Autoimmunity and Hypersensitivity

Question 1

Are there autoreactive T-cells that escape deletion in the thymus?

Answer 1

Yes. The threshold for deletion is arbitrary, and their affinities are lower.

Question 2

AIRE

Answer 2

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.

Question 3

Peripheral tolerance

Answer 3

Because some B and T cells escape central deletion, other mechanisms must exist to prevent pathogenic autoimmunity. These include anergy, ignorance, regulation.

Question 4

Ignorance

Answer 4

Costimulatory signal to activate naive T-cells occurs only in lymphoid tissue.

Question 5

Peripheral anergy

Answer 5

If a t-cell encounters an APC, but costimulation does not occur, the T cell becomes stunned.

Question 6

Tregs Function and Mechanism

Answer 6

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.

Question 7

BAFF

Answer 7

B cell survival factor

Question 8

How are B cells regulated peripherally?

Answer 8

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.

Question 9

Triggers of autoimmune disease

Answer 9

Genetic predisposition, infection (causing molecular mimicry, inability to clear immune complexes, etc.), puberty, exposure to certain antigens.

Question 10

Type II Hypersensitivity Response

Answer 10

Antibody-mediated. Causes opsonization and phagocytosis of cells, recruitment of leukocytes, abnormalities in cellular functions (signaling). Acute inflammation.

Question 11

Goodpasture’s disease

Answer 11

Antibody binds to the basement membrane of capillary grooves in glomerulus. Causes kidney failure. II

Question 12

Grave’s Disease

Answer 12

Antibody to TSH receptor causes unregulated release of thyroid hormone. II

Question 13

Myesthenia gravis

Answer 13

Autoantibodies block binding of Ach to receptors. II

Question 14

Type III Hypersensitivity Reactions

Answer 14

Immune complex mediated. Antigens and antibodies are deposited in tissues and can cause injury. This activates complement and other Fc mediated injury. Acute inflammation.

Question 15

Post-streptococcal glomerulo-nephritis

Answer 15

Child with strep infection. Bacterial products get deposited in kidney. Antibodies bind to antigens in kidney and cause injury. III

Question 16

Systemic lupus erythematosis

Answer 16

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

Question 17

Lupus kidney histology

Answer 17

Granular

Question 18

Type IV Hypersensitivity

Answer 18

Cell-mediated response. Inflammation via CD4s or cell killing via CD8s can occur. Like sarcoid. Granulomas, chronic inflammation.

Question 19

Type I Diabetes

Answer 19

Autoreactive T-cells target pancreatic islets.

Question 20

Contact hypersensitivity

Answer 20

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.

Question 21

DTH

Answer 21

Delayed Type hypersensitivity. Causes granuloma formation. Regulated by Th1 cells which secrete IFN-g and TNFß, delayed onset. PPD!

Question 22

Type I Hypersensitivity

Answer 22

IgE mediated. Mast cells and their mediators cause injury.

Question 23

Mast Cell Activation

Answer 23

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.

Question 24

Systems affected by mast cell degranulation?

Answer 24

GI: Increased fluid secretion, increased motility (diarrhea/vomiting). Airways: Decreased diameter, increased mucus (wheezing/phlegm). Vessels: Vasodilation, increased vascular permeability.

Question 25

How do Th2 cells help in type I hypersensitivity?

Answer 25

Help in antibody production, which will bind to mast cells and activate eosinophils.

Question 26

Asthma Histology

Answer 26

Mucous plug fills bronchiole, inflammatory cells in mucous. Goblet cell metaplasia. Hypertrophy and hyperplasia of bronchial smooth muscle.

Question 27

Mast cell histology

Answer 27

Hard to see with H and E, use toluidine blue

Question 28

RBC casts

Answer 28

A consequence of Goodpasture syndrome, renal capillaries become congested and coagulated.

Question 29

Goodpasture syndrome histology

Answer 29

Glomerular necrosis, acute inflammation, hemorrhage. Can also cause pulmonary hemorrhage.

Question 30

Granular deposits and neutrophils in glomeruli?

Answer 30

Type III hypersensitivity

Question 31

Systemic Vasculitis

Answer 31

Immune deposition in branch points of vessels. Causes neutrophil deposition and fibrinoid necrosis.

Question 32

Diabetes Histology

Answer 32

Infiltrating lymphocytes