Overview of Adaptive Immune Response Flashcards
Immune function depends on circulating ______ to move from blood into tissues via the ________.
Leukocytes; Endothelium
Why do naïve lymphocytes migrate from the blood to secondary organs?
To survey for antigens.
List a few secondary organs/systems.
Spleen. Lymph nodes. Peyer’s patches.
What types of cells migrate across inflames endothelium into infected tissue to fight infection?
Neutrophils. Monocytes. Effector lymphocytes.
List the multi-step model of lymphocyte recruitment into lymph nodes.
- Tethering and rolling by selectins (mucins ligands)
- Adhesion triggering by chemokines
- Firm adherence by integrins/ligands
- Extravasation/Diapedesis (slipping thru endothelium)
What are selectins? Which step in the lymphocyte recruitment are they involved in?
Special type of lectins, which are proteins that bind carbohydrate (sugar) ligands. They function in the earliest step of leukocyte binding to epithelium.
L-selectin functions in what? E-selectins, P-selectins?
In migration into lymphoid organs; allow leukocyte binding to inflamed endothelium.
What are chemokines?
Chemoattractant cytokines.
How do chemokines promote cell adhesion to endothelium?
By triggering integrin activation.
What is the main goal for chemokines?
To get immune cells into lymphoid tissue or sites of inflammation.
What are integrins?
Transmembrane proteins on leukocytes that can be in inactive (low affinity for ligand) and active states.
Integrins are located on ______ only.
Leukocytes.
What signals leukocyte integrins into their active state? How does their shape change?
Signals from chemokine receptors; their shape goes from a bent ball and stick to a straight up ball and stick.
What are integrins required for?
For firm adhesion to endothelium and subsequent transmigration.
What do lymphocytes enter lymph nodes through?
Through blood vessels known as High Endothelial Venules (HEV).
What region produces B cell attracting chemokines? T-zone and dendritic cell attracting chemokines?
B-zones; T-zones
How do immature “sentinel” dendritic cells sample the environment for antigens?
Present in most tissues sampling microenvironment for antigens by pinocytosis and phagocytosis.
What causes DCs to mature?
Detection of danger signals (LPS, viral RNA, bacterial DNA) or inflammatory cytokines (TNF, IL-1).
What happens to DCs as they mature?
Decrease in adhesion to local tissues (keratinocytes), increase expression of receptors for chemokines made by lymphatic endothelial cells and lymphoid organ T zones, upregulate MHC and costimulatory molecules.
Where do DCs migrate to when they mature?
Into lymphoid T-zone baring antigen and interact with T-cells.
B-cells bind intact antigen through what receptor?
Their surface Ig/B cell receptor = BCR
In what medium can B cells bind antigens?
They can bind antigens directly in blood or free antigen that is filtered through the lymphoid tissue.
Describe the early events in B cell responses to protein antigens.
Antigen presentation:
- T-cell activation
- Migration of activated T cells to edge of follicle
- B-cell antigen presentation
- Bi-directinal T-B activation
- Antigen uptake and processing
- B-cell activation
- Migration of activated B-cells to edge of follicle
Describe the mechanisms of helper T-cell mediated activation of B lymphocytes.
- B-cell presents antigen to helper T cell
- T cell is activated
- Expresses CD40L, secretes cytokines
- B-cells are activated by CD40 engagement, cytokines
- B-cell proliferation & differentiation
What stops activated T-cells that have exited lymphoid tissue into the blood from re-entering lymphoid tissue?
Reduced ability to re-enter due to changed surface molecules.
T-cells increased ability to enter inflamed tissue is due to increased expression of?
- Receptors for inflammatory chemokines
- Adhesion molecules (i.e. integrin alpha-4-beta-7)
- Ligands for adhesion molecules expressed on inflamed endothelium (i.e. E- and P-selectins)
How are effector T-cells attracted to sites of injury/infection?
In response to cytokines produced by tissue cells exposed to microbial products (i.e. epithelial cells, keratinocytes, mast cells, macrophages).
What types of cells can express MHC class I and can be recognized/killed by effector CD8 T cells.
All cells except RBCs.
Macrophages and Dendritic cells in tissue present antigens to what type of T-cells?
To CD4 T-cells.
CD4 T cells deliver signals that promote what?
- Bacterial activity of macrophages (increase NO activity)
2. Promote further recruitment of effector cells (more T-cells, neutrophils, eosinophils, monocytes).
