Lecture 18-19 - T4-HS & Autoimmunity Flashcards
T4HS mediators (immune reactants)
TH1, TH2, and CTL
T4HS Antigens are ____ and ____
(Which go with which?)
Soluble and Insoluble
(cell-associated antigen –> CTL)
(Soluble –> Th1 and Th2)
Three syndrome-types caused by T4HS
Delayed type HS (PROTEINS)
Contact Type HS (HAPTENS)
GIT Disease (Gliadin)
**all involve T cells
Causative agent for Poison ivy
pentadecacatechol
First encounter causes ____
sensitization
Steps of a “first encounter” sensitizing process
- skin penetration
- modification of self proteins
- Ag captured by APC, presented in LN
- (in LN) Activate T cells and generate specific T cells)
- –> leads to asymptomatic response
Later encounter of Ag results in ________
hypersensitivity reaction
- Same first steps as first response (skin, mod’ self proteins)
- Presented in LN and in skin
- Memory Tcells are activated
- Activation of downstream effectors and phagocyte recruitment
- DC’s in epidermis
- DC’s in afferent lymphatic
- DC’s in LN
- Langerhans
- Veiled cell
- Interdigitating DC
Lymphocytes found in skin express what three things
- CLA (cutaneous LC antigen)
- P/E selectin ligands
- chemokine receptors (CCR4/8, CCR10)
Skin DTH reaction steps
- penetrates skin
- taken up by langerhans
- present self peptides (haptenated with the agent) to Th1 cells (secrete IFN)
- keratinocytes secrete cytokines and chemokines (secrete IL1, TNFa, etc)
In skin DTH reaction, naive T cells are matured to Th1 cells in…
Lymph node
Th1 cells secretions and their effects
- Chemokines = MQ recruitment
- IFNgamma = Activates MQ
- TNFa and LT = Local tissue destruction
- IL3 & GM-CSF = Monocyte productions by stem cells in BM
Tx for Contact HS
Corticosteroids
(suppress inflammator genes, induce synthesis of anti-inflamm proteins)
Examples of DTH
Tuberculin skin test
Poison ivy
celiac
chromic asthma (Th2)
How to we get immune tolerance to self (B cells?)
B cells anergized or deleted in bone marrow, periphery, germinal centers
How do we get immune tolerance to self (T cells)?
- Autoreactive T cells are deleted in the thymus
- Autoreactive T cells are anergized or deleted in the periphery
5 ways to gain immune tolerance to prevent autoimmunity
- Delete or anergize B cells in BM, periphery, or GC’s
- Delete T cells in thymus…..Anergize or delete T cells in periphery
- Supress Treg (CD4+CD25+)
- Physically separate tissue Ag from immune cells
- Limit MHC2 and B7 expression (reduces activation)
Susceptability factors in AI diseaes
- HLA genotype
- Microbial infection
- injury
- environmental factors and behavior
- gender/sex hormones
Three ways microbial infection increases AI risk
- Adjuvant effect: recruitment and activation of immune cells
- Induction of MHC molecules and B7
- Molecular mimicry
Sympathetic Ophthalmia
Physical trauma in one eye initiates AI in both
- eye anterior is IMMUNE PRIVILEDGED SITE
- Injury in one eye drains to LN
- Immune response of effector T cells
- return to BOTH eyes to react and cause damage/blindness
Most AI diseases affect ___
Which ones dont?
Females
- Psoriasis, UC, AI uvitis, Bechets* hit both equally
- (Ankylosing spondylitis* = males)
What is APECED? What is deficient? What diseases result?
AI polyendocrynology candidiasis ectodermal dystrophy
Mutations in AIRE (AI regulator) gene = Defective Thymic deletion because inability to express peripheral antigens in thymus
Endocrine = Hypoparathyroidism, adrenal failure, ovarian fail
Other = Candidiasis (100%!), Dental enamel hypoplasia, nail dystrophy
IPEX is a _____mutation
FOXP3
(essential for generation of Tregs –> inflamed small intestine)
“immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome”
Celiac CD4 T cells specific for…
How does this happen?
What ends up being made?
gluten peptide
DQ2 and DQ8 present the peptide to CD4 T cells
Anti-transglutaminase autoantibodies = destruction of villi
