Type III and IV hypersensitivity Flashcards
what happens if immune complexes are not cleared effectively?
may be deposited in tissues or in blood vessels and cause:
- Vasculitis if in bloodvessel
- Glomerulonephritis if in kidney
- Arthritis if in joints
CM of Type III hyper
1) fever,
2) rashes,
3) joint pain,
4) lymph node enlargement, and
5) protein in the urine
Type III hypersensitivity reactions May trigger release of inflammatory mediators and vasoactive mediators such as?
Histamins, Proteases (Tryptase)
Examples of Type III hyper. disorders
1) SLE
2) Arthus rxn
3) Serum sickness
Clinical featues of SLE
1) Butterfly facial rash
2) Arthritis
3) vasculitis
4) Nephritis
Which type III hypersensitivty rxn presents w/ Local pain and edema and is associated w/ intradermal injection of Ag into a presensitised (circulating IgG) individual?
Arthus reaction
Antigens invlovled in SLE?
dsDNA, Smith , (other nucleoproteins)
A localized type III hypersensitivity rxn ?
Arthus reaction
————- : An inflammatory reaction induced by injection of an antigen in the skin of a sensitized individual with high levels of circulating antibody (IgG) against the sensitized agent with high levels of circulating antibody against the sensitizing agent
Arthus reaction
An inflammatory Arthus reaction is inititated within ——- hr post injection
4-10 hrs
CM of Arthus reaction
1) Odema
2) Localized bleeding at injection site
3) Fibrinoid necrosis
Example of a transient (short-lived) immune-complex mediated syndrome
* Type III hyper.
Serum sickness
Explain what causes Serum sickness and how the immune complexes are cleared
A systemic type III hyper induced by injection of serum w/ foreign proteins (species) –> development of Abs against forgein Proteins –> antibody-antigen complexs form and deposit in tissues –> complement activation -> inflammation and tissue damage
* serum examples –> theraputic horse anti-serum against snake venoms
Antigens invloved in serum sickness + CM
Ags: Various proteins
CM : Arthritis, vasculitis, nephritis (chills, fever and rash)
The antibodies involved in type III reactions are of ——– class
IgG
Type IV hyper. is mediated by?
antigen-specific effector Tcells
Aka Delayed type hype, (DTH)
**
DTH reactions are elicited by?
CD4+ TH1, TH17 or CD8+ CTLs
–> activate macrophages, recruit neutrophils and induce inflammation
**
Most common type IV hyper?
Contact dermatitis
(after exposure to Toxicodendron species e.g., poison ivy, poison oak, poison sumac)
- she might ask they type of toxins that causes this (not sure)
How can DTH responses be avoided?
avoid the causative agent
- dont think we need to know Tx in general so info
When is DTH initiated?
it is a delyaed reaction that developes in a sensitized individual in 24-72hrs
which 2 pahses are involved in Type IV hyper.?
1) Sensitization phase (initation of DTH)
2) Effector phase (second exposure to sensitized ag)
Exaplin the Sensitization/ Effector phase of DTH
1) Sensitization phase:
initial exposure to Ag triggers the production of CD4+ TH1 subset (but can also include TH17, CD8+T)
2) Effector phase:
Second exposure to sensitized antigens –> Induces the production of inflammatory Cytokines by Effector CD4+ Th1 cells –> These recruit and help activate macrophages in TH1 –mediated responses (cytokines such as IFNγ)
The principal effector cells of the DTH response are ————- , which exhibit enhanced phagocytosis and an increased ability to kill microorganisms
Activated macrophages
When does the effector phase in DTH becomes activated?
Following the initial sensitization, a period of 1–2 weeks is required for antigen-specific T cells to be activated, clonally expand and mature into effector cells
A prolonged DTH response can lead to formation of ————
Garnuloma
(e.g. TB)
Test to detect DTH reactions
Skin Test
* Injection of a small amount of antigen under the skin
what is a positive DHT skin test ?
Development of a red, slightly swollen, firm lesion 48-72 hrs after injection of ag under the skin
- this indicates the presence of Sensitized TH1 or TH17 cells against the Antigen
* test commonly used for TB exposure
Examples of Type IV hypersensitivities
1) Multiple sclerosis
2) Rheumatoid arthritis
3) Type I diabetes
4) Celiac disease
* look at the table p.13 in Type IV lecture
pathogenesis of celiac disease
this is mediated by an immune response to Gliadin
1) Inflammation of the small intestine (villus atrophy) is caused by CD4+ T cells responding to gliadin that is deamidated by tissue transglutaminase (tTG) and presented by HLA-DQ2 class MHC II allele
* know That Gliliadin s involved w/o patho/bio part (HLA bla bla)
All patients w/ celiac disease have serum ————— against tTG (autoantibodies) that constitutes a sensitive and specific test
serum IgA
**
Celiac disease is mediated by an immune response to?
Gliadin
**
CF of celiac disease
Gluten-sensitive enteropathy
(bloating, nausea etc)
A DHT skin test against TB?
tuberculin test ( individuals are injected intradermally with tuberculin)
note:
* Individuals who have been exposed to the bacterium, either by infection or by immunization with the BCG vaccine –> develop a localized T-cell mediated inflammatory response which evolves over 24-72hours
* The response is caused by TH1 cells
* which enter the site of antigen injection, recognize complexes of peptide:MHCclass II on antigen-presenting cells and release inflammatory cytokines such asIFN-γ
