Innate Immunology Flashcards
immune cells
leukocytes
where are immune cells produced
bone marrow
where are immune chemicals produced
by immune cells or damaged cells
what is the immune system
collection of cells and chemicals which work together to protect us from disease
innate immunity
non-specific
fast
adaptive immunity
specific to a pathogen
slower
humoral immunity
proteins dissolved in serum, plasma and tissue fluid
complement in innate
antibodies in adaptive
cellular immunity
cells which have mechanisms to identify and destroy foreign organisms
pathway to immune memory
anatomical barriers
innate humoral (soluble) factors
innate immune cells
adaptive immune cells and antibody
immune memory
cells involved in innate immunity
epithelial barriers
complement
phagocytes
natural killer cells
dendritic cells
cells involved in innate immunity
B cells
T cells
effector T cells
memory t and B cells
where can microbes enter our bodies
respiratory tract
skin
eyes
gastrointestinal tract
genitourinary tract
entrances and surfaces have physical barriers
physical barriers to protect entrances to the body
hair
wax
membranes
specialist epithelial cells
air movement
mucus
tears
what do tears contain
enzymes such as lysozymes
flow of air and fluid q
reduces the chance of micro-organisms attaching
enzymes
secretions contain antimicrobial enzymes
low pH
restricts which pathogens can survive if ingested
defensins
antimicrobial peptides disrupt cell membranes and virus envelopes
normal microbiota
outcompete potentially harmful organisms
epithelial cell tight junctions
restrict movement of microorganisms deep into tissue
goblet cells
produce mucus which acts as a sticky barrier
ciliated cells
move mucus along to flush out pathogens
tissue resident immune cells
recognise, Engulf/phagocytose and kill pathogens
what happens if the barriers are breached
cells are damaged and exposed to the environment
a bump or cut can cause damage and initiate an inflammatory response even without the presence of a pathogen
what is inflammation
part of the body response to damage as a way to protect itself
usually localised to the site of damage and involves the immune system
progresses through a series of stages until it is resolved and tissue returns to normal
cardinal signs of inflammation
rubor
calor
tumor
dolor
functio laesa
rubor
redness
calor
heat
tumor
swelling
dolor
pain
functio laesa
loss of function
receptor:ligand interactions
way cells give and receive information
receptor binding by its ligand causes signals to be passed through cell to change expression of genes
ligand
often a cytokine
e.g. interleukin (IL)
receptor
often a cluster of differentiation (CD)
cardinal signs of acute inflammation can be caused by what
histamine
histamine
released from innate immune cells (mast cells and basophils) and platelets
when histamine binds to histamine receptors what occurs
vasodilation and increased blood flow
exudation of fluid from blood into tissue
when no microbes are present
fragments of cells are released through damage
contain damage-associated molecular pattern molecules
what do DAMPs include
DNA
RNA
proteins
from within the nucleus
bind to receptors to trigger inflammation
what do DAMPs bind to
receptors to activate cells
induce inflammatory cytokine release and trigger inflammation
when microbes enter the wound
release chemicals which are viewed as foreign
can trigger inflammation
some are pathogenic and can grow within tissue, causes more damage to ells
some can enter cells living inside of them
two classifications of pathogens
intracellular
extracellular
examples of extracellular pathogens
bacteria
viruses
fungi
parasites
intracellular pathogens
viral replication and assembly
extracellular pathogens are tackled by what
humoral parts of immune system
also cells
soluble factors
antibodies
actue phase proteins (C reative protein)
complement
acute phase proteins
released from liver
serum amyloid protein
C-reactive protein
fibrinogen
mannose-binding lectin
SP-A
SP-D
function of serum amyloid protein
function of C reactive protein
function of fibrinogen
function of mannose-binding lectin
function of SP-A
function of SP-D
complement pathway
happens instantly when epithelial barriers are breached
triggered in 3 ways but lead to 3 same outcomes
3 outcomes of the complement pathway
opsonisation/phagocytosis
chemotaxis
membrane attack complex
opsonisation/phagocytosis
phagocytes recognise C3b through complement receptor and “eat” microbe
chemotaxis
C3a and C5a recruit phagocytic cells and promote inflammation
membrane attack complex
C3b sets off a pathway regulating in disruption of the cell membrane
3 pathways of complement pathway
alternative
classical
lectin
alternative pathway
spontaneous
binding of C3b to microbe
classical pathway
antibody activated
lectin pathway
recognise sugars on pathogens
DAMPs
damage associated molecular patterns
bind receptors to make innate immune cells aware of tissue damage
PAMPs
pathogen associated molecular patterns
bind receptors to make innate immune cells aware of infection
what do PAMPs and DAMPs bind to
pattern recognition receptors PRRs
common pathogen PAMPs
RNA viruses
DNA viruses
gram positive bacteria
gram negative bacteria
fungi
protists
families of PRR
external: toll like receptors, phagocytic receptors
internal:
cytoplasmic- NOD and RIG-like receptors
endosomal- toll like receptors
phagocytic receptor
induce uptake of pathogens into endosomes and killing of the pathogen
phagocytic receptor examples
complement receptor
scavenger receptor
mannose receptor
Fc receptor
C-type lectin receptor
complement receptor
recognises C3b complement protein bound to pathogen surfaces
what does TLR4 bind t o
LPS
what does TLR5 bind to
flagellin
what does TLR1 2 and 6 bind to
lipoproteins
what does TLR9 bind to
CpG DNA
what do TLR7 and 8 bind to
ssRNA
what does TLR3 bind to
dsRNA
scavenger receptor
recognises lipoproteins in bacterial cell walls
mannose receptor
recognise mannose on the surface of some bacteria
Fc receptors
recognises antibody bound to pathogen surfaces
C-type lectin receptors
recognises beta-glucan sugar in fungal cell walls
TLR signalling
- PAMP binds to PRR, sends signal to nucleus
- adaptors containing TIR domains (MyD88) transmit the message in the cytoplasm
- protein transcription factor called NFkB assembles and binds to DNA
- Instructs the cells to produce new proteins which initiate the next stage of the immune response
how do immune cells communicate
cell to cell contact
release of chemicals (cytokines)
what can cytokines do
inform cells there is danger, turn on inflammation which is a pro inflammatory cytokines
inform cells there is no danger, keeps cells inactive and turn off inflammation which are anti-inflammatory cytokines
examples of proinflammatory cytokines
tumour necrosis factor TNFa
interleukin 6 IL-6
interleukin 1beta
examples of anti-inflammatory cytokines
Interleukin 10 IL-10
transforming growth factor beta
effects of pro-inflammatory cytokines on the local tissue
tight functions open
more fluid exit
diapedesis (monocyte squeeze through interstitial space)
antimicrobial chemicals exit
phagocytes function
ingest microbes by phagocytosis or pinocytosis
pinocytosis
take in fluids and some solutes
how do macrophages kill the pathogen
- pathogen recognised by PRR, macrophages are activated and phagocytosis is induced
- pathogen is internalised in a phagosome, fuses with lysosome
- activated macrophages make pro-inflammatory cytokines which attract and activate other immune cells
- pathogen is killed by oxidative burst and digested enzymes
2 and 3 occur at the same time
what does a lysosome contain
antimicrobial peptides,ezymes and reactive oxygen species
where will immune cells move to to find the pathogen
to where the chemokine concentration is the highest
what do neutrophils do when they arrive
phagocytosis
apoptosis
netosis
netosis
what occurs if the pathogen isn’t cleared
continued release of pro-inflammatory cytokines can be damaging and have systemic effects
damaged blood vessels produce bradykinin which increase vascular permeability, stimulate nerves to cause pain
inflammation may become chronic
intracellular pathogens
can’t be tackled by humeral parts of the immune system
relies on a cellular response
how do cells recognise the intracellular microbes
DAMPs recognised by PRR
PAMPS
infected cells hold up flags to show immune system they’re infected
pathogens recognised outside of cells at certain times in their life cycle
intracellular bacteria
extracellular bacteria recognised by receptors and phagocytosed by cells
phagocyte will try and kill bacteria by acdification and enzymatic digestion
some bacteria thrive in acidic conditions and survive
others can penetrate the cell from outside or escape from phagosomes in cytoplasm
when in cytoplasm bacterial products can be recognised by intracellular PRRS
cytokines released to activate NK cells and adaptive immune cells
what are the most common intracellular pathogens
viruses
what is the difference between bacterial and viral endosomal TLR signalling
in viruses the interferon response factors IRF assemble and bind to DNA
interferons that lead to antiviral response
IRF 3
interferon beta
type 1 interferons
type 1 interferons
INFa and INF beta
increase viral defences and reduce viral replication cytokines make by infected cells
preventing the virus from replicating itself
type 1 interferon antiviral response
IFN alpha and beta bind to IFNa receptor
outcome is activation of genes which degrade viral RNA and halt protein synthesis needed to make viral capsules
also activate natural killer cells
sacrificing the infected cells
natural killer cells kill the virus infected cells and cancer cells by apoptosis
virally infected cells and cancer cells are very similar and killed by the same mechanisms
how do NK cells kill
IFNy and TNFa activate other immune cells
granules containing perforin and granzyme lead to apoptosis
how do NK cells know which cells to kill when none are foreign
recognsie altered self
molecules are up or down-regulated when cells are damaged
cancerous and virally infected cells express less inhibitory and more activating ligands
