BMS106 Pathobiology - Gokhale and Sahal Flashcards
What are the two ways in which cells can die?
Necrosis and apoptosis
When does necrosis occur?
Due to physical trauma (e.g. cuts and burns or extreme temperatures - frostbite) or toxins such as snake venom or bacterial toxins internally. Or acute hypoxia or ischaemia (restricted blood supply to certain tissues) e.g. stroke
When does apoptosis occur?
Physiological situations:
- Tissue size maintenance
- Developmental cell loss
- senescence
- removal of immune cells
Pathological situations:
- DNA damage, e.g. due to radiation or oxidative stress
- Virally infected cells
What are the characteristics of reversible necrosis?
Membrane integrity compromised
Organelle and cell swelling
What are the characteristics of irreversible necrosis?
Increased intracellular calcium Autolysis (destruction of tissue by own enzymes) Cell bursting (lysis) Inflammatory response
What are characteristics of apoptosis?
- Cell shrinkage
- Nuclear breakdown
- Apoptotic bodies
- Phagocytosis
- No inflammatory response
- Requires energy
Why might apoptosis occur at the edge of necrotising tissues?
To restrict spread of cell death
How does apoptosis occur in young frogs?
A surge in thyroid hormone in the blood initiates tail apoptosis in tail cells during metamorphosis
What are neuronal connections refined by?
Survival factors. Not enough survival factor = apoptosis
What are ced genes involved in?
Apoptosis. From recognition of apoptotic signals to the engulfment of apoptotic cells by phagocytes. They can be pro-apoptotic or anti-apoptotic
What are caspases?
Executioners of cell death. C = cysteine at active site asp = aspartic acids - cleavage site in target proteins irreversible pathway 10+ ced3 homologues
What are the 2 types of caspases?
Initiator - activated by apoptotic signals and activate executioner caspases - 1 initiator can activate multiple executioner caspases (amplifying proteolytic cascade)
Executioner - Cleave >1000 proteins
What are 3 main targets of caspases?
Nuclear lamina (cause breakdown of nuclear structure) Prevent DNA repair by cleaving DNA repair enzyme PARP. Cause cytoskeletal changes, e.g. breakdown of actin
What are the two main pathways of apoptosis initiation?
Intrinsic and extrinsic
Describe the extrinsic apoptosis pathway
Indirectly activate initiator caspases. 6 related receptors (the death receptors). Tumour necrosis factor family.
Caspase-8 = initiator caspase
Triggered by DEATH LIGANDS
Describe the intrinsic apoptosis pathway
Triggered by stress signals, such as DNA damage, and development signals.
Caspase-9 = initiator caspase.
Cytochrome c release by mitochondria
In intrinsic apoptosis, what decides whether cytochrome c or other intermembrane mitochondrial proteins are released?
The balance between pro- and anti-apoptotic factors known as Bcl2 family proteins.
Ced9 is anti-apoptic
EGL-1 is pro-apoptotic
When an where was the first case of HIV?
1981 Los Angeles - 30 yr old homosexual man had PCP (rare lung infection) - within 5 months 5 cases documented - flood of similar reports across USA
+ cluster of cases of rare and unusually agressive Kaposi’s sarcoma (a cancer)
By end of 1981 270 reported cases of sever immunodeficiency among homosexual men
Where is HIV most prevalent?
East and Southern Africa, the western and central Africa.
Dramatic increase in Russia in recent years (60% increased)
What is the HIV prevalence in Swaziland?
27%
How is HIV transmitted?
Blood and blood products Vaginal mucus and secretions Semen Any body fluid mixed with infected blood Sometimes breast milk
Is there an asymptomatic period of HIV?
Yes - person will feel and look completely healthy - can last up to 15 years
What are some symptoms of AIDS?
Lip warts Shingles Kaposi's sarcoma PCP Thrush Severe weight loss
What does AIDS stand for?
Acquired Immunodeficiency Syndrome
What does HIV stand for?
Human Immunodeficiency Virus
What is ART?
Anti-Retroviral therapy.
Controls viral replication, allows immune system to recover, allows individuals with HIV to live healthy and productive lives - doesn’t cure HIV infection - controls spread of HIV
How many classes of anti-retroviral drugs are used to prevent the formation of HIV DNA?
3 - integrase inhibitors prevent HIV DNA integration into host DNA - protease inhibitors prevent new viruses being formed
Which cells can be used to give an indication of the immune system’s health?
CD4 cells - HIV uses CD4 as a place to multiply and damages their normal function in immunity
What are CD4 cells normally used for?
Binding of macrophages to helper T cells - stabilises antigen presentation to T-h cell. HIV uses CD4 to invade T-helper cells
What do most strains of HIV need to enter helper T cells? How can this be altered to prevent HIV binding?
Co-receptor called CCR5. ∆32 mutation prevents HIV binding
Where is there a greater frequency of the CCR5-∆32 mutation?
European populations
What does vaccination aim to do?
Protect from infectious disease by producing riskless immunity and immunological memory - very specific to a single antigen
What are the two types of immunity?
Passive and active
What is active immunity?
Protection is provided by the person’s own immune system and takes days or weeks to develop, but is usually permanent. It can be natural or acquired