13. White Blood Cells & Innate Flashcards
the white blood cells
there are many different types, each with a specific function
innate and adaptive immune systems
neutrophil, eosinophil, basophil, monocyte, B lymphocyte, T lymphocyte, natural killer cell
why do we need so many different blood cells
to address the wide range of pathogens, the bvery big eg worms , the big eg bacteria, the small and hidden eg viruses and proteins eg toxins
- is a system, not cells working in isolation
killing large organisms
large organisms such as worms cant be engulfed and digested - cells need to cooperate and destroy them in the tissues while minimising the damage to normal cells by keeping the large organisms localised to a small area to avoid widespread damage by immune cells
major role of eosinophils and basophils
killing small organisms
major role of neutrophils and monocytes
smaller organisms such as bacteria can be engulfed and digested safely within white cells (no damage to tissues)
important to do this quickly and effectively before they can proliferate and cause damage
killing viruses
major role of T lymphocytes and natural killer cells
viruses infect normal cells and replicate inside them by hijacking host machinery, theyre therefore hidden from the immune system. the immune cells must therefore recognise and destroy infected cells whilst not affecting normal cells
destroying toxins
major role of antibody secreting B lymphocytes
Specific proteins free in circulation eg toxins or on the bacterial surface can have a major effect on the body. B lymphocyte system must recognise these proteins and secrete a large amount of antibodies to neutralise or destroy the small protein antigens and ideally have memory if the antigen is encountered again
the innate immune system
the principles have an ancient evolutionary origin similar to free living organisms
eachcell of the innate immune system effectively acts independently, there are many controls but it resembles an independent organism in the way it behaves
the innate immune system - similar to amoeba
amoeba is a free living organism that moves freely, recognises and destroys prey (non self) while recognising other amoeba as non prey (self). this is applies to wbc
white blood cells must be mobile, interacting with and contacting other cells and recognising their features , ignoring the bodies of own cells (self) while recognising invading organisms eg bacteria (non self)
cells of the innate immune system
neutrophils, eosinophils, basophils and monocytes patrol blood and tissues ignoring the normal cells (self) whilst recognising bacteria/ worms (non self)
mechanisms of recognition: pathogens
neutrophils, eosinophils, basophils and monocytes recognise common proteins in bacterial cell walls or released bacterial components (eg bacterial DNA)
eg PAMPs - pathogen associated molecular pattern, recognised by receptors on host cell and indicate the presence of a pathogen
DAMPs (cell walls etc) damage associated molecular patterns (released DNA etc) , recognised as foreign and imply inflammation taking place
pathogen recognition and response
once a pathogen is recognised small molecules are released to help recruit and activate white cells:
- cytokines eg gcsf cause increased production and early release of wbc from bone marrow
- chemokines (small peptide hormones that attract cells ie are chemoattractants) recruit neutrophils to the site of infection
- both cytokines and chemokines additionally cause the white cell to be activated to gain killing function
mechanisms of destruction principles
- Enzymes and other destructive molecules are used to destroy the organism – the combination of enzyme of different types allows cells to kill all pathogens irrespective of type
- The killing can also destroy normal cells so must be balanced by mechanisms that avoid harm to tissues – the different cell types have different methods to do this.
killing bacteria - neutrophils and monocytes
bacteria small sized so neutrophil can bind engulf and internalise bacteria into small vacuoles then fuse the granules with the vacuoles so that the bacteria are safely eliminated without the release of granular contents
as bacteria killed within the neutrophil this means no damage to tissues
neutrophil structure
generally regular shape
multilobed nucleus 3-5 lobes
finely granulated cytoplasm
neutrophil - resting
is a highly motile cell which can migrate into tissues at sites of inflammation/ inn the presence of DAMPS and PAMPS
survives 12-24 hours in blood and 24-48 hours in tissues
most neutrophils are functionally inert in their lifespan, key is to do nothing unless stimulated to avid damaging the body
neutrophil activation
increases glycogen store (energy), heavy granulation(make more enzymes available for killing pathogens) and dohle bodies
enhanced adhesion and movement
cytokines and chemokines are released during inflammation, these enhance neutrophil function
neutrophil: killing mechanisms
adheres to bacteria using adhesion receptors, internalises pathogens into a specialised vacuole called the phagosome
grnaules fuse with the phagosome to destroy bacteria without damage to the neutrophil itself or other tissues.
microbiocidal : myeloperoxidase, lysozyme, acid hydrolases
iron binding : lactoferrin
extracellular trapsL DNA net, an added mechanism is the release of neutrophil DNA which forms an interconnected net that traps bacteria into a local area
neutrophil safety
phagocytoses cells internally so killng is safely enclosed
phagosome contents ie enzymes from the granules work only in low pH or oxidising power which are found only within the cell so if they escape into neutral environment shouldn’t damage cells and tissues
neutrophils die by apoptosis, releases its enzymes internally that destroy its toxic elements and prepare it for safe removal in the spleen
killing bacteria : monocytes
phagocytic cells with a range of functions, main function within tissues is continuing the effects of neutrophils at a later stage
-phagocytic
-walling function to trap infection so doesn’t spread, (forming a granuloma)
-begins tissue repair by removing dead tissues and beginning repair by promoting wound healing
related to adaptive system where it may have an antigen presenting role
soend 17 hours in blood before enterinf tissues where they become tissue macrophages
structure of monocyte
Generally irregular shape
That is dynamically active contacting other cells or migrating
Kidney shaped or irregular nucleus
Blue grey cytoplasm may contain fine granulation
walling in function
performed by monocytes
if infection hard for body to eliminaye its walled in to prevent spread, the infection can then be reduced over a long period or sometimes simply remain localised and prevented from cuasing harm (dominant)
such infections may reactivate in future if the immune system is suppressed
eosinophils and basophils - killing larger organisms problems
killing larger organsms
These multicellular organisms are often well protected by an enzyme resistant sheath, also they are far bigger than a neutrophil so must be killed outside of the cell extracellularly. On the other hand they often do not proliferate in the body so immediate killing is less important.
There are several principles here:
Immobilise to prevent escape by causing local vascular congestion and fluid in tissues.
Recruit white cells to destroy the worm (basophils and eosinophils)
Release substances locally around the worm to destroy it
Since these processes can be toxic and damage cells it is important they are well controlled.
eosinophils and basophils
Eosinophil has dense granules that generally do not overlie the nucleus, when stained they appear red
Basophils have dense granules that overlie the nucleus, when stained they appear blue
The granules are released into the space around pathogens to act – since granules are the main effective element the cells are densely granular.
eosinophils and basophils function
Contain numerous granules that fill the cytoplasm and stain strongly with particular acid dyes – appearing red (eosinophil) or blue (basophil)
GRANULES ARE RELEASED IN TISSUES TO DESTROY PARASITES
granule contents of eosinophils
- Histamine: dilates blood vessels allowing more blood cells to arrive, and causes swelling that traps invading organisms by releasing fluid that congests tissues
Contain multiple active proteins: Nucleases that break down DNA/RNA, Lipases that break down fat, Major basic protein attacks organism surface
: recruit other cells by cytokine release and continue the attack against the parasite
Stop before excess damage: when destroyed the activity of these cells is prevented particularly by helper T cells.
Potentially cause tissue toxicity as all these protein may also damage tissues
granule contents of basophils
Granules contribute to inflammation
Histamine – dilate blood vessels
Serotonin – dilates blood vessels
Heparin – prevents clotting which can interfere with killing
Enzymes (elastase) break down tissue matrix
IL4 – stimulates immune reactions especially IgE
neutrophil: benign disorders
neutrophils are first line of defence so deficiency can lead too serious infections with pathogens that wouldn’t normally affect healthy individuals
Defects:
low neutrophil number or defective function eg immune neutropenia where the immune system attacks and destroys the bodies own neutrophils or inherited disorders that cause chronic infection
Or granules don’t work correctly and cannot kill ingested bacgteria
or high neutrophil number contributes to damage in inflammatory disease eg rheumatoid arthritis
eosinophils and disease
High numbers and granule release can be harmful: heart valve damage
Excess granule release from abnormal eosinophils can lead to catastrophic damage as granules attack normal tissues – shown here affecting skin causing swelling and inflammation but also affecting other organs particularly heart valves where granules are released in the turbulent blood flow around the valve.
basophil disease
In appropriate numbers or incorrect circumstances the granule release can be harmful: e.g. asthma and allergy
Drugs that stabilise used to prevent allergic reactions
Abnormal reactions of basophils (and their tissue equivalent the mast cell) are a major contributor in asthma:
Allergens such as pollen affect the bronchi of asthma sufferer’s this causes release of granules and swelling around the small airways – as they constrict breathing becomes increasingly difficult. Treatment must be used to oppose these effects (e.g. steroids and dilators of the small airways)
