Lecture 14

1.
What is SLE?
Systemic Lupus Erythematosus
2.
What are the disease symptoms for SLE? (3)
"Inflammation (skin, joints, blood vessels, kidneys), photosensitivity, antinuclear autoantibodies"
3.
What is immunological tolerance?
A state of unresponsiveness to an antigen
4.
What are the options for a lymphocyte encountering an antigen?
Activated (immune response) or  be inactivated/eliminated (tolerance)
5.
What are lymphocytes that attack “self” called?
Autoreactive lymphocytes
6.
What does failure of immunological tolerance result in?
Autoimmune response leading to tissue damage
7.
What is central tolerance?
Negative selection of strongly self reactive B and T cells
8.
Where does central tolerance occur? (2)
"Thymus, bone marrow"
9.
What are the steps for T cell education? (2)
"Positive selection, negative selection"
10.
What happens in positive selection?
Lymphocytes that manifest affinity with self MHC complex on cortical thymic epithelial cells. Lymphocytes that do not undergo death by neglect
11.
What happens in negative selection?
"Lymphocytes that manifest strong affinity to self MHC complexes expressed by dendritic cells, macrophages, and medullary epithelial cells. If a lymphocyte manifests strong affinity it undergoes apoptosis"
12.
What can go wrong with negative selection?
Some autoreactive cells can escape
13.
What is a thymocyte? (3)
"Fibroblasts, coritical thymic epithelial cells, medullary thymic epithelial cell"
14.
What are CD4 cells?
T helper cells
15.
What are CD 8 cells?
"Cytotoxic T cells
16.
What do thymocytes start life in the thymus as?
Double negative (DN1) cells
17.
What are T cells that express CD4 and CD8 receptors classified as?
Double positive
18.
Which cells mediate positive selection?
Cortical epithelial cells
19.
20.
Which cells mediate negative selection? (3)
"Medullary epithelial, macrophages, dendritic cells"
21.
How many cells bind too strongly to self MHCs?
20%
22.
How many thermocytes fail to bind self MHC in cortical epithelial cells?
80%
23.
What takes B cells that bind to self MHC out of action
Bone marrow cell
24.
What are the mechanisms of tolerance? (4)
"Clonal deletion, anergy, suppression, ignorance"
25.
What signals activate naive T cells? (3)
"TCR recognises self MHC, B7 molecule signals, cytyokines"
26.
What are the steps to anergising T cells?= ="Dedritic cell provides signals for self MHC but no co-stimulatory signals, if anergised T cell recognises the self MHC a second time (with co-stimulatory signals), it will not be activated"
27.
How do Treg cells inhibit activation of autoreactive T cells?
Produce cytokines (IL-10 and TGF-β that inhibit surrounding autoreactive T cells
28.
What is ignorance-sequestered antigen release?
eg. Sympathetic ophthalamia 
29.
What is sympathetic opthelamia?
Damage to one eye releases antigens that result in autoimmune response against eye proteins in both eyes
30.
What are the requirements for autoimmune diseases? (4)
"Escape of autoreactive clones from central tolerance, autoreactive clones encounter self antigens, peripheral tolerance failure, autoreactive tissue damage"
31.
What types of HS does tissue damage occur in? (2)
"Type II, type III"
32.
What tissues are affected by type II HS?
Specific organs
33.
Which mediators are involved with organ specific HS II? (3)
"K cells, macrophages, complement"
34.
What tissues are affected by HS III?
Systems
35.
How does HS III cause tissue damage?
Immune complex molecules activate immune response
36.
Which tissues are affected by HS III?
"Kidneys, skin, joints"
37.
What cells are involved in HS III? (3)
"Macrophages, neutrophils, complement"
38.
What are examples of organ specific autoimmunity? (4)
"Systemic lupus erythematosus, glomerulonephritis, arthritis, rash"
39.
What is the disease associated with good pastures syndrome?
Antibodies against type IV collagen basement membranes in glomeruli and alveoli
40.
What are the disease conditions associated with myasthenia gravis?
Antibodies block ACh receptors causing muscle weakness
41.
What are the disease conditions associated with pemphigus?
Antibodies against desmogleins between keratinocytes causing blisters
42.
How does Graves disease affect the thyroid?= =Autoantibodies bind thyroid stimulating hormone receptor (agonist) causing hyperthyroidism
43.
How does Hashimoto’s disease affect the thyroid gland?
"Autoantibodies against thyroglobulin, thyroid peroxidase, complement activation and cytoxic T cell attack causing hypothyroidism"
44.
How might UV exacerbate lupus?= =Photosensitivity
45.
How does an epitope contribute to autoimmune diseases?
Through molecular mimicry
46.
What is molecular mimicry?
Where T or B cells bear antigen receptors that recognise both self and pathogen epitope
47.
What is an example of a disease due to molecular mimicry?
Rheumatic fever
48.
What is the molecular mimicry in rheumatic fever?
(2) Human myosin and streptococcus cell wall protein epitopes
49.
"In rheumatic fever, where is the M protein epitope in the body?"
"Synovium, heart muscle, heart valve"
50.
What are the results of acute rheumatic fever? (2)
"Arthritis, heart valve damage"
51.
What happens in genetics of those genetically predisposed to autoimmune diseases?
Normal central tolerance but dysregulated peripheral tolerance
52.
What can contribute to autoimmunity?
"Monozygotic twins, drugs, pathogens, hormones"
53.
54.
What are the treatments for SLE? (3)
"Corticosteroids, azathioprine, cyclophosphamide"
55.
What are treatments for rheumatoid arthritis? (3)
"Corticosteroids, NSAIDS, anti TNF/IL-1 antagonists"