Adaptive Response - where and when? Flashcards
Where are most immune responses initiated in?
secondary lymphoid organs
What do lymphocytes do once produced?
Travel around body in blood and lymph to meet Ag
What are HEV?
High endothelial venules - small blood vessels in lymph nodes that have different structure to other venules
How does cell decide to go to lymph node or not?
Afferent leads to lymph node, if Ag there - stay, if not leave
Lymph node structure”
Medulla paracortex and cortex
Where are B and T cells found in lymph node?
B cells cortexT cells paracortex
What do lymphocytes do if they meet Ag in lymph nodes?
Start dividing and form primary and secondary follicles
Where is the germinal center?
Within secondary follicle
What does dendritic cell usually do (resting to active):
Sits in tissue until meets pathogen. Uses PRR, and engulfes pathogen (phag). Then processes it and moves out to lymph node. No longer Phag but very potent APC with lots of MHCII and B7. Interacts with T cell in lymph node. If cytotoxic T cell - get activated and go to area of infection.
What do germinal centers contain?
B, T (fh), DC, FDC, Macrophages
Germinal centers are sites of 4
B cell class switch, affinity maturation, memory cell generation, Plasma cell precursor generation
Direction of travel in germinal center:
Not definite but:Naive B cell moves from dark zone to basal light to apical light to mature into plasma and memory cells
What cell in the secondary lymphoid used to show Ag to BCR?
FDC- more efficient
What do Tfh cells do in secondary lymphoid?
Help T cells differentiate
Why don’t B cells become plasma cells in GC?
produce lots of Abs and cover up all the Ags
What does the spleen usually deal with? vs lymph?
Spleen usually deals with blood infectionsLymph node usually deals with tissue infections
What are PALS?
T cell area of white pulp of spleen
So are PALS only T cells?
No, they also have follicles with marginal zones and mantle zones containing B cells, in the middle of which you get GC
What Ig protects mucousal surfaces? How?
IgA - very important in protecting mucousa.Stops adhesion of pathogens onto mucousal surfaces
Describe how dimeric IgA gets to surface of mucousa:
It is made by the plasma cells in the lamina propria next to mucousal cell surface. The dimeric IgA then binds to Poly Ig receptors on the basal side of epithelial cells, get endocytosed, go through epithelial cells to luminal surface. Then a once usable enzyme cuts the receptor off but leaves a secretory component on to protect the IgA from gut enzymes and other mucousal enzymes.
What is the back up to IgA used to protect mucousal surfaces?
IgE
IgE action to protect mucousa
Mast cells have an FcEpsilon receptor for IgE. If spec pathogen comes, it triggers mast cell to produce things like vasoactive chemicals histamine and eosinophils and leave blood to enter area. Abs and complement are also attracted
What is the Peyer’s Patch?
Active Immune area of gut
What is the organisation of Peyer’s patch?
Primary and secondary follicle, and germinal center
Where are M cells located? What do they do?
Inductive site of villi of gut, takes Ag from outer surface and shows it to lymphocytes underlying the gut
What happens in Ag in gut?
M cell takes the antigen and shows it to the underlying lymphocytes.When the lymphocytes are activated they drain into the closest local lymph node (in this case mesenteric) to further activate. Then they find their way back to gut using homing molecules.
Gut homing molecule name (how):
MadCAM1 is the gut homing molecule. The lymphocytes underlying the gut imprint on it by making an integrin on their surface that binds to it. After the leave the mesenteric lymph node - find their way to MadCAM1.
2 types of communication during the immune response:
Cell-Cell contact or soluble molecule binding to recpetor
What are the soluble molecules:
Small secreted proteins that act as messengers between cells
Functions of Cytokines (2):
Control haematopoiesis and immune responses
How do cytokines work?
Bind to cytokine receptor and initiate intracellular signalling
What does intracellular signalling of the cytokine receptor lead to? 2
NAME?
6 Main groups of cytokines and jobs:
1- Interleukins - messengers between leukocytes2- Chemokines - chemotactic3- Tumour Necrosis Factor- pro inflammatory4- Interferons - Interfere with viral replication5- Growth Factors - promote growth and differentiation6- Colony stimulating factors - help produce colonies of cells
What do you call it when one cytokine does different jobs?
Pleotrophy
Which two cytokines work to class switch, which two stop to class switch:
IL4 and IL5 work to class switchIL4 and IFN gamma stop class switch (IFNy blocks the signal)
What do Th2 make to act on B cells: what do they do?
IL2, IL4, IL5 - proliferate and class switchIFNy - stop class switch
Which 2 cytokines stim inflammation?
IL 1 and 17
Which cytokines are immunosuppressive?2
IL10 and TGFB
2 antiviral cytokines are:
IFN a and IFNy
Two cytokines leading to T cell proliferation and differentiation are:
IL2 and IL12
Two cytokines leading to B cell proliferation and dif are:
IL2 ad IL13
2 cytokines controlling haematopoiesis are:
M-CSF and GM-CSF
Two chemotactic factors are:
IL8 and CCL5
Which 2 cytokines do Th17 make - what do they do:
IL17 and 22 - proinflammatory
3 Cytokines that Th2 makes and jobs;
IL4 - Th2 cell dif and B cell class switchIL10 - B cell prolif and suppresses Th1 (antiinf)IL13 - Promotes B cell proliferation
2 cytokines that macrophages and Dcs make and jobs:
IL1 - pro inflammatoryIL12 - Promote Th1 diff
What cells make IL 10 - use:
Monocytes, Th2 and Treg - antiinflammatory
3 types of CSF and jobs:
Granulocyte Macrophage (GM-CSF) - acts early in myeloid developmentMonocyte/Macrophage (M-CSF) -Induces Monocyte differentiationGranulocyte CSF - G-CSF - Induces granulocyte differentiation
Example of Cytokine being used therapeutically
IFN alpha for viral infectionsBlocking TNF alpha for RA