The Immune System - Detecting Infection Flashcards
What is the definition of an intra-host microorganism?
a microorganism that the immune system ignores at one anatomical site but will respond to them at another
eg commensal bacteria in the gut which spread to other areas
What is the definition of an inter-host microorganism
microorganisms that can cross species
may not produce disease in one hosts but can in another
eg ebola is asymptomatic in fruit bats but can be fatal in humans
What are zoonotic infections?
infections that spread from animal to human (zoonoses) and vice versa (reverse zoonoses)
What is CFR?
Case Fatality Rates
estimated fatality rate of a pathogen
What is the Hygiene Hypothesis?
our immune system expects to be challenged and may become dysregulated if not exposed to microorganisms and cause disease eg asthma
How does HIV work?
deletes helper T cells
What is SCID?
Severe-COmbined Immunodeficiency
individuals are born with a defect in their T and B cells and have severely impaired immune systems
What are macrophages?
part of innate immunity
engulf bacteria via phagocytosis
talk to T cells at infection site and activate them
example of a sentinel cell
do not migrate
What are eosinophils?
part of innate immunity
secrete cytotoxic granules
What are NK cells?
part of innate immunity
kill infected cells
recruits cytokines which activate macrophages
What are helper T cells?
part of adaptive immunity
- co-ordinate immune responses
- talk to other cells via cytokines
- amplify innate immunity
What are regulatory T cells (Treg)?
part of adaptive immunity
- turn-off immune response
What are cytotoxic T cells (CTL)?
part of adaptive immunity
kill infected cell
What are B cells?
part of adaptive immunity
produce antibodies that:
- neutralise pathogen molecules
- mark pathogens for destruction
What are cytokines?
chemical messengers
target any cell with relevant receptor
can act locally or systemically
Why do cytokines cause a fever?
immune cells work better at higher temperatures and most microbes dont
Where are immune responses coordinated?
lymph nodes and spleen
focal points for immune cell communication
play a v important role in initiating adaptive immunity responses
What is the role of the complement system?
they lyse pathogens (punch holes in them)
recruit immune cells
label microbes for phagocytosis
What is the Alternative Pathway of the immune system?
C3 is always being cleaved into C3a or C3b
C3b binds to amino and hydroxyl groups on microbes, however, amino and hydroxyl groups also on host cells so our cells have defences against C3b
What is the Lectin Pathway of the complement system?
mannose is a carbohydrate found on surface of many pathogens
mannose binding lectin (MBL) detects mannose on pathogen which recruits C3b
What are PAMPs?
Pathogen Associated Molecular Patterns eg mannose
conserved molecules which are shared by various classes of microbes
What are PRRs?
proteins that recognise PAMPs eg mannose binding lectin
innate immune cells have PRRs allowing them to detect danger
What are dendritic cells?
specialised macrophages that specialise in talking with T cells
migrate from infection site to lymph nodes
don’t kill
sample environmental antigens
take AG to lymph nodes to talk w T cells
What are DAMPs and what do they indicate?
Damage-Associated Molecular Patterns
- potential break in barrier
- pathogen that is causing damage whilst invading
How do some pathogens evade immune recognition?
- modification of PAMPs eg salmonella can modify lipopolysaccharide outer layer
- inhibition of PRR signalling pathways eg ebola
- mutate antigen to evade antibodies eg HIV
What causes inflammation and what does it do?
caused by pro-inflammatory cytokines eg TNF-alpha
- recruit immune cells to infection site
- activate immune cells
- production of Acute Phase Proteins
- tissue redness/swelling/heat
What are neutrophils?
- perform phagocytosis of pathogens
- release destructive chemicals
- recruited to site of inflammation
only produced when needed and apoptose shortly thereafter (2 days)
How is inflammation resolved?
neutrophils are short lived and apoptose
macrophages apoptose or revert back to resting state
apoptose or revert back to resting state
What causes sepsis?
if infection is systemic or can’t be cleared
- inhibits heart contractions
- fluid leaks into tissues
- increased blood clotting
- cachexia (muscle wasting)
-which leads to-
- reduced blood pressure
-which leads to-
- septic shock
What are some advantages to PAMPs and PRRs?
- recognising essential evolutionary PAMPs makes it difficult for pathogens to evade detection
- a small number of PRRs can be used to detect a wide range of microbes
- receptors are germ line encoded and don’t need modification, allows quick response
- one cell can express multiple different PRRs
What is an antigen?
molecule recognised by adaptive immune cells
will bind either a T receptor or antibody (B cell receptor) or both
What is an epitope?
precise part of antigen recognised by T or B cell receptor, antigen can have multiple epitopes
What is a paratope?
the part of antibody or T cell receptor that binds the epitope
What are properties of a T cell antigen receptor?
- only membrane bound, called TCR (T cell receptor)
What are properties of B cell antigen receptors?
- membrane bound and secreted
- secreted from called antibody (ab) or immunoglobulin (Ig)
- membrane form called B cell receptor (BCR) or surface immunoglobulin (SIg)
How do T cell receptors recognise antigens?
antigens are presented to T cells by professional Antigen Presenting Cells
recognise protein antigens using 8-25 linear peptide amino acid sequence
allows extreme variation
How do B cell receptors recognise antigens?
recognise anything organic
epitope of antigen can be a linear sequence (continuous or linear) or can cross loops (discontinuous)
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What is the Fc region of an antibody?
region that interacts w the innate system eg complement
What are some differences between T cell receptors and B cell receptors?
T cell receptors are only membrane bound while B cell receptors can be secreted (antibodies)
T cell receptor has one Ag binding site, antibodies have 2
By what process are Ag receptors made?
somatic recombination
where different sections of the V D and J genes are combined
What is junctional diversity?
occurs after somatic recombination
between borders of genes
gives much more diversity to receptors
1. imprecise alignment of V, D and J genes
2. addition of bases
3. deletion of bases (unpaired nucleotides removed)
4. sequence aligns
5. gaps filled in
What is a consequence of junctional diversity?
most receptors die during this process as they are not viable, so wastes resources
however, it allows much more variation
2x chromosome 14 are inherited (one from each parent) which contain the V, D, and J genes. Why is this significant?
2 sets of V, D and J genes so 2 chances to make a productive rearrangement of each chain
allows for another layer of variation
What occurs during clonal expansion of T/B cells?
when they see an antigen they divide, meaning all daughter cells will have identical Ag specificity
What is a downside to the extreme specificity of antibodies?
microbes can evade easily if they mutate or alter their morphology eg HIV, trypanosomes
What is central tolerance?
there are mechanisms present to remove T and B cells capable of recognising self antigens before they are released
What is one downside to central tolerance?
does not remove T cells that recognise innocuous antigens such as in food
Where are self-reactive T and B cells removed?
self reactive T cells removed in thymus
self reactive B cells removed in bone marrow
What are APCs?
Antigen Presenting Cells
present antigens to T cells
eg dendritic cells (DC), macrophages, B cells
What do APCs activate?
naive T and B cells
What are the MHCs I and II?
Major Histocompatibility Complex I and II
MHC I - present intracellular Ag, found on all nucleated cells
MHC II - present extra cellular Ag, only found on professional APC
Why do T cell receptors bind with the peptide which is bound to the MHC?
so the T cell can only recognise the peptide when combined with MHC
MHC genes are codominantly expressed. What does this mean?
the MHC alleles inherited from both parents are expressed equally
What is an MHC haplotype?
the set of MHC alleles present on each chromosome
extremely unlikely that two individuals in a population have exactly the same, MHC genes are highly polymorphic
What role does the MHC haplotype have in organ donation?
foreign MHC molecules activate recipient T cells that then kill the organ
need to match MHC cells as much as possible - tissue typing
What is the sequence of events in the case of an intra-cellular Ag presented by MHC I?
cytotoxic T cells/lymphocytes (CTL)
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only see Ag presented by MHC class I as they both express CD8 on surface
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killed cells infected with intracellular pathogen
What is the sequence of events in the case of an extra-cellular Ag presented by MHC II?
T helper (Th) cells or Regulatory T (Treg) cells
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only see Ag presented by MHC II as they both express CD4 on surface
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coordinate immune responses
