Mechanisms of Inflammation/Parasites Flashcards
function of inflammation
cause damage while removing harmful agents
bad clinically –> anti-inflammatory drugs; immuotherapeutic agents
good for body –> remove pathogen or toxin & repair damage
calor
heat
vasodilation of tissue due to damage - causing inflammation
Rubor
redness
RBCs entering due to tissue damage
Tumor
swelling
recruit immune cells to the site of tissue damage & due to endothelial cell damage
Dolor
Pain
Functio laesa
loss of function
inflammation
localized rxn - produces symptoms that can be internal or external
adaptive response - triggered by noxious stimuli
protective response to invading pathogen or stimuli; involved in repair
what signals lead to an immune response?
PAMPs and DAMPs binding to PRRs on immune cells
necrosis
release the contents of the cell; signal that some damage is occurring
acute inflammation
- early response; beneficial
- remove offending agent & repair tissue
- positive feedback loop
- minutes to hours
- mainly neutrophils
- mild damage
chronic inflammation
- sum of responses by a tissue against an agent
- unable to remove offending agent
- damaging effects –> fibrosis & loss of function; alveolar damage
- anti-inflammatory drugs beneficial in stopping effects
- slower - days to occur
- mainly macrophages/monocytes & lymphocytes
- severe damage
asbestos
- too big to be killed by alveolar macrophages
- irritate tissue & damage alveoli
steps of an immune reaction
- recognition of agent/damage
- recruitment of leukocytes & proteins
- destroy agent
- inflammation resolves
- tissue repaired
Hemostasis - 0 phase
1st step in immune response
vasoconstriction, platelet activation, clot formation
clot - réservoir for chemical mediators; starts recruitment & activation of leukocytes
resident cells
mast cells, macrophages, DCs
recruited cells
neutrophils, macrophages, B and T cells
NFkB pathway
associated with a lot of inflammation
- big target for drugs
- IL-1 and TNF-alpha big inflammatory mediators
chemical mediators
substance that acts on local tissue to facilitate an inflammatory response
-ex. histamine, prostaglandins, complement, etc.
exogenous sources
bacteria & viruses
endogenous sources
plasma, leukocytes, endothelial cells, fibroblasts
stages of immune response
- hemostasis
- recognition of pathogen or damage
- recruitment of leukocytes and proteins
- destroy pathogen through oxidative burst
- Inflammation resolves
- repair damaged tissue
1st phase of recruitment of leukocytes
vasoactive changes
- vasoconstriction 1st, vasodilation follows
- increase blood flow
2nd phase of recruitment of leukocytes
increase capillary permeability
-endothelial swelling or damage –> exudate & edema
extravasation
mobilizes body defenses
- margination = selectins & ICAMs help leukocytes adhere to wall
- diapedesis = leukocytes enter tissue
what do selectins, integrins, & ICAMs do?
line up on endothelial wall when there is damage
- attach to WBCs
- chemokines pull them across
- selectins (endothelium), integrins (immune cells), ICAMs (both)
role of integrins
bring immune cells through endothelial cells to tissue
-ex. CXCL1,7,8 & CCL3,5
big players in acute phase rxn - inflammation
IL-1beta, IL-6, TNF-alpha
what does IL-6 do?
induces hepatocytes to make acute phase proteins - mannon-binding lectin, fibrinogen, C-reactive protein –> opsonize bacteria & activate complement
oxidative burst
usually by neutrophils (also macrophages & DCs)
intracellular killing - release contents of cells
what helps repair tissue damage?
activation of fibroblasts - replace damaged epithelial cells
angiogenesis
role of fibroblasts
lay down collagen for repair - result in scar if not perfect
role anti-inflammatory molecules
shut down the immune response once pathogen is eliminated - apoptosis of immune cells
steps of acute inflammatory rxn
- recognizing agent/damage
- recruitment of leukocytes & proteins
- leukocytes & proteins destroy agent
- inflammation resolves
- damaged tissue repaired
where are acute phase proteins produced?
liver
-need cytokines to signal release
what mediators result in fever/inflammation
IL-1beta
IL-6
TNF-alpha
what immune cells are recruited for bacterial infection?
neutrophils
what immune cells are recruited for viral infection?
lymphocytes
what leads to fever during inflammation?
new hypothalamic set point by cytokines
Transudate
smaller holes in endothelial
- low protein and cell content (low specific gravity)
- no coagulation (clear sample)
- no inflammatory cells
- acute response
Exudate
larger holes in endothelial (larger things pass)
- high protein and cell content (high specific gravity)
- RBCs and immune cells can enter
- has coagulation (opaque)
- has inflammatory cells
- chronic response
Suppurative (purulent) inflammation
severe acute inflammation w/ pus
-pyogenic bacteria: staph aureus, strep pyogenes, E. coli
what is pus?
fluid that contains dead neutrophils, bacteria, plasma proteins, and necrotic tissue
Non-suppurative inflammation
- serous - runny nose, watery fluid, blisters, less proteins and cells
- serofibrinous - snotty nose, fibrin rich, more proteins and cells
- catarrhal - rhinitis, mild inflammation w/ mucus membrane and watery secretion
- Pseudomembranous
- hemorrhagic
- necrotizing
- allergic
cells in acute inflammation
neutrophils (Mickey Mouse), not many T cells, less macrophages
cells in chronic inflammation
lymphocytes (large round nucleus), more macrophages
pathological outcomes of inflammation
- resolution (resolve inflammation; wound healing)
- abscess (aren’t healing)
- ulcers
- fistula
- chronic inflammation (cannot resolve problem)
- scars (fibrosis)
- allergies
role of fibroblasts
make collagen to initiate wound healing - improper wound healing leads to scars
transition from acute to chronic inflammation
- no resolution
- shift from neutrophils to macrophages and lymphocytes
- cycle b/w inflammation, damage, and repair
- fibrosis (collagen deposition)
what immune cells are recruited in acute inflammation?
neutrophils - innate immunity
how can you get rid of bacteria that induce cell damage?
can activate compliment if they are opsonized with antibodies
role of mast cells in acute inflammation
- lead to hypersensitivities
- degranulation by IgE
- release histamines, prostaglandins, leukotrienes
how do immune cells enter through endothelial cells?
inflammatory mediators use receptors to stop and bind the immune cells to enter the endothelial layer –> margination/diapedesis
what is a marker of chronic inflammation?
formation of granulomas
- mainly from activated macrophages
- occurs during fibrosis
what immune cells are recruited during chronic inflammation?
lymphocytes (B, T, plasma) and macrophages
-macrophages most prominent
chronic inflammation characteristics
- longer duration (weeks, months, years)
- delayed type hypersensitivity rxn
- fibrosis
- formation of new blood vessels (angiogenesis)
- not resolved immediately
causes of chronic inflammation
- persistent infections (bacteria, viruses, fungi, etc.)
- hypersensitivity disease (RA, MS, asthma, inflammatory bowel disease etc.)
- prolonged exposure to toxic agents (silicosis, atherosclerosis, alzeihmers, diabetes)
silicosis
body tries to encapsulate particulate silica in a chronic inflammatory process, but silica never goes away (not harmful)
atherosclerosis
cholesterol deposition in the arterial walls
-NOT arteriosclerosis (hardening of arteries)
features of chronic inflammation
- infiltration of site with macrophages, lymphocytes, and plasma cells
- tissue destruction by organism, agent, or inflammatory mediators
- healing by angiogenesis or fibrosis
- granulomas caused by fibrosis
role of macrophages
- release cytokines and growth factors for lymphocyte activation
- destruction and clean up during chronic inflamm.
- release ROS and enzymes to degrade agent
- produce inflammatory response (IL-1, IL-12,IL-23)
- initiate tissue repair
- display antigens to T cells
M1
classical pathway for macrophage activation
-activated by Th1 cells and IFN-gamma
M2
alternative pathway for macrophage activation
-activated by Th2 cells and IL-4,5,13
what do Th17 cells recruit
recruit neutrophils and monocytes through the release of IL-17
B cells and plasma cells in chronic inflammation
-may have antibody response to multiple antigens which can cause autoimmunity
what is a tertiary lymphoid organ?
clusters of macrophages and antibodies
-area of [] immune cells
other immune cells in chronic inflammation
- eosinophils = major basic protein (MBP) –> toxic to parasites
- mast cells = prominent in chronic
- neutrophils = mostly in acute, can also be in chronic if they hand around inflammation sites
granulomas
nodular collection of epithelioid macrophages surrounded by lymphocytes (often Th1)
- reorganization of tissue w/ persistent inflammation
- sometimes associated with necrosis
- transform macrophages to epithelioid Macs by IFN-gamma
what are giant cells?
fused cluster of macrophages - mulitnucleated
2 types of granulomas
- foreign body = form around material such as talc, sutures, or food
- immune granulomas = cell mediated, agent hard to eradicate –> Macs activate T cells to release cytokines forming granuloma to wall off infection
Caseating vs. noncaseating granulomas
Caseating = always associated with TB; epithelioid macrophages, cheese like material, necrotic Noncaseating = sarcoidosis; activated macrophages; always has cells in it, non-necrotic
protozoa
single celled eukaryotes
helminths
worms
ectoparasites
bugs
what is a diagnostic test for trichomonas vaginalis?
cervical wet prep
blood/tissue protozoa is transmitted how?
via mosquitos, tick, or sandfly
protozoa cysts stage
often mode of infection
-initially dormant and enter this stage when exposed to harsh environment
protozoa trophozoite stage
metabolically active, reproductive, and feeding
what 2 protozoa are acid fast?
- cryptosporidia (4 microns; small) - always stains but are unevenly stained
- cyclospora (size of RBC) - sometimes stains, but not always
Acanthamoeba
can enter the brain
-get under contacts causing corneal lesions
Naeglaria
can enter brain through cribriform plate
GI protozoa
- giardia lamblia
- cryptosporidium
- cyclospora
- entamoeba histolytica (outside US)
Giardia lamblia
“farting sulfur”
- sulfurous belching/flatulence
- uncontrollable diarrhea, fat rich floating stool
- # 1 protozoa cause of diarrhea
- high risk when camping (outdoors)
- alien face
cryptosporidium parvum
- watery diarrhea in immunocompetent
- severe diarrhea and dehydration in AIDS patients
- cause of epidemic community diarrhea outbreaks
entamoeba histolytica
traveler’s dysentery = bloody diarrhea, fever, cramps
- can escape gut and cause abscess in liver, lung, brain
- trophozoite contains RBCs in it
- positive fecal leukocyte test
amoebic vs. bacterial dysentery
both have tenesmus (bowel movements) and bloody diarrhea and + fecal leukocyte
- amoebic = variable fever
- bacterial = high fever
CNS protozoa
- toxoplasma gondii
- acanthamoeba
- Naegleria fowleri
- Trypanosoma brucei
Toxoplasmosis gondii
“cat poop parasite”
- risk to pregnant women who have cats
- cat poop, undercooked meat, unwashed vegetables
- ring enhancing lesions found scattered across brain on CT –> neurological deficits (ex. hydrocephaly)
Acanthamoeba
get under contacts causing corneal lesions
-can travel to brain
Naegleria
brain eating disease (rare)
-enters through cribriform plate
trypanosoma brucei
African sleeping sickness (not in US)
- insomnia or sleepiness
- transmitted by tsetse fly
- trypomastigote on blood smear
Hematologic protozoa
- plasmodium falciparum - Malaria - transmitted by mosquito (not in US)
- babesia - similar to malaria but transmitted by tick (in US)
plasmodium falciparum
- transmitted by mosquitos
- black water fever –> pee lysed blood
- cerebral hemorrhage
- cyclic fever
- infects ALL RBCs
- banana shaped gametocyte
babesia
- transmitted by tick
- fever and hemolytic anemia
- easily confused with malaria
- often coinfected with Lyme disease
- diagnostic test –> Maltese cross
Leishmania donovani
- transmitted by sandfly
- cutaneous (slow healing skin ulcers)
- visceral (fevers that can be fatal)
- macrophages with amastigotes
trypanosoma Cruzi
“kissing bug”
- chagas disease - large heart, esophagus, and colon
- romana sign - periorbital swelling
- trypomastigote in blood smear
trichomonas vaginalis
- vaginitis - green discharge
- sexual - cannot survive outside body
- strawberry cervix
- cervical wet prep (motile, swimming pear-shaped trophozoites)
pediculosis pubis
pubic “crab” lice
- will not burrow or jump
- found in course hairs
- passed through close body contact
- pubic itching, burning, irritation
- worse at night
scabies
sarcoptes scabiei - a burrowing mite
- don’t jump - passed b/w close contact
- 7 year itch
- someone who is immunocompromised
- worse at night
