PP of Autoimmune Diseases Flashcards
1
Q
72yo male presents to clinic w/ HA for 1 wk, progressively gotten worse - L side, 7/10, tyelonol doesn’t help, L temporal region swelling and tenderness w/ palpation, fever -
What dx test should you get? Dx? Tx?
A
- ESR
- Temporal Arteritis
- tx: tx now w/ prednisone at 40-60/day and schedule temporal artery bx in next few days
- visual changes are a red flag (need IV abx ASAP)
2
Q
What are the mechanisms hypothesized to be involved in breakdown of tolerance?
A
- failure to delete autoreactive lymphocytes:
central tolerance failure, peripheral tolerance failrure - molecular mimicry
- abnormal presentation of self ags
- epitope spreading (part of ag that is recognized by abs)
- polyclonal lymphocyte activation
3
Q
Source of T cells? Fxn?
A
- derived from thymus
- impt in cellular immunity
- induce B cells to produce abs
- each programmed to recognize unique processed peptide fragment by T cell receptor (TCR)
- circulate in blood, sequestered in spleen and lymph nodes
4
Q
Mechanism of T cell activation?
A
- dendritic cells and macrophages - ag presenting cells (APC)
- major histocompatibility (MHC) - a region formed by genetic loci that play a central role in humoral and cellular immunity
- MHC: HLA group of proteins that participate in APC
- When not self peptide APCs interact and present ag to T cells - CD4 and CD8. Normal ratio CD4/CD8 - 2:1
- CD4 T helper cells, CD8 cytotoxic T cells
5
Q
T cell response? Diff classes of MHC molecules?
A
- CD4 and CD8 expressing T cells are referred to as CD4 adn CD8
- the helper T cells - secrete cytokines and influence all other cells of the immune system
- Class I MHC molecules: assoc w/ recognition of endogenous ags
- Class II: assoc w/ recognition of exogenous ags
- Class III: involved w/ complement system
6
Q
Origin of B lymphocytes?
A
- derived from bone marrow
- 10-20% circulate
- present in: bone marrow, lymph nodes, spleen, tonsils and nonlymphoid organs such as GI tract (peyers patchs)
- after stimulation B cells form plasma cells and secrete immunoglobulins
7
Q
AG processing?
A
- Ag must be taken up by APC
- Ag is then processed inside the cell
- Then it is presented to immune system
- MHC class I/CD8: cytotoxic cell
- MHC class II/CD4 - helper T cells
8
Q
What is immunological tolerance?
A
- state of unresponsiveness specific for a particular Ag
- it prevents the body from attacking itself - self tolerance
9
Q
What is B cell tolerance?
A
- loss of self tolerance w/ development of autoabs is characteristic of number of autoimmune disease: hyperthyroidism in graves is due to autoabs to TSH receptors
filtering autoreactive B cells out of pop:
- clonal deletion in bone marrow
- deletion of autoreactive cells in spleen or lymph nodes
- functional inactivation by anergy
- receptor editing process that changes specificity of a B cell receptor when autoag is encountered
10
Q
What is central mechanisms of T cell tolerance?
A
involve the deletion of self-reactive T cells in the thymus - -immature T cells of a clone that are not auto-reactive T cells are allowed to mature = positive selection -immature T cell clones that have high affinity for host cells are sorted out and undergo apoptosis = negative selection - many autoags are not present in thymus which results in self reactive cells escaping the process: sequestered ags (immunologically priviledged) - CNS, eyes, testes (if these are released then immune response ensues) - therefore there needs to be peripheral mechanism available to deal w/ these
11
Q
Peripheral mechanisms of T cell tolerance?
A
- sometimes no problem exists b/t the self reactive T cells remain immunologically ignorant b/c they cant see Ag (BBB)
- peripheral activation of T cells requires 2 signals -
recognition of peptide Ag w/ MHCs on the APCs
and
secondary costimulatory signals which are often absent - Apoptosis (Fas receptor and Fas ligand)
- Suppressor T cells can also down-regulate autoreactive T cells
12
Q
Mechanisms of self tolerance?
A
- central tolerance: elimination of self-reactive T cells and B cells in central lymphoid organs
- peripheral tolerance:
some of the T cells will become regulatory T cells - products of Tr are cytokines that downregulate the immune response when the pathogen is cleared and help prevent autoimmunity - some escaped T cells won’t recognize MHC self ag and will remain as immature Tc cells
anergy: state of immunologic tolerance to Ag
13
Q
RFs of autoimmunity?
A
much remains unknown but possibilities have been proposed: (5-7% of pop is affected by autoimmunity):
- failure of mechanisms that maintain self tolerance
- genetic factors: genes that are involved in the immune response are the major players (MHC and HLA loci)
- gender: autoimmune diseases affects females more severely and more often than men - hormonal influences play a role (estrogen) - except Ankylosing spondylitis, and acute anterior uveitis
14
Q
Etiology of autoimmune disorders?
A
result from 1 or more mechanisms producing loss of self-tolerance:
- immunologic cells are involved in tissue injury that results in exposure of self-antigen
- precise mechanisms involved in initiating response is largely unknown
- more than one defect may be present in each disease and each mechanism may be involved in more than one disease
15
Q
Possible mechanisms of autoimmune mechanisms:
Failure of T cell mediated suppression?
A
- failure to delete autoreactive immune cells
- increasing ratio of CD4 to CD8 may be involved
