IMI2: the innate immune system Flashcards
what are the Ian 3 steps of the innate immune system?
detect, deflect and destroy
what type of cells are phagocytes?
neutrophils
macrophages
how any types of macrophages are there? what are they and what do they do?
2 types:
- free types –> patrol tissues looking for creepers
- fixed types –> devours anything sus that passes by using cytoplasmic extensions
how does NK cell kill our own cells?
in healthy cells –> MHC1
if cell is infected –> no MHC1 ==> NK cells detect that, poke the infected cell and triggers apoptosis
how do immune cells know where to look in the first place?
- mast cells in connective tissues send out histamine which causes vasodilation that result in redness and heat at the site of infection and causes an increase in the permeability of blood vessels that result in swelling
- neutrophils are triggered when injured cells release chemicals that begin leukocytosis
- monocytes transform into macrophages and they let loose pyrogen chemicals that tap the hypothalamus and raise your body’s thermostat
what is the complement system?
innate immune suste that enhances or complements the ability of phagocytic cells and antibodies to remove microbes and damaged cells from our bodies
does the complement system contribute to the adaptive immune system? if yes how?
yes
it increases the presentation f bacterial fragments to T cells
what are the 3 key roles of the complement system?
- tag or opsonise foreign surfaces
- puncture the membranes of foreign pathogens/cells leading to cell lysis
- signal to the cellular immune system where there is a foreign invader and trigger the recruitment of cells
how many different types of proteins are part of the complement system?
30 different types of proteins
where are the proteins of the complement system?
complement proteins float around in a sort-of passive mode
example of complement attack
- C3 breaks into C3a and C3b
- C3a floods away from the site of battle –> passive immune cells notice C3a, get activated and follow the protein tracks to the site of infection
- C3b dings a target and anchors itself –> C3b changes shape –> grabs other proteins and start a small cascade ==> recruiting platform known as C3 convertase –> activates ore C3 proteins ==> amplification loop
- C3 convertase changes shape into C5 convertase which recruits new proteins that begin the construction of a bigger structure: the membrane attack complex
- the membrane attack complex rips a hole in the bacteria’s membranes ==> kills the bacteria
- phagocytes have C3b receptors on their plasma membrane
are complement proteins more useful against viruses or bacteria?
they are most useful against viruses because they need to travel from cell to cell
when viruses is not in a cell, complement intercepts and cripples them
the viruses become harmless and complement guides the immune system to devour the virus
why do we ever get sick?
because viruses and bacteria adapt
what are the different pathways that can activate the complement cascade?
classical complement pathway
lectin complement pathway
alternative complement pathway
what are anti-microbial peptides (AMPs)?
they are small polycationic peptides that possess a positive charge and are attracted and incorporated into negatively charged bacterial membranes.
what do AMPs do to bacteria and fungi?
they disrupt their membrane resulting in cell lysis and can interfere with DNA and protein synthesis and can function as immunomodulation
what are granulocytes?
cells that contain vesicles in their cytoplasm filled with noxious substances that can be released to fight infections and they also have multi-lobed nucleus
what is another name for granulocytes? examples of granulocytes?
polymorphonuclear cells examples: neutrophils basophils eosinophils mast cells
what does the shape of the granulocytes’ nucleus do?
serves important function allowing granulocytes to easily squeeze through gaps between endothelial cells and rapidly migrate from blood or lymphatic vessels into tissues in response to an infection
what are the first immune cell types to arrive from circulation?
neutrophils
what are the different things neutrophils can do to kil a pathogen?
- phagocytic capability to engulf and destroy pathogens
- release of noxious substances stored into cytoplasmic granules in a process called degranulation
- release of neutrophils extracellular traps (NETs) a process called NETosis
what are the different granules in neutrophils?
3 types:
- primary
- secondary
- tertiary
what is the neutrophils life span?
a few days
what can increase a neutrophil’s life span? for how long?
cytokines released by macrophages and monocytes
for up to 2 weeks
where are eosinophils particularly common? where can it also be found?
in the gut mucosa
they can also be found inn the lung mucosa
how can eosinophils kill a pathogen?
when the eosinophils encounter a parasite, the content of its granules is released which will cause damage to the pathogen’s surface eventually killing it
can smaller pathogens be phagocytosed by eosinophils?
yes
what are basophils? what do they do? to what component do they respond to?
non-phagocytic granulocytes
control parasitic infections and contributes to allergic responses
they mainly respond to components of the complement cascade
what are the 2 types of monocytes?
- patrolling monocytes
- inflammatory monocytes
what are the 2 types of macrophages?
- tissue-resident macrophages
- monocyte-derived macrophages
are DCs part of the adaptive immune system?
no
what do DCs do?
play a role of messenger to the adaptive immune system
they specialise in patrolling tissues in search of antigens to bring it to T cells to activate them to fight infection which is a process called antigen presentation
are DCs phagocytes? if yes what is the process?
yes
they encounter a pathogen–> engulf and digest it –> present parts of it on their major histocompatibility complex (MHC) to show it to T cells and become activated–> activated DCs migrate to secondary lymphoid organs like lymph nodes where they present HC-bound antigens to naive T cells
what are the different lymphocytes?
B cells, T cells and innate lymphoid cells (ILCs)
where can lymphocytes be found?
secondary lymphoid organs including lymph nodes, in tissues
are all lymphocytes part of the adaptive immune system?
no
B and T cells –> adaptive immune system
ILCs and unconventional T cells –> have innate functions
what do unconventional T cells do?
important for surveillance of tissues, the maintenance of self-tolerance and the regulation of autoimmune diseases
what is the difference between unconventional T cells and normal T cells?
unconventional T cells’ T cell receptors (TCRs) are limited in diversity compared to conventional T cells
what are the 3 different types of unconventional T cells?
gammadelta T cells
mucosal associated invariant T cells (MAIT)
NKT cells
why do ILCs behave as innate immune cells?
because they lack variable receptors
there are different types of ILCs. hw do they differentiate?
they differentiate based on the cytokines that rthey secrete and the molecules they express
what do ILCs do?
play an important role in the early sensing of pathogens and produce cytokines that initiate the immune response
what is the most notorious class of ILCs?
NK cells
what are the 2 functions of phagocytosis?
destroying/sequestering a pathogen
processing material for antigen presentation to the adaptive immune system
what are the main phagocytic killers?
neutrophils and macrophages
what phagocytes use phagocytosis to present antigen to T cells?
B cells, DCs and macrophages
are all PRRs phagocytic receptors?
no
are all phagocytic receipted PRRs?
no
what are examples of phagocytic receptors?
PRRs
opsonin receptors
how does phagocytosis work?
phagocytic receptors are activated –> trigger actin filaments reorganisation –> form extension that envelop and internalise the pathogen ==> phagosome –> phagosomes fuse with vesicles that carry ROS and proteolytic enzymes
does phagocytosis vary depending on the cell? if yes how?
yes
in neutrophils –> no drastic change in pH (6)
in macrophages –> formation of phagolysosome that are activated with acidification
in DCs –> acidification is not as dramatic as macrophages
what is efferocytosis? what does it do?
the engulfing of neutrophils by macrophages triggers this process where anti-inflammatory cytokines are released
it promotes macrophages polarisation into non-inflammatory macrophages capable of tampering inflammation
what are the 4 stages of inflammation?
- dilation of blood capillaries to increase blood flow
- structural changes of blood vessels
- newly formed matrix of proteins and liquid within the tissue supports the attachment and survival of leukocytes transmigrated from the circulation
- structural changes which facilitate leukocyte extraversion and migration through the vessel’s wall and migration towards the site of infection or injury
what are the 4 stages of adhesion cascade?
rolling
activation
arrest/adhesion
transmigration or diapedesis
