What is an unregulated Th1 response?
Example?
What are several reasons this can occur? (4)
Type IV Hypersensitivity
(TMMI response gone bonkers)
-uncontrolled and frustrated because there is something in the macrophages that it CANT kill
ex: partial removal of live M. Tuberculosis
(forms a granuloma)
If super antigens are the driver of the unregulated Th1 response, what can be the result?
What are 3 ways super antigens are different from normal antigens?
1) precent antigen UNPROCESSED in MHC II
2) bide on the “side” not in peptide binding groove (test - picture)
3) Massive immediate PRIMARY POLYCLONAL response in T cells
What is an effective strategy for infections of NON - APC type cells and mutations of host cells? (ex: bronchial, mucosa, gut skin)
- recognize abnormal MHC I
NK cells sample cell surfaces and as long as they sense a normal MHC-I they keep their ____ receptors “on”
What are 2 ways the NK cells kill?
Where do NK cells have suppressive roles?
1) Direct cytotoxicity
2) FcR used to signal
3) PREGNANT UTERUS
CD8 will not be optimally functioning (as in HIV) unless what is present?
What does CD8 NOT require?
CD4 Th1 cell
(IFN - Y IL-21, Il-2)
Antibodies are needed when toxins are not readily phagocytosed and are extra/intracellular?
What is the signature cytokine of Th2?
EXTRACELLULAR
T cell helper functions, the B cell internalizes the captured antigen, redisplays it in MHC-II and activates Th2 helper cells
What are the transcription factors and cytokines for the following
What does the Th2 cell secrete?
What are 2 ways that Th2/B cells can phagocytose a toxin?
IL - 4, 5 , 6 , and 10
needed for a toxin
–> phagocytose via C3b or IgG
If there is a lot of FcGamma cross-linking and IgG is complexed in abundance, what signal is initiated?
What is the only Fc receptor that can bind antibody isotope without antigen present?
ITIM - inhibitory signal
on Mast cells, basophils, eosinophils
FcR crosslinking occurs on what cells? (7)
If complement is being cleaved in excess due to a Type III hypersensitivity reaction, what can be measured that would indicate this?
Decreased levels of C3 and C4
If the disposal system is overwhelmed,
complexes will bind wherever the endothelium
Is rich in FcR and C3b receptors.
Skin, kidney & joints are prime targets
Antibody binding specific antigen (ex: in basement membrane of kidney glomerulus) this is an example of what hypersensitivity?
Type 2!!!
type 3 is just the excess formation of Immune complexes
If a patient has a defect in B cells, what is absent?
What if B cells are present but no plasma cell, how will the germinal center look?
Poorly organized germinal center!
What are the following reasons related to:
Result?
HYGIENE HYPOTHESIS
Result: Abnormal Th1/Th2
Balance and higher
Incidence of reaction to allergens
What cytokine makes IgE?
What cytokine and cell is needed for allergic responses? (Type I hypersensitivity)
What happens once the second exposure occurs?
What cytokine recruits eosinophils?
IL - 13
IL-4,10,13 produced
produced the LATE RESPONSE
Eotaxin recruits eosinophils to area of allergic response
What is the basic strategy to Viral infections?
Why are B cell responses necessary in viral infections?
B cell helps capture virus that is exposed once the virus kills cell and exposes itself
- tries to kill via FcR
What are the following examples of:
Viral Ingenuity
- sites that can be exploited to allow viral survival
How can viruses meddle with TLR?(2)
What are 2 areas that Tregs arise from?
What 2 cytokines are critical?
What cytokine is necessary for their survival?
What do they express on their surface that can suppress T cell activation by competing with what?
1.Thymus and Periphery
What controls CTLA 4 expression?
As ____ becomes dominant, FoxP3 up-regulates CTLA-4 which then inhibits the ‘second signal” from APC to the T cell
FOX P3
What are 6 strategies the fetus uses to induce tolerance in the uterus?
What cells in the fetus have tolerogenic &
regulatory functions & are
critical for fetal survival
.
What is the majority of cells in the mom?
NK!!!
Newborn also has strong immunosuppressive milieu
-(T regs and TGF-β) which has to reverse rapidly or will be at risk for infection
If RANKL is unregulated or OPG down regulated, what increases?
What ratio is critical in Adipose tissue?
What is the normal milieu in CNS?