IMI 1: Sensing Damage, Protecting Our Bodies Flashcards
Observe the learning outcomes for this session
T cells, B cells and NK cells are all lymphoid cells
True or false?
What is the other major class?
- true
- the other major class includes myeloid cells
- such as macrophages (and monocyte which are the precursors), mast cells, dendritic cells, neutrophils, basophils and eosinophils
Only B cells are mediators of immune memory
- false
- both B and T cells mediate immune memory
- they are produced at the same time as effector cells at the time of the first infection, but do not participate in fighting the original infection
Without T cells we would not survive in a non-sterile environment
True or false?
- true
- individuals without T cells cannot fight common infections and often die early in infancy
What do NK cells do?
- involved in innate immunity
- they are large cytotoxic lymphocytes that patrol the blood for virally-infected or damaged cells, which they are able to recognise despite lacking variable receptors like the ones found in B- or T-cells
Cells of the innate immune system detect but cannot recognise what sort of pathogen they encounter
True or false?
- false
- cells of the immune system can both detect pathogens, and recognise certain characteristics of the pathogen so that the appropriate type of immune response is mounted
Observe the diagram of some cytokine receptor complexes, their downstream targets and biological functions
What are cytokines?
Why does γC mutation affect the immune system?
- Cytokines are small polypeptides that are used as messengers in the immune system
- Several cytokines utilise receptor complexes that share the common cytokine receptor γ-chain (γC)
- these cytokines have very different biological functions and it is, therefore, unsurprising that a mutation on the γC can lead to such a catastrophic failure of the immune system
Look at the microbes’ actions below and try to match them with the immune responses that each is likely to elicit
What is the first line of defence in our bodies provided by?
- it is provided by a number of physical barriers
Observe this diagram of the relative sizes of different microbes
Give examples of two physical barriers and compare them
- skin:
- acts as a wall or fence
- 2m2 of body surface
- mucosal membranes:
- 400m2
- make up our digestive, respiratory and reproductive tracts
- mucus helps trap pathogens, making it an additional physical barrier
Describe how secretions, such as mucus, can act as physical barriers
- can neutralise pathogens from:
- their pH
- the production of digestive enzymes
- examples:
- tears in our eyes: have lysozymes with powerful digestive abilities
- stomach or vaginal secretions with extremely low pH
- wax in the ears: thought to have limited anti-bacterial properties but is critical to lubricate and protect the ear canal
Summarise the physical barriers of the body has and their mechanical, chemical and microbiological features
What is the second line of defence against an infection agent after physical barriers are compromised?
Briefly describe it
- the innate immune system
- lacks the specificity of the adaptive immune system
- broad actions
- quick: typically starting minutes after an infection
- can last for days
What is the third line of defence?
Briefly describe it
- the adaptive immune system
- can start within hours or days after the start of infection
- the body will not deploy it unless it is absolutely necessary
- involves an array of new cells and proteins
- so costs a lot of metabolic energy
What are the very first cells pathogens usually encounter after getting through physical barriers?
Describe their functions
- tissue resident macrophages
- these are scavenger cells present in all tissues
- they recognise pathogens
- also recognise old and damaged cells
- gobbling up cells in phagocytosis
- can distinguish harmless vs harmful agents
What does the immune system need to be able to discriminate between?
- something that is part of the body and something foreign: ‘self vs non-self’
- and between something that is harmless and harmful
- otherwise it could lead to immune diseases
How can macrophages distinguish between harmless and harmful agents?
- pathogens have structural features that are essential for their survival and these are not usually found in our cells
- called pathogen-associated molecular patterns (PAMPs)
- damaged cells release intracellular molecules called damage-associated molecular patterns (DAMPs)
- both are able to activate the innate immune system
Do T and B cells react to self-antigens and mount an immune response?
- they do react to self-antigens but they will not activate an immune response
- when an antigen-presenting cell (APC), e.g. a macrophage or dendritic cell, sees a self-antigen, it will present it to a T-cell
- the T-cell will ‘see’ the antigen but will know better and will not mount an immune response
- if the APC sees a foreign antigen on any given pathogen it will activate an immune response
What two signals dictated T-cell activation?
- The antigen presented by major histocompatability molecules (MHC)
- Molecules on the APC called CD80 (or B7-1) and CD86 (B7-2)
- these are receptors in the immunoglobin superfamily
- so their structure comprises domains similar to those in antibody molecules
How are molecules on the APC triggered?
- by Pattern Recognition Receptors
- Janeway hypothesised the existence of a new family of receptors that are evolutionarily ancient and present in both vertebrate and invertebrate organisms
- these would directly recognise common microbial patterns in pathogens (the PAMPs) and control the activation of signal 2 (CD80/CD86)
- these receptors would be called Pattern Recognition Receptors
- the first PRR is now known as Toll-like receptor 4 (TLR4)
- in invertebrates, PRR does not just control the innate arm of the immune system but they can also modulate adaptive immune responses
What do PAMPs look like?
- bacterial proteins such as flagellin (important for bacteria to swim using flagellum)
- sugar or lipid structures not found in verterbrates
- nucleic acids (ssRNA/ssDNA/dsRNA/dsDNA) present in forms and/or locations that are not usually found in healthy vertebrate cells
What are DAMPs?
- DAMPs are molecules that are produced by our cells and released upon damage or cell death
- they can still be released from damaged cells following infection, but they are often released from cells that have been damaged by ‘sterile stimuli’
- e.g. by trauma, radiation, burns or chemical toxins
Observe some examples of different PAMPs and DAMPs
Name some PAMPs from bacteria, viruses, parasites and yeast
- bacteria:
- LTA
- PGN
- lipoproteins
- DNA
- flagellin
- LPS
- virus:
- ssRNA
- dsRNA
- DNA
- coat proteins
- parasite:
- Glycosylphosphatidylinisotol (gpi)-anchored proteins
- yeast:
- zymosan
Describe some key differences between innate and adaptive immune systems
- the speed with which they respond to damage or pathogens
- each innate immune cell expresses several different innate receptors capable of recognising different types of pathogens
- the expression of these innate receptors is not restricted to innate immune cells and many are found in other cell types
- e.g. epithelial cells, keratinocytes or even B and T cells
- some innate receptors are not expressed on the cell surface but rather on internal cell membranes
- e.g. those of the endosomal system or in soluble parts of the cytosol