Infection Pathogenesis

Question 1

What is immunopathologic damage?

Answer 1

Tissue injury caused by a dysregulated immune response, often leading to inflammation and functional impairment

Question 2

How does cytokine release by macrophages lead to immunopathologic damage?

Answer 2

Leads to the symptoms of influenza

Question 3

How does cell killing by CTL lead to immunopathologic damage?

Answer 3

May result in organ damage

Question 4

How does dead cells lead to immunopathologic damage?

Answer 4

Secondary inflammatory response to cellular components(DAMPs) such as DNA and RNA

Question 5

What are prostaglandins (PG)?

Answer 5

Lipid compounds derived from anachronic acid, a fatty acid present in cell membranes.

Known mediators of the inflammatory response

Question 6

What are the proinflammatory effects of Prostaglandins (PGs)?

Answer 6

Promoting vasodilation

Increasing vascular permeability,

Sensitizing nociceptors (pain receptors)

Question 7

What is the role of Prostaglandins in immune response?

Answer 7

Recruit immune cells

Amplify inflammatory response

Modulate immune function

Question 8

What is PGE2’s role in inflammation?

Answer 8

Promotes vasodilation

Increases vascular permeability

Sensitizes pain receptor

Question 9

How does PGE2 cause a fever?

Answer 9

PGE2 acts on the hypothalamus to raise body temperature leading to fever.

It is synthesized locally in response to pyrogenic (fever-inducing) substances such as endotoxins or cytokines.

Question 10

How do PGs have a role in pain sensing?

Answer 10

By sensitizing pain receptors and lowering the threshold for pain perception.

Question 11

How do PG cause inflammatory pain?

Answer 11

Damaged tissue release pro-inflammatory cytokines (IL-1 and TNF-alpha).

This stimulates the production of PGs, E2.

Question 12

How does PGE2 sentisation of nociceptors?

Answer 12

PGE2 sensitizes nociceptors by acting on receptors EP1, EP2, and EP4 receptors, which are expressed on sensory nerve fibers.

This sensitization lowers the threshold for activation of nociceptors, making them more responsive to mechanical, thermal, and chemical stimuli.

Question 13

How does PGE2 enhance neurotransmitter release?

Answer 13

PGE2 enhances the release of excitatory neurotransmitters, such as substance P and glutamate, from sensory nerve terminals in the spinal cord.

This amplifies the transmission of pain signals to higher brain centres, contributing to the perception of pain.

Question 14

What is the role of PGE2 in chronic pain?

Answer 14

PGE2 is implicated in the pathophysiology of chronic pain conditions, such as osteoarthritis, rheumatoid arthritis, and neuropathic pain.

Persistent inflammation and dysregulation of PG production contribute to the maintenance of chronic pain states.

Question 15

How does infection cause metabolic changes that affect neuronal activity?

Answer 15

Release of inflammatory mediators.

Disruption of energy metabolism and neurotransmitter synthesis.

Blood-brain barrier dysfunction.

Imbalance of neurotransmitters.

Activation of immune cells in the CNS.

Question 16

What is IDO?

Answer 16

Indoleamine 2,3-dioxygenase (IDO) is an enzyme involved in the metabolism of tryptophan, an essential amino acid. In the context of flu infection, IDO activation has been implicated in increasing pain sensitivity.

Question 17

Through what mechanisms does IDO activation in flu infection increase sensitivity?

Answer 17

Immunomodulation via tryptophan metabolism.

Neuroinflammation and glial cell activation.

Direct activation of pain-sensing neurons.

Contribution to neuropathic pain development.

Question 18

What is type 1 interferon?

Answer 18

Type I interferons (IFNs) are a group of cytokines that play a crucial role in the innate immune response to viral infections and other pathogens.

They are primarily produced by cells such as plasmacytoid dendritic cells, macrophages, and fibroblasts

Question 19

What are acute interferons?

Answer 19

Inhibit virus replication and promote immune response

Question 20

What are chronic interferon

Answer 20

Can contribute to pathogen evasion thus promote pathogen persistence

Question 21

What is the role of interferons?

Answer 21

Induce immune immune suppressive mechanisms including PDL1 and indoleamine 2,3 dioxygenase (IDO)

Question 22

What is the antiviral activity of interferons?

Answer 22

Inducing the expression of numerous interferon-stimulated genes (ISGs) in both infected and neighbouring cells.

ISGs encode proteins involved in various antiviral mechanisms.

Question 23

How are interferons important in immune modulation?

Answer 23

By regulating the activation, differentiation, and function of immune cells, including dendritic cells, T cells, B cells, and natural killer (NK) cells.

Question 24

How are interferons used in induction pathways?

Answer 24

Induced in response to viral infection through pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), and cytosolic DNA sensors.

Question 25

What are the mechanisms of pathogen induced tissue damage?

Answer 25

Direct cell injury

Indirect immunopathology

Invasion and destruction

Toxin production

Immune evasion

Disruption of barrier function

Question 26

How can chronic infection lead to cancer?

Answer 26

• Carry oncogene
• Activate host oncogene
• Can evade immune system thus
  persist and cause chronic inflammation

Question 27

What is human papilloma virus HPV?

Answer 27

A group of viruses that infect the skin and mucous membranes of humans.

HPV is one of the most common sexually transmitted infections (STIs) worldwide

Question 28

What are the manifestations of HPV?

Answer 28

Genital Warts

Cervical Cancer

Other Cancers

Question 29

outline the Initial Entry and Replication of HPV.

Answer 29

Attachment and Entry: HPV attaches to host epithelial cells via cell surface receptors, followed by entry into the cell.

Intracellular Trafficking: Virion undergoes intracellular trafficking to reach the nucleus.

Uncoating and Genome Release: Viral genome is released into the nucleus for replication.

Transcription and Replication: Viral genome is transcribed and replicated by host cell machinery.

Late Gene Expression and Virion Assembly: Structural proteins are synthesized, and virions are assembled.

Release of Mature Virions: Mature virions are released from infected cells, facilitating transmission.

Question 30

How do genes determine the risk of HPV?

Answer 30

• E genes determine the oncogenic risk of HPV
• E6 and E7 are two main oncogenes

Question 31

How does HPV initially evade host immune system?

Answer 31

HPV E6 and E7 interfere with type 1 interferon synthesis and effectors

HPV inhibit MHC class I antigen presentation thus evade from T cell detection

Question 32

What are Tumour-Associated Macrophages (TAMs)?

Answer 32

Macrophages infiltrate the tumour microenvironment in response to signals from tumour cells and the surrounding stroma.

Question 33

What are some tumour promoting activities by macrophages?

Answer 33

Immunosuppression

Tissue remodelling

Resistance to therapy

Question 34

What are some anti-tumour activities by macrophages?

Answer 34

Phagocytosis of cancer cells

Stimulation of antitumour immunity.

Reprogramming TAMs

Question 35

Why chronic inflammation is an important part of oncogenesis?

Answer 35

Chronic inflammation creates a microenvironment conducive to tumour development and progression.