Lecture 26 - Immunity Flashcards
What is immunity?
The state of being unsusceptible or resistant to a noxious agent or process, especially a pathogen or infectious disease
What are examples of pathogens?
- bacteria
- fungi
- parasites
- ‘foreign bodies’
- ‘foreign tissues’
- ‘unwanted cells’ (necrosis, apoptosis, cancer)
What are examples of the first line of defence?
- Skin (epithelium)
- Tears, mucus & saliva
- Cilia
- Stomach acid
- Urine flow
- ‘Friendly bacteria’
What is the first lines of defence?
physical and chemical barriers that are always ready and prepared to defend the body
How does skin act as a defence?
- biggest organ in our body
- barrier function
- its own micro-biome
- the lining of the gut is also an epithelium with barrier functions
How does cilia act as a defence?
- very fine hairs (cilia) lining our windpipe move mucus and trapped particles away from your lungs. Particles can be bacteria or material such as duct or smoke
- cystic fibrosis is caused by mutation of a chloride ion channel that results in thickened mucus that cilia can no linger move leading to lung infection
How do tears, mucus & saliva act as a defence?
- ‘openings’ are potential entry points for pathogens and are protected by secretions
- many contain anti-microbial peptides (defensins) or enzymes such as lysozyme that digest bacterial cell walls
How does stomach acid act as a defence?
- HCI secreted by parietal cells lowers the pH, activating proteases such as pepsin in the stomach and killing pathogens
How does urine flow act as a defence?
Regularly flushes out pathogens from the bladder and urethra
How does friendly bacteria act as a defence?
- naturally occuring friendly bacteria form a microbiome in our guts, skin, mouth, vagina etc, as competition to reduce the ability of pathogen to colonize and grow.
- use of antibiotics, anti-bacterial soaps etc, can disrupt the microbiome and leave areas for colonization by pathogens.
How can the body distinguish between the pathogen (that has made it past the first line of defence) and all the ‘self’ cells?
Things are different between us and the pathogen - e.g. Lipopolysaccharides (LPS) which are components of the gram-negative bacterial cell wall or peptides containing formylated-methionine, an amino acid only used by bacteria.
What are the identification of gram-negative bacterial cell wall (e.g. lipopolysaccharides - LPS) and peptides containing formylated-methionine (an amino acid only used by bacteria) examples of?
Pathogen-associated molecular patterns (PAMPs)
What is the name given to the mechanisms used to identify damaged ‘self’ cells - which is similar to PAMPs?
DAMPs - damage-associated molecular patterns
What is the largest family of receptors that detect PAMPs?
- members of the ‘Toll’ family, collectively known as ‘Toll-like receptors’ (TLRs). 10x TLRs in humans and are highly expressed by macrophages, dendritic cells and neutrophils.
TLRs (Toll-like receptors) are a molecular signalling cascade that signal through downstream effectors through downstream effectors, such as Jun/Fos transcription factors and ultimately change gene expression
Describe features of our blood?
Adults contain approximately 5 litres of blood made up of about 35 trillion cells
- Bone marrow makes around 5 billion new blood cells per day, 2.4 million a second.
What do myeloid white blood cells provide?
provide innate protection and lymphoid cells that generate adaptive immunity
What it is encompassed within the term leukocytes (white blood cells)?
includes both myeloid & lymphoid cells
What do myeloid cells do?
Myeloid cells such as macrophages and dendritic cells (both derived from monocytes) and neutrophils express TLRs (Toll-like receptors) - as well as other receptors that detect pathogen profiles.
Why are cells activated?
Cells that are activated because they recognise a PAMP (pathogen-associated molecular pattern) secrete molecular ligands that attract additional cells of the innate immune system
What does activation of myeloid cells lead to?
- inflammation causing dilation of local blood vessels, pain, redness, heat & swelling
- dilated blood vessels become permeable and endothelial cells become sticky so ‘catching’ white blood cells and facilitating their access.
- Further pro-inflammatory cytokines are released including prostaglandins, histamines & cytokines
- fever inhibit pathogen proliferation and speeds chemical reactions used by antimicrobial peptides, complement cascade etc.
- response appropriate locally can be dangerous systemically (e.g. in response to sepsis). This is shock - loss of plasma volume crash of blood pressure, clotting & cytokine storm.
What are 3 specialist phagocytic cells that can be recruited?
- neutrophils
- macrophages
- eosinophils
What are neutrophils?
short lived phagocytic abundant in blood but not tissues, respond and migrate to sites of infection (neutrophils make up ‘puss’ within wounds, ‘white head’ spots etc.
What are macrophages?
long-lived professional phagocytes abundant in areas likely to be exposed to pathogens (e.g. airways, guts)
What are eosinophils?
are specialists in attacking objects to large to engulf