Cytokine Concepts and the Complement Pathway Flashcards
What are cells of the innate immune system?
Neutrophils, macrophages, dendritic cells, natural killer (NK) cells, eosinophils, complement system
Cells of the adaptive immune system?
T cells: T helper cells (Th) and Cytotoxic T lymphocytes (CTL)
B cells (produce antibodies)
Main role of the adaptive immune system?
Differentiates between self and non-self
Slow, highly specific response
Memory to previously encountered antigens
Main role of the innate immune system?
Detects danger
Rapid, generic response
Communicates danger to adaptive immune system
What are the 2 types of danger signals for the innate system?
PAMPs and DAMPs (recognised by PRRs)
What is ‘negative selection’?
Developing adaptive immune cells that react to ‘self’ molecules will be deleted, so that only functioning mature adaptive immune cells remain
How many complement pathways are there, and what are they?
3:
Classical
Mannose-binding lectin
Alternative
What is the complement system?
Series of soluble proteins in the blood: C1-C9
What are the 3 possible outcomes of the complement pathway?
Anaphylotoxins (inflammation)
Membrane attack complex (lysis)
Opsonisation
What is the classical pathway?
Only occurs when there are antibodies present specific to a foreign antigen.
Antibody complexes on bacteria are bound by complement component C1q > activates component C3
What is the mannose-binding lectin pathway?
Activation through mannose-binding lectin (mannose isn’t present on the surface of host cells)
Activates complement component C3
What is the alternative pathway?
Complement component C3 suddenly activates and binds to nearby membranes
Host cells have control proteins that prevent further compliment activation - bacteria do not
C3 is activated by hydrolysis
Alternative pathway can amplify other already active pathways
What is complement lysis?
Membrane attack complex (MAC) forms in the membrane of bacteria - a barrel-like structure formed from multiple complement components (C6/C9)
This allows water to rush in, ions out, the bacteria swells and bursts
What is opsonisation?
Marks cells for phagocytosis
Membrane bound complement components (ie C3b) bind to the surface of bacteria
Phagocytes have Complement Receptors which bind membrane-bound complement
Encourages phagocytosis and killing (ie macrophage engulfs the membrane bound bacterium > lysosome fuses with phagosome to create a phagolysosome and destroy bacteria)
What is complement anaphylotoxins?
Fragments of complement components (C5a, C3a) are released on complement activation
Anaphylotoxins are toxins that can cause anaphylaxis
Fragments can act on epithelium to cause oedema (makes blood vessels leaky) > recruitment of immune cells > activation of mast cells (release histamine)
5 different classes of cytokines
Chemokines (cause cells to move)
Interleukins
Interferons
TNF family
TGF superfamily
What are the 4 chemokine groups and what are they based on?
Can have homeostatic or inflammatory effects on leukocyte migration
4 groups based on position of cysteine residues that mediate disulphide bridge formation in 3D structure:
XCL - binds to XCR receptors
2 genes (lymphotactin-1 and -2)
CCL - binds to CCR receptors
27 genes (CCL1-CCL28, CCL9=CCL10)
CXCL - binds to CXCR receptors
17 genes (CXCL1-17)
CX3CL - binds to CX3CR receptors
1 gene (fractalkine)
The chemokine-receptor cell moves up the chemokine gradient to the chemokine producing cell
Chemokines in the lymph node
T cells express CCR7 > mediates migration to T cell area > secrete ligands CCL19 and CCL21
B cells express CCR7 + CXCR5 > migrate to B cell area > secrete ligand CXCL13
Inflammatory cytokine IL-1beta and TNF-alpha
Induce blood vessels to become more permeable, enabling effector cells and fluid containing soluble effector molecules enter infected tissue > inflammation at site of infection
Inflammatory cytokine IL-6
Induces fat and muscle cells to metabolise, make heat and raise the temperature in the infected tissue > inflammation
Inflammatory cytokine CXCL8
Recruits neutrophils from blood and guides them to infected tissue > inflammation
Inflammatory cytokine IL-12
Recruits and activates natural killer (NK) cells that secrete cytokines that strengthen the macrophages response to infection > inflammation
Cytokine receptor families
Type 1 Cytokine Receptor
IL-2, IL-6, IL-12
Dimeric
JAK/STAT signalling
Type 2 cytokine receptor
IL-10, IFNs
Dimeric
JAK/STAT signalling
TNF receptor family
TNF
Trimeric
NFkappaB/MAPK signalling
IL-1 receptor family
IL-1, IL-33
Has Ig domains
NFKB/MAPK signalling
TGF receptor family
TGF-beta
SMAD signalling
Chemokine receptors
7 transmembrane domains
G protein coupled signalling
Which two interleukins can bind to and signal through the same receptor?
IL-4 and IL-13 (thus, both have to be blocked to generate an effect)
