B & T Cells and Cytokines Flashcards
How do cells of the immune system communicate between themselves, and with other non-immune cells ?
Cell-cell contact, signalling through receptor-ligand interactions between membranes of different cells. (e.g. MHC and TcR)
Secretion of soluble factors
Cytokines
Chemokines
Function of secretion of soluble factors
Initiate responses and signals by binding to specific receptors.
Function of cytokines
Drive forward the inflammatory response
- released by cells in response to an activating stimulus
Can act in an autocrine / paracrine / endocrine manner
Autocrine manner of cytokines
Effects on the cell that secretes it
Paracrine manner of cytokines
Effects on adjacents
Endocrine manner of cytokines
Effects on distant cells (limited by ability to enter circulation and half-life)
Function of chemokines
A class of cytokines that has chemoattractant properties.
i.e. induces cells to migrate towards the source
Interleukines
Cytokines secreted by leukocytes
What is the ‘gold standard’ treatment for a range of conditions ?
EXAM Q
Inhibiting the action of many pro-inflammatory cytokines (typically through monoclonal antibody therapy)
- Inflammatory bowel disease
- Arthritis
Tocilizumab
Anti-IL6 receptor
Used in Covid-19
Intervention with monoclonal antibody therapies, to take out pro-inflammatory cytokines can transform a disease.
State the 2 main groups of chemokine
CC - bind to receptors CCR1 - CCR9
CXC - Bind to CXCR1 - CXCR5
IL-8
Part of the CXC class
Chemotactic factor
Recruits neutrophils and T cells to site of infection
Source of (what releases) IL-8
Monocytes
Macrophages
Fibroblasts
Keratinocytes
Endothelial cells
Receptors of IL-8
CXCR1
CXCR2
Target cells of IL-8
Neutrophils
Naive T cells
Major effects of IL-8
Mobilises, activates and degranulates neutrophils
Angiogenesis
IL-2
Activator of T cells: T cell growth (proliferation)
IL-4
Activates B cells, switches them to produce IgE, therefore important in allergy.
Class switching cytokine
Key function of IL-4
Allows B cells to swap the antibody we secrete.
Class switching cytokine
Interferon gamma (IFN-gamma)
Strong activator of a huge number of different types of cells.
Activates strong cell mediated responses e.g. CTL
Upregulates a lot of immune gene expression in cells.
TNF alpha
Activates vascular endothelium and increases vascular permeability.
Source of TNF alpha
Secreted by T cells and macrophages
Function of TNF alpha
Activator of pro-inflammatory cytokines
- Arthritis
- IBD
(driven by TNF alpha)
IL-12
Differentiates CD4 cells
IL-6
Pro-inflammatory
Antibody inhibitor therapy (of IL-6), useful in covid 19 infections.
Key function of interleukins, interferons and TNF
Pro-inflammatory
Drive forward other immune responses
What secretes cytokines ?
Cytokines secreted by phagocytes recruit cells to sites of infection.
Symptoms caused by IL-6
Lymphocyte activation increased antibody production.
Causes fever and induces acute phase protein production. (can be responsible for severe respiratory response)
Symptoms of IL-1
Fever
Production of IL-6
How do neutrophils access infection sites ?
Diapedesis
Diapedesis
Cells that are normally floating in the bloodstream, bind to vessels walls through the gaps between them, and then go to a site of inflammation.
TNF-alpha function
Release triggers local protection, but can induce a systemic shock.
What do T cells secrete ? (interleukin)
T cells secrete IL-2, that induces self-proliferation
Describe the IL2- receptors on T cells
Naive T cells express the low-affinity IL-2 receptor.
Activated T cels express the high-affinity IL-2 receptor and secrete IL-2.
Binding of IL-2 to high-affinity receptor sends a signal to the T cell.
The signal sent from IL-2 receptor induces T-cell proliferation.
CD4
Helper T cell
State the 2 types of CD4 T cell
TH1 cell
TH2 cell
Describe the TH1 T cell
Macrophage activation
B cell activation
Production of opsonising antibodies (e.g. IgG1)
What do TH1 cells secrete ?
Secrete cytokines which activate things like macrophages.
Describe the TH2 T cell
General activation of B cells to make antibodies
What do TH2 cells secrete ?
Secrete cytokines that activates B cells.
Function of Th1 cytokines
Produce cell mediated immunity
Function of Th2 cytokines
Produce antibody responses
What cytokines do Th1 cells secrete ?
EXAM Q
TNF alpha
Interferon gamma
(helps macrophage activation)
What cytokines do Th2 cells secrete ?
EXAM Q
IL-4
IL-10
(helps B cell activation)
IL-10 function
Dampens down immune response
- Immunosuppressive cytokine
Turns of immune response once its done its job.
How do you get a specific B cell antibody response ?
By the B cell taking up the pathogen and driving forward antigen presentation pathways.
What are dendritic cells ?
Professional antigen presenting cells that sit at the interface between the innate and adaptive immune response.
Where are dendritic cells found ?
Found in most surface epithelia, waiting to detect problems with infections
Action of dendritic cells
Highly phagocytic
Sampling their external environment, to see normal vs abnormal
Upon stimulation, cease phagocytosis and migrate to lymph nodes to start immune response
What do dendritic cells do in lymph nodes ?
Activate T cells, and also influence B cells.
What do dendritic cells express ?
Pattern Recognition receptors, which are members of the toll-like receptor family (TLR).
Several PMN cells also express PRR, hence linked to innate immunity.
What are pattern recognition receptors members of ?
The Toll-like receptor family (TLR)
TLR receptors function
Sit on dendritic cells and looking for signs of an infection.
Things that would not normally be present in you unless an infection was present.
(e.g. bacterial/viral)
They move that fragment of the pathogen to the lymph node, chop it up, present it to MHC molecules and you have an immune response.
What is the membrane attack complex ?
Component of the final stage of the complement pathway.
Barrel shaped structure that punches holes in bacteria and their contents leak out and bacteria dies.
What innate cells kill virally infected cells ?
Natural Killer cells
How do virally infected cells respond ?
Secretion of interferon alpha and beta.
This makes the other infected cells around a bit more retractile to virus infections, and dampens down their protein production.
Helps protects from viruses spreading to nearby cells.
Which Ig molecules are dimers and pentamers ?
IgA - dimer
IgM - pentamer
What does the Fab and the Fc bit of an Ab do ?
Fab - antigen binding site (pathogen recognition site)
Fc - activates complement
What does a CD8 and CD4 T cell do ?
CD8- killer T cells
CD4 - helper T cells, secrete cytokines
What key cytokines distinguish a Th1 and a Th2 cell ?
Th1 - interferon gamma, TNF alpha
Th2 - interleukin 4
