L 21 Flashcards
What are the 4 classes of hypersensitivity reactions?
1: IgE, allergies
2: tissue specific (IgM/G)
3: soluble Ab-antigen complexes (IgM/G)
4: T cell only reactions, delayed
What is the costim between helper T and macrophages for macrophage activation?
T : Macro
CD40 L : CD40
What cytokine do Th secrete for macrophage activation? What are the hallmarks of macrophage coactivation?
IFN gamma
- ↑coexpression
- ↑MHC
- ↑cytokines = IL 1, 12, TNF
- ↑phagosome killing via ROI
What are the 2 main forms issue injury due to T cells in type 4 HST?
- CD8 directly killing tissue
- INLFAM –> tissue injury
- overactivation Th activation of neutrophils & macrophages
Which cells are important for limiting delayed-type HST?
Th2 & Th17
Inhibit Th1 cells –> no inflam via macrophages
Explain DTH in words.
Someone who has previously been sensitized to an antigen - infection or vaccination
Represent the same antigen
Reaction fully develops slowly - mononuclear infiltration
Th1 activated @ site - secreting IFN gamma & TNF
Leads to macrophage activation - secreting TNF & IL1
But antigen is persistent = continued macrophage activation = chronic DTH response
Leads to damage to surrounding tissue –> fibrosis
Is T cell recruitment to an antigen site antigen dependent or indep? What about retention at the site?
T cells from blood –> site = T cell INDEP
T cells staying @ site = T cell DEP
What is a common symptomatic presentation associated with DTH?
Granulomas = activated macrophages w/ Th rim
What are some diseases caused by DTH reactions to bacteria (Th17)?
TB
IBD including Crohns
What are some autoimmune disease mediated by DTH responses to self antigens (Th1)?
RA
MS
Diabetes type 1
Wegner’s Granulomatosis
What diseases heavily rely on a CD8 response with or without a CD4 DTH?
Graft rejection
Viral hepatitis
Contact dermatitis
Explain how a PPD is an example of DTH.
For TB
The PPD doesn’t have any PAMPs or adjuvant (this would be the vaccine) –> no stimulation of innate
If you’ve had TB before (or the vaccine), your memory T cell response will kick in to create swelling around the injection site
Delayed because takes 48 hrs to see this
See mononuclear cell infiltration on histo @ site
When blood vessels are exposed to TNF, what is the order of leukocyte entry? (Which cells, not the steps)
1st Neutrophils
Monocytes
Last T cells
What cells are unique to granulomas?
Giant cells
Fibroblasts on periphery keritanizing cells that are normal - persistent tissue damage
What kind of antigens stimulate granuloma formation?
Anything that continues to stimulate T/macrophages
Microbe that does or does not secrete toxins
Which Th defend against extracell bacteria and fungi? Name the related cytokines.
Th17
IL 17 - neutrophil chemotaxis
IL 22 - ↑antimicrobial peptides & barrier fxn
Which 2 Th cell types are mostly likely to implicated for autoimmune disease?
Th1 & 17
What is a feature of granulomas unique to TB?
Caseous necrosis think tuberculosis!
What are the 2 different type of leprosy? Th1 vs Th2?
Lepromatous leprosy (LL) = Th2 response, spread out Tuberculoid leprosy (TT) = Th1, better control of the immune response keeps skin lesions localized
Why should you test patients for latent TB before treating their RA?
RA medication is often TNF alpha inhibitor
If latent TB, likely being held in check by Th1 which works via TNF
Block TNF - will resolve RA, but allow TB to become active
What determines your likelihood to get one type of TB over another?
State of Th1 immunity
Defective Th1 - lean towards Th2 - disseminated rash
What are self molecules work as antigens in RA?
Type 2 collagen
Heat shock proteins
What are self molecules that work as antigens in type 1 diabetes?
Insulin
What are self molecules that work as antigens in MS?
Myelin of neurons
What are 5 pieces of evidence that indicate T cells are involved in an auto-immune disease?
- T cell in the lesions
- Antigen specific T cells in blood/organ
- T cell stimulation in adjacent tissues
- Adoptive transfer - T cells from patient give disease to a non-infected person
- Blocking the disease if you interfere with T cell activation
Explain contact dermatitis reactions.
Chemical in poison ivy/nickel - binds self antigens
Makes modified self antigens
Create DTH rxn
What is an example of a super-antigen mediated disease? Explain the mechanism.
Toxic Shock Syndrome
Cross link MHC & TCR
Can stimulate large # Tcells regardless of TCR specificity
