exam 2 Flashcards
Tolerance
Active state of specific non-responsiveness (induced by prior exposure)
** very specific
*Tolerance is an ACTIVE response of the immune system that exhibits antigenic specificity and memory
Failure of tolerance eg (allergies)
Autoimmune diseases
Pathologic conditions resulting from the failure of the tolerance mechanisms to keep autoimmune T & B cells in check
Tolerogen
cells with antigen-specific receptors can be tolerized
Central tolerance
Negative selection step
- occurs during lymphocyte development
- removal of T or B cells that recognize self antigen during development
Peripheral tolerance
*mature lymphocytes
- when mature lymphocytes encounter antigens without the required co-stimulatory signal
-can be induced as a result of repeated stimulation by antigen in peripheral tissues
eg allergy shots
Mechanisms for tolerance (4)
Deletion
Anergy
Suppression
Antigen sequestration
Deletion (tolerance)
-more central tolerance
Removal of auto reactive lymphocytes
-can occur in the primary lymphoid organ during lymphocyte development
-Apoptosis of lymphocytes in the periphery can occur due to repeated stimulation (desensitizing allergies)
Anergy (tolerance)
Occurs to T or B cells when co-stimulatory signal is absent or too weak to activate
- cells do not undergo apoptosis, but they can NEVER respond to the antigen
- they continuously circulate
Suppression (tolerance)
- temporary inhibition done by the secretion of TGF-beta, and ceases when TGF-beta is gone
- inhibits the proliferation of CD4+ and CD8+ T cells by preventing the transcription of IL-2
Antigen Sequestration (tolerance)
“Hiding” antigens in immunologically privileged sites when lymphocytes rarely circulate (eyes, testes, placenta, brain)
-an immune response can occur if the barrier preventing these antigens is breached (eg injury/trauma)
2 ways to develop an autoimmune dz
1) Failure to develop tolerance to self antigens (negative selection)
2) loss of tolerance due to dis regulation of immune system or previously hidden antigens (injury trauma from antigen sequestration)
Genetic susceptibility (tolerance)
The strongest associations with autoimmunity are with the HLA genes, especially those with MHC II
eg HLA B8 = graves dz
HLA B27 = IBS, psoriasis, SLE, MS
HLA DR2 = Hay fever, HLA DR4 = RA, type 1 diabetes
Infectious agents (tolerance) -autoimmunity is not a direct result of the infectious agent, is a result of the immune response
- Bystander activation
- Molecular mimicry: Abs made to foreign antigens are cross reactive to host
- Superantigens: autoreactive T cells that activate B cells to produce autoantibodies
- Alteration of tissues: trauma or injury (disrupts antigen sequestration)
Rheumatoid Arthritis (RA) systemic autoimmunity
- Auto-reactive IgM
- chronically inflamed synovium (inflammatory CD4+ T cells, CTLs, activated macrophages, complement, neut, cytokines)
- Type III reaction
Systemic Lupus Erythematosus (SLE)
-systemic autoimmunity
- Auto-antibodies against DNA and histones
- affects many organs in the body, and is thus hard to Dx
- Kidney failure is common cause of death
Multiple Sclerosis (MS) systemic autoimmunity
Mediated by autoreactive T cells
-Demyelination dz of the CNS
Myasthenia Gravis
-organ specific autoimmunity
-Auto-antibodies against ACh receptor at the NMJ
**Antagonist Abs block the binding of ACh to its receptor
-results in muscle weakness
death eventually occurs from respiratory failure
Autoimmunity
Low-affinity of self-reactive T cells and B cells (always present)
Hashimoto’s Thyroiditis
organ specific autoimmunity
Auto-antibodies against thyroid proteins
- Progressed destruction of thyroid follicles
- results in hypothyroidism from an enlarged goiter, which at some point destroys the thyroid, causing decreased thyroid hormone output
Grave’s dz
Organ specific autoimmunity
- Agonist auto-antibodies are against TSHR resulting in overproduction of thyroid hormone
- Hyperthyroidism
causes: weight loss, Afib, hair loss,
Type I Insulin-Dependent Diabetes Mellitus (IDDM)
-organ specific autoimmunity
Chronic inflammatory destruction of the insulin-producing cells of pancreas
- Mediated by CTLs
- can treat with replacement therapy
