Immune system Flashcards
1
Q
MALT
A
- The lymphoid tissue found in submucosal sites around the body
- It is populated by lymphocytes (B cells, T cells and macrophages)
- M cells are also present, which sample antigen from the lumen and deliver it to the lymphoid tissue
2
Q
GALT
A
- Gut associated lymphoid tissue
- Peyer’s patches are a component of GALT, found in the lining of the small intestine
3
Q
mannose receptor
A
- It is a pattern recognition receptor present on the surface of macrophages
- It recognises terminal mannose attached to glycans present on the surface of some microorganisms, that play a role in the innate and adaptive immune response
- A number of pathogenic organisms including C.albicans display glycans on their surface with terminal mannose residues that are recognised by the mannose receptors
- Upon recognition, the receptor internalises the bound pathogen and transports it to the lysozymes for degradation via the phagocytic pathway
- They mediate phagocytosis but do not initiate the inflammatory response
4
Q
Tuberculosis
A
- It is taken up by phagocytosis mediated by mannose receptors which internalise the pathogen once it is recognised
- This facilitates infection by mycobacterium tuberculosis
- The bacteria multiply inside the macrophage, preventing formation of the phagolysosome to avoid degradation
- It is latent and can manifest itself later
5
Q
Pattern recognition receptors
A
- They are key in innate immune response
- They are proteins expressed by cells of the immune system to identify 2 classes of molecules: pathogen associated molecular patterns (PAMPs), which are associated with microbial pathogens and damage associated molecular patterns (DAMPs), which are associated with components of host’s cells that are released during cell damage
6
Q
Types of PRRs
A
- Receptor kinases
- Toll-like receptors, they trigger the secretion of cytokines
- C-type lectin receptors, mannose receptors
7
Q
Toll like receptors
A
- A type of PRR
- Upon activation, TLRs recruit adaptor proteins in the cytosol of the immune cell
- The adaptor proteins initiate downstream cascade that results in the inflammatory response
- They span the membrane
8
Q
NLR
A
- A type of PRR
- They span the cytoplasm
- If a micorbe evades the phagocytes it will probably be picked up by the NLRs
9
Q
PAMPs
A
- Molecules associated with groups of pathogens that are recognised by cells of the innate immune system
- They are recognised by PRRs (including TLRs)
- Different molecules can serve as PAMPs including glycans
- PAMPs activate innate immune responses
- Bacterial LPS, flagellin, lipoteichoic acid peptidoglycan are considered to be PAMPs
10
Q
How to bacteria counteract recognition and killing?
A
- Escape from vacuole into cytoplasm by action of Listerolysin from Listeria monocytogenes
- It releases a cytolysin, it is cholesterol dependent, it does not attack its own membrane as it does not have cholesterol
- It lyses the cell membrane
- The cell membrane of eukaryotic cells has cholesterol
11
Q
Listeria
A
EXTRACELLULAR
- Whilst it is extracellular it can secrete listeriolysin (LLO), which can damage the membrane
INTRACELLULAR
- If listeria is taken up into a phagosome, it lowers its pH which produces more LLO
- The phagosome ruptures, which allows the cell to become intracellular
- It spreads
- It turns on other genes that recruit actin tails that push it along
- It can push through and infect another cell, it is now in a double membrane bound vacuole
- It produces another phospholipase that breaks down the double membrane
12
Q
Salmonella
A
- Salmonella use the TLRs to ensure they get a protective niche and then secrete proteins into the cell to prevent further damage
- Salmonella want to be taken up into vacuoles
- The TLRs recognise components on the surface of Salmonella
- It leads to signalling which lowers the pH of the vacuole
- Salmonella has engineered itself to hijack the TLRs to enable it to survive
- When it is in a Salmonella containing vacuole, it secretes effectors proteins (spi) which prevent fusion with the lysosome
- The effectors are only secreted at this pH
- In macrophages that do not have TLRs, the pH is not lowered, so no effector proteins are released and the vacuole fuses with a lysosyme
13
Q
Shigella
- induces cell death
- uses a type III secretion system to produce the effectors that help it escape from macrophages
- Intracellular spread to neighbouring enterocytes
A
- The shigella goes in through the M cells into a macrophage
- Shigella can escape the macrophage and travel to enterocytes in the gut through intracellular spread
- In order to escape the macrophage it must induce cell death in the macrophage by secreting T3SS effectors
- NLRs are going to recognise parts of the cell that are in the cytoplasm
- By putting these T3SS in the cytoplasm, the NLRs recognise them and tell the cell to rupture
- It allows shigella to escape and enter the neighbouring cells
14
Q
What is autophagy
A
- An intracellular degradation system that delivers cytoplasmic constituents to the lysosome
- It consists of several steps:
- Sequestration
- Transport to lysozymes
- Degradation
- Utilisation of degradation products
- Proteins ready to be degraded are tagged by ubiquitin
- It is benfeifical in clearning infectious diseases
15
Q
Autophagy process (a fall back mechanism to phagocytosis)
A
- Autophagy induction
- A cup shaped membrane sac called the isolation membrane starts to form
- The isolation membrane elongates and closes to form a double membrane vesicle called the autophagosome
- The outer membrane of the autophagosome fuses with a lysosome to form an autolysosome, leading to the degradation of the cytoplasmic contents inside the autophagosome
- The genes responsible for autophagy (ATG) genes
- The autophagosome can engulf bacteria if they are in the cytoplasm (xenophagy)
- Even before lysis of the vacuole membrane, the isolation membrane can wrap around it
- If the bacteria are able to escape the phagosome, the isolation membrane can wrap around it in a autophagosome and give it to a phagosome
