B + T cells + cytokines Flashcards
- what are 2 main ways of communication between immune cells?
- what are 3 ways cytokines can behave?
- what are chemokines?
- direct cell-cell contact, signalling through receptor -ligand interactions between membranes of different cells, eg MHC molecules bind short peptides and show them to T cells by a direct interaction
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Secretion of soluble factors that initiate responses and signals by binding to specific receptors
- Cytokines: usually small polypeptides, around 25,000 molecules released by cells in response to an activating stimulus.
- Can behave
- autocrine: affects on cell that secretes it.
- Paracrine: effects on adjacents.
- Endocrine: effects on distant cells (limited by ability to enter circulation and half-life.
- Chemokines: a class of cytokine that has chemoattractant properties, ie induces cells to migrate towards the source. e.g (Interleukins: cytokines secreted by leucocytes)
what are two main groups of chemokines?
two main groups of chemokine:
- CC (which bind to receptors CCR1 to 9)
- CXC (which bind to CXCR1 to 5)
what are 5 interleukins (chemokines) to know about?
- IL-2 - secreted by T cells and activates T cells, proliferation
- IL-4 - secreted by T cells and activates B cells, switches them to produce IgE, therefore important in allergy reactions
- IL8 - chemotactic factor, recruits neutrophils and T cells to site of infection
- IL10 - stops immune response (anti-inflamatory cytokines, also TGF beta), turns off T cells
- IL12 - causes a differentiation of the CD4 population of T cells
what are two other chemokines to know about?
- IFN-gamma - secreted by T cells and activates strong cell mediated responses such as macrophages and upregulates HLA molecules eg CTL.
- TNF-alpha - very active pro-inflammatory cytokine - activates vascular endothelium and increases vascular permeability
what cells secrete cytokines?
- lots of different cells secrete them and they have activities in lots of different types of immune cells
- several cytokines are secreted by phagocytes recruit cells to sites of infection: macrophages secrete cytokines such as
1. IL-12 which activates NK cells and induces the differentiation of CD4 T cells into Th1 cells
describe the role of interluekin 8 (IL-8) in how neutrophils access infection sites by diapedesis?
chemotactic factor, IL-8 is released during vascular endothelial inflammatory responses in which you get a weakening of the junctions between cells which allows inflammatory cells, white blood cells, to start sticking to the vascular walls and pass through gaps between cells to the site of inflammation
describe how TNF-alpha release triggers local protection but can also induce systemic shock?
- TNF alpha release is part of the local inflammatory responses which increases migration of cells from the bloodstream into the site of inflamation
- however, if it reaches a widespread production within the body this can lead to vascular degradation, multi-organ failure and sepsis
describe the steps of how T cells secrete IL-2 which induces self-proliferation?
- naive T cels express the low-affinity IL-2 receptor
- when activated, these T cells express the high-affinity IL-2 receptor and secret IL-2
- Binding of IL-2 to the high affinity receptor sends a signal to the T cell
- The signal sent from the IL-2 receptor induces T-cell proliferation
describe the two types of CD4 T cells? (note: CD8 T cells are killer cells, kills virally infected cells)
Th1 cell: (T helper 1 cell)
- macrophage activation via macrophage activating cytokines: IFN-gamma and TNF-alpha
- in general Th1 cytokines produce cell mediated immunity
Th2 cell: T helper 2 cell
- secretes cytokines and activated B cells using B-cell-activating cytokines: IL4
- Th2 produce antibody responses
describe 6 actions of activated Th1 cells, which drive forward inflammatory cell response
- activate macrophages to destroy engulfed bacteria
- kills chronically infected macrophages, releasing bacteria to be destroyed by healthy macrophages
- induces T-cell proliferation, increasing the number of effector T cells
- induces macrophage differentiation in the bone marrow
- activates endothelium to induce macrophage adhesion and exit from blood vessel at site of infection
- causes macrophages to accumulate at the site of infection
describe the 2 steps of Th2 cells + B cells, which are involved in differentiating regulating antibody responses
- antigen recognition induces expression of CD40 ligand and cytokines by the TH2 cell, which activates the B cell
- B-cell proliferation and differentiation to antibody-secreting plasma cells
- what are dendritic cells?
- where are they found?
- what is their characteristic?
- give 4 examples of dendritic cells?
- professional antigen presenting cells that sit at the interface between the innate and adaptive immune response - look for pathogens or foreign bodies to phagocytose
- found in most surface epithelia (mucosal)
- highly phagocytic, sampling their external environment and upon stimulation, if what is being phagocytosed is bad, it ceases phagocytosis and migrates to lymph nodes
- variety of names:
- langerhans cells in skin
- interdigitating cells
- follicular dendritic cells (FDC) in lymph nodes
- veiled cells when migrating in circulation (blood stream)
Dendritic cells in lymph nodes activate T cells, and also influence B cells, what are the steps in this process?
- recirculating B cells enter lymphoid organs through high endothelial venules
- antigen-specific B cells are trapped by antigen-specific TH2 cells and stimulated to proliferate
- B cells migrate to medulla and differentiate into plasma cells. antibody:antigen complexes bind to FDC
- a few activated B cells migrate into a nearby follicle forming a germinal center where rapid proliferation and somatic mutation occurs
- mutated B cells that retain the capacity to bind antigen on follicular dendritic cells survive, while others die
- activated B cells producing high-affinity ig migrate in blood to become plasma cells in the bone marrow
follicular dendritic cells can hold on to antigens for extended periods of time, possibly many days. why is this done?
the complexes do not appear to undergo internalisation because the dendritic cells hold onto the antigen, to improve and immune responses (this is done through improving B-cell responses - affinity maturation)
- what do dendritic cells express?
- what do these receptors do?
- they express sensitive molecules: Pattern recognition receptors (PRR), members of the Toll-like receptor Family (TLR) - used to detect pathogens
- several PMN (polymorphonucleic) cells also express PRR, hence link to innate immunity
- they express sensitive molecules: Pattern recognition receptors (PRR), members of the Toll-like receptor Family (TLR) - used to detect pathogens
- toll-like receptors on DC - which recognise a bacterial or viral infection
