Immunity system Vs Pathogens L16 Flashcards
what is a microbiome
microbial communities of tissues (skin, oral mucosa, gastrointestinal tract)
effect of microbiome
cause no damage to host, can perform important functions
are different microbiomes recognised
Immune system must be able to recognise difference
what cells are humans mainly made of
more prokaryotic than eukaryotic cells
when do commensals become pathogens
when in the wrong location
what is the difference between pathogens and commensals
whether they cause damage
what is the distribution of PRRs
have more effect on pathogens and less effect on commensals
what are the cell surface receptors
toll-like receptors
what are the pathogenic factors
virulence factors so they can attach/invade (NLR’s)
what are indigenous microbiota like
non-invasive
what do commensals interact with
only apical surface TLRs
what does the microbiome do
evolved to lessen inflammation
what is on the apical surface
Microbiome on apical surface of villi – microvilli
what happens when invasion occurs in mucosa
invading come into contact with cytosolic NLR’s
what are the TLRs like on the apical surface compared to basolateral
TLR’s on apical surface are less responsive than ones on host basolateral side of epithelial cells
where do commensals interact with
less responsive apical side
how is inflammation lessened
by dampening epithelial cell TLR signalling
what is the mucosal immune system
area of an intestinal villus
mucosal immunity functions independently of regional lymph nodes to control inflammation induced by microbiota or to stimulate
what are IECs
intestinal epithelial cells
what respiration do bacteria have
anaerobic and aerobic
what shape are bacteria
cocci and bacilli
what gram are bacteria
gram-positive
gram-negative
what is a capsule
protects against phagocytosis
what do bacteria contain
toxins
what are flagella for
attachment
motility
injection needle
how are flagella used as injection needle
allows bacterial factors to come into the host cell through end of the flagella
what is bacteria attachment for
help attach bacteria to the surface
how does phagocytosis work against bacteria
Host immune cell recognises the bacteria, engulfs it and breaks it down in phagolysosome
how does bacteria counter phagocytosis
covers self in capsule so isn’t recognised
what do antibodies do to help against bacteria
immune system has an antibody that recognises the capsule so can be taken up by macrophage/neutrophil
prevent toxins entering cell
what does the complement assist
phagocytosis and enhances inflammation
what do helper T cells activate
activate macrophage to kill intracellular bacteria in MHC recognition
what do cytotoxic T cells kill
kill infected host cells and activated macrophages
how does bacteria escape phagosome
using hemolysins
how does phagosome-lysosome fusion become inhibited
secreting proteins into host cytosol, which interfere with the signalling pathways that cause the fusion
what does bacterial evasion induce
Induce production of anti-inflammatory cytokines
what is inhibited by bacterial evasion
Inhibit signal transduction of proinflammatory cytokines
what is expressed in bacterial evasion
Express proteins that can cause apoptosis of T cells
what happens after pathogen escapes phagosome
the host cells can form an autophagosome
what is the immune system like
highly regulated mechanism
what is delivered in immune system
intracellular pathogen to lysosomes
what is one of the most common causes of gastroenteritis in the world
Campylobacter jejuni
what is Campylobacter jejuni characterised by
abdominal pain, fever and diarrhoea
what is the flagella of Campylobacter jejuni important for
colonisation
what happens if Campylobacter jejuni
invasion
Invasion of host cells activates production of cytokines
what is sialylation
addition of sialic acid groups onto oligosaccharides
what is LOS
Lipooligosaccharides
what can flagella be used as in Campylobacter jejuni
can be used to as an apparatus to secrete proteins such as Campylobacter invasion antigen (cia)
what is GBS
Guillain-Barré Syndrome
what does LOS do
mimic structure of human gangliosides (molecular mimicry)
what can antibodies against the C. jejuni LOS lead to
autoimmune response, resulting in Guillain-Barré Syndrome
is GBS fatal
can be fatal
what are the symptoms of GBS
vary from mild muscle weakness to potential paralysis
what is CDI
Clostridium difficile infection
what does clostridium difficile toxins cause
cause severe inflammatory reaction leading to microulcerations
what are the two main toxins of Clostridium difficile
TcdA and TcdB
what are the toxins like that clostridium difficile secrete
Large secreted proteins
what do clostridium difficile toxins interact with
epithelium cause inflammatory response
what is SLP
surface layer proteins
what does TcdA cause
apoptosis in monocytes
what is SLP like
highly variable across different strains, may have role on evasion of host immune response
where are defensins secreted
by specialist cells in intestinal epithelia, can reduce tissue damage due to toxins
what do defensins do
reduce inflammatory cytokine production, thereby regulating the immune response
what is staph aureus
Common human pathogen; component of the commensal flora and major cause of invasive infection
what us staph aureus responsible for
majority of skin and soft tissue infections in humans
what can staph aurea cause
invasive and life-threatening infections
what is the problem with the treatment of staph aureus
complicated by the emergence of methicillin-resistant S. aureus (MRSA) strains, which are becoming increasingly resistant to multiple antibiotics
what does staph aureus interfere with
innate immune response
what does staph aureus express
wide variety of virulence factors
Expresses SpA protein
what does SpA protein that staph aureus expresses cause
binds to antibodies and prevents opsonophagocytic killing
what is needed to clear staph aureus
neutrophils
what are NETs
neutrophil extracellular traps
what are NETs made of
comprised of DNA and antimicrobial peptides
what do antibodies do to viruses
Antibody blocks ability of virus to invade cells
how do antibodies prevent virus entry into cell
Antibody recognizes the PAMPs and virus cant get into the cell
what happens to cell surface if infected
MHC class 1, if infected can express peptides on surface of that pathogen
what happens if MHC class 1 on cell surface
Cytotoxic lymphocytes can recognise and kill the pathogen
if no expression of MHC class 1 what happens
natural killer cells compensate, recognise no MHC class 1 on surface so has to kill cell
what do viruses do to prevent MHC class 1 on surface
avoid NK cells recognition viruses can display a decoy MHC I-like molecule on cell surface (human cytomegalovirus)
what do viruses do to down regulate MHC
viruses make proteins that down regulate MHC class I molecules on infected host cell surface
what do tetherin act against
enveloped viruses
where does tetherin bind to
Binds to the surface glycoproteins
what do tetherin act against
Act against a wide range of viruses (retroviruses; ebolaviruses)
what does tetherin prevent
release of the virus while budding
Retained particles are targeted for degradation
what does tetherin trigger
inflammation
what is CMV
cytomegalovirus
what is Vpu
viral protein U
how is tetherin degraded
HIV expresses Vpu, which triggers degradation of Tetherin
what is tetherin co-opted for
entry pathway of CMV
what does ebola glycoprotein inhibit
inhibits Tetherin association with a viral surface protein
what can yeast be
filament
yeast
what does the immune system recognise in fungi
cell wall
what is fungi part of
commensal flora
what can fungi cause
infection in absence of an effective immune response
what do dendritic cells do to fungi
phagocytose fungal cells
what peptides are expressed in relation to fungi
MHC class 2
what is required for effective immune response against C. albicans
Both CD4 and CD8 T cell
how are T cells activated
Need the peptides to be presented by MHC class II on dendritic cells to get activation of T cell response
effect of CD8 T cells on fungi
CD8 T cells been shown to inhibit fungal cell growth
what can help clear fungi infection
innate immune system
what are the main four divisions of protozoa
flagellates
amoebas
ciliates
sporozoa
what causes malaria
Plasmodium falciparum
where do plasmodium falciparum replicate
can only replicate in erythrocyte
effect of antibodies on Plasmodium falciparum
can inhibit uptake into erythrocytes and hepatocytes
how does erythrocytes differ
Erythrocytes naturally don’t have MHC class I on surface (un-nucleated cells)
effect of Plasmodium falciparum
down regulate T helper cytokines
what is virulence mainly associated with
immune evasion
what are polymorphic proteins
immunologically distinct
what does Plasmodium falciparum cause
highly polymorphic surface proteins
what is there a lack of in Plasmodium falciparum
Lack of MHC class I on RBC’s protect from CD8 T cells
What are the immune attack
Opsonising antibodies
Complement deposition
Invasion blocking antibodies
What does opsonising antibodies lead to
Phagocytosis
What does complement deposition lead to
Phagocytosis
Lysis
What are the immune evasion strategies
Varying sequence while maintaining function
Redundancy in multi-gene families
Reduced antigenicity
what is trypanosomiasis
sleeping sickness
what is trypanosma brucei like
extracellular
what protects against trypanosma brucei
Variant surface proteins to protect from immune system
what can dampen inflammatory response
Saliva from infected tsetse fly
what are helminths
Worms that live like parasites
what are helminths like
Mostly extracellular, move to organs
what is the immune system problem with helminths
cannot phagocytose them
what are the symptoms of Schistosoma mansoni
Diarrhoea, blood in faeces, organ damage
what is Schistosoma mansoni associated with
chronic (long term) disease
what does Schistosoma mansoni have to protect against
both eggs and adult worms
what does Schistosoma mansoni cause
Venous blood release of eggs into environment
Granuloma formation to contain eggs
