Innate immunity

Question 1

What are the three main ways in which the innate immune system can detect pathogens and how does it recognise it?

Answer 1

• discriminates between self and nonself using Pattern recognition receptors, which recognise:
• PAMPs: pathogen-associated molecular patterns( Detect conserved microbial structures e.g. flagellin, lipopolysaccharide),

DAMPs( Detect metabolic consequences of cell infection or injury) and 
missing self ( as they downregulate certain self molecules)

Question 2

what does innate use?

Answer 2

Uses cellular and humoral (soluble).

Question 3

What are the main phagocytic cells? List some important features.

Answer 3

Neutrophils
-short lived
-70% of leukocyte
-multi-lobed nucleus
-first to be recruited
Primary granule: site of enzyme that will kill the phagocytosed pathogen.
Secondary granule: replenish primary granules and regulate toxin produced.

Monocytes/Macrophages:
Macrophages found in tissues
Monocytes are blood form of macrophages.
-engulf and kill invading organsims
-secrete cytokines, in particular interleukin-1 (IL-1), IL-6, IL-8 and tumour necrosis factor alpha (TNF-α).

Question 4

What is the observable difference between primary and secondary granules?

Answer 4

Primary granules stain DARKER.

Question 5

Describe how neutrophils move out of the blood vessels and into tissue.

Answer 5

• some damage will be present or a macrophage will be activated
• chemokines released, bind to local endothelial layer
• neutrophils will roll along with low affinity interactions (binding to selectin)
• integrin will be in the low affinity state, but chemokine activate this, converting to high affinity
• integrin binds strongly to integrin ligand and neutrophil is immobilised
• cells follow a chemokine gradient and move.

Question 6

What is diapedesis?

Answer 6

movement of a cell across the endothelial layer.

Question 7

What are the two main opsonins and what are opsonins for neutrophils?

Answer 7

-opsonins act as adaptor molecules which bind to the pathogen and link it to receptors present on the phagocyte.
Antibodies and complement proteins

Question 8

Describe the action of these opsonins.

Answer 8

Antibodies bind to receptors on the pathogens.
Complement glycoproteins bind directly to the surface of the pathogen.
These act as adaptors and can then bind to the neutrophil, activating it and stimulating phagocytosis/ lyse it.

Question 9

What are the mechanisms by which neutrophils kill phagocytosed pathogens and which is the most important?

Answer 9

Oxygen-dependent and oxygen-independent ( create optimal conditions for enzymes to be able to kill the pathogens.
-most important: oxygen dependant (releases reactive oxygen species)respiratory burst.

Question 10

What is phagolysosome?

Answer 10

when granules fuse with vacuole.

Question 11

What happens when neutrophils are highly activated?

Answer 11

• Release nets that help trap extracellular bacteria and immobilise them.

Question 12

What’s the difference between macrophages and monocytes and what do they do to help immunity?

Answer 12

Monocytes leave circulation and differentiate into macrophages.

• Macrophages are bigger in size.
• they have lysosomes and are phagocytic
• macrophages have PRR: pattern recognition receptors.

RELEASE Cytokines!!!
-helps recruit other cells.

Question 13

What are cytokines? List some characteristics

Answer 13

Cytokine are small secreted proteins that act as messengers.
They are short-lived.
Powerful biological effects at low concentration.

Question 14

Give some examples of cytokines and what they do?

Answer 14

Interferons: have anti-viral effects
Interleukins: communication between leukocytes
Growth factors: required for development of cells of the immune system
chemokines: chemotaxis and recruitment of cells
cytotoxic- can induce cell death i.e. tumour necrosis factor TNF

Question 15

whats the difference between types of interferon

Answer 15

only immune cells produce type 2 interferons, lots of other cells produce type 1 interferon.

Question 16

What type of responses can we have when when cytokines bind to a receptor on target cells?

Answer 16

Autocrine: the cell that secretes it, expresses a receptor for it so cytokine affects the cell that secreted it.
Paracrine: acts on nearby cells e.g. type 1 interferon
Endocrine: long distance- go into circulations and travel to distant cells.

Question 17

Describe the onset and consequences of septic shock.

Answer 17

Massive release of alarm cytokines by activated macrophages causes septic shock.
Bacterial endotoxins causes a massive release of (TNF-alpha and IL-1) by activated macrophages. Severe drop in blood pressure + Increase in vascular permeability

Question 18

where are dendritic cells located and what do they do?

Answer 18

Located at sites of likely infection

• can recognise PAMPs- part of innate immunity
• migrate once captured the antigen to the lymph nodes to activate T lymphocytes.
• Direct link between acquired and adaptive immunity
• produce cytokines once activated

Question 19

What cytokines are secreted by activated macropages?

Answer 19

IL-1:ALARM CYTOKINE, FEVER
TNF- alpha : ALARM CYTOKINE
IL-6 ACUTE PHASE PROTEINS (LIVER)
IL-8 :CHEMOTACTIC FOR NEUTROPHILS

Question 20

What is the complement system and what does it consist of and where is it produced and what happens when it is activated?

Answer 20

• forms a triggered enzyme cascade system
• small initial response can be rapidly amplified
• produced mainly in liver but also by monocytes and macrophages
• synthesised as INACTIVE precursors and have to be cleaved.
• when activated it becomes active enzymes that catalyse the cleavage of lots of molecules down the chain
• it can convert the next molecule along to become active enzyme

Question 21

What are the three ways in which complement is activated? Explain how exactly they activate compliment.

Answer 21

Classical Pathway – antigen binding to antibody causes a conformational change – activates complement
Alternative Pathway – direct contact with the pathogen surface activates complement
Lectin pathway – activated by lectin (which is a PRR) and lectin binds to carbohydrates that are only found on pathogens

Question 22

What is the final cause of cell lysis?

Answer 22

Classical and alternative converge at C3b which leads to formation of MEMBRANE ATTACK COMPLEX (MAC), this causes cell lysis.

Question 23

What happens to the cleaved fragments during the complement cascade?

Answer 23

They are pro-inflammatory molecules, which can bind to receptors on mast cells and cause degranulation giving rise to an inflammatory response.

Question 24

How are complement controlled?

Answer 24

• components are short lived
• complement is diluted in body fluids
• there are specific regulatory proteins which help regulate the activity of complement ( e.g. CD59 is expressed by human cells so it isn’t lysed)

Question 25

Other than lysis and opsonisation, what are the other roles of complement?

Answer 25

Activated inflammatory response by binding to receptors and cause mast cell degranulation.

• fragments are proinflammatory
• complement removes immune complexes so they don’t cause inflammation of the blood vessels.
• red cells have a receptor for complement, which binds to immune complexes to take them OUT of the circulation to be dealt with in the spleen.

Question 26

What are the two types of mast cell and what do mast cells release and what can they do?

Answer 26

HISTAMINES (involved in allergy response)
Mucosal: lung
Connective Tissue: skin and peritoneal cavity
-recognise, phagocytose and kill pathogens.

Question 27

What can activate mast cells and what is the result of activation?

Answer 27

Pro-inflammatory products from complement - ANAPHYLATOXINS

-Vasodilation and increased Vascular permeability

Question 28

Describe, in full, a typical inflammatory response to a bacterial pathogen.

Answer 28

Bacterial infection will firstly activate tissue resident macrophages, which begin producing alarm cytokines and chemokines. These cytokines recruit neutrophils and lymphocytes to the area of infection. Complement is activated by the classical or alternative pathways. The pro-inflammatory products of complement bind to mast cells and cause degranulation leading to an inflammatory response.
Skin becomes red due to increased vascular permeability.

Question 29

What acute phase proteins are involved in the systemic acute phase response and why does acute phase response happen, where is acute phase protein produced?

Answer 29

-sometimes inflammatory response is accompanied by systemic response.
-produced in the LIVER
-Is induced by cytokines that act over a long distance.
Proteints:
C-reactive protein(CRP): MASSIVE production
Mannan-binding lectin (MBL) : opsonin for monocytes and activates complement
Fibrinogen: clotting

Question 30

What is the clinical indicator for inflammation?

Answer 30

CRP- susceptible to upregulation

c-reactive protein.

Question 31

State some basic features of NK cells.

Answer 31

• They are large cytotoxic lymphocytes
• They are granular
• Secrete interferon gamma
• important defence against tumour cells and viral infections

Question 32

Describe how NK cells communicate with target cells.

Answer 32

They don’t have antigen specific receptors. Instead they have activating and inhibitory receptors and depending on the balance between the two signals they decide whether to attack the cell.

Question 33

What are the two types of target cell recognition by NK cells? Explain how they work.

Answer 33

Missing Self – when infected, cells will downregulate the expression of MHC Class I, which acts as an inhibitory signal. The loss of the inhibitory signal means that NK cells are more likely to kill the target cells.
Induced Self Recognition – cells will change the pattern of their self-proteins due to stress. These stress-induced patterns will be recognised by activating receptors on NK cells and lysed.