ICAM-1)
- leukocyte function-associated antigen (LFA-1)
describe signal 2, specifically, B7 (co-stimulator)
- important co-stimulators: B7 molecules (CD80 and CD86)
- expression increases in APCs when antigen is encountered
- guarantees response to a foreign antigen
- recognized by receptor CD28 on T cells
- CD28/B7 signaling is essential for the response of naive T cells
describe signal 2, specifically, CD40 (co-stimulator)
-
CD40 ligand (CD40L or CD154) on T cells and CD40 on APCs
- instead of activating T cells, they activate APCs to express more B7 co-stimulators and to secrete cyotkines (e.g. IL-12) to enhance T cell differentiation
- proteins homologous to CD28: CTLA-4 or PD-1 are involved in terminating the immune response
describe clinical correlates with the co-stimulators
- protein antigens used in vaccines fail to elicit T-cell dependent immune response
- need to activate APCs: adjuvant (one of its uses)
- bind to PRR on the innate, and activate APCs
- need to activate APCs: adjuvant (one of its uses)
- agents that block B7:CD128 (aka 28) are used in treatment of rheumatoid arthritis, graft rejection, etc.
- antibodies to CD40: CD40L interaction have been tested for graft rejection
- antibodies that block CTLA-4 or PD-1 have been used to enhance immune response in cancer patients
the first cyotkine to be produced by CD4 T cells is ____ (1-2 hours after activation)
the first cyotkine to be produced by CD4 T cells is IL-2 (1-2 hours after activation)
- autocrine signal
- suvival, proliferation and differentiation
describe the generation of effector CTLs
- licensing of dendritic cell by TH1
- co-stimulatory signal
- IL-2 production by TH1
- CTL-P becomes CTL
- proliferation and cytotoxic function
describe the CTL mechanisms of killing
describe conjugate formation (step 1 of CTL-mediated death)
- cell adhesion (LFA-1 on CTL binds ICAM on target cell)
- recognition of MHC 1: Ag on target cell
describe membrane attack (step 2 of CTL-mediated death)
- granules in CTLs
- perforin
- granzymes
- exocytosis of granule contents
- Perforin action similar to C9
- granzymes act as nucleases
describe activation vs inhibition of NK cells
- activation is determined by a balance between activating and inhibitory receptors
- NK cells do not have capability of recognizing MHC
- recognize altered cell surface molecules (lowered class I MHC)
describe the function of NK cells
- recognize tumor or virus-infected cells
- A) cytotoxic granule mediated cell apoptosis (perforin, granzymes, alpha- defensins)
- B) induce infected macrophages ot kill: respond to IL-12 with IFN-γ production
- C) antibody-dependent cell mediated toxicity
