Hypersensitivity II Flashcards
Serum Sickness:
At the same time that there is a measurable decrease in serum complement levels and antigen:antibody complexes forms, what happens?
fever
vasculitis
arthritis
nephritis
if you have an autoimmune disease and the antigen is constantly present, these symptoms never really go away
after the complexes have been cleared, symptoms go away and disease resolves itself
where parasitic allergies are endemic, they do not have allergies (both IgE mediated)
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Arthus Reaction is what?
timing?
what is activated/recruited?
cutaneous form of the Type III hypersensitivity reaction
reaction happens in 4-8 hrs
activation of complement and neutrophil recruitment
Arthus Rxn:
- locally injected ag in immune individual with IgG antibody
- local immune-complex formation activates complement. C5a binds to a C5a receptor on a mast cell
- binding of immune complex to Fc receptor on mast cell induces degranulation
- local inflammation, increased fluid and protein release, phagocytosis, and vessel occlussion
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what dominates in the arthus type III hypersensitivity rxn?
neutrophils!
systemic lupus erthematosus have characteristic butterfly rashes on their face. effects women more than men and predominantly AAs
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SLE has antibodies against what?
nuclear antigens - anti-nulcear antibodies (ANA)
anti-dsDNA abs are highly specific for SLE!!!!
SLE cannot bind to nuclear antigens inside intact cells, so what is the source of antigens?
nuclei extruded during rbi maturation in BM
SLE - Ag-Ab immune complexes are soluble (systemic)
serum complement levels can be significantly decreased
associated with C2, C4 deficiencies
kidneys most severely affected, can result in end-stage renal disease (dialysis, transplant)
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good pasture syndrome has ab against kidney GM?
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Type I has what antibody?
IgE
Type II/III has what antibody?
IgG/IgM
Type IV is most similar to what rxn?
Type I but takes a day or two more to develop
IV Hypersensitivity (DTH) is also called contact hypersensitivity or contact dermatitis... Can be to nickel, poison ivy, or cosmetics
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Rxn mechanism for DTH:
- Ag is introduced into subcutaneous tissue and processed by local ag-presenting cells
- a Th1 effector cell recognizes antigen and releases cytokines which act on vascular endothelium
- recruitment of T cells, phagocytes, fluid, and protein to site of antigen injection causes a visible lesion
occurs over 24-72 hrs
often with hapten molecules
- the happens cause them to bind to self proteins and cause a reaction
- activates Th1!!!
- recruitment of macrophages with the release of IFN-gamma by Th1 cells
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DTH reaction has mononuclear cells (not neutrophils), and perivascular accumulation (cuffing)
They are CD4 cells generally
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Th2 is type 1 hypersensitivity
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common sources of Th2 rxns?
plant leaves
industrial products made from plants
synthetic chemicals in industrial products
metals
The tuberculin test is an example of what type of reaction?
Type IV hypersensitivity
1-3 days (delayed)
Involves Th1 T cells (MHC class II on APCs)
Activation and recruitment of macrophages
IFN-gamma
Can also have a Type IV hypersensitivity reaction to histoplasma or coccidiodies immitis
Usually DTH positive if have lived there for awhile
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DTH skin test - allergen patch test….Takes a few days for this test to develop
Atopic individuals have a propensity toward these allergic reactions
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Use of DTH to test for T cell function in immunodeficient patients….
what is it called?
a person with a severe T cell immunodeficiency (AIDS, malnutrition, immunosuprressive therapies) will NOT display a DTH response towards a panel of common recall antigens (mumps, tetanus, candida, tricophyton)
this is called “anergy” or the pt is considered “anergic”
clonal anergy - lack of costimulatory signal - signal 2
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Type IV hypersensitivity is any CMI hypersensitive reaction…
CD4 - inflammation with neutrophils and CD8 with cell death and tissue injury
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Any T cell mediated hypersensitivity might be included under Type IV hypersensitivity…
four examples?
- CTL mediated
lesions due to measles or herpes, Hepatitis, damage to liver - granuloma formation (CD4+/macrophage)
e.g. tuberculosis, leprosy
-transplant rejection, GVHD
-celiac disease - gluten hypersensitivity
In general, CMI phenomenon such as transplant rejection, cell-mediated autoimmune phenomenon are seldom referred to as Type IV Hypersensitivities
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Arthus - type III
Wheal and flare - Type I
DTH - Type IV
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Type I - seconds to minutes
Type III - hours
Type IV - days (1-3)
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Type I - fluid/rbcs
Type III - neutrophils (fix complement, C5a)
Type IV - T cells/macrophages
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Type I - mast cells/mediators
Type III - complement/C5a
Type IV - cytokines, IFN-gamma,TNF-alpha
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what is urticaria?
hives
accumulation of mononuclear cells at the site of ag injection would be a type IV reaction
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transplantation - rejection can involve multiple effector mechanisms
strong reject mediated by?
weak rejected associated with?
strong - MHC incompatibilities
weak - differences in minor histocompatibility ags
HLA is highly polymorphic
Tightly linked as a unit
Codominantly expressed on all cells
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Typing for HLA antigens was originally done with serology (ab) but now is with DNA sequencing
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We type for what HLA ag?
A, B, DR
old terminology of 6 antigen match refers to these alleles (we are heterozygous so 2x3=6)
Also match for ABO blood groups!!
What is MLR?
Cellular Typing
what does it show/measure?
MLC-mixed leukocyte culture
You mix lymphocytes from two different people
-Measure T cell proflieration
-Measure T-cell cytotoxicity
Detects mainly HLA-class II differences (HLA-D) CTL usually not done for HLA-typing
Shows the extreme allo reactivity of lymphocytes against MHC mismatches
It is an in vitro correlate of transplant rejection
Autograft
skin from one part of body to another (autologous stem cell transplant)
syngeneic graft
genetically identical twins
allograft
normal situation
donors between two matched but not identical people
“allogenic for MHC”
xenograft
cross species
Hyperacute graft rejection occurs because of…
immediate, preformed antibodies
acute graft rejection comes from…
HLA incompatibilities (week to 10 days)
chronic graft rejection comes from…
minor histocompatibility antigens (months to years later)
Transplant sensitization
- dendritic cells from the donor or host present antigen to lymphocytes in lymph node/spleen - mediate a response
- leads to cytokine release/killing - leads to rejection
both class I and class II differences can cause graft rejection
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direct allorecognition?
allogeneic antigen presenting cell (dendritic cell) with allogeneic MHC for donor reacts with a host T cell
T cell recognizes unprocessed allogeneic MHC molecule on graft APCs
indirect allorecognition
T cells recognize a processed peptide of allogeneic MHC molecule bound to self MHC molecule on host APC
Hyperacute rejection activates complement and get immediate damage… During the operation. Can be due to mismatched ABO groups or antibodies against the HLA antigens (host was pregnant previously or had a previous transplant)
Causes occlusion of blood vessel
Graft becomes engorged and purple colored because of hemorrhage
Technically would be a Type II hypersensitivity response!
perform cross matching beforehand (donor does not have Abs that bind to HLA on graft)
Have complement activation, endothelial damage, inflammation, and thrombosis
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Acute graft rejection is due to HLA incompatibilities and mediates STRONG graft rejection…
Have parenchymal cell damage (functional part of organ), interstitial inflammation, endotheliatitis
Don’t worry about this because we type beforehand
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We are more worried about Chronic rejection - has to do with minor changes
Chronic inflammatory reaction in vessel wall, intimal smooth muscle proliferation, vessel occlusion (thickening of vessel walls and organ failure)
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Bone Marrow Transplant has what problem?
Graft vs. Host Disease (GVHD)
Bone marrow is immunocompetent - might recognize the host as the antigen. T cells in marrow reject the host.
Target organs are usually the skin, gut, and liver
Bone marrow transplant can be allogeneic or autologous…. some require it to be allogeneic (some leukemias for ex)
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GVHD mechanism:
- allogeneic bone marrow transplant contains mature and memory T cells
- T cells circulate in blood to secondary lymphoid tissues. Alloreactive cells interact with dendritic cells and proliferate
- effector CD4 and CD8 T cells enter tissues inflamed by the conditioning regimen and cause further tissue damage
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If a child needs a transplant, what are the changes for matches with a sibling with heterozygous parents?
2 haplotype match 1:4
1 haplotype match 1:2
0 haplotype match 1:4
