white blood cells Flashcards
what is innate immunity?
rapid re-programmed response to a broad range of microbes
what are characteristics of innate immunity?
o No time lag
o Not antigen specific
o No memory
what is acquired immunity?
slower learnt responses to specific microbes
what are characteristics of acquired immunity?
o Lag period
o Antigen specific
o Development of memory
where is IgA found?
found in mucosal areas, such as gut, respiratory tract and urogenital tract
Also in saliva, tears, and breast milk.
what is the function of IgA?
Prevents colonization by pathogens
what is the function of IgD?
mainly acts as an antigen receptor on B cells that haven’t been exposed to antigens
Shown to activate basophils and mast cells to produce antimicrobial factors
what are the functions of IgE?
Binds to allergens + triggers histamine release from mast cells + basophils.
o Involved in allergy.
o Protects against parasitic worms
why is IgE less common in serum?
bc it binds tightly to basophils and mast cells before interacting with antigen
what is the function of IgG?
provides majority of antibody-based immunity against invading pathogens
what is the most common antibody?
IgG
how is IgM found?
monomer on the B cell surface
what is the structure of secreted IgM?
pentamer
what is the function of IgM?
Eliminates pathogens in early stages of humoral immunity before there’s enough IgG
what is the first antibody to be made?
IgM
what are epitopes?
fragments of protein presented on the surface of cells
where do all cells present their epitopes?
MHC1 site
where are foreign epitopes displayed?
MHC2 site
where are MHC2 sites found?
only on APCs
what do foreign epitopes do?
stimulates certain immune cells attracted to the site by chemokines to make antibodies specific to the FE
what do antibodies do?
Antibodies bind to the original pathogens and help the immune cell recognise and attack the pathogens
where do granulated WBCs come from?
myeloblasts in the myeloid cell line
what do monocytes differentiate into?
macrophages
dendritic cells
what are sentinels?
lookout cells
how do macrophages move around?
amoeboid movement
what do macrophages do?
- Engulf and digest cellular debris, foreign substances + microbes by phagocytosis
- Meanwhile they also send out chemokines that attract other WBCs to infection site
what are alveolar macrophages?
move around inside alveoli – remove dust particles that have evaded the mucus lining in the upper airways
what are osteoclasts?
found in bone. Remove debris from bone breakdown
what are histiocytes?
generic name for tissue resident macrophages
where are Kupffer cells found?
liver
where are microglia cells found?
brain
where are intestinal macrophages found?
gut
what are toll like receptors?
Proteins on the surface membrane of macrophages
Can bind to many antigens found on bacteria/fungi surfaces
how do macrophages kill bacteria?
- macrophages send out pseudopods w TLRs on the end
- stick to bacteria, retract and engulf bacteria into a phagosome
- phagosome and lysosome fuse to make phagolysosome
- digestive enzymes secreted into phagolysosome and break down and digest bacteria cell wall
- kill bacteria and indigestible material is ejected
what is a lysosome?
small membrane bound sacs of digestive+other enzymes
name a defence mechanism of TB
- have a waxy material in their cell wall that resists penetration by the lysosome enzymes
- can be phagocytosed by cant kill them fast enough to stop replication so they can grow inside the lysosomes
describe the structure of a ghon focus
- at the centre is a caseous necrosis
- layer of macrophages surround this - trying to ingest the bacteria
- surrounded by lymphocytes which try and kill any escaping bacteria
- ring of fibroblasts
- calcium on outer layers
what is the caseous necrosis?
mass of dead tissue containing live TV bacteria found in the centre
what are dendritic cells?
specialised type of macrophage
where are dendritic cells found?
• Present in tissues that are in contact with the external environment e.g. skin, inner lining of the nose, lungs, stomach and intestines
describe the structure of dendritic cells
Have extensive membrane processes - can be finger-like projections or folded into sheets –> large surface area to expose TLRs
how do dendritic cells stimulate B cells to make antibodies?
TLRs of dendritic cells bind to bacterium, phagocytose and break down bacterial cell wall
- epitope presented and they move to a lymph node
- display bacterial epitope to T helper cell –> stimulates B cells to make antibodies to the epitope
what antibody do dendritic cells have on their membrane?
IgG
what are langerhan cells?
Dendritic cells found in the dermis, epidermis, mucosa of the mouth, foreskin and vaginal epithelium. Can be found in other tissues such as lymph nodes
what role do Langerhan cells play in skin infections?
In skin infections, local Langerhan cells take up and process microbial antigens to become APCs
what is Langerin and what is its suggested role?
- Langerin – lectin (carbohydrate binding protein) made by Langerhan cells
- Suggested langerin in the genital epithelium protects against HIV-1
what are mast cells?
• Granulocytes that are formed directly from the common myeloid progenitor cell line
what is the function of mast cells?
Act as sentinels in tissues, esp near/in epithelial surfaces in the respiratory tract – detect pathogens that are inhaled
what do mast cells contain?
histamine and heparin
what is found on the surface of mast cells?
• Have TLRs on the membrane but can also display various classes of antibodies – enable mast cells to bind to known antigens
how do mast cells help in allergic reactions?
• Antigen binding triggers degranulation of mast cells – release histamine and other cytokines
what % of WBCs are neutrophils?
60%
what is neutropenia?
low neutrophil count
what type of white blood cell are neutrophils?
granulated leucocytes
what are polymorphonuclear leucocytes?
When released from bone marrow its spherical and its nucleus has 3-4 lobes
what causes neutrophil activation?
contact with chemokines by sentinel cells - attracts them to the site
what happens to the neutrophil when its activated?
- Changes shape –> amoeba like and can extend pseudopods
- Number of lobes of the nucleus increases – sometimes to 6 or more bc of increased protein production – specifically of granules for release on to pathogens
describe the stages of neutrophil migration
- activated neutrophils become amoeboid and attach to the endothelium
- roll along it and squeeze between the endothelial cells into extra-cellular space
- chemotaxis guides them to site
- stimulation of TLRs and IgG on surface causes release of granules
- adhesion depends on selectin and integrin proteins
what process guides neutrophils to the site of bacterial infection?
chemotaxis
what causes the release of granules from neutrophils?
stimulation of TLRs and IgG on their surface
what does neutrophil adhesion depend on?
selectin and integrin proteins
what are the 3 main methods for directly attacking micro-organisms?
- phagocytosis
- degranulation
- generation of neutrophil extracellular traps (NETs)
name some enzymes that neutrophil granules contain.
what other molecules do they contain?
myeloperoxidase, bactericidal-permeability-increasing protein (BPI), defensins, and the serine proteases neutrophil elastase and cathepsin G
also contain molecules that make ROS e.g. peroxides
what happens to neutrophils once they’ve released their granules?
they die by apoptosis - causes release of web-like structures of chromatin and serine proteases – trap bacteria and kill them
what process does the release of neutrophil granules cause?
triggers local inflammation in the infected tissue
define inflammation
process occurs locally in vascularised tissue which is designed to destroy/remove pathogens and to initiate repair of damaged tissue
what are the 5 signs of inflammation?
redness, heat, pain, swelling, loss of function
describe the process of inflammation and what causes each of the signs of inflammation
- Sentinels detect pathogens via TLRs –> release chemokines –> trigger neutrophils to migrate to pathogen site
- Histamine from mast cells increases local vascular permeability –> allows fluid, protein, phagocytic neutrophils to enter the infected tissue –> swelling and reddening of the tissue
- Increased blood flow to the site makes it feel warm
- These events cause pain – stimulates nociceptors in the tissue
what happens if neutrophils and macrophages dont kill the bacteria?
basophils migrate out of the blood into infected tissue
what are basophils
granulocytes that stain blue in standard blood stains
what % of WBCs are basophils?
0.5-1%
what is the main difference between basophils and mast cells?
main difference is that mast cells have more granules
what do the basophil granules contain and what do these compounds do?
o Serotonin makes capillary ends constrict
o Histamine increases vascular permeability
o Both cause increased extravasation of plasma + increase migration of WBCs to infection site
o Heparin prevents clots forming in the capillaries of infected areas
what do eosinophils arise from?
myeloblasts
what % of WBCs do eosinophils make up?
1-3% of WBCs
where are eosinophils found normally and in disease?
lower GI tract, ovaries, uterus, spleen + lymph nodes
o In normal conditions they’re NOT found in; lungs, skin, oesophagus – associated w disease
what is the main role of eosinophils?
attack multicellular parasites e.g. plasmodium species/intestinal worms (hence why they’re in the gut). Can also trigger asthma and allergy mechanisms
what chemicals do eosinophils contain?
• Contain powerful chemicals e.g. peroxidases + enzymes to kill cells inc ribonucleases, deoxyribonucleases, lipases, plasminogen and major basic proteins
what are eosinophil granules released?
released following activation by contact with parasites
how are osteoclasts formed?
- Derived from macrophages + monocytes – migrate into bone to become osteoclast progenitor cells – express RANK (receptor activator of nuclear factor kappa B)
- RANKL (ligand for RANK) expressed by resident bone cells e.g. osteoblasts + osteocytes – triggers differentiation of osteoclast progenitor cell into osteoclast
what is osteoprotegerin?
inhibits osteoclast formation – produced by osteoblasts and binds to RANKL so macrophages/monocytes can’t interact with it.
what are NK cells?
Large granular lymphocytes – arise from common lymphoid progenitor cell line
how do self-epitopes affect NK cells?
activate an inhibitory receptor on the NK cell – prevents attack by NK
how do NK cells know to attack infected cells?
• Cells with viruses in them have additional fragments of viral protein on their epitope on the MHC1 that they’ve been forced to manufacture disable inhibitory receptor NK attacks infected cell
why are NK cells important in the respiratory system?
NK cells are rlly important in the respiratory system bc they can kill cells infected with an inhaled virus
how do NK cells kill infected cells?
NK cell attaches to the target cell and releases perforin – creates hole in the cell membrane
• NK cell then injects granzyme enzymes through the pore into the target cell cytoplasm
• Granzyme activates caspases – trigger apoptosis of target cell death of target cell and contained viruses
