Helper T Cells and Cytokines Flashcards
Cytokines
Secreted proteins that regulate the amplitude and duration of immune and inflammatory responses
Simple molecules with low Molecular Mass
Produced transiently & locally
Extremely potent as they bind to receptors on cell surfaces to change cell behaviour
How does cytokine action work
Through pulling the two chains of its receptors together, it sends a signal through the cell so it can carry out its function
Examples of cytokines
Interleukins Tumour Necrosis Factors Interferons Colony-stimulating factors (CSF) Chemokines
What happens if TH0 is activated into TH1 with IL12 (and vice versa TH2 IL4)
Th1 produces cytokines (like IL2 and IFN Gamma) which aid in cell-mediated immunity. These cytokines inhibit the production of Th2 cells
Otherwise IL4 prompts the specialisation of TH0 cells into TH2, which produces more IL4 and IL10 to aid in antibody production. This inhibits production of TH1 Cells
How do Th2 cells help with antibody production
APC presents antigen on HLA II to Th2
Cytokine involvement causes signal 3 which specialises T helper cell into Th2
Simultaneously, T cell is being recognised by B cell on surface receptor
Antigen is phagocytosed in B cell and presented on HLA II; presents antigen to same Th2 Cell
T cell provides cytokines to activate and stimulate B cell to Produce antibodies and become Plasma cell
Where do APC, T cell and B cell interactions take place
APCs pick up protein fragments and travel to the lymph node via afferent lymphatics
Lymph node is stuffed full of naive lymphocytes. Here, APC presents antigen/peptides and activates the lymphocytes to cause them to divide rapidly and travel to site of infection
Site of infection –> Lymph Nodes –> Blood Circulation via thoracic duct –> Site of infection
Discuss sites of lymphocyte activation and activated B cell maturation
T cells activated by dendritic cells and B cells by T cells in paracortex of lymph node
B Cells matured in germinal centre of lymph node
Somatic Mutation
Random mutations in B cells as they mature and divide, which can increase or decrease affinity for the antibody; those with better affinity proliferate more
**Similar to clonal selection I think
What happens during B cell maturation
Division
Somatic Mutation
Class Switching
Formation of plasma and memory cells
Cytokines released by Th2 Cell
Release IL-4 to cause B cells to class switch to produce IgE; also activates mast cells Also stimulates Th0 to become Th2/inhibits Th1 production
Release IL-5 and assist in eosinophil activation
How do Th1 cells activate macrophages and improve their digestion
TCR recognises peptide on MHC class II; Th1 releases IFN gamma to improve its intracellular digestion
It is activated via CD3 sending signal, CD28 sending signal and cytokines giving us Th1
How do mycobacteria evade intracellular digestion
Many digestion mechanisms, but focus on their release of lipoarabinomannin which blocks the ability of macrophages to respond to the activating effects of IFN gamma (causing Th1 gammas to be useless)
Granulomatous Inflammation
T Helper cells bind to HLA II and specialise into Th1
They release IFN gamma which normally activates immature macrophages
In presence of mycobacteria, production of cytokines can chronically stimulate macrophage into an epithelioid cell; with stimulation of TNF they fuse to become multinucleate giant cells to form a granulomatous inflammation
Clinical Manifestations of Granulomatous Inflammation
Tuberculosis - Parenchymal streaking in lungs, multinucleate cells
Leprosy - Tuberculoid Leprosy Th1 cytokine driven disease (IFN gamma) Some inflammation from macrophage activation but mycobacteria destruction Normal Ig levels
Lepromatous Leprosy
Th2 cytokine driven disease (IL-4)
Growth of mycobacteria and severe tissue damage as antibodies cannot access intracellular bacteria
High Ig levels
