lecture 23/34 - cell mediated immunity Flashcards
What are the cells involved in cell mediated immunity and what purpose do they serve?
Cytotoxic T lymphocytes: kill virus infected cells
T helper cells (CD4)
Th1: activates infected macrophages
Th2: provides help to B cells for antibody production, and switching to IgE
Th17: enhances neutrophil response to promote barrier integrity
Follicular helper: B cell help isotype switching and antibody production
Regulatory t cells: suppression of T cell responses
NK and macrophages
In summary describe the the difference in cell mediated immunity between viruses and bacteria
Virus (or cytosol replicating pathogens) → cytosol → effector T cell is cytotocis (CD8) → MHC class I antigen recognition → killing of infected cell
Bacteria/parasites (non-cytosolic) → macrophage vesicles → Th1 cells → MHC class II on infected macrophage → activation of infected macrophage
Describe the initiation of T cell mediated responses
Entry through mucosal surfaces, antigen taken up by langerhans cells, or immature dendritic cells, and migration to draining lymph nodes
Mature dendritic cells enter lymph nodes to transfer antigen to resident dendritic cells, B7 positive dendritic cells stimulate the naive T cells which have to be primed to become an effector T cells
Describe the process of activation by APC. What 3 signals are required and what is needed for each?
T cell binds peptide
Activation of T cell and binding of B7 1or 2 to CD 28
Cytokine - determined by the type of infection
What determines humoral vs. cell mediated immunity
The differentiation of CD4+ Th0 cells into Th1 or 2 and cytokine signal 3
TH1: IL12 or IFN gamma → STAT4 activation, regulating development of TH0 into TH1
IL4 (allergen): STAT 6 activation → induction of Th2 development
FoxP3→ T reg → TGF and IL10
How is CD8 activated? What is the importance of CD8?
APC interactions with CD4+T cells with CD40[L] → production of IL-2 from CD4+
Dual interaction allows expression of 4 1 BBLigand, give T cell full thrust to start converting into an effector cel
What is the importance of IL2 for CD8+ T cells?
Naive CD8+ T cells have gamma and beta subunits that bind IL2 with low affinity→
After activate → synthesis of the alpha chain which is CD 25 which is a high affinity for IL2, allowing survival and higher reproduction → ready to kill
What do LFA1 and CAM do?
Non specific adhesion molecules that slow down T cells next to infected cells
LFA expressed by T cell, interacts with ICAM on tissue cell
Allows time to bind TCR to peptide to initiate killing
What does a MTOC do?
Microtubule organizing center, allows aligning of path to get cytotoxic molecules to travel in one direction to maximize efficiency and hit target
What effector molecules are associated with killing molecules
Perforins: holes in membrane target to allow delivery of killing enzymes
Granzymes serine esterases: apoptosis inducers via cleavage od BID and activation of ICAD
IFN-gamma:
Lymphotoxin tumour necrosis factor beta: works with IFN gamma to induce apoptosis
How else can t cells induce cell death?
Fas ligand expressed by activated CD8 T after binding ot Fas (CD95) to induce apoptosis
What are the two major classes of T cells in cell mediated immunity
CD4+ i TH1: exogenous antigen presented by MHC classII CD8+: endogenous antigen presented by MHC class II
How are pathogens killed after p[hagocytosis?
Elastase: produced in phagolysosome
Inducible nitric oxide synthase:
Oxidase producing reactive oxidase intermediate
Induces cell death
How does TH1 cells help macrophages?
Binds them and expresses interferon gamma to bind receptors on macrophage, increasing MHC class II expression, activating them to become microbicidal
Causes expression of peptide and binding of secretion
Activated macrophages increase expression of CD40 and TNF receptors and secrete TNF-alpha
IL12 production also induced by macrophage activation
Describe the role of natural killer cells
Early line of defense in nonspecific
Activated by type 1 interferons within 24h after infection
Produce interferon gamma (type II interferons)
