Lecture 3: Leukocyte Circulation and Migration into Tissue Flashcards Preview

Immunology 2.0 > Lecture 3: Leukocyte Circulation and Migration into Tissue > Flashcards

Flashcards in Lecture 3: Leukocyte Circulation and Migration into Tissue Deck (40):

Recirculation is the ability of lymphocytes to repeatedly

  • Home to secondary lymphoid organs 
  • Reside there transiently 
  • return to the blood 


Inflammation is triggered by recognition of ___ and ____ in _____ immune responses and refined and prolonged during _____ immune responses 

Inflammation is triggered by recognition of microbes and dead tissues in innate immune responses and is refined and prolonged during adaptive immune responses 


A cascade of adhesive and activation events underlies the trafficking of all subsets of circulating leukocytes which include: 

  • Tethering
    • Occurs through transient interactions of selectins and integrin with their ligand
  • Rolling
    • allows chemokine receptors on leukocytes to bind chemokines expressed on endothelium
  • Adhesion and Stop
    • Receptors signal and activate integrins on leukocytes which interact wiht ligands expressed on endothelium and trigger adhesion to the endothelium
  • Transmigration in the tissue
    • Leukocytes transmigrate into extravascular space where they can migrate down chemokine gradients toward specific areas


Do healthy endothelial cells epxress adhesion molcules on their surfaces 

No (endothelial cells at sites of infection and tissue injury are activated by cytokines secreted by resident immune cells at these sites, which leads to adhesion molecule expression)



_____ comprise a set of several adhesion molecules on the surface fo the endothelial cells



____ are plasma membrane carbohydrate-binding adhesion molecules that mediate an initial step of low-affinity adhesion of circulating leukocytes to endothelial cells lining post-capillary venules 

Selectins (Note similar to C-type lectins becuae they bind carbohydrates)


Selectins are expressed on 

  • Leukocytes 
    • L-Selectin (CD62L)
  • Endothelial cells
    • P-selectin (CD62P)
      • moves to lumenal surface in response to histamine and thrombin
    • E-selectin (CD62E)
      • Synthesized and expressed on the endothelial cell surface within 1 to 2 hours in response to the cytokines 
        • IL-1 
        • TNF
        • (note that microbial products such as LPS can also stimulate its expression) 


Ligands for P-selectin (CD62P)

  • Sialy Lewis X on PSGL-1 and other glycoproteins
  • Neutrophils, monocytes, and T cells (effector, memory)


Ligands for E-selectin (CD62E)

  • Silayl Lewis X (e.g., CLA-1) on glycoproteins
  • Nuetorphils, monocytes, T cells (effector, memory)


Ligands on L-selectin (CD62L)

  • Sialyl Lewis X/PNAd on GlyCAM-1, CD34, MadCAM-1, other; endothelium (HEV) 


____ are heterodimeric cell surface proteins composed of tow noncovalently linked polypeptide chains that mediate adhesion of cells to other cells or to extracellular matrix, through specific binding interactions with various ligands



There are more than 30 different integrins, all with the same basic structure, containing

one of more than 15 types of alpha chains and one of seven types of beta chains 


What are the two important integrins expressed on leukocytes 

  • LFA-1 (leukocyte function-associated antigen 1)(CD11aCD18)
  • VLA-4 (very late antigen 4) (CD49dCD29)


The extracellular portion of ICAM-1 is composed of globular domains, called ______, which share a sequence homology and structural features with domains foudn in Ig molecules

immunoglobulin (Ig) domains 


Ligands for LFA-1 (CD11aCD18)

  • ICAM-1 (CD54)
  • ICAM-2 (CD102)
  • ICAM-3 (CD50)


Ligands for Mac-1 ( CD11bCD18) 

  • ICAM-1 (CD54)
  • ICAM-2 (CD102)


Mac-1 (CD11bCD18) is an integrin found on 

  • Neutrophils 
  • Monocytes
  • Dendritic cells


L-selectin (CD62L) ligand expressed on HEV is called 

  • Peripheral node addressin (PNAd) 


VLA-4 (CD49aCD29) is an integrin found on 

  • Monocytes 
  • T cells (naive, effector, memory) 


Where is the integrin Alpha4Betadistributed

  • Monocytes
  • T cells (gut homing, naive, effector, memory) 
  • B cells (gut homing)


What is the ligand for integrin Alpha4Beta7

  • VCAM-1 (CD106) 
  • MadCAM-1
  • endothelium in gut and gut-associated lymphoid tissues 


The term integrin comes from the function of these proteins, which is 

  • Integrate signals triggered by extracellular ligands with cytoskeleton-dependent motility, shape change, and phagocytic responses


Integrin are able to resond to intracellular signals by 

  • increasing their affinity (integrin activation)
  • Integrin activation occurs in all leukocytes in response to chemokine binding to cehmokine receptors 


In T lymphocytes integrin activation occurs for formation of the immunological synapse when antigen binds to ____



integrins on blood luekocytes are normally in a ___-affinity state



There are about ___ human chemokines, which are classified into four families on the basis of the number and location of N-terminal cysteine residues, what are the families 

  • 50
  • C cehmokines
    • in which there is a single cysteine
  • CC chemokines (beta chemokines)
    • in which the two defining cysteine residues are adjacent
  • CXC  (alpha chemokines)
    • in which the two cysteine residues are separated by one amino acid
  • CX3C chemokines 
    • in which two cysteines are separated by three amino acids


Neutorphils and monocytes enter the tissue though post-capillary venules except _________ (_______) where all blood cells enter though capillaries 

parenchymal tissues (liver, lungs, kidney) 


Activated resident macrophages produce cytokines ____ and )))) that induce the rapid induction of expression of pre-formed P-selectin on the surface of enothelial cells 

  • TNF and IL-1 


The interaction between P-selectin and ligands on leukocytes initiates ___ on the endothelium, which is further stabilized by L-selctin binding to ligands on enothelial cells 



After rolling has been initiated enothelial cells present a chemokine _______ that is recognized by receptors on neutrophils and ___ on monoctyes 

  • IL-8 (CXCL8)  for neutrophils
  • MCP-1 (CCL2)


L-selectin ligands expressed on HEV have been collectively called 

peripheral node addressins (PNAd)


What chemokines are expressed on the surface of the HEV. and them binding to ____ activates integrins 

  • CCL19 and CCL21
  • CCR7


Naive T cells have low levels of ____ because the receptor is internalized after binding S1P in the blood. Naive T cells that have recenlty entered a LN cannot sense S1P concentration gradient between the T cell zone of the node and the lymph. Naive T cells cannot exit the node for several hours until _____ is re-expressed and the cell exit the LN by mechanism of chemotaxis. If The T cell is activated by an anitgen then the _____ re-expression takes several days tthus allowing for clonal expansion to occur before the T cell leaves the Lymph node 

  • S1PR1 (spingosine 1-phosphate receptor 1) 
  • S1PR1
  • S1PR1


CD44 can mediate rolling interactions with vascular endothelial cells that express ___, its natural ligand, or even _______ 

  • Hyaluronic acid​
  • E-Selectin 


Engagement of CD44 with HA may rigger GPCR-dependent upregulation of 

VLA-4 to VCAM binding 



As they mature, B cells express the chemokine receptor _____, which promotes their movement into the white pulp in response to a chemokine called ____



Homing of B cells to lymph nodes require chemokine of ______ and _____  on HEV and their chemokine receptors _____ and ____ on naive B cells

  • CXCL12 and CCL19/CCL21
  • CXCR4 and CCR7


IN the stroma of the lymph nodes, B cells migrate into follicles driven by _____ recognized by _____ expressed on naive B cells 

  • CXCL13
  • CXCR5