1.4.2 T-Cell Responses to Antigens Flashcards
What does Th1 CD4+ T cells release to increase activity of both macrophages and CD8+ T cells?
IFNgamma and TNFalpha
What are two of the main ways that pathogens get inside of cells?
1) Life cycle of pathogen requires an intracellular component (virus) 2) Phagocytosis
What of type of immune system mediator is unable to reach pathogens within cells?
Ab’s
What are the main types of ag’s that MHC class I respond to? Class II?
Class I: Intracellular Class II: Extracellular
For an intracellular pathogen to be recognized and presented on MHC class II, what must occur?
It must have an extracellular phase in which it gets phagocytosed and presented on MHC class II.
What is required of MHC class I to present antigen?
Cross-presentation, in essence, the DC phagocytoses the infected cell which contains the antigen. It then can process the antigen and present it on its MHC class I molecule.
What are some of the effector cells that CD4+ T cells can differentiate into?
Th1, Th2, Th17, or Tfh
Which chemokine receptor is used in homing T cells into the lymph nodes?
CCR7
What is the basic cellular processes that allow an effector T cell to leave the LN and travel to the site of infection?
Change expression of adhesion molecules and chemokine receptors (switch from LN homing to tissue homing)
What are macrophages doing at the site of infection that aids in the migration of effector cells to the site of infection?
Producing chemokines that attract effectors, Prod. inflammatory cytokines (IL-1 and TNFalpha) that act on endothelial cells
Expression of what on endothelial cells aids in the migration of effector cells to the tissue?
Adhesion molecules (selectins and integrins)
In Th1-mediated immunity, where are the effector cells? What are they and what are they working on?
At the site of infection; CD4+ T cells working on macrophages or CTLs working on infected MHC class I expressing cells
What are the two branches of Th1-mediated immunity?
1) CD4+ Th1 cells lead to the activation of phagocytes 2) CTLs kill cells harboring intracellular pathogens
What are the two ways that Th1 cells can activate macrophages?
Direct contact via CD40L-CD40 interactions or Cytokine IFNgamma
How does Th1 activation affect the function of macrophages?
Positive feedback; telling the macrophage to do more of the same: capture pathogen in phagolysosome, lysosomal proteases destroy pathogen, produce ROS and NO
When CD4+ cells engage macrophages via INFgamma and CD40L, expression of what is induced?
Proteases and ROS/NO-producing enzymes
What are the three activation responses of activated macrophages?
Killing of phagocytosed microbe, secretion of cytokines (TNF, IL-1, chemokines, IL-12), increased expression of MHC molecules and costimulators (B7 molecules)
What are cytokines used in the communication between macrophages and Th1 effector T cells?
Macrophage to Th1: IL-12 Effector Th1 to Macrophage: INFgamma
What happens to the granules when a CTL recognizes an Ag and has conjugate formation?
Granules move towards the side of CTL activation (cytoplasmic rearrangement) and the CTL granules exit via exocytosis
What are the two main types of products found within the granules? What do they do once inside the target cell?
Granzymes and Perforin; Perforin (as its name suggests) creates a pore on the surface of the cell, then the granzymes enter that hole and induce apoptosis
Aside from granule release, what is another way that CTLs can induce cell death?
FasL (on CTL) interacting w/ Fas on the infected cell
What types of cells use similar cytotoxicity mechanisms as CTLs?
NK and NKT cells
What is the amplification loop b/t Th1 cells-macrophages?
Macrophages secrete IL-12 which acts on naive T cells to differentiate them into Th1 cells. Th1 cells activate macrophages to secrete more IL-12.
What is the amplification loop b/t Th1 cells-endothelial cells?
Th1 cells produce TNFalpha, which acts on endothelial cells to increase adhesion molecules. Adhesion molecules recruits more T cells
NK cells are designed to attack what type of cells? What does this prevent?
NK cells target cells that lack MHC class I. By attacking these types of cells, it kills pathogens that are trying to evade CTLs
NK cells have what two types of receptors? Which is dominant?
Activating receptor (AR) recognizes a variety of ligands on target cells and inhibitory receptors (KIR) that recognize non-polymorphic residues on MHC class I; Inhibiting is dominant.
What is used to present antigens to NKT cells? What is it similar to?
CD1; MHC class I-like molecule
What type of antigens are recognized by NKT cells?
Glycolipid Ag’s
What are four identifiable traits of NKT cells?
NK cell markers, TCR w/ limited variability, Specific for glycolipids + CD1, Kill via perforin/granzyme or FAS/FASL
What branch of immunity is responsible for delayed type hypersensitivity? What pathogen is commonly associated with delayed type hypersensitivity?
Classic Th1 response, mycobacterium tuberculosis
What is responsible for the 24-48 hr delay in DTH?
Th1 cells need to to home to site of infection, Th1 cells respond to Ag, induce detectable response
What are 3 physical characteristics of DTH?
T cell/monocyte infiltration, increased vascular permeability-edma, fibrin deposition
What is the issue with M. tuberculosis if it can be ingested by macrophages?
The macrophages cannot eliminate it
Macrophage and T cell activation within the lungs in response to TB causes the formation of what? What can develop within this tissue?
Granulomas; caseous necrosis
What are some of the TNFalpha blockage drugs? Why must pt’s be tested for TB before being put on these drugs?
Infliximab (Remicade), Adalimumab (Humira), Etanercept (Enbrel), Certolizumab (Cimzia), Golimumab (Simponi) B/c TNFalpha is important in the formation of granulomas. Granulomas help wall the body off from further damage of TB.
What are some of the ways that pathogens have developed resistance to Th1-mediated immunity?
Prevent phagolysosome fusion, escape to cytoplasm, inhibit MHC class I, decoy receptors (soluble INFgamma receptors)
What is occuring in slides a-d? (Hint: this is T cell interaction w/ target cell)
a) small CTL approaches target cell
b) CTL makes contact w/ target cell
c) 2 min after contact - CTL is round and granules reorientate
d) 10 min after contact - granules move into position for release
Describe the various aspects of the image.
Dr. Yankee may have used/drawn this illustration 100x.
