Lecture 5- Immunological tolerance Flashcards
…. is a state of unresponsiveness for a particular antigen
immunological tolerance
Immunological tolerance is…., very specific and induced by… and includes tolerance to non-self antigen
- LEARNED
- prior exposure to antigen
…. is the physiological state in which the immune system does not react destructively against self tissue
self tolerance
… occurs in generative lymphoid organs (bone marrow/thymus) involving immature self-reactive lymphocytes recognizing self antigen
central tolerance
…. occurs in peripheral sites involving mature self-reactive lymphocytes encountering self antigen
peripheral tolerance
tolerance can be… or …
natural (oral)
induced (immunization)
Immunological tolerance is NOT
simply a failure to recognize an antigen
Reactivity is prevented by processes that occur during…. rather than…
- development
- being genetically pre-programmed
The most important aspect of tolerance is…
self tolerance
… selection occurs in the medullary region of the thymus and is mediated by … interactions with self antigen
Negative
high avidity
… selection and…. occurs in the cortical region of the thymus and is mediated by … interaction with self antigen
Positive
lineage commitment
low avidity
Those lymphocytes that do not bind MHC through their TCR are destined to
die by apoptosis
During maturation in thymus, most immature T cells that recognize antigens with high avidity are deleted. Some self-reactive … that see self antigen in the thymus are not deleted but instead…
- CD4+ T cells
- differentiate into regulatory T cells
Choice between lymphocyte activation and tolerance is determined by:
- properties of antigens
- state of maturation of the Ag-specific lymphocytes
- types of stimuli received when these lymphocytes encounter self antigens
Recognition of self antigen in central tolerance can lead to….
(3)
- apoptosis
- change in receptors (receptor editing; B cells)
- Development of regulatory T lymphocytes (CD4+ only)
Recognition of self antigen in peripheral tolerance can lead to….(3)
- anergy
- apoptosis
- suppression
or ignorance?
Central tolerance in B cells occurs in … in the …
Potentially autoreactive cells can be… or… by contact with self antigen
- immature B cells
- bone marrow
- eliminated
- inactivated
… and… of the self antigen determine fate of B cells
Nature and concentration
Fate of B cells with a multivalent Ag
B cell death
Fate of B cells with high concentrations of Ag
B cell death
Fate of B cells with low concentrations of small, soluble self Ag
B cell anergy
Ways immune regulation can maintain state of tolerance:
- … inhibits functions of APCs (IL-12 secretion, B7 expression)
- … inhibits T cell proliferation
- …. inhibits action of IFN-y
- ….inhibit macrophage activation
IL-10
TGF-beta
IL-4
IL-10 and TGF-beta
oral administration of Ag favors…. induction and there is a state of…. following oral administration of an antigen
tolerance
hyporesponsiveness
Autoimmunity results when… and.. is broken
central and peripheral tolerance
7 factors that can predispose an individual to various autoimmune diseases
MHC associations familial concordance gender climate chemical agents infectious agents immune dysregulation
Rheumatoid arthritis is typically more aggressive in…
females
Multiple sclerosis can differ in … between females and males
clinical course
Females with MS tend to have a ….. disease course
relapsing-remitting
Males with MS tend to have a …. disease course
chronic progressive
2 categories of autoimmune disease
systemic and organ specific
Systemic autoimmune disease is thought to be due to ….
aberrant regulation of many clones of lymphocytes
Organ specific autoimmune disease is thought to be due to …
failure of self tolerance in only a few clones of cells which react to a limited number of antigens
What initiates an autoimmune response?
- incomplete….
- aberrant stimulation of…
- altered regulation of…
- incomplete deltion of self reactive cells
- aberrant stimulation of “normally” anergic self reactive cells
- altered regulation of anergic self reactive cells
… is an autoimmune disease where the immune system targets CNS via myelin specific T cells
MS
…. is a systemic autoimmune disease in which a variety of autoantibodies (DNA, nucleoproteins, platelets, lymphocytes) can cause multisystem damage
Systemic Lupus Erythematous
…. can result in a butterfly rach, pleural effusions, heart problems, lupus nephritis, arthritis, raynauds pehnomenon
Systemic Lupus Erythematous
2 common systemic autoimmune diseases
Systemic Lupus Erythematous (SLE)
Rheumatoid Arthritis (RA)
2 common organ specific autoimmune disease
Insulin dependent diabetes melitus (IDDM)
Multiple Sclerosis
SLE: increased risk associated with?
HLA DR2
HLA DR3
SLE: female/male predominance
10:1
Symptoms of SLE
fatigue fever alopecia mucosal ulceration butterfly rash joint and muscle pain
Onset age of SLE
15-25
SLE can have serious complications of the…. (4)
heart
lungs
kidney
CNS
MS: Increased rick associate with?
HLA DR2
Female/male predominace of MS
3:2
Typical onset age of MS
women: childbearing age
men: >40
Symptoms of MS
- impaired vision
- ataxia
- spasticity
- bladder dysfxn
- weakness/paralysis of limbs
- temperature sensitivity
- cognitive impairment
MS treatments
- immunomodulatory drugs
- corticosteroids
- immunosuppressive therapy
