Innate Immunity

Question 1

Why is the adaptive immune system not effective immediately?

Answer 1

The adaptive response is too slow to protect us against new pathogens

• Cytotoxic cells start working after 3-4 days
• antibodies produced after 5 days post infection

Innate immunity occurs within hours
> resolution of infection requires both innate & adaptive immune systems

Question 2

How do macrophages recognise pathogens?

Answer 2

Macrophages have phagocytic receptors that bind microbes and their components
Macrophages recognise pathogens via passive sampling, scavenger receptors or engulfing apoptic cells e.g.
- Mannose receptor
- Complement receptors
- Lipid receptors
- Scavenger receptors
- Dectin-1 β-glucan receptor

Question 3

What is the role of NK cells?

Answer 3

Kill certain tumours and virally infected cells caused by cytotoxic molecules (granzymes and preforins)

Question 4

What are the roles of cytokines?

Answer 4

Act to modify behaviour of cells in immune responses
Most of these are interleukins e.g.
IL-1 enduces acute ohase secretions
IL-8 is a chemoattractant for neutrophils
IL-12 directs immune response to Type 1 pro-inflammatroy cytokine secretion

Question 5

How are NK cells activated?

Answer 5

Activated by loss of self
- NK cells possess ability to recognise and lyse virally
infected cells and certain tumour cells
- selectivity is conferred by loss of self MHC molecules
on target cell surfaces and up regulation of activating
ligands

Question 6

Why are PAMPs a good way of identifying specific pathogens?

Answer 6

PAMP molecules only present on pathogens (not host cells)
They are essential for pathogen survival and are invariant structures shared by
entire classes of pathogens

Question 7

What is the function of chemokines?

Answer 7

Act as chemotactic factors creating [ ] gradients which attract/repel specific cell types to a site of production / inflammation

Question 8

What are the sites of microbe entry?

Answer 8

• Conjunctiva (eyes)
• arthropod
• capillaries
• respiratory tract
• alimentary tract
• anus
• skin
• scratch/injury

Question 9

What is the effect on innate immunity associated with inherited complement defects?

Answer 9

Core defects (e.g. C3) linked to autoimmune disease developments (e.g. Lupus)
non core defects link to susceptibility of specific pathogen types (e,g, Neisseria)

Question 10

What are cytokines and chemokines?

Answer 10

Glycoprotein hormones that affect immune responses

Question 11

How do inherited macrophage deficiencies effect innate immunity?

Answer 11

Chronic granulomatous disease (CGD) - no oxidative burst for bacterial killing
IRF8 mutations linked to TB susceptibility

Question 12

Name examples of PAMPs

Answer 12

Gram positive bacteria
- teichoic acid, lipotechoic acid, peptidoglycan found in outermembrane

Gram negative bacteria
- lipopolysaccharides found in outermembrane

Bacterial flagellin
Abnormal protein glycosylation
Abnormal nucleic acids (viruses)

Question 13

What is the result of inherited defects to the innate immune system?

Answer 13

Aicardi-Goutieres syndrome is associated with constitutive production of inflammatory
cytokines
Lack of interferon-responsiveness causes sensitivity to viral infections (e.g. measles)

Question 14

What are the components of innate immunity?

Answer 14

Physical barriers - skin, mucosal surfaces 
Chemical barriers - pH, secreted factors
Phagocytes - monocytes, macrophages, neutrophils, 
                       granulocytes 
Inflammation 
Acute phase response 
Cytokines and chemokines 
Complement proteins 
Natural Killer (NK) cells

Question 15

What are PRRs?

Answer 15

Pattern recognising receptors (PRRs) host factors that specifically recognise a particular PAMP
They are germline coded and there are several PRR classes but functionally they are either extracellular, intracellular or secreted

Question 16

How is the inflammatory response initiated?

Answer 16

Triggered by the release of pro-inflammatory cytokines and chemokines at site
of infection causing:
- Enhanced permeability and extravasation
- neutrophil recruitment
- enhanced clotting and cell adhesion

Question 17

How does the interferon system work?

Answer 17

Infected cells triggering Type 1 interferon production are secreted and are likely to die as they release a lot more viruses - intending to replicate in adjacent cells

However interferon production stops this occurring by binding to receptors on other cells triggering 400+ enzymes creating a hostile environment
- viral replication doesn’t occur

Question 18

What are complements?

Answer 18

A system of secreted proteins made in the liver that recognise PAMPs on microbial surfaces and tag them
- microbes are then cleared by phagocytosis, opsonised
or have holes punched in them

Question 19

How do damaged cells aid inflammatory responses?

Answer 19

Damaged cells release chemicals (histamine, bradykinin and prostoaglandins) causing blood vessels to leak fluid into the tissues creating swelling
This helps isolate the foreign substance from further contact with body tissues

Question 20

What are natural killer cells?

Answer 20

Large granular lymphocytes (4% of WBCs)

- like lymphocytes but are larger with granular cytoplasm

Question 21

How are complements activated?

Answer 21

1. Recognition of LPs and other PAMPs by Clq component
   of classical pathway
2. Non host glycosylation recognised by MBP and other
   lectins activate the lectin pathway
3. Membranes recognised as ‘non-self’ activate
   alternative pathway

Complement activation involves a proteolytic cascade

Question 22

What is the inflammatory response?

Answer 22

A generic defence mechanism which localises and eliminates injurious
agents as well as removing damaged tissue components