Innate Immune System Flashcards
What are the different components of Innate Immunity
Phagocytosis
Complement System
Interferons
Natural Killer Cells
What is another term for innate immunity? Adaptive Immunity?
Innate: natural
Adaptive: acquired
Does infection have to result in disease?
No - it does not have to result in disease. Infection and disease are very different. Overtime we brush our teeth for example we get an infection, but we do not acquire a disease from this
What are the different soluble factors involved in innate immunity? Adaptive Immunity?
Innate: lysozyme, complement system, acute phase proteins (C-reactive proteins)
Adaptive: antibodies
What cells are involved in innate immunity? Adaptive immunity?
Innate: natural killer cells and phagocytes
Adaptive immunity: T lymphocytes
Difference between innate immunity and adaptive immunity
Innate: non specific, no memory, resistance not improved by repeated contact
Adaptive: specific, memory, resistance improved by repeated contact
Defences against entry into the body
- lysozyme in most tears, nasal secretions and saliva
- sebaceous gland secretions( fatty acids in the skin tend to have more antimicrobial properties active against gram positive)
- commensal organisms in gut and vagina
- spermine in the semen
- mucuous
- cilia lining in the trachea
- acid in the stomach
- skin
What kind of bacteria can typically survive the acid of the stomach
spore forming bacteria (can survive pH of typically 2)
Does the innate immune system change over time?
Yes, but it can only weaken (as we age) - it cannot improve and get stronger
What are the main mechanisms to limit entry in the innate immune system?
Skin, membranes and normal flora
How does skin limit entry into body?
- normally impermeable to a number of infectious agents
- hostile environment for many bacteria
- lactic acid and fatty acids in sweat and sebaceous secretions lower the pH
- loss of skin – burns can cause serious infections
What do burn units do to protect their patients?
are all positively pressured - air cannot get into rooms carrying microorganisms this way
How do membranes limit entry inside the body?
- line the inner surfaces of the body and secrete mucous
- inhibit bacterial adherence, inhibit entry
- ciliary action– remove microbes and other foreign particles
- flushing action - tears, saliva, urine, all protect epithelial surfaces
- presence of antimicrobial compounds (acid in gastric juice, spermine and zinc in semen, lactoperoxidase, and lysozyme in nasal secretions, tears and saliva)
How does normal flora limit entry into the body
bacteria and fungi are permanent residents on the body surfaces (skin and mucosal membranes), they also suppress the growth of pathogenic microbes (have a protective layer, compete for nutrients and produce inhibitory compounds such as acids and colicins)
More about normal microflora….
- prevents the attachment of pathogens because of a lack of space on the tissue and lack of food for the pathogens to feed on
- normal microflora can also produce antibacterial properties that kill off pathogens (lowering pH, for example as happens in the vagina)
When does c. difficile usually colonize the gut
usually colonizes the gut when the gut microflora is depleted after being on antibiotics (clostridium is a spore former and can survive in the gut at very low pH’s)
How does the innate immunity limit growth of pathogens?
- phagocytosis ( macrophages, polymorphonuclear granulocytes)
- soluble chemical factors( bactericidal enzymes)
What are macrophages?
- promonocytes (in bone marrow) -> circulating blood monocytes -> mature macrophages in tissues
- concentrated in lung, liver, lining of lymph nodes , well placed to filter off foreign material
Polymorphs
- dominant white cell in the bloodstream
- share common haemopoietic precursor
- no mitochondria (capable of carrying out very fast glycolysis reactions)
- non-dividing, short lived, segmented nucleus
- granular cytoplasm
Explain phagocytosis
- There are specific molecules on the pathogen, and specific molecules on the phagocytes that mediate this interaction between the pathogen and the phagocyte
- The phagocyte does not recognize the bacterial cell - it only recognizes the irregular patterns on the pathogen
- there is only an interaction between PAMPS and PRRs
PAMPS
pathogen associated molecular pattern
-on the microbe (LPS, protein)
PRRs
pathogen recognition receptors - on the phagocyte
What is a way that the pathogen can hide from the bacterial cell
It can hide inside the bacterial cell
- micobacterium tuberculosis does this and hides inside the phagocyte
- mutations on the PAMP can also cause misidentification of the pathogen- mutation changes the marker on the pathogen that the phagocyte is looking for, so the phagocyte is not recognizing the pathogen anymore
What is the most common PRR
light toll receptors (LTRs)
- PAMPS can be any protein that is present on the bacterial cell
What is the significance of granules in phagocytosis?
- inside the granules that are inside of the phagocyte, the phagocyte can release a large amount of antimicrobial properties (if the pathogen is not contained within the vacuole of the phagocyte though, the antimicrobial properties released can cause death of the phagocyte itself)
- inside the vacuole, the phagocyte can pump in reactive O2 of N species via the granules and can cause complete degradation of the pathogen
- in O2 dependant killing, the degraded microbe is released to the outside
What are the 4 steps of phagocytosis
- attachment by pattern recognition receptors
- pseudopodia forming a phagosome
- granule fusion and killing (complete formation of the phagolysosome)
- release of microbial products
Phagocytosis and the complement system
- contact dependant
- formyl methionyl peptides attract leukocytes - move by chemotaxis until the pathogen is engulfed
(weak signal however) - complement proteins work by the cascade reaction - product of one reaction serves as the initiator of the next reaction
- blood clotting, for example (highly controlled)
Which components of the alternative complement pathway cause mast cell degranulation
C5a and C3a
C5a and C3a release chemicals that mediate what?
- Increased vascular/ capillary permeability that allows flow of fluid and plasma components to site of infection (acute inflammatory response)
- chemotactic attraction of polymorphs through blood vessel walls to C3b-coated bacteria
Polymorphs have what on their surface to allow them to bind tightly to bacteria, allowing phagocytosis to occur?
C3b
When do acute phase proteins come into play?
They increase in concentration in plasma in response to injury and inflammation
- C-reactive protein, mannose binding protein, bind to PAMPS, can fix complement ans opsonize bacteria
- acute phase proteins let us know how long ago an infection has occurred
What do antimicrobial factors do
They act within phagocytic cells but also within body fluids
- tears and saliva contain lysozyme
- blood contains lactoferrin , which binds iron and makes it unavailable for bacteria to use
What are interferons
They are soluble factors that are released in response to a viral infection
- interferons prevent the viral replication in neighbouring cells
- the infected cells are the ones that secrete the interferons, causing other cells around them to be resistant to the viral replication
- interferons protect against al related viruses that share the same receptor
When are interferons used treatment
For LAST resort in treatment in hepatitis and some cancers
- tends to be a lot of side effects
- these act as the hormones of the immune system- sensing of higher than normal levels of interferons, the immune system kicks in and causes a large number of side effects
Natural Killer Cells
- bind to receptors on virus-infected cells, causing activation of the natural killer cell and release of granules
(perforin that inserts into the host membrane forming a MAC) - allows the entry of a second molecule, granzyme B that leads to apoptosis
(this is used when our body gets infected by a virus - our body can kill the cell that is infected to prevent the spread and replication of the virus)
Can viruses replicate on their own?
No- they’re obligate intracellular parasites and do not have the machinery to carry out replication on their own - they use host cell tissue for this
Eosinophils
- these combat large parasites (like helminths)
- these are two large to be engulfed by phagocytes
- these bind to C3b which cause activation
- several toxic compounds released that damage the membrane via hole formation
What are the 4 steps of phagocytosis?
- attachment by pattern recognition receptors (PAMP and the receptor)
- pseudopodia forming a phagosome
- complete formation of the phagolysosome (fusion of the granule with the vacuole)
- release of the microbial products
Why do we need the complement system? Why can’t we just rely on phagocytosis?
Phagocytosis is contact dependent
- clearly this cannot happen unless both become physically close to each other - there is a need for a mechanism that mobilized the phagocytes from a far - bacteria do produce formyl methanol peptides that attract leukocytes from far away (known as chemotaxis)
- this is a weak signal however! This is why the body relies on the complement system
What protein does the complement system start off with?
C3
When C3 becomes activated at the start of the complement system, what are its two breakdown products?
C3b and C3a
What is the difference between the C3a and C3b proteins?
C3a is a mediator of inflammation, while C3b goes on to activate the MAC, or can start opsonization
What does C3b go on to produce in the complement pathway?
C3b complexes with Factor B
-> C3bB is acted upon by enzyme factor D to produce C3bBb (aka C3 convertase)
What does C3 convertase do initially in the complement system?
Split C3 into more C3b and C3a
Under what situations does C3bBb require to have action inside the cell
C3bBb is a very unstable enzyme and degrades easily, but in the presence of carbs or other bacterial surface molecules, C3 converts is no longer susceptible to breakdown
- ONLY works when its needed!
What are the different roles of C3b in the body?
- C3b binds to microbial surface on the cell and acts as opsonin - opsonin is the molecule that coats the bacterial surface and allows for phagocytic recognition
- C3b and C3 converts can also act on the next component, C5
- C5 is split into C5a and C5b
- C5b is joined by C6, C7, C8, and C9
- these together get inserted into the lipid layer and form the membrane attack complex- this leads to cell lysis
What are the 2 different things that C3a and C5a can do in the cell?
- they cause mast cell degranulation and release chemical mediators that:
1. increase vascular/ capillary permeability - allows flow of fluid and plasma components to the site of infection - part of the acute inflammatory response
2. chemotactic attraction of polymorphs through blood vessel walls to C3b coated bacteria - polymorphs have a receptor for C3b on surface so they bind tightly to the bacteria and phagocytosis occurs
