Lecture 8 Flashcards
What are the four factors which determine what happens as a result of antigen recognition?
Adhesion molecules, these are important in binding lymphocytes to antigen-presenting cells and also in directing lymphocytes and phagocytic cells to parts of the body where they are needed
Co-stimulator molecules which pass on signals through surface-surface interactions triggering or inhibiting antigen specific effects
Cytokines these are soluble glycoproteins that signal cells expressing specific chemokine receptors
Hormones these are soluble molecules produced by the neuroendocrine hormone that modulate the response of antigen activated cells
What are the different processes that adhesion molecules are implicated in?
Holding cells together and directing them to particular sites in the body (cell trafficking) they are also involved in lymphocyte activation, growth and development of tissues, interaction of cells and extra cellular matrix, wound healing and tumour invasion
What are the different types of cell adhesion molecules?
Selectins which mediate weak, transient interactions between cells Integrins which mediate strong cell-cell interactions IgSF molecules (Immunoglobulin superfamily molecules) these are ligands for integrins Cadherins these mediate homophilic cell-cell binding involved in embryogenesis and tissue development
What is the role of selectins in the immune system?
These are the first step of lymphocyte trafficking from the blood stream into tissues
They are also important in getting lymphocytes and APCs or lymphocytes and their targets together in order for other interactions
They provide rapid association and dissociation meaning that adhesion is generally short term and liable
How are selectins named>?
They are typically named according to the cells which express them such as
L-Selectin which is expressed on all circulating leucocytes except for memory lymphocytes
P-selectin which is stored in the a granules of platelets and in preformed Weibel-Palade bodies of endothelial cells
E-selectin which is induced on vascular endothelial cells by cytokines such as IL-1 and TNF
What is the role of integrins in the immune system?
They are versatile and diverse families of adhesion molecules important in cell to cell adhesion and cell to extracellular matrix adhesion
Their adhesiveness can be rapidly regulated by chemokines such as IL-8
How are integrins classified?
These proteins have an alpha and beta unit and are classified according to the beta-subunit
What are some examples of integrins?
Vascular cell adhesion molecule on endothelial cells which provides an important means of leucocyte to endothelium adhesion
LFA-1 found on lymphocytes and neutrophils and involved in neutrophil adhesion to endothelium, and in lymphocyte-lymphocyte or lymphocyte-APC interactions
The b3 integrin is found on platelets and is involved in platelet adhesion to fibrinogen, fibronectin, von-Willebrand factor and vitronectin
The b7 integrin is found on lymphocytes and mediates homing of lymphocytes to peyers patches in the gut
What can result from hereditary deficiency of some integrins?
This can result in leucocyte adhesion deficiency, in this condition leucocyte trafficking to sites of inflammation is impaired and patients are susceptible to recurrent pyogenic infections
What are immunoglobulin superfamily molecules?
These are the ligands for integrin molecules, they have a structure which consists of immunoglobulin like domains and fibronectin-like repeats
They include intracellular adhesion molecules which are involved in binding leukocytes to the endothelium and also in T/APC and T/B cell interactions
Include a mucosal addressin cell adhesion molecule on high endothelial vessels of peyer’s patches and are recognized by integrins on lymphocytes to direct them to these gut associated secondary lymphoid organs
What is the process of neutrophil migration from blood to tissues?
It beings with rolling where there is adhesion through selectins this triggers activation of the expression of integrins which allow strong adhesion where integrins strongly bind their ligands tethering the cell to the vessel wall this will eventually result in migration of the neutrophil through the capillary wall
What are the two ways in which bacterial products can affect the cells of blood vessel walls in their immediate vicinity?
The cells express more selectins and ligands for selectins acting as flags showing the neutrophils where they are needed
The spaces between the cells expand to allow neutrophils to squeeze through them more easily
What occurs in interactions between T-Lymphocytes and APCs?
There are transient adhesive interactions between T cells and APC which initially use low affinity LFA-1:ICAM-3 interactions
The subsequent binding of T cell receptors signals LFA-1 causing a conformational change in the molecule which increases affinity and prolongs cell-cell contact allowing other signalling events to occur
What are co-stimualtor interactions?
Certain molecules are induced on antigen presenting cells and lymphocytes only under particular conditions and function to modulate what happens to the lymphocytes when they recognize antigen
What is an example of a co-stimulator interaction?
B7 which is a molecule which is found on the surface of antigen presenting cells only if the antigen being presented are foreign and potentially dangerous Th cells which recognize the presented antigen will only respond if they also have their CD28 bind to B7 if they can recognize the antigen when B7 is nor presented then they will undergo anergy as mechanism of peripheral tolerance
