lecture 5, chronic diseases

Structure of the granuloma

Inside, there are macrophages, T cells, and a fibrous layer.

m1 and what affects it

m1→ is very proinflammatory.

in TB the bacteria shift from M1 to M2

TNF alpha → a very important factor M1

KLF4

wants more M2 and less M1

NO

more M1 and less M2, radical oxygens killing M1

what type of necrosis do we have in TB?

Caseous necrosis = a type of cell death where tissue turns into a soft, white, “cheese-like” material

• Immune system tries to kill TB

• TB resists → chronic inflammation

• Cells die in the center

👉 So:

• Outside = immune cells

• Inside = dead material (caseous necrosis)

two types of giant cells

1) Foreign body giant cells: Nuclei are scattered randomly

2) langhans : the nuclei are moslty periphery (seen mostly in TB) in a horse shoe formation

what causes the most industrial plagues?

virus

explain the extracellular state of viurs

A virion = complete virus particle outside a cell
Envelope (sometimes present)

• Lipid layer from host cell

• Has spike proteins

👉 Used for:

• entering host cells

• recognition

intracellular state

when capsid is removes and it exits in the cell, ( some nucleic acid)

three big groups of viruses?

helical

polyhedral

complex

what is the subunit of capsids?

capsomere

Helical symmetry (rod-shaped)

Structure:

• Capsid proteins wrap around genome like a spiral (helix)

• Looks like a rod / tube

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🧠 Key rules (from your slide):

👉 Length = genome length

• More RNA/DNA → longer virus

👉 Width = protein size

• Determined by capsid subunits

Icosahedral symmetry (spherical)

• 20 triangular faces

• Looks like a sphere (but actually geometric)

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🧠 Key idea:

👉 “Most efficient way to build a closed shell”

💡 Why?

• Uses few proteins

• Very stable

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💡 Example:

• Human papillomavirus (HPV)

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🔥 Easy way to remember:

👉 “Icosahedral = soccer ball shape”

Where can viruses replicate, and how are different types of viruses grown/studied?

BACK (Answer):

👉 Replication:

• Viruses replicate only in specific host cells or organisms
  → (host specificity / tropism)

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👉 Bacterial viruses (bacteriophages):

• Easiest to grow

• Use bacteria as hosts

• Common model systems

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👉 Animal viruses:

• Grown in:

  • Cell cultures

  • Tissue cultures

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👉 Plant viruses:

• Hardest to study

• Often require whole plant growth

What are the phases of viral replication?

• Attachment (adsorption) of the virus to a susceptible host cell

• Entry (penetration) of the virion or its nucleic acid

• Synthesis of virus nucleic acid and protein by cell metabolism as redirected by virus

• Assembly of capsids and packaging of viral genomes into new virions (maturation)

• Release of mature virions from host cell

example of an early stage protein?

NEF

example of late stage protein

VPU

What are the three mechanisms of entry of animal viruses?

• Direct penetration
  → Viral genome enters directly through the membrane

• Membrane fusion
  → Viral envelope fuses with host cell membrane

• Endocytosis
  → Cell engulfs virus into vesicle → uncoating releases genome

HIV is an exception, and it keeps the capsid unti it gets to the nucleas.

What is the eclipse phase in viral replication?

Eclipse phase = period after entry where NO infectious virus particles are detectable

• Virus has entered cell

• Capsid is removed (uncoating)

• Virus exists only as nucleic acid

• Viral components (proteins + genome) are being made

❗ No complete virions yet → cannot detect virus

What IS happening during eclipse?

Inside the cell:

• Early enzymes made

• Viral genome replicated

• Viral proteins made

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💥 Then what happens?

👉 After eclipse:

• Assembly starts

• New virions form

👉 Then graph goes 📈 UP FAST

Virulence factors

Antiphagocytic factors:

• Factors prevent phagocytosis by the host’s phagocytic cells

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👉 Bacterial capsule:

• Composed of chemicals not recognized as foreign

• Slippery; difficult for phagocytes to engulf bacteria

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👉 Antiphagocytic chemicals:

• Prevent fusion of lysosome and phagocytic vesicles

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👉 Leukocidins:

• Directly destroy phagocytic white blood cells

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What are the stages of infectious disease and what happens in each?

• Incubation period:
  No signs or symptoms; pathogen is multiplying

• Prodromal period:
  Vague, general symptoms (e.g., mild fever, fatigue)

• Illness:
  Most severe signs and symptoms; peak pathogen levels

• Decline:
  Signs and symptoms decrease as immune system gains control

• Convalescence:
  No signs or symptoms; recovery phase

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explain listeria

non spore,gram positive

no enzymes or toxins,

uses lysom o to destroy the fusion of lysosome and phagosom,

survives in our cells,uses the cell actin to infect the cells next to it,

What is tuberculosis and what are the three types of TB?

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Tuberculosis (TB):

• Respiratory disease caused by Mycobacterium tuberculosis

• Increasing in Canada and the United States

• Pandemic in other parts of the world

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👉 Three types of tuberculosis:

• Primary TB:
  Results from the initial infection with M. tuberculosis

• Secondary TB:
  Reestablishment of active infection after period of dormancy

• Disseminated TB:
  Results when infection spreads throughout the body

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What are the key features of Mycobacterium cell wall and what do they cause?

Cell wall contains a waxy lipid called mycolic acid

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👉 Results in unique characteristics:

• Slow growth

• Protection from lysis after phagocytosis

• Capacity for intracellular growth

• Resistance to Gram staining, detergents, many antimicrobial drugs, and desiccation

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What is cord factor and what does it do in Mycobacterium tuberculosis?

Cord factor:

• Glycolipid produced by virulent strains of M. tuberculosis

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👉 Functions:

• Cells remain attached end-to-end → form “cords”

• Inhibits migration of neutrophils and is cytotoxic

• Prevents fusion of endosomes (phagosomes) and lysosomes

• Stimulates granuloma formation via cytokine production

What is granulomatous inflammation and what is the structure of a granuloma?

Granulomatous inflammation:

• A distinctive pattern of chronic inflammation evoked by agents like Mycobacterium tuberculosis

• Characteristic feature = granuloma

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👉 Granuloma structure:

• Small (0.5–2 mm) collections of modified macrophages (epithelioid cells)

• Surrounded by a rim of lymphocytes → nodular appearance

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👉 Additional components:

• Vascular elements

• Fibroblasts and collagen (it can calsify and become harder)

• PMNs and plasma cells

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