9. Helper T cells and cytokines Flashcards
properties of cytokines
secreted proteins that regulate the duration and amplitude of immune and inflammatory responses
bind to specific cell surface receptors and trigger intra-cellular signalling pathway
produced transiently and locally
potent
change cell behaviour
what are the 5 different types of cytokines?
interleukins
tumour necrosis factors-> anti tumour properties, pro-inflammatory
interferon
colony stimulating factors
chemokines- help with chemotaxis
cytokines produced by t cells are particularly important
what is the action of cytokines on their receptors?
- cytokine receptors have at least 2 chains, cytoplasmic domains bind JAKs
- cytokine binding dimerises receptor, bring JAKs together-> activate each other and phosphorylate receptor
- transcription factors bind to phosphorylated receptors and are in turn phosphorylated by JAKs
- phosphorylated STATs form dimers- move into nucleus- transcription
why are cytokines important between dendritic cells and t cells
influence type of t cell generated
what is the main cytokine present in the environment
IL4-> Th2
role of Treg
produce cytokines to dampen immune response
role of Th17
produce cytokines and chemokines for inflammation
Th2 and B cell activation
in paracortex of lymph node
- Th cells with TCR specific for peptides are activated by surface interactions with DC and cytokines from DC (IL 1)
- Th cells interact with peptides and HLA II- activates B cells as cytokines secreted (IL 4)
- B cells differentiate into plasma cells
B cells can also take up pathogen and present it on MHC II
what happens in germinal centres?
•Division - increases size of response
•Somatic mutation - increases affinity of the response
- Class switching - increases defenceeffector functions
- Formation of plasma cells and memory cells
explain this diagram
antigens in immune complexes (antibody bound to antigen) are recognised by follicular dendritic cells in follicles
antigen transported by dendritic cells into paracortex (interdigiating dendritic cells)- activate Th cells and B cells
how do lymphocytes enter lymph node
B cells: post capillary venules- migrate through T cell area to follicle
T cells PCV, high endothelial venule
leave via efferent
some lymphocytes enter nodes via afferent and subcapsular sinus (most via HEV)
how to lymphocytes adhere to HEV
selectins and intergrins
dendritic cell migration to lymph node and characteristics
enter via afferent lymph vessels
large SA so many T cells can contact to increase chance of correct specific receptor
DC secrete IL 1 that induces Th to secrete Il 2 that induces own proliferation
characteristic of B cell so it can be physically linked to T cell
T cell epiptope can be taken up by B cell
can high levels of cytokines cause issues?
yes- it can cause disease
Th2 cells and atopic (type 1 allergy) responses
Th2 cells release IL4 causing Ig class switchingof B cells to IgE which causes mast cells to degranulate as they express Fcgamma receptors
Th2 can also release IL5 which activates eosinophiles (also bind to IgE)
important in large parasites but can cause atopic allergies
Th1 and macrophage activation
Th1 release interferon gamma that activates macrophages
what can chronic stimulation of Th1 cells lead to
increase lymphocytic infiltration of tissues thus resulting in granuloma formation
(macrophage in granuloma= epitheloid)
leakage of digestive enzymes from macrophage can cause destruction of tissues
fusing of macrophages can result in multinucleated giant cell
what are the two types of leprosy and how do they differ?
tuberculoid leprosy: activation of Th1-> IFNγ → phagocytosis
- tissue damage, inflammation, but mycobacterium is destroyed
Lepromatous leprosy: activation of Th2 and also inhibits Th1 → IL4 → antibodies (not useful as bacteria inside macrophage) so mycobacteria proliferates
- severe tissue damage, growth of bacteria
borderline leprosy: both
