lect 15.3 Flashcards
what is the result of type 3 hypersensitivity
formation of antigen antibody complexes that deposit in tissues
- systemic pathogenic effects or locatlized to kidney, skin, joints
what is the importance of size of ag/ab complexes formed in type 3 hypersensitivity
- Large complexes rapidly removed
- small or intermediate complexes more
pathogenic
what are the ags in type3
foreign proteins, microbial
antigens, self antigens
what is important in ype 3
integrity of mononuclear phagocytic system
what is the mechanism for type 3
activation of complement and inflammatory responses
neutrophils involved
immune complex mediated hypersensitivity
where are small immune xomplexes deposited when not cleared
in the subepithelium
where are large immune xomplexes deposited when not cleared
in the blood vessels and kidneys
systemic immmune complex disease
ags stimulate ab production and complexes formed which are noramlly cleared from circualtion but deposit in tissues inthis disease
lead to inflammatory response
what is the inflammatory repsone in type 3
- complement activation
- MAC formation
- recruitment of neutrophils
- Platelet aggregation
- blood clots
what kind of disease is serum sickness
systemic immune complex disease identified in pre antibiotic era
what is the HAMA response
human anti mouse antibodies
explain how serum sickness occurs
- Patients treated for infectious diseases (tetanus,
diptheria) with horse Ab’s; - Ab’s to foreign Ab produced
- Anti-horse Ab’s bind Ab and prevent further therpeutic
benefit - clinical manifestations: fever, pain, skin eruptions,
glomerulonephritis
occurs in patients treated with monoclonal antibodies made in rodents
HAMA response
what does the formation of circulating immune responses lead to
- autoimmune diseases (SLE, RA)
- drug reactions (penicillin, sulfonamides)
- infectious diseases (poststreptococcal
glomerulonephritis, meningitis, malaria)
goodpastures syndrome
type 3 and 2 hypersensitivity
- Production of Abs in response to viral respiratory infections
- Cross-reaction with normal tissue antigen in lung and kidney (molecular mimicry)
ADCC in type 2
Ig complexes in tpye 3
arthurs reaction
type 3 hypersensitivity
involves neutrophils and C3b formation of immune complexes
localized reaction
steps of arthurs reaction
PREVIOUSLY FORMED ag ab complex with igG antibodies
complement actication, thromobiss, hemmorage, acute inflammation
swelling, redness, necrosis
wehen does the lozalized reaction in arthurs ocur
4-8 hours after exposure to antigen
arthurs reaction responsible for reactino to
enviromental toxins
if patient has precipitating igG against specific protein like mold, re exposure leads to insoluble complex formation in lung tissue and
severse respiratory distress within 6-8 hours
what are some pulmonary typr 3 reactions
pigeon breeders disease
cheese washers disease
what is the response time of type 1 reactions
15-30 min
and late phase is 4-6 hours
what is the response time for type 2
mintues to hours
what is the response time for type 3
hours
what is cell mediated hypersensitivity
delayed type hypersensitivity (DTH)
what is delayed type hypersensitivity mediated by
Th1 response
what does delayed type hypersensitivity occur in response to
some Ags/pathogens
tuberculin reaction
timeline for delayed type hypersensitivity
1st exposure- TH1 response
- sensitization phase
2nd exposure (1-2) weeks
- effector phase
-macrophage recruitment
reaction
-effector phase
-firm, red swelling
what are some of the DTH mediating cells that occationally participate
TH17
TH2
CD8+
what are the antigen presenting cells for DTH response
macrophages
langerhans cells
what does the TH1 reponse in DTH in the effector phase secrete
cytokines- IFN Y
and chemokines
activates macrophages
what do activateed macrophages in DTH effector phase cause
inc in class 2 MHC molecules
inc in TNF receptors
inc in oxygen radicals
inc in nitric oxide
what do pateints sufferingfrom aids have a reduction of
CD4+ T cells
and therefore
loss of DTH
lead to deveopment of life threatening infctions that wouldnt be life threatening if it was intact DTH resopnse
Examples of Type IV DTH Responses
TH 1-mediated
contact sensitivity
granulomatous hypersensititvity
tuberculin type hypersensitivity
allograft rejection
Chemicals causing contact sensitivity are
lipid-soluble
- penetrate the skin
- form hapten-carrier conjugates with
various self proteins
what test can be used for contact sensitivity
patch test
solution of the suspected Ag is spread on the skin and
covered; the appearance, within 3 days, of a raised, firm, red
area indicates sensitivity
when would we check the patch test to determine sensitivity
within 3 days
what chemical indueces contact sensitivity in virtually all individuals
DNCB
can be used to assess patient cell mediated immunity
what do giant cells cause
displacement of normal tissue
form nodules
release high concentration of lytic enzymes
destroy surrounding tissue
what causes granulomatous hypersensitivity
ag no cleared
prolonged damaging DTH response
inflammatory rxn- visible granulomatous respone
activation of mcarophages which adhere to each other
fuse to for mmultinucleated giant cells
what is the alternative of TH1 granuloma reposne
loprosy by mycopacterium loprae that infects macrophages in
tuberculoid form
lepromatous form
what is the tuberculoid form of leprosy
cell mediated granuloma formation
destroy most bacteria
slow disease progression
better survival
what is the lepromatous form of leprosy
high Ab production
depressed cell mediated immunity
many infected macrophages
extensive nerve, bone, and tissue damage
what is the tuberculin test used for
evidence of exposure to DTH causing organisms
example of tuberculin test
mantoux test
intraepidermal injection of purified m tuberculosis protein
tuberculin test resutl
previously exposed - tuberculin like lesion at site of injection 1-2 days later
2-4 days later - full reaction
positive test indicated prior exposure
limiation of mantoux test
doesnt differentiate between exposure to pathogen and vaccination
what hypersensitivity does penicillin induce
any of the 4 types
what antibody of lymphocyte is induced in type 1
igE
what antibody of lymphocyte is induced in type 2
igM and igG
what antibody of lymphocyte is induced in type 3
igG
what antibody of lymphocyte is induced in type 4
Th1 cells
how does obesity lead to chronic inflamation
adipose tissue secreted proinflammatory cytokines
what are the causes of chronic inflammation
genetics plays a role in almost all of it
inectious and non infectous causes
obesity
what does insulin normally signal
to cells that they should import glucose for the cell to prevent hyperglycemia
what are signalling events that link obesity and inflammation to insulin resistance
FA bind to receptors that prevent glucose transport that was signalled by insulin
lead ot catiation of proinflammatory singnals and isnulin resistance
- Storage of glucose as
glycogen in the liver is
impaired - Use of glucose by muscle,
fat, B cells, brain cells, etc
is impaired
what receptors are involved in insulin resistance
TLR
IL6R
TNFR
