Disease Examples

Trisomy 13 or Patau syndrome

Results in 3 copies of chromosome 13. Risk increases with maternal age, 95% of cases cause miscarriage, live briths rarely survive.

Results in heart defects, seizures, and intellectual disabilities.

Cri du chat syndrome or 5p monosomy

A deletion in 5p chromosome, occurs during development and is ususlly not inherited.

Causes a weak, cat cry, physical deformities and intellectual disabilities.

What does ionising radiation (X-rays) do to DNA?

Formation of ROS causes physical breaks to DNA.

Toxicity = damage to vascular endothelia, cell death, bleeding, scarring.

Misrepair = Chromosome translocation

What does UV radiation (sunlight) do to DNA?

C to T transversions causes physical damage.

Toxicity = damage to keratinocytes = peeling sunburn

Misrepair = skin cancer

What does alkylation do to DNA?

E.g. aflatoxin B1

G to T transversions causes chemical damage.

Toxicity = liver damage

Examples of inadequate and excessive apoptosis

Inadequate = autoimmune disease, cancer

Excessive = stroke, myocardial infarct, Parkinson’s, etc.

SIRS/sepsis

Storm of pro and anti-inflammatory cytokines induced by DAMPs, complement, ROS.

How does tuberculosis cause a successful infection?

Must cause coughing to transmit. Must suppress systemic disease to avoid death of host.

What happens when there is immediate host control of TB?

Mtb bateria is inhaled and TNFa and IL-1 recruit neutrophils. Apoptosis.

What happens when there is adaptive immunity and control of TB?

Macrophages migrate to lymph nodes as antigen presenting cells to activate TH1. IFNy release causes macrophage activation. TH17 releases IL-17, recruiting neutrophils. Necrosis as collateral damage.

What happens when there is escape of Mtb and dormancy in TB?

Lung environment has been conditioned for Mtb growth. M0 activation is inhibited, causing macrophages to support proliferation. Granulomas from, TH1 is suppressed.

Goospasture’s syndrome

An organ specific (T2 HS) autoimmune disease. Antibodies are against type 4 collagen in the basement membrane. This causes kidney dysfunction and bleeding lungs.

Myasthenia gravis

An organ specific (T2 HS) autoimmune disease. Ach receptors are blocked causing muscle weakness.

Pemphigus

An organ specific (T2 HS) autoimmune disease. Antibodies are against intracellular adhesion molecules, causing blisters.

Graves disease

A thyroid autoimmune disease. Autoantibodies mimic thyroid stimulating hormone causing increased thyroxine from the brain. This signals that actual thyroid stimulating hormone is not required. Result is hyperthyroidism.

Hashimotos disease

T2 HS. Autoantibodies against proteins produced by thyroid cells. Hypothyroidism.

Systemic lupus erythematosus

T3 HS. Inflammation autoantibodies are against DNA and other cellular processes.

EPEC Adhesion

Adheres very closely with the cell due to the locus of enterocyte effacement which codes for a type 3 secretion system.

Helicobacter Pylori - causing an infection.

Secretes urease, creating an ammonia cloud to avoid stomach acid, swims into the mucus layer. Avoids host as TLR4 does not recognise LPS and TLR5 does not recognise things either, this causes an increase in cytokines. It also mimics the host by a plasminogen and cholesterol cloak.

It causes damage in the antrum by stopping D cells, causing increased stomach acid and a duodenal ulcer.

It causes damage in the body by stopping P cells, creating decreased acid and a gastric ulcer.

Cholera toxin

Vibrio cholera is the bacteria. The B subunit binds GM1 and is taken up into the ER. A and B subunits dissociate and cAMP is accumulated, causing CFTR and diarrhea.

EHEC

Shiga-like toxin causes cell death, bloody diarrhea, and kidney failure. B subunit binds Gb3 and goes into the ER. The ribosome is permanently inactivated, there is platelet clumping and increased inflammation.