Immunology of the respiratory system Flashcards
(88 cards)
1
Q
describe innate immunity
A
first line of defence, there when you are born
- No time lag
- Not antigen specific
- No memory
2
Q
describe adaptive immunity
A
- Slower learnt responses to specific microbes
- Lag period
- Antigen specifc
- Development of membrane
3
Q
what are antibodies
A
- These are plasma proteins that are made in the liver that are part of the immune system
4
Q
what does IgA do
A
- mucosal areas such as the gut, respiratory tract and urogenital tract
- prevents colonization
- also in saliva tears and breast milk
5
Q
what does IgD do
A
Functions mainly as anantigenreceptor on B cells that have not been exposed to antigens.
Shown to activate basophils andmast cellsto produce antimicrobial factors.
6
Q
what does IgE do
A
Binds toallergensand triggers histaminerelease frommast cells and basophils, and is involved inallergy.
Protects againstparasitic worms
7
Q
what does IgG do
A
Provides the majority of antibody-based immunity against invading pathogens.
8
Q
what does IgM do
A
Expressed on the surface of B cells (monomer) and in a secreted form (pentamer) with very highavidity.
Eliminates pathogens in early stages of B cell-mediated (humoral) immunity before there is sufficient IgG.
9
Q
what is the antibody that is largest in concentration
A
IgG
10
Q
What antibody is produce first
A
IgM and then IgG
11
Q
what type of MHC do all cells have
A
MHC1
12
Q
what MHC is on APCs
A
MHC2
13
Q
what do foreign epitopes on MHC2 sites do
A
- Foreign epitopes on MHC2 sites stimulate certain immune cells to manufacture antibodies that are specific to these epitopes. The antibodies bind to the original pathogens and help the immune cells recognize and attack the pathogens
14
Q
what are the APC cells
A
dendritic and macrophages
15
Q
describe what a multipotental haematopeitc stem cell develops into
A
- Multipotential haemotapoietic stem cell develops into a common myeloid progenitor
- Some leukocytes (white blood cells or WBCs) are granulated (they contain releasable granules)granulated white blood cells come from myeloblasts in the myeloid cells line the same one that produces erythrocytes
- Divide into megakaryocyte, erythrocyte, mast cell, myeloblast
16
Q
what does a myeloblast divide into
A
- Myeloblast differentiated into the basophil, neutrophil, eosinophil, monocyte (develop into macrophages and dendritic cells )
17
Q
what do monocytes differiate into
A
monocytes migrate out of the blood and differentiate into macrophages and dendritc cells
18
Q
the more active neutrophils are the ..
A
- More active they are the more nuclei they have, neutrophils when they first differentiate have 3 or 4 lobes but when they are battling bacteria they become more activated and can have 6 or 7 lobes (HSN)
- Monocytes have kidney bean shaped nuclei
19
Q
describe what macrophages do
A
- Macrophages are motile – they send out pseudopods and pull themselves along, the pseudopod attaches to the local tissue and this enables it to move
- Once they recognise the bacteria and start trying to engulf it not only do they display the epitote of the bacteira protein, they send out chemokines, which diffuse into the local capillaries and cause the attraction of other white blood cells to the site of infection in particular and initially neutrophils
20
Q
where are monocytes formed
A
- Monocytes formed in the bone marrow spontaneously migrate out of the blood and into various different tissues
21
Q
what happens when monocytes enter the target tissue
A
- they become lookout cells that identify and attack invading bacteria
22
Q
where are macrophages found
A
- they are found in all tissues
- they are part of the mononuclear phagocyte
23
Q
how do macrophages move around
A
amoeboid movement
24
Q
how do. macrophages kill foreign particles
A
- Macrophages engulf and digest cellular debris, foreign substances, & microbes that they contact in a process called phagocytosis.
25
name some different types of macrophages
Alveolar macrophages move around inside alveoli and remove dust particles that have evaded the mucus lining the upper airways.
Osteoclasts are found in bone and remove debris from bone breakdown.
‘Histiocytes’ is a generic name for tissue resident macrophages.
Kupffer cells are in the liver, microglia in the brain, intestinal macrophages in the gut
26
what are toll like receptors
- TLR are on the pseudopods of the macrophages and these TLRs will bind to common antigenic surfaces on bacteria and fungi
- they are how it is known that something is foreign
27
how do macrophages use there toll like receptors
- Macrophages at rest send out long pseudopods projections with TLRs on the end
- These stick to any bacteria they touch if a bacterium is detected the pseudopod retracts and the bacterium is pulled back and engulphed in a phagosome
28
describe the process of phagocytosis
- there is chemotaxis and adherence of a microbe to a phagocyte this happens by use of the TLRs
- then the microbe is ingested by the phagocyte
- there is the formation of the phagosome which is the phagocytic vesicle
- then there is the fusion of the phagosome with a lysosome to form a phagolysosome
- digestion of the ingested microbe by enzymes
- formation of the residual body containing indigestible material
- discharge of waste materials
29
what are the roles of macrophages
- Antigen presentation
- Triggers an inflammatory response
- Phagocytosis
30
how has TB evolved to prevent phagocytosis
- Some bacteria have evolved defenses against the killing enzymes and free radicals in the phagolysosome.
- They have a waxy material in their cell wall that resists penetration by the lysosome enzymes.
- Macrophages phagocytose these bacteria but cannot kill them (fast enough) to stop bacterial replication
- the bacteria can actually grow (albeit slowly) inside the lysosomes!
31
what is found in the lungs of people with TB
Gohn focus
32
how is a Gohn focus formed
- In the centre of the cell is a mass of dead tissue called caseous necoriss that contains live TB bacteria
- Surrounding this is a layer of macrophages that have ingested the bacteria and are trying to kill them
- Reinforcements in the form of lymphocytes surround the macrophage to kill any bacteria escaping outwards
- Ring of fibroblasts on the outside
- Calcium gets deposits on the outer layers and therefore the Ghon focus can be seen on a chest x ray
33
what do some monocytes develop into
- Some monocytes develop into a specialised kind of macrophage called a dendritic cell
34
what tissues are dendritic cells found in
Dendritic cells are present in those tissues that are in contact with the external environment, such as the skin, inner lining of the nose, lungs, stomach and intestines
35
describe the structure of dendritic cells
- Dendritic cells have very extensive membrane processes which may be finger-like projections or folded into sheets. This means they have a very large surface area to expose Toll-Like Receptor
36
describe how dendritic cells carry out there function
- When TLRs bind to a bacterium, dendritic cells act in a similar way to macrophages to phagocytose the bacterium, and break down the bacterial wall proteins into epitopes.
- Once they have produced the epitope dendritic cells migrate out of the tissue and into the nearest lymph node.
- In the lymph node they display the bacterial epitopes to ‘T helper cells’ which then stimulate B lymphocytes to make antibodies to the epitope.
37
what antibodies can dendritic cells have on them
IgG antibodies on their membranes
38
what happens when the IgG antibody on the dendritic membrane is activated
- When IgG is activated by the corresponding antigen the dendritic cells stimulate lymphocytes to make more of the same antibody.
- Once the TLR is bound to a bacterium and has brought it into the cell and has started to digesting it they migrate to a lymph node, they then display the bacterial epitopes to the B and T lymphocytes and then the adaptive immune system works
39
what are langerhans cells and where are they
- Langerhans cells are dendritic cells resident in the dermis and epidermis, as well as in the mucosa of the mouth, foreskin, and vaginal epithelium
- they can be found in other tissue such as the lymph nodes
40
what do langerhans cells do in skin infections
- In skin infections, the local Langerhans cells take up and process microbial antigens to become fully functional antigen-presenting cells.
41
what is a langerin
- Langerin is a lectin (a carbohydrate-binding protein) synthesised by Langerhans cells.
42
what do langerins do
- it has been suggested that Langerin on the surface of Langerhans cells in the genital epithelium protects against HIV-1.
- Langerin can bind to antigen on HIV-1 viruses and thus the viruses can be internalized and destroyed
43
what are mast cells
- Mast cells are granulocytes that are formed like erythrocytes directly from the common myeloid progenitor cell line
44
what are the two classes of leukaemia
- Acute myeloid leukaemia – tumours of the myeloid line
| - Acute lymphoid leukaemia – cancer of the lymphoid cell line
45
where are the mast cells usually present
- Mast cells, like macrophages & dendritic cells act as sentinels resident in tissues, especially near or in epithelial surfaces in the respiratory tract
46
what is the function of the mast cell
their function is mainly to detect pathogens that are inhaled rather than those that enter the body through injury. as they are mainly in the epithelial surfaces in the respiratory tract
47
what do the mast cells contain
- Mast cells are large granulated WBCs that contain quantities of histamine and heparin.
48
how does the mast cell release histamine and other cytokines
- mast cells have Toll-like receptors on their membranes
- But they can also display various classes of antibodies.
- These antibodies enable mast cells to bind to known antigen such as pollen grains or animal dander.
- Antigen binding triggers degranulation of mast cells and the release of histamine and other cytokines.
- Mast cell degranulation is one of the main components of an allergic reaction such as an asthma attack or anaphylactic shock.
49
what are the key components to an allergic reaction
eosinophils and mast cells
50
what are neutrophils derived from
- These are derived from myelocytes
51
how much of leucocytes do neutrophils make up over
- Largest component of the leucocyte family made up over 60% of all the white blood cells
52
what is a low neutrophil count termed as
A low neutrophil counts is termed neutropenia.
53
what type of leucocyte is a neutrophil
- they are granulated leucocytes
54
describe how neutrophils increase in the number of lobes
- When released from the bone marrow the neutrophil is spherical and its nucleus has 3-4 lobes. Hence they are often called polymorphonuclear leucocytes.
- Neutrophils are attracted to the site of an infection by chemokines released by macrophages and other sentinel cells
- A neutrophil becomes activated by contact with chemokines released from macrophages or dendritic cells.
- After activation the neutrophil changes shape and becomes amoeba-like and can extend pseudopods.
- The number of lobes of the nucleus increases, sometimes to six or more as there is greatly increased protein production, specifically of granules for release on to pathogens.
55
how do neutrophils migrate
- Activated neutrophils become amoeboid and attach to the endothelium, roll along it and then squeeze out between endothelial cells into the extracellular space.
- Chemotaxis guides them to the site of the bacterial infection.
- - The adhesion of the neutrophil depends on selectin and integrin proteins that are expressed on the activated neutrophils
56
what does amoeboid mean
esembling an amoeba specifically in moving or changing in shape by means of protoplasmic flow.
57
what do neutrophils have on there surface and what causes them to release neutrophils
Neutrophils have Toll-Like-Receptors and sometimes IgG immunoglobulins on their surface.
Stimulation of TLRs or immunoglobulins by the pathogens cause the neutrophils to release their granules
58
what is the main job of a neutrophil
There main job is to release granules bind to the bacteria generate free radicals which helps kill the bacteria and then they die
59
what are the actions of neturophils
= Neutrophils express and release more cytokines, which in turn amplify inflammatory reactions by several other cell types.
=. neutrophils have three methods for directly attacking micro-organisms: phagocytosis, degranulation (release of soluble anti-microbials), and generation of neutrophil extracellular traps (NETs).
- Neutrophil granules contain many enzymes used for killing microbes. They include myeloperoxidase, bactericidal-permeability-increasing protein (BPI), defensins, and the serine proteases neutrophil elastase and cathepsin G.
- The granules also contain molecules that generate reactive oxygen species such as peroxides which help oxidise and kill the bacteria around them.
= The apoptosis causes the release of web-like structures of chromatin and serine proteases; these trap bacteria and kill them. This represents a third mechanism for killing bacteria
60
what happens once a neutrophil has released their granules
= Once they have released their granules neutrophils die by apoptosis, so during an infection new neutrophils are synthesized at an increased rate in the bone marrow.
61
what are the 3 direct methods for attacking microorganism that neutrophils use
- phagocytosis,
- degranulation (release of soluble anti-microbials),
- generation of neutrophil extracellular traps (NETs
62
what is inflammation
Inflammation is a biochemical, structural and cellular protective process occurring locally in vascularized tissues which is designed to destroy or to remove pathogens and to initiate repair of damaged tissue. It may also act to restrict pathogens to one area and prevent them spreading across the body
63
what are the five classical sings of inflammation
- Rubor – redness
- Calor - heat
- Dolor – pain – it is painful because some of the things that are released by neutrophils such as the reactive oxygen species activate C5 receptors in the area
- Tumour- swelling
- Functio lasea – loss of function
64
describe how inflammation happens
- Mast or other sentinel cells detect pathogens via TLRs and release chemokines;
- these triggers neutrophils to migrate to the pathogen site.
- Histamine from mast cells increases local vascular permeability, allowing fluid, proteins, and phagocytic neutrophils to enter the infected tissue.
- These events result in the swelling and reddening of the site, and the increased blood flow to the site causes it to feel warm.
- Inflammation is also associated with pain due to these events) especially the released granules) stimulating pain nerve receptors (nociceptors) in the tissue.
65
why is inflammation associated with pain
- Inflammation is also associated with pain due to these events) especially the released granules) stimulating pain nerve receptors (nociceptors) in the tissue.
66
what is the role of histamine in inflammation
- Histamine from mast cells increases local vascular permeability, allowing fluid, proteins, and phagocytic neutrophils to enter the infected tissue.
67
what are basophils
- Basophils are large granule-containing WBCs that stain blue in standard blood stains
68
how much of leucocytes do basophils make up
They are relatively rare in the blood, comprising only about 0.5-1% of WBCs
69
what is the difference between a basophil and a mast cell
- mast cells contain more granules than the basophils. (One mast cell normally contains ~1000 small granules while a basophil contains ~ 80 bigger granules).
70
how do basophils work against infection
- When they reach infected tissue the basophils release granules containing several different compounds, including histamine, serotonin and heparin.
- Serotonin makes the ends of the capillaries constrict;
- this, together with the increased vascular permeability due to the histamine, greatly increases extravasation of plasma and increases migration of white cells to the infected area.
- The heparin prevents clots forming in the capillaries in the infected area, (which would impede migration of immune cells out of the blood).
71
how does pus form
Pus from the infeciton is produced from the corpses of the neutrophils and the bacteria
72
what are 3 things that basophils release
- histamine
- serotonin
- heparin
73
what cell do eosinophils arise from
- Eosinophils*, like the other granulocytes arise from myeloblasts.
74
how much of the percentage of leucocytes do eosinophils make up
- They make up about 1–3% of white blood cells.
75
where do eosinophils reside
- they reside mainly in the lower gastrointestinal tract, ovaries, uterus, spleen, and lymph nodes,
- but not in the lungs, skin, & esophagus, under normal conditions: The presence of eosinophils in these latter organs is associated with disease).
76
what is the main role of eosinophils
- Their main role is to attack multicellular parasites such as plasmodium species or intestinal worms
77
how do eosinophils carry out and kill pathogens
- Eosinophil granules contain powerful chemical weapons against multicellular invaders, such as peroxidases and enzymes to kill cells including ribonucleases, deoxyribonucleases, lipases, plasminogen, and major basic protein.
- The granules are normally released following activation of the eosinophil by contact with parasites.
- Unfortunately these chemicals can also kill or remodel the host tissues, a form of ‘collateral damage’ that is very apparent in chronic infections.- same enzymes kill your cells, this is one of the things that happen in chornic asthma when the eosinophils are active in the lungs
78
where are osteoclasts derived from
- Osteoclasts are also derived from macrophages
79
what cells do osteoclasts expression
- These cells express RANK – receptor activator of nuclear factor kappa B
- RANKL (the ligand for RANK), is expressed by resident bone cells such as osteoblasts and osteocytes, and triggers differentiation of the osteoclast progenitor cell into a mature osteoclast
80
what does RANKL do
triggers differentiation of the osteoclast progenitor cell into a mature osteoclast.
81
how is osteoclast formation inhibited
Osteoclast formation is inhibited by osteoprotegerin (OPG), which is produced by osteoblasts and binds to RANKL thereby preventing monocyte/macrophage interaction with RANKL
82
what is RANK
receptor activator of nuclear factor kappa B
83
what are NK cells
- part of the innate immune system
- Natural Killer (NK) cells are large granular lymphocytes (LGL) and arise from the common lymphoid (not myeloid) progenitor cell line
84
how do NK cells work
- NK cells patrol tissues and blood, reading the MHC1 epitopes on the cells they contact.
- Cells containing viruses present additional epitopes on their MHC1 site which are fragments of viral protein that they have been forced to manufacture.
- These epitopes disable the inhibitory receptor, and the NK cell then attacks the virally infected cell. .
- NK cells stick to all the cells but if they have the right epitope they inhibit the cells from doing anything else
85
how does the NK cell prevent attack by itself
- NK cells contain a library of antigens which are known to be innate (ie ‘self’). The ‘self’ cell epitopes activate an inhibitory receptor on the NK cell. Activation of this inhibitory receptor prevents attack by the NK cell.
86
how do NK cells kill cells
- NK cells migrate into infected tissues by interaction with chemokines released from sentinel cells.
- If a cell does not have the correct epitopes on its MHC1 site the NK cells attach themselves to the target cell & release the compound perforin.
- Perforin creates a pore or hole in the cell membrane.
- The NK cell then injects granzyme enzymes through the pore into the target cell cytoplasm.
- Granzyme enzymes activate caspases, which trigger apoptosis of the target cell, resulting in the death of the target cell and also its contained viruses.
87
what system are NK cells important in
- They are particularly important in the respiratory system as they can kill cells infected with an inhaled virus.
88
describe the lymphoid cell family
- Some stem cells form lymphoid progenitors. These cells differentiate into lymphocytes and NK (natural killer) cells.
- NK cells are part of the innate immune system
- The lymphocytes are however part of the ADAPTIVE immune system
