module 01 section 02 (innate immune system) Flashcards
when does the innate immune system develop?
present at birth
what are 5 characteristics of the innate immune system?
(1) unchanging
(2) immediate
(3) nonspecific reactivities
(4) broad range of targets
(5) no memory
define “unchanging” with respect to the innate immune system
continuous protection without rearragement or alterations in the response
define “immediate” with respect to the innate immune system
response to patogens occurs within minutes
define “nonspecific reactivities” with respect to the innate immune system
innate immune reaction can be to a common component on multiple pathogens
define “broad range of targets” with respect to the innate immune system
any element which is identified as foreign will ellict a response
define “no memory” with respect to the innate immune system
this response is present from birth and is not improved through repeated exposure
the innate immune system has barriers that aim to keep foreign particles out of the body and prevent spreading, how many are there and what are they?
2
- physical
- chemical
what are the physical barriers of the innate immune system?
- mucous membranes
- cilia/hairs
- epithelial barriers
what is the function of mucous membranes w respect to the innate IS?
trap pathogens and foreign materials
what is the function of cilia/hair w respect to the innate IS?
to move trapped pathogens out of the respiratory system via a concerted sweeping motion
what is the function of epithelial barriers w respect to the innate IS?
provide an example
- skin, GI tract and respiratory tract all produce peptides with natural antibiotic funtion
- e.g. defensins (cys rich peptides) are present in the skin and abundant in neutrophil wbc granules
which cells are most importatnt for the function of the innate IS?
wbcs (aka leukocytes)
what is the function of wbc’s?
protect the body by identifying and eliminating foreign invaders
how are wbc’s derived?
- from hematopoietic stem cells in the bone marrow
- specialization results in several types of leukocytes
where are wbc’s found?
blood and lymphatic tissue
what are the possible groupings of leukocytes?
phagocytes, granulocytes and NK cells
can some cells be more than one type of leukocyte? why or why not?
- yes: can be both phagocyte and granulocyte
- neutrophils are both !
what are phagocytes?
cells that ingest foreign particles, bacteria and dead/dying cells
what are granulocytes?
leukocytes with secretory granules in its cytoplasm
what are the three types of phagocytes?
neutrophils, macrophages and dendritic cells
define “neutrophils”
what percent of the innate IS cells corresponds to these?
- the frist responding leukocytes to migrate to the site of infalmmation and to ingest microbes to be killed
- they become increasingly segmented as they mature
- 50-70% of cells in the innate IS
define “macrophages”
what percent of the innate IS cells corresponds to these?
- most professional
- ingest aged neutrophils and bacteria
- secrete cytokines that stimualte inflammation and recruitment of other immune cells to the site of injury/infection
- 1-6% of cells of the innate IS
define “dendritic cells”
what percent of the innate IS cells corresponds to these?
- found on tissues in contact with the external environment
- serve as a link btwn the innate and adaptive IS’s
what are the types of granulocytes?
eosinophils, basophils, mast cells, neutrophils
define “eosinophils”
what percent of the innate IS cells corresponds to these?
- secrete histamines and free radicals once activated by parasitic infection
- important mediators for allergic responses
- 1-3% of cells of the IS
what is the role of histamines?
vasoactive amine: causes contraction of sm and dilation of capillaries
define “basophils”
what percent of the innate IS cells corresponds to these?
- secrete heparin and histamine in response to parasitic and allergic inflammatory reactions
- <1% of cells of the IS
define “mast cells”
what percent of the innate IS cells corresponds to these?
- role in allergy and anaphylaxis through heparin and histamine rich granules
- have protective role in wound healing, angiogenesis and blood-brain barrier function
- <1% of cells in the IS
what is angiogenesis?
formation of new bvs
define “NK cells”
- large, granular, cytotoxic lymphocytes that do not have T or B cell receptors
- play a fundemental role in surveillance of altered cells (cancer)
- play a major role in the host-rejection of both tumours and virally infected cells
do NK require activation to kill cells that they identify as non-self? explain.
no - they kill in an antibody independent manner
can NK cells interact with antibodies? why or why not?
- yes
- during antibody-dependent cell mediated cytotoxicity for a faster immune response upon subsequent exposures to the antigen
define “antibody-dependent cell mediated cytotoxicity”
a cell mediated rxn in which nonspecific cytotoxic cells that express Fc receptors recognize the bound antibody on the target cells and subsequently cause lysis of the target cell
where are specialized NK cells found?
in the placenta - may play a role in pregnancy
list 4 important proteins of the innate IS
(1) complement proteins
(2) mannose-binding lectin (collectin)
(3) c-reactive proteins (pentraxin)
(4) coagulation factors
define the role of complement proteins
mark pathogens for destruction (opsonization or cell lysis)
define “opsonization”
process by which a pathogen is marked for phagocytosis and may occur in different immune responses
define “opsonins”
proteins that coat the pathogen and promote attachement of phagocytes
define the role of mannose-binding lectin
involved in opsonization of microbes and activation of complement system via the lectin pathway
define the role of c-reactive proteins
- involved in opsonization of microbes and activation of complement system
- these are a member of the acute phase proteins that are secreted by hepatocytes of the liver in response to inflammation
define the role of coagulation factors
involved in coagulation of blood and repair of damaged vessels
what occurs following infection?
- an acute inflammatory response as an inflammatory barrier alongside coagulation
- there will be swelling of the capillaries near the infection
what are the signs of inflammation?
- erythema (tissue redness)
- edema (tissue swelling)
- heat
- pain
define “phagocytosis”
an important method of eliminating invading pathogens
what is phagocytosis activted by?
the recognition of PAMPs
what are PAMPs?
- i.e. pathogen-associated molecular patterns
- small molecule motifs conserved within a group of pathogens that are recognized by phagocytes of the innate IS
define the role of opsonins in phagocytosis
these can act as attachment sites for receptors that aid in the phagocytosis of pathogens
explain the state of neutrophils and macrophages after phagocytosis
- neutrophils are short-lived and form pus
- macrophages are long-lived and continue to form lysosomes
what are the 5 steps of phagocytosis
(1) attachment
(2) ingestion
(3) fusion
(4) digestion
(5) release
define the “attachment phase”
this phase of phagocytosis is dependent on what?
- (initiation of phagocytosis)
- attachment phase = recognition and binding of the microbe
- macrophages and neutrophils express many cell surface receptors that may bind microbes for subsequent phagocytosis
- the attachment phase is dependent on these specific receptors recognizing a variety of microbes
explain the role of LPS receptors in the initation (attachment phase) of phagocytosis
- most highly conserved component of gram-neg bacteria
- LPS binding to the LPS receptor is the innitation of an inflammatory singnalling cascade
- LPS receptor = CD14-toll-like receptor 4
explain the role of scavenger receptors in the initation (attachment phase) of phagocytosis
- these are a family of receptors that are integral to the removal of any foreign substances and waste materials
- they bind to a wide variety of ligands, including LDLs
explain the role of monnose receptors in the initation (attachment phase) of phagocytosis
- monnose expression is exclusive to microbes
- this receptor acts as a pattern regonition receptos (PRR) that is capable of recognizing several different microbes
define “PRRs”
- proteins expressed on cells of the innate IS that identify two classes of molecules:
(1) pathogen-associated molecular patterns: associated with microbial pathogens
(2) damage-associated molecular patterns: associated with cell components released during cell damage or death
explain the role of N-formyl methionyl receptors in the initation (attachment phase) of phagocytosis
- bacteria produce f-met-leu-phe (fMLP) proteins that have an amio-terminal N-formylated met
- fMLP will also recruit inflammatory cells such as neutorphils
define “unenhanced attachment”
what does this?
- type of attachment done by LPS, monnose and the N-formyl methionyl receptors
- it is the nonspecific innate recognition of PAMPs through PRRs
- the attachment step can be enhanced such that phagocytosis of a microbe is more efficient and specific
define “enhanced attachment”
what does this?
- attachment of an opsonized microbe to the phagocyte
- opsonization can occur via IgG antibodies, complement proteins or acute phase proteins such as mannose binding lectin and C-reactive proteins
list the receptors that may innitiate phagocytosis upon attachment
LPS, N-formyl methionyl, mannose, scavenger
list the opsonins we have covered
recall opsonins are proteins that coat pathogens to promote the attachment of phagocytes
complement proteins, mannose-binding lectins, C-reactive proteins, coagualtion factors
describe ingestion
- (encapsulation of the microbe)
- following attachment, pseudopods surrond and engulf the microbe placing it in a phagosome (endocytic vesicle)
- an electron pump brings protons into the phagosome
- this lowers the pH to ~4, preparing for the next steps of phagocytosis
describe fusion
- (creating the phagolysosome)
- phagocytes contain lysosomes which travel along microtubules within the phagocyte and fuse with the phagosomes to create phagolysosomes
what is a lysosome?
where are they created?
where can they be found?
- organelle containing proteolytic/digestive enzymes
- derived from the golgi apparatus and are found in the cytoplasm
describe digestion
- (killing of the microbe)
- microbes are broken down by lysosomal enzymes in the phagolysosome
- phagocyte oxidase in the phagolysosome membrane generates reactive o2 intermediates (ROI) which are strong oxidizing agents
- inducible nitric oxide synthase (iNOS) synthesizes nitric oxide which creates oxidative toxins that further damage the biological molecules
describe release
- (residual body exocytosis)
- the indigestible materials remaining in vesicles = residual bodies
- these can be released via exocytosis or displayed via MHC-antigen complexes through the exogenous antigen processing pathway
define “MHC-antigen complexes”
the interaction of self molecule detecting protein MHC with a self or non self molecule (antigen)
define “exogenous antigen processing pathway”
an antigen processing pathway used by specialized antigen presenting cells to present peptides derived from proteins that the cell has endocytosed
