What are the 3 states of activation of T cells?
Naive, Memory, Effector
What the two locations that memory T cells tend to reside?
Lymph node (waiting for Ag presentation via an APC), Tissues (surveilling for that particular Ag)
What APC is best for naive T cells?
What are some APCs that can activate effector T cells?
Macrophages, B cells, DCs
Describe these features of classical DCs: surface markers, major location, expression of toll-like receptors, major cytokines produced, and postulated major function.
surface markers: CD11c, CD11b (complement proteins) major location: tissues expression of toll-like receptors: TLR 3, 4, 5, 8 high major cytokines produced: TNF, IL-6, IL-12, IL-23 postulated major function: Induction of T cell response against most Ag
How do most naive T cells enter the lymph nodes?
High endothelial venule (HEV)
Where within the lymph node do T cells and DCs interact w/ one another?
Where within the lymph node are naive B cells most commonly aggregated?
Follicles of the cortex
Via what vessel do DCs enter the lymph node? exit?
Enter: Afferent lymphatic vessel Exit: Efferent lymphatic vessel
Where are plasma cells primarily located within the lymph node?
Primarily medula, also been indicated to reside in the paracortex
Describe the process a DC must go through from when it encounters an Ag in the epithelia and goes on to present that Ag to T cells in the lymph node.
1) Ag capture (epithelia) 2) Activation of the DC 3) Migration of the DC 4) Maturation of the migrating DC 5) Mature DC presentation to naive T cell (paracortex of lymph)
Where are blood borne Ag's most often found by DCs?
Which of the following does a patient have a higher risk of after a splenectomy? A) Autoimmunity B) Periodic fever syndrome C) Sepsis D) Uncontrolled viral infection
Sepsis It isn't D because viral infections require host cells, the host cells would be encountered by DCs then the viral Ag's could be presented to the naive T cells within the lymph nodes
What is the term for T cells only being able to recognize peptide Ag in the MHC molecule?
What is the name of the genomic section that codes for the MHC complex? Draw it and its components.
Human leukocyte antigens (HLA)
Are MHC genes highly conserved or highly polymorphic? Why?
highly polymorphic, allows for greater repertoire of recognition of adaptive immune system, ensures at least some members of the population will be able to present a particular microbial protein Ag
What do the polymorphic residues of the MHC genes determine?
Which Ag peptide is presented by which MHC
Describe the expression of MHC?
Codominantly expressed - alleles inherited from both parents expressed equally
How many haplotypes of MHC do all heterozygous individuals have?
Describe the Class I MHC.
alpha 1 and 2 (polymorphic) form the peptide binding cleft alpha 3 (constant): CD8 binding site 1 TM region
Describe the Class II MHC
Alpha 1 and Beta 1 (polymorphic): peptide binding cleft beta 2 (constant): CD4 binding site
What length of peptide is suitable for class I MHC? class II MHC?
Class I: 8-11 Class II: 10-30
What is the name of the phenomenon that MHC is capable of presenting many different peptides?
For an functioning MHC molecule to be expressed on the surface, what must occur?
Acquire peptide during assembly inside cells
Do MHC molecules display self peptides?
Yes, expression of MHC I is crucial for survival of self cells. The trick is that the within healthy individuals the cells only respond to foreign Ag
What type of cells expressed MHC class I?
All nucleated cells
What type of cells express MHC class II?
APCs (DC, ME, B cells), thymus, induced on other cells by IFN-gamma
Describe the process of MHC II peptide loading.
1) Uptake of extracellular proteins into vesicular compartments of APC 2) Processing of internalized proteins in endosomal/lysosomal vesicles 3) Biosynthesis and transport of class II MHC molecules to endosomes 4) Association of processed peptides w/ class II MHC molecules in vesicles 5) Expression of peptide-MHC complexes on cell surface
What prevents the Class II MHC from binding self peptides while it resides in the ER?
The invariant chain that block binding of self Ag's while in the ER is cleaved into CLIP while in endosomes. What removes CLIP to allow the Ag peptide to be loaded?
Describe the process of MHC I peptide loading.
1) Cytosolic proteins are degraded by the proteasome IFN-g increases efficiency 2) Peptides are transported into the ER by the TAP complex (TAP: transporter associated with antigen processing)—TAP1/TAP2 3) Chaperones-calreticulin and calnexin bind immature, unstable class I 4) Passed off to chaperone tapasin, which mediates the interaction between TAP and MHC class I 5) MHC class I loaded with peptide 6) Stable MHC/peptide complex goes to cell surface
What is cross presentation? What cells are capable of it?
It is the process in which cells infected with intracellular microbes, such as viruses, are ingested (captured) by professional APCs, and the antigens of the infectious microbes are broken down and presented in association with the major histocompatibility complex (MHC) molecules of the APCs; a subset of DC
How do immune reactions to superantigens differ from immune reactions of standard antigens?
Polyclonal; Since Sag doesn't need to fit within the peptide binding groove because it can cause association of TCT and MHC w/out doing so, it is able to activate many types of T cells. Polyclonal activation leads to a cytokine storm
What type of Ag's are recognized by alpha/beta T cells?
Of what chemical moiety are the Ag's that are bound by B cells?
Proteins, polysaccharides, lipids, small chemicals
What is the special type of cell used to display Ag to B cells w/in LN?
Follicular Dendritic Cells (FDCs)
What the Ags on FDCs coated w/?
Ab's or complement byproducts
NKT cells have what type of receptor? What does it bind?
Invariant TCR, Lipids expressed on CD1d
What type of Ag's do gamma/delta T cells bind?
Variety of Ags
A mutation in TAP1, TAP2 or tapasin expression would lead to what type of deficiency?
Bare lymphocyte syndrome Type I: HLA class I deficiency; no MHC I expression
A mutation in 1 of the 4 genes that encode txn factors that regulate MHC II expression (CIITA, RFX5, RFXAP, or RFXANK) will lead to what type of deficiency?
Bare lymphocyte syndrome Type II: HLA class II deficiency; no MHC II expression
What type of Ag's are involved with MHC Class II peptide loading? MHC Class I?
MHC Class II: extracellular Ag (Ag cleaved in endosome) MHC Class I: intracellular Ag (cleaved by proteasome in cytosol)
Where do naive, memory, and effector T cells reside?
Naive and Memory: Lymph node Effector: Skin, Mucosa
What is this an image of?
MHC class I
What is this an image of?
MHC class II