HC16: Invaders

Pathogenesis

All invaders can make people ill. They are micro-organisms which interact with a host. Humans are full of micro-organisms, which usually don't do anything.

There are 10¹⁴bacteria in the body. Some of these take place and colonize the bowel and mouth, forming protection from other bacteria. Others are only carried and don't cause any harm, or reside in the body in latent form.

Disease symptoms are mainly caused by the human immune host response → it takes 2 to tango. There are only a few micro-organisms which actually cause disease without there being an immune response.

Virulence factors

A virulence factor is any component, product or characteristic that contributes to the ability of a micro-organism to cause disease:

• Structural components
  • Survival of the adverse environment
  • Attachment to human structure
  • Entry into the human body
  • Induction of an inflammatory response
• Products
  • Toxins
  • Enzymes
• Tricks
  • Kill a cell
  • Decreasing the normal immune response
  • Evading the normal immune response
  • Latency

These factors help the virus to:

• Get inside
  • Adhesion proteins or glycoproteins
  • Endocytosis induced by micro-organisms
  • Fimbriae
  • Hyphae
  • (Lipo)techoic acid
• Do harm
  • Enzymes destructing tissue
  • Hyphae
  • Lipopolysaccharide (LPS)
  • Lipoteichoic acid
  • Peptidoglycan
  • Toxin that activated adenylate cyclase
  • Toxin acting as a superantigen
  • Toxin inhibiting the release of neurotransmitters
  • Toxin with cytotoxic activity
• Turn off/hide from the defender
  • Antigenic shifts
  • Antigenic variation
  • Biofilm
  • Protein inhibiting opsonization
  • Intracellular survival
  • Capsule
  • Molecular mimicry
  • Ability to remain latently in the host

It isn't necessary to memorize these factors.

Streptococcus pyogenes

Streptococcus pyogenes is a primary pathogen. It acts via a transient carrier in the throat.

Diagnostics show that it is a:

• Catalase test → gram positive cocci
• Culture plate → Group A b-hemolytic cocci

Symptoms:

Symptoms of an infection with streptococcus pyogenes are:

• Local or disseminated infections
  • Tonsillitis, otitis media
  • Impetigo, erysipelas
    • Erysipelas are skin infections
  • Childbed fever, sepsis
• Exotoxin-mediated syndromes
  • Scarlet fever
  • Streptococcal toxic shock syndrome
• Immunological effects
  • Acute rheumatic fever
  • Acute glomerulo-nephritis

Adhesion:

S. pyogenes has little hairs on its cell wall that touch the epithelial cell. The cell wall of s. pyogenes contains:

• Peptidoglycan
  • S. pyogenes is a gram positive bacteria
• Lipoteichoid acid
• Potrusions connecting to components on the human cell
  • Without these, adhesion wouldn't be possible → the bacteria would be gone after swallowing

Virulence factors:

Several other virulence factors pay an important role:

• Streptolysin → a toxin which makes pores in the cell
  • Belongs to a class of pore-forming, membrane-active, exotoxins
    • After formation of the pore, the epithelial cell dies
  • Causes the lysis of red blood cells that is visible on a culture plate → b-hemolysis
• Streptokinase → lysis of clot
  • In case blood clotting is involved → the bacteria can go anywhere
    • Blood clots usually block the infection from spreading
• C5a peptidase → spreading of infection
  • C5a is a complement factor → a peptide mediator of inflammation and phagocyte recruitment
    • C5a peptidase causes the inflammation to be postponed
• Hyaluronidase → spreading of infection
  • Hyoluronic acid is component of interstitial tissue → if it is cut by hyaluronidase, it causes infections → the bacteria spreads within the tissue
• M-proteins → prevents opsonization
  • Visible as "sticks" on s. pyogenes
  • Makes attacking of the bacteria more difficult

Exotoxin-mediated syndromes:

10% of streptococcus pyogenes have toxins or superantigens:

• Erythrogenic toxin → scarlet fever ("roodvonk")
• Superantigenic toxin → toxic shock syndrome
  • Works without antigens → all T-cells respond → a storm of cytokines → results in death
  • Can also be caused by staphylococcus aureus

Streptococcus pneumoniae

S. pneumoniae is a bacterium that lies in pairs of 2. It has a capsule made of polysaccharides around it. This capsule interferes with the complement system → it prevents opsonization by the complement system. If antibodies against this capsule are made, the bacteria can be opsonized and cleared away easily, but it does take a while for the antibodies to be made.

This capsule is very important for 3 pathogens:

• Streptococcus pneumoniae
• Neisseria meningitis
• Haemophilus influenzae B
  • This is not an influenza virus, but a bacterium

Influenza A virus

The influenza A virus is a primary pathogen (a host defense disorder isn't necessary → everyone can get ill) which can cause either a mild disease or severe disease.

The risk of death is increased in patients with:

• Comorbidity
• Very young or very old age
• Impaired immunity

Virulence factors:

The influenza virus is an enveloped RNA virus. It has several "spikes" on the outside:

• Hemagglutinin spikes: makes it possible for the virus to attach to the cyodic acids of the epithelial cell
• Neuraminidase spikes: releases the virus from the epithelial cell

These are the main virulence factors of the influenza A virus.

DNA-polymerase proofreads newly made DNA to prevent mutations. RNA-polymerase doesn't do this→ mutations are frequent. This can cause antigenic drifts and antigenic shifts:

• Antigenic drift
  • This causes a new influenza-flue every winter
  • 2 or more RNA-strands combine to create a new subtype of the virus
• Antigenic shift
  • 1 cell has both a human and animal influenza virus → reassortment of genome segments → can cause a flue pandemic

In conclusion, the influenza virus has several virulence mechanisms:

• Adhesion
  • Hemagglutinin
• Toxins
  • Not present
• Enzymes
  • Neuraminidase
• Immune evasion
  • Antigenic drift and shift

Drugs:

There are several drugs against the influenza virus:

• Oseltamivir
• A neuroaminidase inhibitor

Treatment only is indicated if:

• The patient is immunocompromised
• The disease is very severe

Human immunodeficiency virus

The human immunodeficiency virus (HIV) is an enveloped RNA-virus. It carries reverse transcriptase → makes double-stranded DNA from RNA. This normally doesn't happen in nature. Integrase makes the double-stranded DNA go into the DNA of the human host → it gets in and cannot get out. The main target cells of HIV are T-helper cells.