Autoimmunity and Hypersensitivity Flashcards
Are there autoreactive T-cells that escape deletion in the thymus?
Yes. The threshold for deletion is arbitrary, and their affinities are lower.
AIRE
Autoimmune regulator, a protein made in the thymus that causes thymic epithelial cells to turn on genes that are otherwise expressed only in the periphery. This way, thymus can delete T cells that react to peripheral proteins.
Peripheral tolerance
Because some B and T cells escape central deletion, other mechanisms must exist to prevent pathogenic autoimmunity. These include anergy, ignorance, regulation.
Ignorance
Costimulatory signal to activate naive T-cells occurs only in lymphoid tissue.
Peripheral anergy
If a t-cell encounters an APC, but costimulation does not occur, the T cell becomes stunned.
Tregs Function and Mechanism
Suppress responses of other T cells. Express FoxP3. Secrete TGFß and IL-10 which are inhibitory. Also inactivate APCs by expressing high levels of CTLA 4.
BAFF
B cell survival factor
How are B cells regulated peripherally?
Antibody production with an isotype switch requires Th cells. If Th cells have been regulated (anergy) by peripheral mechanisms, they can’t cause isotype switching in b cells.
Triggers of autoimmune disease
Genetic predisposition, infection (causing molecular mimicry, inability to clear immune complexes, etc.), puberty, exposure to certain antigens.
Type II Hypersensitivity Response
Antibody-mediated. Causes opsonization and phagocytosis of cells, recruitment of leukocytes, abnormalities in cellular functions (signaling). Acute inflammation.
Goodpasture’s disease
Antibody binds to the basement membrane of capillary grooves in glomerulus. Causes kidney failure. II
Grave’s Disease
Antibody to TSH receptor causes unregulated release of thyroid hormone. II
Myesthenia gravis
Autoantibodies block binding of Ach to receptors. II
Type III Hypersensitivity Reactions
Immune complex mediated. Antigens and antibodies are deposited in tissues and can cause injury. This activates complement and other Fc mediated injury. Acute inflammation.
Post-streptococcal glomerulo-nephritis
Child with strep infection. Bacterial products get deposited in kidney. Antibodies bind to antigens in kidney and cause injury. III
Systemic lupus erythematosis
Autoantibodies develop to DNA, histones, other self antigens. When cells break and these things end up in blood, immune complexes are formed, which deposit in tissues. III
Lupus kidney histology
Granular
Type IV Hypersensitivity
Cell-mediated response. Inflammation via CD4s or cell killing via CD8s can occur. Like sarcoid. Granulomas, chronic inflammation.
Type I Diabetes
Autoreactive T-cells target pancreatic islets.
Contact hypersensitivity
Response to haptens like poison ivy. Bind to skin macrophages (Langerhans Cells), activate Th1 cells, which secrete IFN-g and other cytokines. Other macrophages activate in response to TNF alpha, and IL-1.
DTH
Delayed Type hypersensitivity. Causes granuloma formation. Regulated by Th1 cells which secrete IFN-g and TNFß, delayed onset. PPD!
Type I Hypersensitivity
IgE mediated. Mast cells and their mediators cause injury.
Mast Cell Activation
IgE’s produced by plasma cells will bind to mast cells after first exposure, which then will patrol areas of inflammation together. When IgE encounters allergen on second exposure, mast cell degranulates. Also affected by anaphylatoxins, and certain drugs.
Systems affected by mast cell degranulation?
GI: Increased fluid secretion, increased motility (diarrhea/vomiting). Airways: Decreased diameter, increased mucus (wheezing/phlegm). Vessels: Vasodilation, increased vascular permeability.
How do Th2 cells help in type I hypersensitivity?
Help in antibody production, which will bind to mast cells and activate eosinophils.
Asthma Histology
Mucous plug fills bronchiole, inflammatory cells in mucous. Goblet cell metaplasia. Hypertrophy and hyperplasia of bronchial smooth muscle.
Mast cell histology
Hard to see with H and E, use toluidine blue
RBC casts
A consequence of Goodpasture syndrome, renal capillaries become congested and coagulated.
Goodpasture syndrome histology
Glomerular necrosis, acute inflammation, hemorrhage. Can also cause pulmonary hemorrhage.
Granular deposits and neutrophils in glomeruli?
Type III hypersensitivity
Systemic Vasculitis
Immune deposition in branch points of vessels. Causes neutrophil deposition and fibrinoid necrosis.
Diabetes Histology
Infiltrating lymphocytes
