IMMUNOLGY- ULTRA NOTES
- 3 major lines of defence: 1. PHYSICAL BARRIER- first line of defence
-prevents pathogens from easily entering the body
- skin and mucous membranes (digestive tract,
respiratory tract, reproductive tract)
-Anatomical barriers: Skin (tight junctions, multiple
layers, replicate frequently, desquamation, cilia, antimicrobial peptides, FA in sebum)
Mouth, upper alimentary canal
(enzymes, antimicrobial peptides, sweeping of surface by flow of fluid to stomach)
Stomach (low pH, digestive
enzymes, antimicrobial peptides, fluid to intestine) Small intestine (digestive
enzymes, antimicrobial peptides, flow to large intestine, peristalsis, epithelial cell shedding ,digestive enzymes,
bile stars )
Large intestine (normal
intestinal flora compete with pathogens, faeces expelled) Airways( cilia sweep mucous
outward, coughing, sneezing, macrophages in alveoli) Eyes(enzymes, flushing)
-Mucocilliary escalator-mucous membranes are
alimentary, respiratory, urogenital tract, eyes -mucous is viscous and traps
pathogens -Acid Mantle- skin secretes protective layer antimicrobial
peptides(psoriasin) and fatty acids in sebum -fatty acids decrease pH
- Digestive defences- mucosal surface of GI tract = ~200-
300m2 -saliva- IgA, lysozyme, peroxidase,
lactoferrin -gastric juice lowers pH by HCl+
digestive enzymes -active antimicrobial peptides created
from pepsin cleavage or precursors => lactoferrin -neutralization of gastric juice during
passage into small intestine -PANETH CELLS- defensins:-
defend from pathogens, shape microbiota, protect stem cells - PEYERS PATCH- lymphoid tissue
2.INNATE IMMUNITY – 2nd line of defence
- “innate” because it is a defence that all animals
naturally have -quick reaction, combats invasive pathogens
-pattern recognition receptors- PRRs- recognise
danger signals - can detect
PAMPS- pathogen associated molecular patterns (LPS) and DAMPS- damage associated molecular
patterns- damages cells -Toll like
receptor(TLRs)- TLR4 used by macrophages to detect LPS, TLR7 (single stranded RNA of viruses),
TLR9(double stranded DNA of bacteria)- in membranes of phagolysosomes, alert cells bacteria, viruses have
been phagocytosed -Effector molecules: Defensins: alpha and beta,
produced in intestine, low beta defensins increase risk of colonic Chron’s disease
Cathelicidin- only one type in
humans=> LL37- antimicrobials, binds and neutralizes LPS
RELM beta-goblet cell molecule
associated with expulsion of parasite Trichuris muris
-defender cells: MACROPHAGE- have receptors on
their surface - recognize “danger molecules” characteristic of common microbial invaders
, -when it encounters a
bacterium, => engulfs it in a pouch (vesicle) called a phagosome =. it fuses with another vesicle - lysosome -
contain powerful chemicals, enzymes which destroy bacteria
-exit the bone marrow
enter blood stream=> monocytes (~ 2 billion of these cells circulating in blood at any one time)
-remain in the blood ~ three days, travel to the capillaries
- can leave the blood, enter the tissues=> mature into a macrophage
-secrete proteins =>
cytokines - hormone-like messengers which facilitate communication between cells of the immune system
-some monocytes and other immune system cells traveling in nearby capillaries
-can exist in three stages of readiness: “resting” state -in tissues, keeping
our tissues free of debris -dying cells give off “find me”
signals that attract macrophages -healthy cells display “don’t eat
me” signals on their surface=> protect from macrophage ingestion -express very few class II MHC
molecules on their surface
-activated -macrophages take larger gulps
and upregulate expression of class II MHC molecules -function as an antigen
presenting cell, engulfs invaders -use its class II MHC molecules
to display fragments of the invaders’ proteins for helper T cells to see - cytokine=> interferon gamma (IFNγ)-
prime a resting macrophage , produced mainly by helper T cells and natural killer cells
- good antigen presenters
-hyperactivation- higher state of
readiness -if they receive a direct
signal from an invader- lipopolysaccharide (LPS) can bind to receptors on the surface of primed macrophages
-bind to “danger signals” LPS or mannose => knows there has been an invasion=> stops proliferating
-increase production of
reactive oxygen (H2O2), increase of lysosomes- can release on parasites
NEUTROPHILS: ~20 billion neutrophils in circulation
-live a very short time , ~five days.
-not antigen presenting cells
-only takes neutrophils about half an hour to exit the blood and become fully activated
=> incredibly phagocytic
-produce battle cytokines (TNF) -alert other immune system cells
, -display PRR-TLR
-give off destructive chemicals which are pre-made and stored inside the neutrophil until needed
represent ~ 70% of the WBC
-give off chemicals that destroy both invaders and tissues
- can release web-like structures - neutrophil extracellular traps (NETs)- composed of cellular
DNA that is coated with proteins derived from the granules in which neutrophils store the chemicals they use to
do their destructive work -play a role in
protecting us against certain invaders, neutrophil function usually is tightly controlled to limit unwanted tissue
damage
-exist in inactive state - swept along by the blood at high speed
- intercellular adhesion molecule (ICAM)- on the surface of the endothelial cells that line blood
vessels - another adhesion molecule- selectin ligand (SLIG) - expressed on the surface of neutrophils
-activated macrophages => cytokines, interleukin 1 (IL-1) and TNF=> endothelial cells that line
nearby blood vessels receive signals=> they begin to express a new protein on their surface- selectin (SEL)-
adhesion partner for selectin ligand, functions like Velcro to grab neutrophils
- integrin bind with ICAM on endothelial cells=> stops rolling
-C5a fragment and f-met peptides from bacteria serve as chemoatractants
- activated by TNF as they pass through tissue
NATURAL KILLER (NK) - mature in the bone marrow, shortlived, with a half life of only about a week
-most found in the blood, spleen, liver (two organs that store blood), few reside in
tissues that are not under attack
-use the “roll, stop, exit” strategy to leave the blood and enter tissues at sites of infection
– and once in the tissues, they proliferate rapidly to build up their numbers
- can destroy some tumor cells, virus-infected cells, bacteria, parasites, and fungi
-do not have T cell receptors
-play two roles in defending us against infections: 1. give off cytokines (IFNγ) that help
with the defense -resting NK cells produce some cytokines
and can kill, several signals can activate natural killer cells, and each of these signals is generated only when the body
is under attack -can be activated by IFNα or IFNβ given off by other immune
system cells
2.“injection system” - perforin
proteins help deliver “suicide” enzymes (granzyme B) into a target cell -protein Fas ligand on the NK cell
surface interacts with a protein called Fas on the surface of its target, signaling the target cell to self-destruct
- Class I MHC molecules are found in varying amounts on the surface of most healthy
cells in our bodies=> presence of this surface molecule is an indication that a cell is doing okay
- “kill” signals involve interactions between the activating receptors on the surface of an
NK cell and unusual carbohydrates or proteins on the surface of a target cell
-peculiar surface molecules act as flags which indicate that the target cell has been
“stressed,” usually because it has been infected by a
virus or is becoming cancerous
- 3 major lines of defence: 1. PHYSICAL BARRIER- first line of defence
-prevents pathogens from easily entering the body
- skin and mucous membranes (digestive tract,
respiratory tract, reproductive tract)
-Anatomical barriers: Skin (tight junctions, multiple
layers, replicate frequently, desquamation, cilia, antimicrobial peptides, FA in sebum)
Mouth, upper alimentary canal
(enzymes, antimicrobial peptides, sweeping of surface by flow of fluid to stomach)
Stomach (low pH, digestive
enzymes, antimicrobial peptides, fluid to intestine) Small intestine (digestive
enzymes, antimicrobial peptides, flow to large intestine, peristalsis, epithelial cell shedding ,digestive enzymes,
bile stars )
Large intestine (normal
intestinal flora compete with pathogens, faeces expelled) Airways( cilia sweep mucous
outward, coughing, sneezing, macrophages in alveoli) Eyes(enzymes, flushing)
-Mucocilliary escalator-mucous membranes are
alimentary, respiratory, urogenital tract, eyes -mucous is viscous and traps
pathogens -Acid Mantle- skin secretes protective layer antimicrobial
peptides(psoriasin) and fatty acids in sebum -fatty acids decrease pH
- Digestive defences- mucosal surface of GI tract = ~200-
300m2 -saliva- IgA, lysozyme, peroxidase,
lactoferrin -gastric juice lowers pH by HCl+
digestive enzymes -active antimicrobial peptides created
from pepsin cleavage or precursors => lactoferrin -neutralization of gastric juice during
passage into small intestine -PANETH CELLS- defensins:-
defend from pathogens, shape microbiota, protect stem cells - PEYERS PATCH- lymphoid tissue
2.INNATE IMMUNITY – 2nd line of defence
- “innate” because it is a defence that all animals
naturally have -quick reaction, combats invasive pathogens
-pattern recognition receptors- PRRs- recognise
danger signals - can detect
PAMPS- pathogen associated molecular patterns (LPS) and DAMPS- damage associated molecular
patterns- damages cells -Toll like
receptor(TLRs)- TLR4 used by macrophages to detect LPS, TLR7 (single stranded RNA of viruses),
TLR9(double stranded DNA of bacteria)- in membranes of phagolysosomes, alert cells bacteria, viruses have
been phagocytosed -Effector molecules: Defensins: alpha and beta,
produced in intestine, low beta defensins increase risk of colonic Chron’s disease
Cathelicidin- only one type in
humans=> LL37- antimicrobials, binds and neutralizes LPS
RELM beta-goblet cell molecule
associated with expulsion of parasite Trichuris muris
-defender cells: MACROPHAGE- have receptors on
their surface - recognize “danger molecules” characteristic of common microbial invaders
, -when it encounters a
bacterium, => engulfs it in a pouch (vesicle) called a phagosome =. it fuses with another vesicle - lysosome -
contain powerful chemicals, enzymes which destroy bacteria
-exit the bone marrow
enter blood stream=> monocytes (~ 2 billion of these cells circulating in blood at any one time)
-remain in the blood ~ three days, travel to the capillaries
- can leave the blood, enter the tissues=> mature into a macrophage
-secrete proteins =>
cytokines - hormone-like messengers which facilitate communication between cells of the immune system
-some monocytes and other immune system cells traveling in nearby capillaries
-can exist in three stages of readiness: “resting” state -in tissues, keeping
our tissues free of debris -dying cells give off “find me”
signals that attract macrophages -healthy cells display “don’t eat
me” signals on their surface=> protect from macrophage ingestion -express very few class II MHC
molecules on their surface
-activated -macrophages take larger gulps
and upregulate expression of class II MHC molecules -function as an antigen
presenting cell, engulfs invaders -use its class II MHC molecules
to display fragments of the invaders’ proteins for helper T cells to see - cytokine=> interferon gamma (IFNγ)-
prime a resting macrophage , produced mainly by helper T cells and natural killer cells
- good antigen presenters
-hyperactivation- higher state of
readiness -if they receive a direct
signal from an invader- lipopolysaccharide (LPS) can bind to receptors on the surface of primed macrophages
-bind to “danger signals” LPS or mannose => knows there has been an invasion=> stops proliferating
-increase production of
reactive oxygen (H2O2), increase of lysosomes- can release on parasites
NEUTROPHILS: ~20 billion neutrophils in circulation
-live a very short time , ~five days.
-not antigen presenting cells
-only takes neutrophils about half an hour to exit the blood and become fully activated
=> incredibly phagocytic
-produce battle cytokines (TNF) -alert other immune system cells
, -display PRR-TLR
-give off destructive chemicals which are pre-made and stored inside the neutrophil until needed
represent ~ 70% of the WBC
-give off chemicals that destroy both invaders and tissues
- can release web-like structures - neutrophil extracellular traps (NETs)- composed of cellular
DNA that is coated with proteins derived from the granules in which neutrophils store the chemicals they use to
do their destructive work -play a role in
protecting us against certain invaders, neutrophil function usually is tightly controlled to limit unwanted tissue
damage
-exist in inactive state - swept along by the blood at high speed
- intercellular adhesion molecule (ICAM)- on the surface of the endothelial cells that line blood
vessels - another adhesion molecule- selectin ligand (SLIG) - expressed on the surface of neutrophils
-activated macrophages => cytokines, interleukin 1 (IL-1) and TNF=> endothelial cells that line
nearby blood vessels receive signals=> they begin to express a new protein on their surface- selectin (SEL)-
adhesion partner for selectin ligand, functions like Velcro to grab neutrophils
- integrin bind with ICAM on endothelial cells=> stops rolling
-C5a fragment and f-met peptides from bacteria serve as chemoatractants
- activated by TNF as they pass through tissue
NATURAL KILLER (NK) - mature in the bone marrow, shortlived, with a half life of only about a week
-most found in the blood, spleen, liver (two organs that store blood), few reside in
tissues that are not under attack
-use the “roll, stop, exit” strategy to leave the blood and enter tissues at sites of infection
– and once in the tissues, they proliferate rapidly to build up their numbers
- can destroy some tumor cells, virus-infected cells, bacteria, parasites, and fungi
-do not have T cell receptors
-play two roles in defending us against infections: 1. give off cytokines (IFNγ) that help
with the defense -resting NK cells produce some cytokines
and can kill, several signals can activate natural killer cells, and each of these signals is generated only when the body
is under attack -can be activated by IFNα or IFNβ given off by other immune
system cells
2.“injection system” - perforin
proteins help deliver “suicide” enzymes (granzyme B) into a target cell -protein Fas ligand on the NK cell
surface interacts with a protein called Fas on the surface of its target, signaling the target cell to self-destruct
- Class I MHC molecules are found in varying amounts on the surface of most healthy
cells in our bodies=> presence of this surface molecule is an indication that a cell is doing okay
- “kill” signals involve interactions between the activating receptors on the surface of an
NK cell and unusual carbohydrates or proteins on the surface of a target cell
-peculiar surface molecules act as flags which indicate that the target cell has been
“stressed,” usually because it has been infected by a
virus or is becoming cancerous
