L2 - Overview of cells and molecules of the immune system Flashcards
The four stages of an immune response
1 - Prevention
2 - Awareness-recognition
3 - Innate response
4 - Adaptive response/immunity (b/plasma cells)
How do cells detect pathogens that need to be phagocytised?
Using TLRs (a type of pathogen recognition receptors (RRs)) to detect:
* Damage-associated molecular patterns (DAMPs)
* Pathogen-associated molecular patterns (PAMPs)
DAMPs: what are they and what structures do they have that allow them to be detected?
Damage-associated molecular patterns
- *
PAMPs: what are they and what structures do they have that allow them to be detected?
Pathogen-associated molecular patterns
- *
PRRs: what are they and what do each type detect?
Pathogen recognition receptors
TLRs (toll-like receptors) - detect DAMPs and PAMPs
- RIG (retinoic-acid inducible gene) like receptors (RLRs) - viral recognition - RIG-1 and cytosolic receptors
- C-type lectin receptors (CLRs) - yeast and some bacteria and parasitic worm recognition
- NOD (Nucleotide-binding domain) like receptors (NLRs) - cytosolic receptors - NOD2, NLRP3, NLRP1, etc
TLRs: what are they, what do they detect, and how do they detect them?
Family of PRRs used to detect PAMPs and DAMPS
- Recognise highly conserved structures in PAMPs
- Recognise danger patterns in damaged cells like Uric acid and heat-shock proteins (HSPs)
CLRs: what are they, what are they used to detect, and how do they do this?
C-type lectin R
- Fungi (yeast)
- (worm) parasites
- Bacteria
Binds (beta-glucan/mannose) carbohydrate structures
Four steps to phagocytosis
0 - detection (?)
1 - Attachment
2 - Ingestion
3 - Killing
4 - Degradation
Cytokines: what are they, what types are there, and what do they do?
Hormone-like molecule used in the immune system (and others) secreted by activated macrophages
- Interleukins (1-41) - Diverse
- Interferons - Anti-viral
- Colony stimulating factors - Haematopoesis
- Tumour necrosis factor - Inflammation
- Chemokines - Chemotaxis
Endocrine, paracrine, and autocrine definitions
Endocrine - acting far away from the release site (uncommon)
Paracrine - acting on nearby cells
Autocrine - acting on the cell itself
The inflammasome: what is it, what is it caused by, and what does it do?
Innate immune system receptors/sensors that regulate the activation of caspase-1 and induce inflammation in response to infectious microbes and molecules derived from host proteins
Some NLRs i.e. NLRP1, NLRP3, and NLRC4
Enables signalling molecules to come together to:
* initiate a type of programmed cell death
* secretion of active cytokines (IL1b and IL18)
IL-1b and IL-18: why do they have special activation requirements?
IL-1b and IL-18 are strongly pro-inflammatory cytokines and need to be tightly regulated.
Inflammasome mediated activation of IL-1b prevents excessive release
Two signals (pathogen and damage) are required to trigger IL-1b maturation and release.
What are the processes of inflammation
1 - bacteria enter tissue and macrophages begin the local immune response
2 - Vasodilation, enhanced vascular permeability, and chemotaxis of neutrophils and monocytes
3 - oedema from acculated plasma fluid and proteins
4 - Immune amplification
5 - IL-6 and TNFα activation activates IL-1
6 - The brain responds to IL-1 and trigger anorexia, fever, and somnolence
7 - The liver responds to IL-6 and secretes acute phase proteins
Mast cells: what do they do when activated?
They degranulate, releasing their inner contents
Immediate products:
* Histamine
* Heparin
* Enzymes - tryptase, chymase
Delayed products:
* Protstaglandins
* Leukotrienes
* Cytokines
Acute phase proteins: what examples are there and what do they do?
- Fibrinogen - clotting
- Haptoglobulin – binds iron
- Complement C3 cleaved to make C3a and C3b an opsonin
- Mannose binding lectin (MBL) – opsonin, trigger complement
- Serum amyloid-inhibits fever and platelet activation
- C-reactive protein (CRP) – binds phosphoryl choline, opsonin, can trigger complement
- Surfactant proteins SP-A, SP-D- opsonins
Opsonins
Substances that bind to cells that need to be phagocytised and direct the phagocytes towards the cells by binding to opsonin receptor on the phagocyte
Some Opsonins of the innate immune system
- C-reactive proteins binds to Phosphoryl choline and targets bacteria, fungi, parasites, and damaged cells
- Mannose binding lectin binds to mannose-fucosyl residues and targets bacteria, fungi and damaged cells
- C3b binds to -OH or -NH2 and targets anything (inactivated by host cells)
- SP-a, SP-D damaged cells binds to various LPS and targets bacteria, fungi, and viruses
Complement: what is it, what happens after activation, what pathways are there, and what is the function of it?
Collection of soluble proteins like in plasma that circulate in inactive form
Once triggered, a cascade occurs, resulting in protein activation
- Classical Pathway - initiated by antibody/CRP-C1 binding
- Alternative Pathway - triggered by c3b-target binding
- Lectin pathway- initiated by MBL-C4B binding
Target lysis, chemotaxis (e.g. c3b), activate mast cells (e.g.C3a, c5d), clearance of immune complexes (c3b)
Interferons: what are they and what do they do?
Inflammatory cytokines
- Inhibit viral replication in infected cells by binding to cells expressing interferon receptors – rendering them resistant to infection by activating machinery that resists infection
- Also activates macrophages and natural killer cells
Activated by infected cells, it may act on the cell itself (autocrine) or cells nearby (paracrine)
NK cells: what are they, what do they do, and what pathways does it have?
Natural killer cells
Releases lytic granules that kill infected cells
Perforin/granzyme pathway - creates pores in the target cell’s membrane, allowing granzymes to enter and trigger apoptosis
Fas/FasL pathway - NK cells Fas ligand (FasL) on their surface binds to Fas receptors on the surface of target cells, leading to the activation of caspases and apoptosis
TRAIL pathway - TNF-related apoptosis-inducing ligand binds to death receptors on the target cell surface, causing caspases and apoptosis
Antibody-dependent cell-mediated cytotoxicity (ADCC) - NK cells express Fc receptors on their surface that can bind to the Fc portion of antibodies already bound to tumour cells, leading to granzyme release and apoptosis
Innate cells: what are they, what are some examples, and what do they do?
First response to infection, generally supports the adaptive response
- Eosinophils - anti-pathogen, roles in immune cell recruitment, obesity
- Basophils - anti-pathogen, may support the generation of adaptive immunity
- Innate Lymphoid Cells - lymphoid lineage, currently 3 subtypes are defined by cytokine profile, can support gut immune responses, critical role in barrier function
- Dendritic cells - direct adaptive immunity
Innate vs adaptive system
Innate:
* Immediate
* Varied methods of attack
* Not always specific
* Helps direct adaptive
* “Memory”- imprinting
* neutrophils, macrophages,
* natural killer cells
Adaptive:
* Later
* Targeted and SPECIFIC killing
* Has Memory
* B lymphocytes,
* T lymphocytes
