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46 Cards in this Set

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What are 6 pathogen associated molecular patterns (PAMPs) that stimulate an immune reaction?
Laugh n Dump
-LPS
-Flagella
-N-formyl peptides
-dsRNA
-Unmethylated CpG DNA
-Mannose
-Phosphorylcholine
What time of immune reaction responds to PAMPs?
Innate recognition and inflammation
Is the innate system totally random?
No; there are specific Pattern recognition receptors (PRRs) for each PAMP.
Is the innate system as specific as the adaptive?
NO
What is the cell-mediated immune response designed to combat?
Intracellular microbes
What are 2 general categories of intracellular microbes?
-Intravesicular
-Cytoplasmic
What is NOT involved in cell-mediated clearance of intracellular microbes?
Antibodies
What branch of cell-mediated immunity engenders the response to
-Intravesicular organisms
-Cytoplasmic organisms
Intravesicular: Thelper/NK
Cytoplasmic: Tkiller/NK
What are NK cells actually a part of?
Innate immunity
During a reaction to microbes, how many times do Tcells encounter antigen?
Twice
1. In peripheral lymphoid organs (immature are activated/prolif)
2. At the actual site of infection (clones migrate)
So the 2 types of effector T cells in cell-mediated immunity are:
1. CD4+ Thelper cells
2. CD8+ Tkiller cells
What do Thelper cells recognize?
Antigen on MHCII
What are the 2 subcategories of Th cells?
1. TH1 - against intracellular microbes
2. Th2 - against parasites and allergens
How do Th1 cells act in general?
By activating or ramping up inflammation - they activate macrophages and cause Ab to secrete IgG
How do Th2 cells act in general?
By causing plasma cells to secrete IgE, and activating Eosinophils which aid in mast cell degranulation.
What are the effector cells that stem from Tc cells?
CTL's - cytotoxic T cells
What are the 2 ways in which CTLs are activated?
1. Directly by Ag + APC
2. Indirectly by Ag + Th1 cell
When mature Tcell clones recognize Ag at peripheral sites of infection, how is the recognition different from the first time in lymphoid organs?
It doesn't require a 2nd costimulatory signal.
When Thelper cells differentiate into effector cells in peripheral lymphoid organs, what determines whether they'll become Th1 or Th2 cells?
The cytokine environment in which they are immersed.
IL-12 --> Th1
IL-4 --> Th2
How do effector T cells know where to migrate to from peripheral lymphoid organs?
By the expression of specific integrins and CAM's on the endothelium near the inflammatory site.
What two molecules activate endothelial cells and elevate chemokine production during innate immunity?
-TNF
-IL-1
When chemokines bind to endothelial surface proteoglycans, how does it alter the endothelial surface at the infection site?
-Lose L-selectin so lymphocytes don't track back to lymph tissue
-Gain E-selectin and P-selectin
What integrins are on the lymphocyte surfaces, and what happens to them during differentiation?
LFA-1
VLA-4
Affinity increases for tighter adhesion to the endothelium.
What does Effector Tcell recruitment and migration mimic?
The inflammatory response - chemotaxis and diapedesis.
When the Tcells migrate from the peripheral lymphoid organs to the site of infection, is it ONLY the mature clones?
NO - it's independent of Ag-recognition; NONSELECTIVE migration.
Why is Tcell migration nonselective?
To maximize the effectiveness of the cell-mediated immune response so ANY antigens will be recognized at the infection site.
What happens to the SPECIFIC clonal Tcells that do recognize antigen at the site?
VLA expression and affinity increases to enhance adherence to the matrix.
Where are L-selectin ligands?
On high endothelial venules in lymph nodes.
What are the molecules on endothelial cells at peripheral tissue sites that allow adherence to lymphocytes?
-E-selectin ligand
-P-selectin ligand
-ICAM1 (receptor for LFA-1)
-VCAM1 (receptor for VLA-4)
Are ICAM-1 and VCAM-1 only on endothelial cells?
No; they're also on APC's
What would be a more effective antibody to prevent leukocyte trafficking; TS1, to block P-selectin, or Efalizumab / Raptiva which blocks LFA1/ICAM1 binding?
LFA1-ICAM1 blocker - so Tcells can't have antigen presented to them.
What is Alicaforsen?
A drug that blocks transcription of ICAM-1, so endothelial cells and APCs can't bind the LFA-1 on Tcells.
Does all endothelium express ICAM1 or VCAM1?
No; only activated endothelium
What activates Endothelium?
IL1 and TNF
What cells express L-selectin?
Naieve Tcells
What is the ligand for L-selectin?
L-selectin ligand
What is the function of L-selectin binding to L-selectin ligand?
Adhesion of naieve Tcells to high endothelial venules in lymph nodes.
What cells have E and Pselectin?
Activated endothelium.
What is the ligand for E or P selectin?
E or P selectin ligand
What cells have E/P selectin ligand?
Activated effector and memory Tcells.
What is the function of E/P selectin ligands binding E/P-selectins?
Initial weak adhesion of the cells to activated endothelium at periphal sites of infection.
What is this weak interaction called?
Rolling
What cells have LFA-1 or VLA-4?
Activated effector and memory Tcells
What is the ligand to LFA-1 or VLA-4 and what cells have them?
LFA-1: ICAM1
VLA-4: VCAM1
-on endothelial cells
What is the function of LFA-1 or VLA-4 binding ICAM1 or VCAM1?
Stable arrest of activated Tcells to the endothelium so diapedesis can occur at specific tissue injury sites.
Once the effector Tcells diapedese into the tissues, what happens?
-If the antigen is there, the TCR will bind and recognize it
-If not there, the Tcells return to circulation.