Innate and Adaptive Immunity Lecture Oct 2 Flashcards
Mast cells are the sentinels that really coordinate the initiation of the inflammatory response. There are three mechanisms they use to do this. What are they?
THe mast cell will recognize a pathogen through:
- direct interaction between the pathogen PAMP and the TLR
- Mast cell Fc receptor binding to antigen-covered antigen
- Complement receptor mediation
THe response mechanism will the threefold as well:
- Secretion of IL1, TNF, and IL6 will stimulate the acute phase response
- Secretion of Gm-CSF to stimulate leukocyte production
- Secretion of CXCL8 , which is a chemokine to recruit leukocytes to the inflammatory site
WHat are the steps in neutrophil extravasation?
- Neutrophils are continuously contacting the endothelia lining by transient binding of the selectin on the endothelium to s-Le on the WBC (marginalization), but don’t usually stick
- Also in inflammation, CXCL8 concentation is higher, and the leukocytes have receptors for that. Thus, the WBCs will follow th CXCL8 to the site of inflammation
3, In areas of inflammation, cytokines (like CXCL8) induce the expression of additional adesion molecules on the leukocytes (integrins)
- This integrin can bind to I-CAM molecules on the endothelium (there are special “zip code” pairs or integrins and CAMs so that the WBC will get to the right place)
5, This connection induces the WBC to diapeses through the endothelial lining into the tissue
- It will then undergo further chemotaxis up the CXCL8 gradient to reach the actual inflammatory site
How do macrophages direct responses?
THey secrete a range of cytokines when activated
What are the 5 main cytokines secreted by macrophages? WHat do they do?
IL-1: vascular response and fever
TNF: fever, mobilization of immune cells, shock
IL-6: induces acute phase protein production and activates lymphocytes
CXCL8: chemotactic factor recruits WBCs
IL-12: induces differentiation of T cells into TH1 cells, also activates NK cells
What are the effects of IL1/TNF/IL6 cytokines on the following organs?
liver
bone marrow/endothelium
hypothalamus
fat, muscle
dendritic cells
liver: actue phase proteins for activation of complement opsonization
bonemarrow/endothelium: neurophil mobilization
hypothalamus: increase body temp set point - fever
fat/muscle: protein and energy mobilization to increase body temp - fever
dendritic cell: stimulate migration to lymph nodes and maturation to aid in adaptive immune response
IL-6 induces production of acute phase proteins by the liver, including mannose0binding lectin, fibrinogen, C-reactive protein, and serum amyloid protein.
What do these do?
CRP: binds phosphocholind on bacterial surfaces and acts as an opsonin. also activates complement
Mannose-binding lectin: binds mannose residues on bacteria acting as an opsonin and activates complement
serum anyloid protein: ?
Fibrinogen: involved in fibrosis
Which cell is mainly responsible for initiating the flushing of the infection/wound?
mast cell
What are some qualities of the adaptive immune system?
it’s highly efficient
it’s anticipatory and specific - somatic hypermutation
has memory
What are the prmary lympoid organs?
THis is the primary site for gene rearrangement in the naive lymphocytes:
bone marrow (hematopoiesis, lymphoid progenitor cells, mature B cells)
Thymus (mature B cells, Helper T cells, Gytotoxic T cells, and T regulatory cells)
Fetal liver (mast cells for mesenchyme and astrocytes for blood brain barrier)
What goes into positive selection within the primary lymphoid organ?
What goes into negative selection within the primary lymphoid organs?
Positive selection - they want to tell if the lymphocyte has a receptor that can actually elicit a response (will it work in theory). THis happens first.
In negative selection the nurse cells make sure the lymphocyt’s receptors aren’t recognizing any self proteins
What happens in the secondary immune organs? WHat are the secondary immune organs?
Secondary immune organs are the GERMINAL CENTER located in:
lymph nodes
peyer’s patches
spleen
vermiform appendix
tonsils
These are the sites of lymphocyte education where naive T cells and mature B cells are matched to antigen.
T cells differentiate into effector T cells and B cells differentiate into plasma cells.
What does an immature dendritic cell do to become a mature dendritic cell?
Immature dendritic cells have TLRs on their surface and roam around to the sites of inflammation and pick up PAMPs and other junk from the debris (after neutrophil action)
THe dendritic cell that has recognized non-self material will begin to express CCR7 and becomes a mature dendritic cell.
What does a mature dendritic cell do?
The mature DC is recruited to a nearby lymph node by the chemoattractant CCL19.
On its way to the lymph node it begins to increase its expression of MHCII, CD80 and CD86.
Within the lymph node, it will present the antigen it picked up on all it’s MHCII and thorugh its CD80 and CD86 will interact with immature T cells until it finds a T cell with the same antigen specificity, which it will activate
If a T0 cell has specificity for for the antigen being presented on the DC, what will it secrete?
It will secrete IL2 as an autocrine, which will stimulate it’s own maturation.
How do naive T cells enter the lymph node?
T0 cells express a selectin called CD62L which permits its entry into the node through a special region of the post capilary beds in the lymph node - called the High Endothelial Venule
