Immunology 1

Question 1

What mechanical barriers protect against infection by viruses?

Answer 1

• Epithelial cells joined by tight junctions
• Longitudinal flow of air or fluid
• Movement of mucus by cilia
• Tears

Question 2

What chemical barriers protect against infection by virus?

Answer 2

• Fatty acids
• Low pH
• Antimicrobial enzymes
• Pulmonary surfactant

Question 3

What is the cytolytic action of influenza?

Answer 3

Influenza causes acute cell death of ciliated resp epithelial cells + removes mucus-secreting cells + blocks function of muco-ciliary escalator

Question 4

What are the layers of defence?

Answer 4

1. Immediate innate
2. Induced innate
3. Adaptive

Question 5

How long is immediate innate immunity?

Answer 5

0-4 hrs

Question 6

How is the virus recognised in immediate innate immunity?

Answer 6

• Soluble effector molecules = defensins, lactoferrin + lysozyme
• Resident effector cells in infected tissue = macrophages, mast cells + cDc’s + some memory T cells + NK cells

Question 7

How long is induced innate immunity?

Answer 7

4 hrs - 4 days

Question 8

What are the sentinel cells of the body and what is their role?

Answer 8

= macrophages, dendritic cells, few NK cells + v few memory type lymphocytes

Detection

Question 9

What are Langerhan cells?

Answer 9

Distinct sub population of self-renewing DC’s

Question 10

Where can viruses uncoat and where do PRR’s exist?

Answer 10

Plasma membrane + within endosomes

TLRs 3, 7, 8, 9 = located in endosomes

Question 11

3yo with high fever, right sided tonic-clonic seizures + paralysis right face + arm
MRI - lesions in left parietal lobe + left thalamus
WBC - 180 (normal <5), 97% lymphocytes
PCR - HSV-1 in CSF
History - viral encephalitis at 6 mo

What is the diagnosis?

Answer 11

Recurrent herpes simplex encephalitis

Associated with genetic defects in TLR-3 signalling pathway + failure of neurones to produce type 1 interaction

Question 12

Where is the primary site of infection for HSV-1?

Answer 12

Oral mucosa

Then transported through sensory neurones > trigeminal nerves + ganglia where it establishes latent infection

Question 13

What are the consequences of triggering TLRs?

Answer 13

Communication

Macrophages produce range of cytokines upon sensing virus

Question 14

18 yo male
Pyrexia, persistent pharyngitis + cervical lymphadenopathy

What is the diagnosis?

Answer 14

• EBV
• Gains entry to tonsillar B lymph + replicates rapidly
• EBV virions pass via afferent lymphatics into cervical nodes
• Causes B lymph prolif > CTL kill infected B cells > symptoms

Question 15

What are the classic signs of viral infection?

Answer 15

Malaise 
Sleepiness 
Myalgia 
Loss of appetite 
Chills + fever

Question 16

What cytokines do macrophages produce in response to virus?

Answer 16

• Pyrogenic cytokines - act on hypothalamus to increase body temp, act on muscle to increase fat + protein utilisation
• IL-1 & IL-6 = endogenous pyrogens + can actually cross into hypothalamus + bring about PGE2
• PGE2 production = innervation of sympathetic system = shivering, non-shivering thermogenesis + skin vasoconstriction

Question 17

What are interferons?

Answer 17

Class of cytokines which defend against viral infections

Question 18

What interferons are capable of producing interferons alpha and B and how?

Answer 18

• All cells
• Interferon response activates NK cells to kill virus-infected cells
• Cause systemic symptoms associated with viral infections
• IF alpha + beta = induced + released within hours of infection

Question 19

How to TLR’s lead to transcription of type 1 IFNs alpha + beta genes?

Answer 19

• Interferon response factors phosphorylated

- Then enter nucleus to initiate interferon mRNA synthesis

Question 20

What is the role of interferon stimulated genes (ISGs)?

Answer 20

• Suppress viral entry, viral replication + alter cellular metabolism to generate anti-viral state
• Virus detected by PRRs > activation IRFs > enter nucleus + initiate transcription of IF alpha + beta
• These bind to IFN receptors to trigger JAR/STAT activation > transcription ISGs

Question 21

How do IFNs protect neighbouring cells?

Answer 21

Induce antiviral state in neighbouring uninfected cells

Question 22

What does the cytosolic detection of viral infection by PRRs (RIG like receptors) lead to?

Answer 22

• RLRs enable cells to make type 1 interferon
• Many viruses infect cells by direct membrane fusion
• Host cell evolved PRR’s to detect viral nucleic acids in cytosol
• RLR’s detect abnormal RNA molecules + trigger response

Question 23

What effect do most pathogenic viruses e.g. ebola have on the antiviral state?

Answer 23

Shut off supply of IFNs + prevent antiviral state

Question 24

What is the role of plasmacytoid dendritic cells (pDCs)?

Answer 24

• Increase capacity for producing IFNS alpha
• Mainly in blood + lymphoid tissues
• Significant during viraemia
• Express high levels of TLRs 7 + 9

Question 25

What is the role of conventional dendritic cells (cDCs)?

Answer 25

- Activation of naive T cells | - Localised in peripheral tissues in absence of infection

Question 26

Why not administer measles, mumps + rubella vaccines singly and a week apart?

Answer 26

- Interferon response to 1st vaccine would suppress replication of 2nd and therefore diminish immune response to 2nd - Immune response to 1 live virus vaccine might be impaired if administered within 30 days of another

Question 27

How do NK cells detect changes at surface of infected cells?

Answer 27

- Combination of activatory + inhibitory receptors found on NK cell surface - Triggering of NK cells dependent on balance of receptors

Question 28

How do NK cells kill virally infected cells?

Answer 28

Release of perforins + granzymes that perforate membranes of target cells + induce caspase mediated death

Question 29

Describe the kinetics of immune response to viral infection

Answer 29

1. Production of IFN-alpha & beta, TNF-alpha and IL-2 2. NK cell killing of infected cells 3. T cell killing of infected cells