Immunology Block: Imm # 11 - Regulation Of Immune Responses

Front 1

why do we need tolerance mechanisms and where/when do they come into play?

Back 1

need tolerenace because we're constantly generating new B and T cells with randomly reactive sites. Tolerance means they're tested for reactivity before being put out into the circulation against self library.

examples are central elimination of B and T cells that are too reactive.

Front 2

what's neonatal tolerance?

Back 2

fetal exposure to antigens induces future tolerance those antigens - it's how we build our library of self antigens.

these are called "toleragens"

Front 3

talk about primary lymphoid organ vs. circulating ways of building tolerance:

Back 3

primary lymphoid organs have clonal anergy, where whole subsets are wiped out for being too reactive.

circulating is a different story. it can rely on the "costimulators" of T-cells not binding right, leading to apoptosis or anergy.

also remember that there are regulatory T cells which can produce IL10 and TGF beta to suppress everything.

Front 4

what qualities of the antigen might make it immunogenic or toleragenic?

Back 4

its structure (if soluble, it's a good tolaregen)

its dose - if it's really low or really high dose, it's a toleragen (low = sub immunogenic and tolerases T cells, high = clonal exhaustion and stop responding to it).

persistance - if it sticks around a long time, more likely to be a toleragen.

route of administration - if it's oral, better tolarence (why food allergens aren't too common). if it's IV, better tolaregan (don't give vaccines IV, because no LN's to encouner).

subcutaenous or IM are good IMMUNOGENS. likely to encounter WBC"s.

Front 5

What kinds of autoreactivity can there be? is it common?

Back 5

Loss of self-tolerance. Can be TH1 driven cellular issues or TH2 drive antibody issues.

autoreactivity is super common - happens all day, it's why only 5% of T cells make it out. Autoimmune disease is rare.

Front 6

what causes most autoimmune diseases?

Back 6

most of the time, it's secondary to something - trauma, burns, drugs, surgery, infection. all this can alter self antigens into something you don't recognize.

can be inherited, bad HLA type. can be exogenous, or can be a somatic mutation.

Front 7

increases or decreases in TH1 vs TH2 - what's most often seen in autoimmunity?

Back 7

Upped TH1, low TH2. seems weird.`

Front 8

what's cross reactivity?

Back 8

it's one way you can get auto antibodies that are bad for you.

usually, if a B cell presents a self antigen to a T cell by mistake, it doesn't "return the favor" and make IL-4 to turn it on.

if however the B cell presents an antigen from outside that looks a lot like a self antigen, the T cell will activate the B cell and you'll get an antibody made that might react with self antigens.

Front 9

acute vs. chronic inflammation - do you usually see antibodies or cells driving it?

Back 9

if it's acute, typically see antibody driven response. ADCC, complement is how it goes down.

if it's chronic, more likely to be cellular driven.

Front 10

is diabetes type I or type II

Back 10

type I...involves cellular infiltrates into the pancreas that stick too much. also too much MHC class 1/2 expression.

Front 11

what about RA?

Back 11

RA is both type 1 and type 2, so it's antibody and cell driven. Get complement deposition and neutrophils accumulating, which is type 2. Also, lots of cells invade the joints, that's type 1.

Front 12

what about pernicious anemia?

Back 12

both Type 1 and type 2. you chronically destroy gastric mucosa with autoantibodies against parietal cells AND intrinsic factor.

cellular infiltrates too.

Front 13

what's SLE?

Back 13

this is mostly type 2 driven.

remember it's all about immune complexes in the joints and kidney and skin and heart.