PRELIM LECTURE L2: INNATE IMMUNITY Flashcards
some cards can be lengthy as it also functions as notes
which lines of defenses are under nonspecific defense mechanism
first line and second line of defense
which line of defense is under specific defense mechanism
third line of defense
components of first line of defense
physical, chemical, and biological barriers
components of second line of defense
cellular (phagocytic cells) and humoral factors (APRs, complement, cytokine)
components of third line of defense
lymphocytes and anitbodies
define innate immunity
ability to resist infection by means of normally present body functions
T or F:
innate immunity is not present at birth since the immune system of newborns are not fully developed
F
it is present at birth
why is innate immunity considered non-adaptive or non-specific?
It responds the same way to all infections and does not retain memory of past encounters
what does physical barriers do
block or limit access to the body
what does humoral and cellular factors generally do
initiate activation of immune mechanism
skin should always be ____ to remain protected from infections
intact, unbroken
what maintain the pH of the skin, inhibiting the growth of some microorganisms
lactic acid in sweat
fatty acids in sebum
pH of the skin
5.6
what protein has an antibacterial effect against gram-negative bacteria (E. coli)
psoriasin
which cells produce psoriasin
keratinocytes
complication where keratinocytes have excessive production of psoriasin
psoriasis
attacks the cell wall of microbes, especially gram positive bacteria
lysozyme
what does lysozyme digest
Beta (1,4)-glycosidic bonds
NAM stands for
N-acetylmuramic acid
NAG stands for
N-acetyl glucosamine
where is the point of digestion of lysozyme in the bacterial cell wall
between NAM and NAG
mechanism of the respiratory system as first line of defense
repels foreign pathogen through coughing and sneezing
components of respiratory system that aids repelling of pathogens
mucus, surfactants, and cilia
mechanism of the urinary system as first line of defense
flushing action through urination, slight acidity
what substance that is found in the genital tract that destroys pathogens with its acidity + pH
lactic acid, 5
this inhibits the growth of bacteria and fungi in female reproductive tract
acid mantle of vagina
mechanism of the digestive system as first line of defense
halts microbial growth and helps eliminating pathogens with its hydrochloric acid
this bacteria can withstand the pH of HCl and causes peptic ulcer
Helicobacter pylori
mechanism of the lacrimal and salivary glands as first line of defense
lysozyme in tears defend against gram positive bacteria
who demonstrated the antibacterial activity of lysozymes through crystallization of tears
Alexander Flemming in 1992
mechanism of the auditory canal as first line of defense
has earwax that serves protection against pathogens
non-pathogenic organisms in some parts of the body that deter growth of pathogens
normal flora (microbiota)
two ways the microbiota can deter growth of pathogens
competitive exclusion
producing substances
define competitive exclusion
two species that compete for the same source cannot coexist; inferior species will be eliminated
example of competitive exclusion
vaginal normal flora competes with C. albicans
substance that is produced by gut bacteria that binds and penetrates to negatively charged surface of certain bacteria
colicins
these cells monitor the entrance of a pathogen
sentinel cells
cells present in the peripheral blood
neutrophil
eosinophil
basophil
monocytes
cells present in the tissues for primary defense
macrophages
mast cells
dendritic cells
primary granules of neutrophil
myeloperoxidase, lysozymes, etc.
secondary granules of neutrophil
lysozyme, lactoferrin, respiratory burst components, etc.
main function of neutrophils in the immune system
phagocytosis, antimicrobial properties
lysozymes are aka
muramidase
it is an iron-binding glycoprotein that competes with bacteria
lactoferrin
myeloperoxidase is important for
respiratory and oxidative burst
also serves as an adhering molecule of neutrophil for it to adhere to epithelial cells
lactoferrin
granules of basophils
histamine, small amount of heparin, eosinophil chemotactic factor-A
when this immunoglobulin binds to basophil or mast cell the cell will degranulate
IgE
what happens after basophil or mast cell degranulates
induce or maintain allergic reactions through release of inflammatory mediators such as histamine and heparin
mechanism of eosinophil chemotactic factor-A
calls eosinophil to the site of allergen
granules of eosinophils
acid phosphatase, major basic proteins
this eosinophil factor recognizes IgE on helminth parasites
epsilon receptor (FceR)
how does eosinophil degranulate during presence of helminths
when IgE binds to FecR of eosinophils, the IgE will also bind to the helminth, leading to degranulation of eosinophils and MBP will be released to digest the helminth
why are monocytes considered “agranulocytes”
its granules are not visible under the microscope (fine-dustlike granules)
the MBP is rich in what amino acid
arginine
this is released by eosinophils to lessen hypersensitivity reactions
amine oxidase
mechanism of amine oxidase in lessening hypersensitivity reactions
neutralizes histamine
T or F:
macrophages do not contain peroxidase
T
why is macrophage less efficient in phagocytosis
because of its slow mobility (because it is located in the tissue)
important functions of macrophage
secretion of cell mediators and antigen presentation (APC)
macrophage of the central nervous system
microglial cells
macrophage of the kidney
mesangial cells
macrophage of the liver
Kupffer cells
macrophage of the lung
alveolar macrophage (dust phagocytes)
macrophage of the lymph node
lymph node macrophage
macrophage of the spleen
splenic macrophage
macrophage of the synovial fluid
synovial A cells
macrophage of the connective tissues
histiocytes
macrophage in the bone marrow
promonocyte, monocyte
aerobic macrophage
alveolar macrophage
anaerobic macrophage
M1 macrophage
lineage of mast cells
mesenchymal lineage
T or F:
mast cells have longer life span than basophils
T
longer lifespan because they reside in tissues
granules of mast cells
ACP, ALP, proteases, histamine
main functions of mast cells
allergic reaction and antigen presentation
most potent phagocytes
dendritic cells
main function of dendritic cells
phagocytose antigen and present it to helper T lymphocytes
group of non-specific serum components that enhance the effect of antibody
complement
3 types of complement
classical pathway
alternative pathway
mannose-binding lectin pathway
enzyme with antibacterial activity found in tears saliva and other cells
lysozyme
major functions of complement
opsonization
chemotaxis
lysis of cells
inflammation
serum protein with bactericidal and viricidal effects in the presence of the third complement component of magnesium ions; stabilizes the complement
properdin
overall function of complement
mediation of inflammation
heat stable cationic substance with bactericidal activity found in the serum
betalysin
family of glycoproteins produced by all animal cells that exert virus-nonspecific but host-specific antiviral activity
interferon
how does interferon act as an antiviral agent
by interfering with viral replication
aside acting as antiviral agent, interferon can also act as
immunomodulators
antineoplastic agents (interferes with cancer cell multiplication)
what IFN is produced by leukocytes
IFN-alpha
what IFN is produced by fibroblasts and epithelial cells
IFN-beta
function of IFN-alpha and beta
antiviral
increases MHC class 1 expression
what IFN is produced by T cell and NK cells
IFN-gamma
function of IFN-gamma
major macrophage activator
induces MHC class 2 and can synergize with TNF
what happens to cells with no MHC class 1
attacked by NK cells (so it should be found in normal, healthy cells)
MHC-HLA stand for
major histocompatibility complex- human leukocyte antigen
MHC-HLA is used for what test
organ compatibility testing
this stimulates the recruitment of neutrophils and monocytes to sites of infection and activates them to eradicate microbes
tumor necrosis factor
TNF-alpha is knows as
cachectin
target cells of cachectin
macrophages, nk cells
prominent biological activities of cachectin
local inflammation
endothelial activation
TNF-beta is known as
lymphotoxin
target cells of lymphotoxin
t cells, b cells
prominent biological activities of TNF-beta
killing
endothelial activation
what consequence can happen when TNFs gain access to the circulation during infection
they mediate a series of reaction, induce shock and result to SEPTIC SHOCK
naturally occurring proteins that mediate communication between cells
interleukins
function of interleukins
regulate cell growth, differentiation, motility
stimulate immune responses (e.g. inflammation)
interleukin:
proinflammatory cytokine; induces fever
IL1
interleukin:
activates nk cells to become lymphokine activated killer cells (LAK)
IL2
formerly known as t-cell growth factor
IL2
interleukin:
induces hematopoiesis
IL3
formerly known as multi colony-stimulating factor
IL3
interleukin:
key regulator in humoral and adaptive immunity; induces transformation of naive helper T cell to TH2 cell
IL4
interleukin:
induce acute phase response of inflammation along with IL1 and TNF
IL6
interleukin:
principal secondary mediators of inflammation produced by several cells
IL8
define acute phase reactants
glycoproteins that are normal in serum but rise at different rates and levels during inflammation
cells that synthesize APRs
hepatocytes
how long do hepatocytes synthesize APRs
12-24 hours
what triggers hepatocytes to rapidly synthesize APRs
cytokines
triggers of pro-inflammatory cytokine production
IL-1 beta
IL-6
TNF-alpha
example physiologic trigger of APR release
strenuous exercise (due to heat production)
which cells produce pro-inflammatory cytokines
monocyte and macorphage
2 types of APRs
positive and negative
examples of positive APRs
CRP, mannose binding protein, serum amyloid A
examples of negative APRs
albumin, transferrin, antithrombin
actions of APRs
bind to microorganisms and promote adherence (phagocytosis)
limit destruction caused by proteolytic enzymes from WBCs
cause of albumin to decrease in inflammation
capillary impermeability
cause of transferrin to decrease in inflammation
production of CRP
cause of antithrombin to decrease in inflammation
since it is used in modulation of infection to promote adherence and phagocytosis
a primitive form of antibody (thought to be an antibody because it precipitated with C-polysaccharide of pneumococcus bacteria)
CRP
who discovered CRP
Tillett and Francis in 1930
functions of CRP
opsonization
agglutination
precipitation
complement activation (classical pathway)
main substrate of CRP
phosphocholine
T or F:
CRP binding is calcium-dependent and specific
F
non-specific
response time of CRP
4-6 hours
normal concentration of CRP
0.5 md/dL
times of increase of CRP
1000x
CRP peaks within how many hours
48 hours
T or F:
CRP rises faster than ESR but slower than WBC count
F
rises faster than both
T or F:
CRP rapidly declines even without stimulus
T
most widely used indicator of acute inflammation
CRP
physical properties of CRP
do not cross the placenta
thermo-labile
temperature and time CRP can be destroyed
56 C for 30 minutes
why it is necessary to heat CRP and destroy it in the serum in some testing
so it will not interfere with some testing for presence of antibodies
electrophoretic mobility of CRP
gamma region
apolipoprotein transported by HDL site of infection
serum amyloid A (SAA)
functions of SAA
helps remove cholesterol from cholesterol filled macrophages in tissue injury
helps recycle cell membrane cholesterol and phospholipids for building new cells
help clean up of injured area
how many hours does SAA peak
24-48 hours
response time of SAA
24 hours
normal concentration of SAA
5 md/dL
times increase of SAA
1000x
T or F:
SAA increases more in bacterial infection than viral infections
T
SAA can be found in what conditions
atherosclerotic lesions
T or F:
high levels of SAA can be toxic to the heart
T
contribute to inflammation in coronary artery disease
major component of alpha band in serum electrophoresis
alpha 1-antitypsin (AAT)
function of AAT
inhibits leukocyte proteases
regulate pro-inflammatory cytokines (inhibit WBC)
inactivate serin proteases (produced in complement cascade and fibrinolysis)
leukocyte protease that damages lungs during chronic inflammation
neutrophil elastase
deficiency of AAT can lead to what conditions
emphysema
hepatic disorders
what happens if lungs lack AAT
open to damage by neutrophil elastase
how can abnormalities in AAT cause liver damage
due to it being trapped in the liver
protein cleaved to make up fibrin clot
fibrinogen
function of fibrinogen
stimulates fibroblast proliferation and growth
increased levels of fibrinogen can increase the risk of
coronary artery disease
response time of fibrinogen
24 hours
normal concentration of fibrinogen
200-400
times increase of fibrinogen during inflammation
2-5x
binds to free hemoglobin released during intravascular hemolysis
haptoglobin
haptoglobin binding: reversible or irreversible
irreversible
function of haptoglobin
protect the body (esp. kidney) from oxidative damage
conserves iron
electrophoretic mobility of haptoglobin
a2
why is haptoglobin initially low in early inflammation
because of intravascular hemolysis (CC1 principle)
copper transporting protein
ceruloplasmin
ceruloplasmin deficiency
Wilson’s disease
function of ceruloplasmin
binds to copper
convert ferric iron (toxic) to non-toxic (ferrous)
end-game of complement pathway is always:
cell lysis
response time of complement C3
48-72 hours
normal concentration of complement C3
60-140 mg/dl
times increase of complement C3
2x
function of complement c3
opsonization
lysis
response time of haptoglobin
24 hours
normal concentration of haptoglobin
400-290 mg/dl
times increase of haptoglobin
2-10x
response of ceruloplasmin
48-72 hours
normal concentration of ceruloplasmin
20-40 mg/dl
times increase of ceruloplasmin
2x
overall reaction of the body to injury or infection
inflmmation
1st objective of inflammation
localize and eradicate irritant and repair surrounding tissue
stages of inflammation
vascular response
cellular response
resolution and repair
5 cardinal signs
rubor
calor
tumor
dolor
functio laesa
T or F:
inflammation should always lead to recovery
T
what are the two main processes involved in the vascular response during inflammation?
vasodilation
increased capillary permeability
what causes vasodilation
mediators such as histamine from injured mast cells
purpose of vasodilation
to increase blood flow to site
T or F:
vasodilation is only experience by peripheral sites of the body (e.g. skin)
T
cardinal signs under vasodilation
rubor and calor
causes plasma leakage to tissues
increased capillary permeability
cardinal signs under increased capillary permeability
dolor and calor
what are the two main processes involved in the cellular response during inflammation?
neutrophil activation
migration of macrophage and other cells
process of migration to tissue from blood vessels
diapedesis
directed migration of WBCs toward infection or injury due to chemical signals (chemokines)
chemotaxis
diapedesis of neutrophils takes how many hours
24-48 hours
how long does it take for neutrophil to move
30-60 minutes
which attract WBCs to site of injury
chemokines
release chemokines that cause vasodilation and induce selectins
resident macrophages and mast cells
cause circulating WBCs to toll along the vascular wall
selectins
cause leukocytes to bind firmly to endothelial cells
chemokine-induced integrins (on WBCs)
purpose of integrins in diapedesis
enable leukocytes to crawl between endothelial cells
migration of macrophage and other cells involves:
phagocytosis= clearing
why macrophage and dendritic cells arrive late on the site of infection
they clean up debris released from neutrophils
“janitors”
two classes of chemotaxis
positive chemotaxis
negative chemotaxis
chemotaxis towards the stimulus
positive
chemotaxis away from the stimulus
negative
T or F:
without chemotactic factors, cell motion is random
T
How do opsonins enhance phagocytosis?
coat pathogens, making them more recognizable to phagocytes
3 ways resolution and repair can result to
1) affected area totally repaired
2) injury can lead to formation of abscess and lead to functio laesa
3) granuloma formation of cell sue to delayed hypersensitivity reactions (e.g. MTB)
who first described functio laesa
Rudolf Virchow in 19th century
two classes of phagocytosis
direct and indirect
direct or indirect phagocytosis:
enhanced by opsonization
indirect
direct or indirect phagocytosis:
do not need opsonins
direct
direct or indirect phagocytosis:
via primitive pattern recognition receptor (PPRP)
direct
direct or indirect phagocytosis:
via opsonins (Antibody, Complement, CRP)
indirect
direct or indirect phagocytosis:
use of toll-like receptors (TLR)
direct
direct or indirect phagocytosis:
use of cell surface reseptors (FcR, C’R)
indirect
steps of phagocytosis
1) adherence (physical contact; pseudopod formation)
2) engulfment
3) formation of phagosome
4) granule contact
5) formation of phagolysosome
6) digestion
7) cytopepsis
8) excretion
components in pathogens that aid in direct phagocytosis
pathogen-associated molecular patterns (PAMP)
PAMP of gram + bacteria
peptidoglycan
PAMP of gram - bacteria
lipoprotein
PAMP of flagellates
flagellin
natural receptors that detect PAMP
pathogen recognition receptors (PRRs)
T or F:
PAMP is always present in bacteria
T
how many TLRs in human
10 (TLR1-TLR10)
types of PPRs
TLRs
C-type lectin receptors (CLRs)
Retinoic acid-inducible gene-I-receptors (RLRs)
Nucleotide-binding oligomerization domain receptors (NOD)
PRR that detect mannans and beta glucans in fungi
CLRs
PRR that detects RNA from RNA viruses
RLRs
PRR that detects peptidoglycans of gram + bacteria and intracellular protozoans
NOD
what part of antigen does opsonin bind
epitope
what organism is Toll discovered
fruit fly Drosophila
TLR for MTB
TLR1
TLR for gram + bacteria
TLR2
TLR for gram - bacteria
TLR4
TLR is found highest in which cells
macrophage, monocyte, neutrophil
APR that activates macrophage and monocyte
SAA
TLR for motile bacteria
TLR 5
TLR for viral dsDNA
TLR 3
