3 - Leukocyte Recirculation and Migration into Tissues Flashcards
1
Q
Immune system cell migration
A
The major cellular components of the immune system constantly move through the blood, into tissues, and often back into the blood again, in a highly regulated way
2
Q
Acute inflammation
A
The accumulation of leukocytes, plasma proteins, and fluid derived from the blood at an extravascular tissue site of infection or injury
3
Q
Steps of acute inflammation
A
- Begins when tissue is injured
- PAMPs and DAMPs activate macrophages, dendritic cells, mast cells (sentinel cells)
- Cytokines and other mediators are produced
- Vasodilation and increased vascular permeability (fluid and proteins enter tissues)
- Complement, antibodies, and antimicrobial proteins kill microbes
- Adhesion molecules and chemokines cause leukocyte migration into tissue
- Phagocytosis and killing of microbes
4
Q
Homing
A
Migration of a leukocyte out of the blood and into a particular tissue, or to a site of an infection or injury
5
Q
Lymphocytes recirculation
A
Recirculate repeatedly to secondary lymphoid organs, reside there transiently,
and return to the blood
6
Q
4 cardinal signs of inflammation
A
- redness
- swelling
- heat
- pain
7
Q
Basic components of an inflammatory response
A
- Vasodilation
- Increased vascular permeability
- Emigration of white blood cells
8
Q
Steps of leukocyte recruitment into tissues
A
- Rolling
- Integrin activation by chemokines
- Stable adhesion
- Migration through endothelium
9
Q
Integrin activation
A
- Integrins on blood leukocytes are normally in a
low-affinity state.(LFA-1) - If a leukocyte comes close to endothelial cells, (such as when selectin-dependent rolling of leukocytes occurs) then chemokines displayed on the endothelial surface can bind chemokine receptors on the leukocyte.
- Chemokine receptor signaling then occurs, which activates the leukocyte integrins, increasing their affinity for their ligands on the endothelial cells.
10
Q
Selectins
A
- Plasma membrane carbohydrate binding adhesion molecules that mediate an initial step of low affinity adhesion of circulating leukocytes
- A mechanism by which leukocytes are recruited to sites of inflammation
11
Q
What are the two types of selectins that are expressed on endothelial cells
A
- P selectin (CD62P)
- E selectin (CD62E)
11
Q
E selectin
A
- Synthesised and expressed on the endothelial cell surface within 1 to 2 hours in response to cytokines interleukin-1 (IL-1) and tumour necrosis factor (TNF) which are produced by tissue sentinel cells in response to infection
- Microbial products such as LPS also stimulate E selectin expression
12
Q
P selectin
A
- Stored in cytoplasmic granules of endothelial cells
- Rapidly redistributed to the luminal surface in response to histamine from mast cells
- The major carbohydrate ligand for P-selectin is sialyl Lewis X
13
Q
L selectin (CD62L)
A
- Expressed on leukocytes not endothelial cells
- Ligands for L selectin are sialomucins, whose expression may be increased by cytokine activation of the cells
- L-selectin on neutrophils promotes the adhesion of the cells to endothelial
cells at sites of inflammation - Required for naive T and B lymphocyte homing into lymph nodes through high endothelial venules (HEVs)
14
Q
PNAd
A
Collective term for the sialomucin ligands on HEVs that bind to L-selectin on naive lymphocytes
15
Q
T lymphocyte recirculation pathway
A
- Naive T cells leave the blood and enter lymph nodes across the high endothelial venules
- Dendritic cells bearing antigen enter the lymph nodes through afferent lymphatic vessels
- Naive T cells that do not recognize antigen after several hours return to the circulation
- If the T cells recognize antigen, they are activated and generate effector and memory T cells, which leave the lymph node via efferent lymphatic vessel and return to the circulation
- Effector and memory T cells leave the blood and enter peripheral tissues
16
Q
Naive and effector T lymphocyte migration
A
- Naive T lymphocytes home to lymph nodes as a result of L-selectin binding to peripheral node addressin (PNAd) on HEVs, which are present only in secondary lymphoid organs, and as a result of binding chemokines (CCL19 and CCL21) displayed
on the surface of the HEV - Activated T lymphocytes, including effector cells, home to sites of infection in peripheral tissues, and this migration is mediated by E-selectin and P-selectin, integrins, and chemokines that are produced at sites of infection
17
Q
Mechanism of egress of lymphocytes from lymphoid organs
A
- S1P is present at relatively high concentration in blood and lymph and at lower concentration within lymphoid tissue
- Circulating naive T cells express low levels of S1PR1 because the receptor is internalized after binding S1P in the blood
- Naive T cells entering a lymph node cannot sense the S1P concentration gradient between the T cell zone of the node and the lymph in the medullary sinus and efferent lymphatics, and these T cells cannot exit the node
- After activation of a naive T cell by an antigen, surface expression of S1PR1 is blocked for several days, and the activated cells will not leave the node
- S1PR1 is re-expressed after several minutes to hours for naive T cells, or days for activated and differentiated effector T cells, and these cells can then sense the S1P gradient and exit the node
18
Q
Steps in CD4 + T cell–mediated immune responses.
A
- CD4 + T cells recognise peptides that are derived from protein antigens and presented by dendritic cells in secondary lymphoid organs
- The T lymphocytes are stimulated to proliferate and differentiate into effector (and memory) cells, which enter the circulation and migrate to sites of infection in peripheral tissues.
- In the tissues, effector T cells recognise the antigen and respond by secreting cytokines that recruit more leukocytes and activate phagocytes
19
Q
Induction and effector phases of CD8 + T cell responses.
A
- Naive CD8 + T cells recognise antigens presented by dendritic cells in secondary lymphoid organs and are stimulated to proliferate and differentiate into effector cells (cytotoxic T cells) and memory cells
- CTLs migrate to tissues at sites of infection, tumor growth, or graft rejection, where they recognise the antigen and respond by killing the cells where the antigen is produced
20
Q
MIgration of B cells
A
- Naive B cells enter lymph nodes and mucosal associated lymphoid tissues through high endothelial venules (HEVs), migrate into follicles, become activated
- Activated B cells differentiate into antibody producing cells (some are plasmablasts)
- IgG secreting plasma cells may be generated in any lymphoid tissues
- Other B cells that enter follicles differentiate into memory B cells, some of which enter circulation
21
Q
IgA secreting plasma cells
A
Produced mainly in mesenteric lymph nodes of mucosa associated lymphoid tissues and home back to mucosal tissue
