Lecture 2- The Response to Infection Flashcards
What’s the first stage of any immune response?
Awareness- recognising that you’ve got an infection.
can be at level of epithelium, also with cells that actually live in the tissue. Lots of innate cells that we call resident cells that are there all the time in case of infection.
Macrophages and dendritic cells.
What bridges the two parts of the immune system together?
The dendritic cells.
link innate and adaptive immune response
What families of receptors do macrophages have to recognise infected cells?
- Mannose receptor- bind to carbohydrate structure (mannose) which are found on yeast, parasites and bacteria.
- Dectin 1 (beta glucan receptor)- bind beta glucan structures. Anti-fungal response usually.
- Scavenger receptor- bind low density lipoproteins, sialic acids. These are found in bacteria and yeast.
- Lipid receptor- directs immune function and metabolism.
- Complement receptor- recognise specific parts of the complement cascade. like CR3 and CR4.
- Toll-like receptor-
What are Toll-like receptors?
A huge family of Pattern Recognition Receptors. They recognise these highly conserved structures on pathogens called Pathogen associated Molecular Patterns (PAMPs).
Can also recognise DAMPs- Danger-associated Molecular Patterns. These are things that the cell releases when there’s damage e.g. calcium that alerts the body there’s damage.
What do toll-like receptors form?
Homodimers and heterodimers. Different ones recognise different DAMPs and PAMPs. E.g. flagellin, dsRNA etc. in bacteria and viruses.
so these can recognise a broad spectrum of pathogens.
What do TLRs recruit?
Usually NYD88 which recruits lots of stuff-> cascade. TF changes transcription. (from TLRs on the membrane) Endosome ones (viral) usually work through TRAF3 or IRAK pathways not NYD88.
What are some more damage receptors?
- NLR- nucleotide binding domains/ (NOD)-like receptors e.g. NOD2. NLRs are usually cytosolic so intracellular, Many of these recognise intracellular damage and initiate a platform called the inflammasome. This recrutis caspase 1 and il1-beta which initiates a death signal.
- RLR- retinoic acid inducible gene-like receptor
- CLR- c-type lectin receptor
- P2X7R- recognises extracellular ATP
What happens as a consequence of awareness?
Will activate the immune response- e.g. phagocytosis. Will also make cytokines.
What are the main cytokines we think about?
- Interleukines (1-37)
- Interferons (anti-viral) alpha, beta, gamma
- Colony stimulating factors- drive haematopoiesis.
- Tumour necrosis factor- inflammation
- Chemokines- small cytokines that drive chemotaxis. attracts immune cells to the site of infection.
What happens once the macrophage has been activated by awareness of infection?
the receptors have been activated so we’ve activated the NYD88 pathways and will start secreting cytokines. e.g. Interleukins, tumour necrosis factor, cxcl8 (chemokine)
What are the variety of ways cytokines can act?
- Endocrine- made in one place and act far away
- Paracrine- made in one place and acts close to there
- Autocrine- made in one cell, acts on the same cell that made it.
What does the cytokine activity cause?
Inflammation
What is the first step of inflammation?
We get the local inflammatory response. This happens wherever the pathogen has got in. e.g. in your wound or cut or in the intestine if it’s got in there.
This switches on the resident macrophages nearby. They release cytokines. The cytokines have an effect on the blood vessels. There are gaps in the blood vessel.
What is the second step of inflammation?
after local inflammatory response
Vasodilation. More gaps between the cells of the blood vessel too. Becomes more permeable. This enables immune cells to be recruited efficiently to the site of infection. the first ones will be neutrophils and monocytes. (remember they are phagocytic)
What is the third step of inflammation?
after vasodilation and immune cells have been recruited
Oedema. Plasma and proteins accumulate because of the leaky blood vessel etc.
Swelling.
