Regulation Tolerance Flashcards
control of the immune response
- response must be turned down when the antigen has been destroyed
- failure may result in an AI
CTLA-4 competes with
CD28 for B7
-CTLA-4 causses an inhibitory response
PD-1
inhibitory receptor found on cytotoxic T cells
-it interacts with PD-L1 found on tumor cells and PD-L2 found on dendritic cells and macrophages thereby inhibiting the immune response
pembrolizumab and nivolumab
-anti-PD-1 checkpoint inhibitors
activation induced cell death
-activated T cells develop Fas Ligand that interacts with Fas normally presents on t cells results in apoptosis
T regulatory cells
-produce IL-10 and TGFbeta which supress T cells
IFN gama inhibits
TH2 cells
-produced by TH1
IL-4 inhibits
- TH1
- produced by TH2
immunological tolerance
- lack of response to a specific antigen
- failure to induce specific immunity to that antigen
self tolernce
- unresponsiveness to self
- occurs in the thymus (negative selection)
- this is called a Central tolerance
peripheral tolerance
-cells that escape central olerance are dealt with by mechanisms of peripheral tolerance. This involves clonal deletion and clonal anergy
clonal deletion
-how is this mediated
- continuous exposure to self antigens causes continuous stimulation of T cells causing apoptosis of autoreactive lymphocytes
- this occurs by the process of activation-induced cell death (Fas-L)
clonal anergy
-absence of co-stimulatory signals especially B7-CD28
adult tolerance
- difficult to induce
- lack of co-stimulatory signals B7 and CD28 would fix but also would suppress the system overall
- high dose of an antigen could cause tolerance under special circumstances but this is not useful in human situations
- oral tolerance possible under special circumstances but this does not work in human trials
- antigens without adjuvants may cause tolerance
autoimmune diseases
- immunological response against self antigens due to loss of self tolerance
- failure of negative selection in the thymus
- failure of immunological control mechanisms
- fundamental problem is an imbalance between immune activation and immune control
autoimmune hemolytic anemia
- body creates antibodies against RBC’s
- blood film shows broken and fragmented red cells typical of hemolytic anemia
immunological factors that could give rise to autoimmunity
- exposure of hidden antigens (sympathetic opthalmia). damage to cell releases hidden antigen and immune response ensues
- polyclonal lymphocyte activation: viruses (EBV) stimulate B cells nonspecifically or superantigens stimulate T cells
- defective T cell regulation (TREGS and CTLA-4)
super antigens
- attaches to the outside of the T cell receptor and to the MHC class 2 molecule causing T cell activation
- this happens nonspecifically
- staphylococcal food poisoning and toxic shock syndrome
- massive IL2 and IFN gama
defective T cell regulation
- T cell regulators (TREGS)
- CTLA-4: competes with CD28 for B7, if CTLA-4 is defective then there will be uncontrolled activation of the T cell
genetic factors of autoimmunity
- more common in family members.
- increased incidence in twins
- associated with many different MHC types
microbial factors in AI
- molecular mimicry
- abnormal activation of lymphoid cells (EBV)
- microbes may damage tissue leading to release of hidden antigens
- microbes may function as adjuvants and stimulate immune responses
Rheumatic fever
-caused by a strep infection that turns someones own immune system against them (molecular mimicry)
hormonal factors of AI
- most AI diseases are much more common in females
- NZB/NZW mice
- females die at 9 months
- males die at 13 months
damage to the tissues in AI may be mediated by
- antibodies: autoimmune hemolytic anemia
- T cells: crohns disease, IDDM, psoriasis, MS
- both humoral and CMI: hasimotos thyroiditis or rheumatoid arthritis
delayed sensitivity may cause
-these are t celll mediated AI diseases
- insulin dependent diabetes mellitus
- rheumatoid arthritis
- multiple sclerosis
- crohns disease
- psoriasis
- celiacs disease
- these are primarily through t cell attack and may be followed by a secondary antibody production
fetal tolerance
-fetuses are very easy to induce immunological tolerace in
sympathetic opthalmia
-damage to one eye releases hidden antigens which will mount an immune response that could cause damage to the other eye
polyclonal lymphocyte activation
- this is an immunological factor contributing to AI
- causes non-specific activation of lymphocytes
- EBV (mono) stimulates B cells
- superantigens stimulate T cells
how could we treat t cell mediated AI diseases?
- blocking the mhc-tcr interaction in the specific area which is being attacked
- may be able to use antibodies to do so
what is the most common AI disease in this country
-grave disease in women (hyperthyroidism)
