Exam #3 Flashcards
general characteristics of viruses
three shapes:
icosahedral
helical
complex
protein coat capsid: protects nucleic acids, carries required enzymes
composed of identical subunits capsomeres
capsid plus nucleic acids called nucleocapsid
non-enveloped (naked) viruses
lack envelope; more resistant to disinfectants
enveloped viruses have lipid bilayer envelope
matrix protein between nucleocapsid and envelope
Names of viruses
Viruses often referred to informally
groups of unrelated viruses sharing routes of infection
respiratory route: respiratory viruses
oral-fecal route: enteric viruses
zoonotic viruses cause zoonoses (animal to human)
arboviruses (from arthropod borne) are spread by arthropods; often can infect widely different species
important diseases:
dengue fever
yellow fever
West Nile encephalitis
Zika virus
Chikungunya
animal virus replication
5-step infection cycle:
1.attachment
2. penetration and uncoating
3. synthesis (replication)
antigenic shift, antigenic drift, reverse transcription
4. assembly
5. release
- Attachment
- attachment
viruses bind to receptors
usually glycoproteins on cytoplasmic membrane
often more than one required (for example, HIV binds to two)
normal function unrelated to viral infection
specific receptors (tropism) required; limits range of virus
-dogs don’t contract measles from humans…
Nonstructural proteins
Nonstructural proteins include enzymes and transcription factors that are needed for viral replication but are not part of the viral particle
Variants have many mutations in a key region of the viral spike protein called the receptor binding domain, which is required to infect cells
penetration and uncoating: fusion
Enveloped viruses can fuse with host cell membrane.
non-enveloped viruses cannot fuse, enter host cell by endocytosis
Synthesis
expression of viral genes to produce viral structural and catalytic genes (capsid proteins, enzymes required for replication)
synthesis of multiple copies of genome
most DNA viruses multiply in nucleus
enter through nuclear pores following penetration
three general replication strategies depending on type of genome of virus
1. DNA viruses
2. RNA viruses
3. reverse transcribing viruses
replication of DNA viruses
usually in nucleus (poxviruses - exception: replicate in cytoplasm, encode all enzymes for DNA, RNA synthesis)
dsDNA replication straightforward - follows central dogma
replication of ssDNA viruses
ssDNA similar except complement
first synthesized to generate double-stranded DNA.
Newly synthesized strand acts as template to produce more ssDNA
Replication of RNA viruses
majority single-stranded; replicate in cytoplasm
require virally encoded RNA polymerase (replicase - RNA directed RNA polymerase),
- uses RNA template to synthesize new RNA strand
which lacks proofreading, allows antigenic drift
->influenza viruses
replication of RNA viruses
majority single-stranded; replicate in cytoplasm
require virally encoded RNA polymerase (replicase - RNA directed RNA polymerase),
ss (+) RNA
Viral RNA binds host ribosomes and gets translated to make viral proteins, including a viral replicase that is used to synthesize more copies of the viral genome.
To do this, it
makes multiple copies of the complementary (-) strand using the original (+) strand as a template.
these (-) strands act as templates to produce more viral (+) strand RNA packaged as genomes into new virons that are forming.
genomes are functional mRNAs
Polio virus, Rhinovirus, Coronavirus, Flaviviruses:
Synthesis of SS(-) RNA
replication of RNA viruses
require virally encoded RNA polymerase (replicase - RNA directed RNA polymerase),
- lacks proofreading – generates mutations during replication.
ss (–) RNA cannot be directly translated
must be copied into a (+) strand.
Measles virus, Ebola virus Influenza virus:
A replicase is carried into host cell.
Once (+) strand produced, it can also be
translated to make viral proteins and
used as template for synthesizing
new (-) RNA strands.
RNA-dependent RNA polymerase (RdRp)
synthesis of complementary strand of RNA in single-stranded RNA viruses requires replicase not found in host cells:
virally encoded RNA polymerase lacks proofreading, allows antigenic drift
Dengue viral architecture of
RNA-dependent RNA polymerase
(NS5) consisting of fingers, palm, and thumb structure characteristic of known polymerase structures
catalytic site
divalent metal ions Zn2 and Mg2
high rate of error during copying (≈10−4)
antigenic drift
mechanism for variation in viruses
involves accumulation of mutations in genes that code for antibody-binding sites.
continuous, ongoing process resulting in emergence of new strain variants.
example: influenza viruses can change through antigenic drift, a process in which mutations to the virus genome produce changes in the viral H or N.
Hemaglutinin - glycoprotein on surface, binds cells
with sialic acid on membrane
Neuraminidase - surface protein - enables viral release from cell.
Oseltamivir (Tamiflu) - neuraminidase inhibitor
Why RNA viruses recombine
Recombination in RNA viruses involves the formation of chimeric molecules from parental genomes of mixed origin. – requires that 2 or more viruses infect the same host cell.
Co-infection of a cell by genetically distinct viral strains can lead to the generation of recombinant viruses.
Coronavirus is an unsegmented RNA virus.
natural selection acts on recombinants
Antigenic shift
some RNA viruses segmented
reassortment results in
antigenic shift
Reassortment of segmented viruses genomes causes antigenic shift – there is a sudden change in spikes because the virus acquires a new genome segment.
-two or more different strains of a virus, or strains of two or more different viruses, combine to form new subtype having mixture of surface antigens of original strains.
replication of reverse-transcribing viruses
encode reverse transcriptase: makes DNA from RNA
retroviruses have ss (+) RNA genome (HIV)
reverse transcriptase synthesizes single DNA strand
complementary strand synthesized
dsDNA integrated into host cell chromosome
can direct productive infection or remain latent
cannot be eliminated
If RNA virus is retrovirus, different enzyme required, not found in host cells:
reverse transcriptase – synthesizes strand of DNA from RNA template.
reverse transcription and genome integration
HIV-encoded reverse transcriptase makes DNA copy of viral RNA genome
RNA template degraded; cDNA strand is made, yielding double-stranded DNA copy of viral RNA
copy circularized, then moved into host nucleus
Integrase inserts in linear form into host chromosome
no specific host sequence needed
once inserted, provirus is permanent part of that cell’s genome
RNA slides into the reverse transcriptase through a path where polymerase and Rnase H active sites are located
reverse transcriptase frequently makes mistakes, lacks proofreading ability
allows HIV to evolve quickly, avoid immune response
Assembly and release
assembly
protein capsid forms; genome, enzymes packaged
takes place in nucleus or in organelles of cytoplasm
release
most via budding
viral protein spikes insert into host cell membrane; matrix proteins accumulate; nucleocapsids extruded
covered with matrix protein and lipid envelope
-some obtain envelope from organelles
non-enveloped viruses released when host cell dies, often by apoptosis initiated by virus or host
acute and persistent infections
acute:
rapid onset
short duration
persistent:
continue for years
or lifetime
persistent infections chronic or latent
chronic infections: continuous production
of low levels of virus particles
may or may not
have symptoms
latent infections: viral genome (provirus)
remains silent in host cell; can reactivate
some viruses exhibit both
(HIV)
Hepatitis B
Hepatitis B virus infection may be either acute (self-limiting) or chronic (long-standing) - persons with self-limiting infection clear the infection spontaneously within weeks to months
Virus transmitted through contact with the blood or other body fluids of an infected person.
-> occupational hazard for health workers; can be prevented by currently available safe and effective vaccine. (CDC)
virus replicates and circulates in blood for years, often asymptomatically, which increases spread
Children less than 6 years of age who become infected with the hepatitis B virus are the most likely to develop chronic infections.
first vaccine approved in early 1980s, administered to all infants before leaving hospital
viruses and human tumors
cancerous or malignant can metastasize; benign do not
proto-oncogenes and tumor suppressor genes work together to stimulate, inhibit growth and cell division
mutations cause abnormal and/or uncontrolled growth
usually multiple changes at different sites required
viral oncogenes similar to host proto-oncogenes; can interfere with host control mechanisms, induce tumors
Tumor suppressor genes
Tumor suppressor genes are normal genes that slow down cell division, repair DNA mistakes, or tell cells when to die (apoptosis or programmed cell death).
When tumor suppressor genes don’t work properly, cells can grow out of control, which can lead to cancer.
Proto-oncogene
proto-oncogene: often encodes proteins that stimulate cell division, prevent cell differentiation or regulate programmed cell death (apoptosis)
Src was first discovered as an oncogene in a chicken retrovirus:
An oncovirus is a virus that causes cancer.
Studies of avian Rous sarcoma virus (RSV) led to the discovery of the viral oncogene src.
productive infections, latent infections, tumors
virus-induced tumors rare; most result from mutations
Plant viruses
plant viruses - common
don’t attach to cell receptors; enter via wounds in cell
wall, spread through cell openings (plasmodesmata)
plants rarely recover, lack specific immunity - many viruses
extremely hardy
transmitted by soil, humans, insects, contaminated seeds, tubers, pollen, grafting
Viroids
viroids: small single-stranded RNA molecules
-246–375 nucleotides, about 1/10th smallest RNA virus
-forms closed ring; hydrogen bonding gives ds look
-thus far only found in plants; enter through wound sites
Prions
composed solely of protein; no nucleic acids
linked to slow, fatal human diseases; animal diseases
usually transmissible only within species
mad cow disease in England killed >170 people
prion proteins accumulate in neural tissue
neurons die
tissues develop holes
brain function deteriorates
characteristic appearance gives rise to general term for all prion diseases: transmissible spongiform encephalopathies
cells produce normal form
PrPC (prion protein, cellular)
proteases readily destroy
infectious prion proteins
PrPSC (prion protein, scrapie)
resistant to proteases; become insoluble, aggregate
unusually resistant to heat, chemical treatments
hypothesized that PrPSC converts PrPC misfolding to PrPSC
Innate and adaptive immunity
innate immunity is routine protection, present at birth
although considered non-specific, involves pattern recognition of specific molecules
Innate immunity is an evolutionarily ancient defense system that provides multicellular organisms with immediate defense mechanisms without requiring prior exposure.
adaptive immunity develops throughout life in response to exposure to microbes and foreign material
antigens cause response, system produces antibodies to bind
can also destroy host cells
overview of the innate defenses
first-line defenses are barriers blocking entry if invaders breach, sensor systems detect, send out signals
sentinel cells use pattern recognition receptors (PRRs)
effector actions:
innate defenses work to destroy invaders
first-line defenses
skin
difficult for microbes to penetrate
epidermis: many layers of
epithelial cells
outermost cells are dead, filled with keratin
repels water, maintains dry environment
continually slough off along with any attached microbes
dermis: tightly woven, fibrous connective tissue
mucus membranes
line digestive, respiratory, and genitourinary tracts
bathed with mucus and other secretions
constant turnover of epithelial cells that are shed with any attached microbes
mucociliary escalator
propels mucus, trapped particles out of respiratory tract
normally keeps lower respiratory tract free of microbes
cilia of epithelial cells beat synchronously
upper respiratory system
nose and nasal cavity, pharynx (throat), epiglottis
lined by mucous membranes
Goblet cells produce mucus, a slimy glycoprotein
traps air-borne dust and particles including microbes
The BAM model Bacteriophage adhering to mucus provide a non–host-derived immunity
Mucus is produced and secreted by the underlying epithelium.
(2) Phage bind variable glycan residues displayed on mucin glycoproteins via variable capsid proteins (Ig-like domains).
(3) Phage adherence creates an antimicrobial layer that reduces bacterial attachment to and colonization of the mucus, which in turn lessens epithelial cell death.
(4) Mucus-adherent phage are more likely to encounter bacterial hosts, thus are under positive selection for capsid proteins that enable them to remain in the mucus layer.
(5) Continual sloughing of the outer mucus provides a dynamic mucosal environment.
first-line defenses antimicrobial substances
protect skin, mucous membranes
salt accumulates from perspiration
lysozyme degrades peptidoglycan
peroxidase enzymes break down hydrogen peroxide
lactoferrin- binds iron
AMPs (antimicrobial peptides)
defensins - form pores in
microbial membranes
short antimicrobial peptides
found within mucous
membranes and phagocytes
nonspecific antimicrobial factors
Innate immune defenses – antimicrobial substances
Lactoferrins and defensins in the cervical plug protect the fetus and separate the vagina, which is normally colonized with multiple microorganisms, from the normally sterile intra-uterine compartment.
transferrin - limits pathogen access to iron
normal microbiota (flora)
competitive exclusion of pathogens
cover binding sites, consume available nutrients
production of toxic compounds
Propionibacterium degrade lipids, produce fatty acids
E. coli synthesizes colicins in intestinal tract
Lactobacillus in vagina produce low pH
disruption of normal microbiota (antibiotic use) can predispose person to infections
Clostridium difficile in intestine
Candida albicans in vagina
Skin - normal microbiota
adapted to dry, salty, cool habitat
use substances in sweat, sebum as nutrients
produce by-products that inhibit other microbes
breakdown of sebum yields fatty acids - toxic to many bacteria
outermost layers bathed in secretions
sweat evaporates, leaves salty residue that inhibits microbes
sebaceous glands open into hair follicles, secrete oily sebum
too dry, salty, acidic, and toxic for most pathogens…
those that tolerate often shed with dead skin cells
production of toxic compounds
A colicin is produced by and toxic to some strains of E. coli. Colicins are released into the environment to reduce competition from other bacterial strains.
Colicins bind to outer membrane receptors, using them to translocate to the cytoplasm or cytoplasmic membrane, where they exert their cytotoxic effect, including depolarisation of the cytoplasmic membrane, DNase activity, RNase activity, or inhibition of murein synthesis.
Virtually all colicins are carried on plasmids.wikipedia
cells of the immune system
red blood cells (erythrocytes) carry O2
platelets (from megakaryocytes) involved in clotting
white blood cells (leukocytes) important in host defenses
formation, development termed hematopoiesis
blood cells originate from hematopoietic stem cells
-found in bone marrow
-induced to develop by colony-stimulating factors (CSFs)
move around body, travel through circulatory system
always found in normal blood
-numbers increase during infections
some reside in various tissues
four types of leukocytes (white blood cells)
- granulocytes contain cytoplasmic granules
neutrophils highest numbers, engulf and destroy bacteria, other
material – most abundant, first responders
basophils involved in allergic reactions, inflammation
mast cells similar; found in tissues
eosinophils fight parasitic worms
also involved in allergic reactions
Mononuclear phagocytes
comprise mononuclear
phagocyte system (MPS)
includes monocytes (circulate in
blood) and cell types that develop as they leave blood stream
macrophages differentiate from
monocytes
often named after location where
found in body
The growth and differentiation of macrophages depends on lineage-determining cytokines, and interactions with supporting tissue in haematopoietic organs.
Dendritic cells and lymphocytes
- dendritic cells
sentinel cells, function as “scouts”
engulf material in tissues,
bring it to cells of adaptive immune
system for “inspection”
usually develop from monocytes - lymphocytes
responsible for adaptive immunity
B cells, T cells highly specific in recognition of antigen
generally reside in lymph nodes, lymphatic tissues
natural killer (NK) destroy certain types of cells
What is the role of the sensor systems in innate immunity?
They detect invasion by microbes.
How are the roles of neutrophils and macrophages similar?
They are both phagocytic cells.
Macrophages descend from monocytes.
cell communication
communication allows coordinated response
surface receptors serve as “eyes” and “ears” of cell
usually span membrane, connect outside to inside
binding to specific ligand induces response
adhesion molecules allow cells to adhere to other cells
- endothelial cells can adhere to phagocytic cells, allow them to exit bloodstream
cytokines are “voices” of cell
produced by cells, diffuse to others, bind appropriate receptors to induce changes: growth, differentiation, movement, cell death
act at low concentration; effects local, regional, systemic
Cytokines
chemokines: chemotaxis of immune cells
colony-stimulating factors (CSFs): multiplication and differentiation of leukocytes
interferons (IFNs): control of viral infections, regulation of inflammatory response
interleukins (ILs): produced by leukocytes; important in innate and adaptive immunity
tumor necrosis factor (TNF): inflammation, apoptosis
…act together to promote response
pattern recognition receptors (PRRs) detect pathogen-associated molecular patterns (PAMPs)
cell wall components (lipopolysaccharide, peptidoglycan, lipoteichoic acid, lipoproteins), flagellin subunits, viral RNA molecules
may be called MAMPs (for microbe-associated)

some are DAMPs (for danger-associated), which indicate host cell damage
pattern recognition receptors (PRRs)
cells “see” PAMPs in extracellular environment
others in phagosomal or endosomal membranes of organelles -
characterize ingested material
following detection, signal
transmitted to nucleus where it
induces gene expression,
inflammatory response, antiviral
response
Toll-like receptors (TLRs)
recognize a variety of pathogen-associated molecular patterns (PAMPs).
Recognition of lipopolysaccharide (LPS) by TLR4/TLR2 recognizes a broad range of structurally unrelated ligands and functions in combination with other TLRs, including TLR1 and TLR6.
TLR3 - double-stranded (dsRNA)
TLR5 - bacterial flagellin
TLR9 - unmethylated CpG motifs, abundant in bacterial DNA.
G+, Gram-positive; G–, Gram negative; GPI, glycophosphoinositol; RSV, respiratory syncytial virus.
(PRR) NOD like receptors
NOD-like receptors (NLRs) found in cytoplasm
detect bacterial components indicating cell has been breached; some
detect damage
unleash series of events to protect host - some at expense of cell
some NLRs join cytoplasmic proteins to form an inflammasome
- activates inflammatory response by cytokine expression
NOD-like receptors –
growth cycle of some pathogenic microorganisms involves infection of the cytoplasm
Viral genes are often transcribed and translated in the cytoplasm, and virus particles are assembled. In addition, some bacteria and parasites have a series of escape mechanisms, such as making holes in the phagosome membrane and entering the cytoplasm.
nucleotide-binding domain and leucine-rich repeat-containing proteins (NLRs)
Inflammasome
a subset of NLRs (named NLRP1) are able to assemble and oligomerize into a common structure
Inflammasomes play an important role in the induction of inflammatory cascades and coordination of host defenses, both via the activation and secretion of pro-inflammatory cytokines and the induction of a specialized form of immune-stimulatory programmed cell death termed pyroptosis.
RIG-like receptors (RLRs) found in cytoplasm
detect viral RNA indicating infection, produce interferons
viral RNA often 3 phosphates at 5′ end (no capping as in cytoplasmic RNA),
often double-stranded
interferons cause neighboring cells to express inactive antiviral proteins (iAVPs) (protein kinase R, RNase L)
activated by dsRNA to degrade mRNA,
stop protein synthesis, undergo apoptosis
effector action – destroy invader
Interferon response
Interferons are proteins that are part of your natural defenses. They tell your immune system that germs or cancer cells are in your body. And they trigger killer immune cells to fight those invaders. Interferons got their name because they “interfere” with viruses and keep them from multiplying.
Interferons (IFNs) — the body’s first line of antiviral defence — are cytokines that are secreted by host cells in response to virus infection. By inducing the expression of hundreds of IFN-stimulated genes, several of which have antiviral functions, IFNs block virus replication at many levels.
complement system
Three pathways lead to three different outcomes:
opsonization - enhancing phagocytosis of antigens
chemotaxis - attracting macrophages and neutrophils
cell lysis - rupturing membranes of foreign cells
Complement proteins
complement proteins:
circulate in the blood and in the interstitial fluid.
interact with each other in chain reactions (cascades).
Complement acts as a linker between the innate and the adaptive immune response.
complement system
complement activities of adaptive immune system
proteins circulating in blood and bathing tissues
proteins named in order discovered: C1 through C9
can split into fragments, for example, C3 splits to C3a and C3b
activated by three different pathways that lead to
formation of C3 convertase, which splits C3
Alternative pathway quickly triggered – provides early warning that an invader is present.
Initiated by C3b binding a foreign cell surface. After C3b binds, other complement proteins attach, eventually forming the C3 convertase.
C3 convertases are unstable (half-life 10 – 20 min)
Three outcomes of formation of C3 convertase
inflammatory response: C5a attracts phagocytes to area; C3a and C5a increase permeability of blood vessels, induce mast cells to release cytokines, histamine
- lysis of foreign cells: membrane attack complexes (MACs) formed
by proteins C5b, C6, C7, C8, and C9 molecules assembling in cell
membranes of Gram negatives - opsonization: C3b binds to bacterial cells and foreign particles, promotes engulfment by phagocytes
How can C3b be both a product of complement activation and an activator of the complement system?
Small amounts of C3b are always present, so there will always be some available to activate the system. Large amounts of C3b are needed to function as opsonins, and this will only be available if the system is activated.
Opsonization and migration - neutrophil
C3b – opsonin – triggers phagocytosis
C5a – chemoattractant – neutrophil migration
How do MACs cause cells to lyse?
They form pores in the cell membrane:
Certain complement components assemble in cell membranes, forming a doughnut-shaped membrane attack complex (MAC).
This creates pores in the membrane, disrupting the cell integrity.
anaphylotoxins – complement peptides
Anaphylatoxins, or complement peptides, are fragments (C3a, C4a and C5a) that are produced as part of the activation of the complement system.
Complement components C3, C4 and C5 are large glycoproteins that have important functions in the immune response and host defense.
Anaphylotoxins cause smooth muscle contraction, histamine release from mast cells, and enhanced vascular permeability – and mediate chemotaxis, inflammation, and generation of cytotoxic oxygen radicals.
Anaphylotoxins trigger degranulation of mast cells or phagocytes. If the degranulation is widespread, it can cause a shock-like syndrome similar to that of an allergic reaction.
complement system - recognizing self
regulation prevents host cells from activating
molecules in host cell membranes bind regulatory proteins that inactivate C3b, preventing opsonization or triggering alternative pathway
Some pathogens attract complement regulatory proteins to their surfaces. How would this help the pathogens avoid destruction?
The regulatory proteins inactivate C3b, thereby preventing the molecule from:
activating the complement system (alternative pathway) and
opsonizing the bacterium
The complement system is an ancient innate immune system that provides protection from pathogen invasion by surface pattern recognition.
C3 is present in Cnidaria, suggesting a primitive version of the alternative pathway was established more than 500 million years ago.
Phagocytosis
phagocytes engulf and digest material, pathogens
chemotaxis: phagocytes recruited by chemoattractants (products of microorganisms, phospholipids from injured host cells, chemokines, C5a)
recognition and attachment: direct (receptors bind mannose) and indirect (binding to opsonins)
engulfment: pseudopods surround, form phagosome
phagosome maturation and phagolysosome formation: endosomes fuse, lower pH; lysosomes bring enzymes
destruction and digestion: toxic ROS* and nitric oxide produced; pH decreases; enzymes degrade; defensins damage membrane of invader; lactoferrin ties up iron
exocytosis: vesicle fuses with cytoplasmic membrane, expels remains
leukocytes: defense mediators and sentinels.
Phagocytosis in immune cells is activated by attachment to pathogen-associated molecular patterns (*PAMPS)
Macrophages
macrophages are scavengers and sentinel cells
phagocytize dead cells, debris, destroy invaders
live weeks or months; regenerate lysosomes
always present in tissues; can call in reinforcements
TLRs on surfaces and in phagosomes detect invaders
cytokines produced in response
can become activated macrophages to increase power
if insufficient, can fuse to form giant cells
macrophages, giant cells, T cells form granulomas
wall off and retain organisms or material resistant to destruction
prevent escape but interfere with normal tissue function
tuberculosis and other diseases
phagocytosis - neutrophils
specialized attributes of neutrophils
neutrophils: rapid response - move into area and eliminate invaders
critical role in early stages of inflammation
first to be recruited from bloodstream to site of damage
more powerful than macrophages, but short life span of 1–2 days in tissues
die once granules used
kill microbes via phagocytosis and release of granule content
can release DNA to form neutrophil extracellular traps (NETs) catching microbes, allow enzymes and peptides from granules to destroy
NET (Neutrophil Extracellular Trap)
Neutrophils release granule proteins and DNA into extracellular space to trap bacteria or viruses during infection: NETs (neutrophil extracellular traps).
NETs disarm pathogens with antimicrobial proteins such as neutrophil elastase and histones bound to DNA. NETs also serve as physical barrier that prevents spread of pathogens.
avoiding host defenses
Avoiding recognition and attachment
capsules: interfere with opsonization; some bind host’s regulatory proteins that inactivate C3b
Streptococcus pneumoniae
MECHANISM OF DNA UPTAKE during transformation
dsDNA bound to the cell surface
fragmentation of dsDNA occurs upon binding
ssDNA fragments transported across the membrane via transformation pseudopilus, evolutionarily related to type IV pili
transport possibly driven by proton motive force.
retraction (disassembly) of pseudopilus allows exogenous DNA to cross peptidoglycan
All components of the DNA uptake machine are encoded by genes belonging to the competence regulon except EndA.
EndA contributes to virulence by allowing pneumococci to escape from neutrophil extracellular traps, which are made of DNA
inflammatory response
tissue damage results in inflammation
purpose is to contain site of damage, localize response, eliminate invader, and restore tissue function
results in swelling, redness, heat, pain, sometimes loss of function
pattern recognition receptors (TLRs, NLRs) trigger
detect PAMPs, DAMPs
host cells release inflammatory mediators (cytokines, histamine, TNF acts on liver to release acute-phase proteins)
inducers include microbes, tissue damage
blood vessel damage starts two enzymatic cascades
lead to coagulation and increased permeability
1.redness (erythema) 2. swelling (edema) 3. heat 4. pain 5. altered function
inflammatory response
histamine is produced by mast cells.
-increases permeability of capillaries to white blood cells
-allows them to target pathogens in infected tissues
Inflammatory process involves cascade of events
dilation of small blood vessels
greater blood flow (heat, redness); slower flow rate
leakage of fluids (swelling, pain)
migration of leukocytes from bloodstream to tissues
endothelial cells “grab” phagocytes, slow them down
phagocytes squeeze between cells of vessel (diapedesis or extravasation)
clotting factors wall off site of infection
dead neutrophils, tissue debris accumulate as pus
Chemotactic response to inflammatory stimulus – diapedesis (extravasation)
endothelial cells “grab” circulating phagocyte
phagocytes make adhesion molecules in response, causing them to tumble to a halt
they squeeze between the endothelial cells
