L2 - Overview of cells and molecules of the immune system

Question 1

The four stages of an immune response

Answer 1

1 - Prevention
2 - Awareness-recognition
3 - Innate response
4 - Adaptive response/immunity (b/plasma cells)

Question 2

How do cells detect pathogens that need to be phagocytised?

Answer 2

Using TLRs (a type of pathogen recognition receptors (RRs)) to detect:
* Damage-associated molecular patterns (DAMPs)
* Pathogen-associated molecular patterns (PAMPs)

Question 3

DAMPs: what are they and what structures do they have that allow them to be detected?

Answer 3

Damage-associated molecular patterns

• *

Question 4

PAMPs: what are they and what structures do they have that allow them to be detected?

Answer 4

Pathogen-associated molecular patterns

• *

Question 5

PRRs: what are they and what do each type detect?

Answer 5

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

Question 6

TLRs: what are they, what do they detect, and how do they detect them?

Answer 6

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)

Question 7

CLRs: what are they, what are they used to detect, and how do they do this?

Answer 7

C-type lectin R

• Fungi (yeast)
• (worm) parasites
• Bacteria

Binds (beta-glucan/mannose) carbohydrate structures

Question 8

Four steps to phagocytosis

Answer 8

0 - detection (?)
1 - Attachment
2 - Ingestion
3 - Killing
4 - Degradation

Question 9

Cytokines: what are they, what types are there, and what do they do?

Answer 9

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

Question 10

Endocrine, paracrine, and autocrine definitions

Answer 10

Endocrine - acting far away from the release site (uncommon)

Paracrine - acting on nearby cells

Autocrine - acting on the cell itself

Question 11

The inflammasome: what is it, what is it caused by, and what does it do?

Answer 11

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)

Question 12

IL-1b and IL-18: why do they have special activation requirements?

Answer 12

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.

Question 13

What are the processes of inflammation

Answer 13

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

Question 14

Mast cells: what do they do when activated?

Answer 14

They degranulate, releasing their inner contents

Immediate products:
* Histamine
* Heparin
* Enzymes - tryptase, chymase

Delayed products:
* Protstaglandins
* Leukotrienes
* Cytokines

Question 15

Acute phase proteins: what examples are there and what do they do?

Answer 15

• 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

Question 16

Opsonins

Answer 16

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

Question 17

Some Opsonins of the innate immune system

Answer 17

• 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

Question 18

Complement: what is it, what happens after activation, what pathways are there, and what is the function of it?

Answer 18

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)

Question 19

Interferons: what are they and what do they do?

Answer 19

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)

Question 20

NK cells: what are they, what do they do, and what pathways does it have?

Answer 20

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

Question 21

Innate cells: what are they, what are some examples, and what do they do?

Answer 21

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

Question 22

Innate vs adaptive system

Answer 22

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