1. Immunology Chapter 20 Richard L. Myers, Ph.D. Department of Biology
Southwest Missouri State
Temple Hall 227
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2. Autoimmunity
Autoimmunity results when the immune system responds to self-components
tolerance usually protects an individual
protection is through clonal anergy or clonal suppression
A breakdown in tolerance can lead to self-reactive clones of T or B cells
can cause serious damage to cells and organs

3. Organ-specific disease
Humoral or cell-mediated damage can be directed to target organs
Cellular damage
antibodies or lymphocytes bind to cell-membrane antigens
cause cellular lysis/inflammatory response
function of the organ is gradually lost

4. Hashimoto’s thyroiditis
Autoantibodies are produced
also sensitized TDTH cells
Characterized by infiltration of lymphocytes, macrophages and plasma cells into the thyroid
the inflammatory response causes a goiter
an enlargement of the thyroid gland
Autoantibodies react with thyroid proteins, interfering with iodine uptake

5. Autoimmune anemias
Includes 1) pernicious anemia, 2) autoimmune hemolytic anemia and 3) drug-induced hemolytic anemia
Pernicious anemia caused by antibodies to an intestinal protein, intrinsic factor
prevents uptake of vitamin B12
Autoimmune hemolytic anemia caused by autoantibodies to RBC antigens
results in complement-mediated lysis or antibody-mediated opsonization

7. Goodpasture’s syndrome
Autoantibodies specific for basement membrane antigens produced
bind to membranes of kidney glomeruli and alveoli of the lungs
complement activation leads to cell damage and inflammatory response
Damage is progressive kidney damage
and pulmonary hemorrhage

8. Insulin-dependent diabetes
Insulin-dependent diabetes mellitus (IDDM)
caused by autoimmune attack on the pancreas
large numbers of TDTH cells and macrophages
directed to insulin-producing cells (beta cells)
Result is decreased production of insulin
therefore increased levels of blood glucose
Beta cell destruction mediated by cytokines
also lytic enzymes from activated macrophages
autoantibodies may also contribute

10. Normal islets (left) and diabetic (right)
Normal islets (left) and diabetic (right). Note selective loss of beta cells (brown) and infiltlration by lymphocytes

11. Diseases caused by autoantibodies
Antibodies bind to hormone receptors
stimulate inappropriate activity
Graves’ disease is a good example
thyroid-stimulating hormone (TSH) binds to a receptor on thyroid cells
activates adenylate cyclase to stimulate thyroid hormones
In Graves’ an autoantibody is produced to the receptor for TSH

16. Diseases caused by blocking-autoantibodies
Autoantibodies bind to hormone receptors
act as antagonists
inhibit receptor function
Myasthenia gravis is the prototype disease
autoantibodies are produced to the acetylcholine receptors
on motor end-plates of muscles
inhibits muscle activation

19. Systemic autoimmune diseases
Represent a generalized defect in immunity
hyperactive T and B cells
cause tissue damage
from autoantibodies and cell-mediated also
immune complexes important

20. Systemic lupus erythematosus
SLE is the best example of a systemic autoimmune disease
Usually occurs in young women
characterized by fever, weakness, joint pain, erythematous lesion, pleurisy and kidney dysfunction
Patients produce autoanibodies to a variety of tissue antigens like DNA, histones, etc.
diagnosis made by identifying ANA

21. Animal models for autoimmunity
We understand more about autoimmunity because of animal models
autoimmunity develops spontaneously
can also be induced experimentally
Examples of spontaneous autoimmunity
systemic lupus erythematosus
nonobese diabetic (NOD) mouse

22. Experimentally induced autoimmunity
Several experimental animal models are very similar to certain autoimmune diseases
Experimental autoimmune encephalomyelitis
an excellent model for understanding autoimmunity
produced by immunizing animals with MBP
in Freund’s adjuvant
animals develop cellular infiltration of myelin sheaths resulting in demyelination and paralysis
model for multiple sclerosis

25. Role of CD4 in autoimmunity
CD4 is the primary mediator of autoimmunity
However, to become autoimmune
must possess MHC and T-cell receptors capable of binding self-antigens

26. Evidence for association of MHC
There is association between expression of a particular MHC allele and susceptibility to autoimmunity
Can be shown by using antibodies to HLA alleles
some allelles occur at higher frequency among autoimmune individuals
association expressed as relative risk
values above 1 indicate association

28. Mechanism for induction
Autoimmunity usually develops from a number of different events
Sequestered antigens
myelin basic protein is a good example
normally sequestered from the immune system
by the blood brain barrier
trauma or an infection releases antigens
i.e., sperm after vasectomy, lens protein after eye damage and heart antigens after infarction

29. Molecular mimicry
Some bacteria and viruses possess antigens identical to the host
fairly common
i.e., cross-reacting antibodies causing rheumatic fever
another example are the heat-shock proteins
produced by cells following fever
these proteins found in a variety of pathogens
therefore, when you make a response to a pathogen’s heat-shock proteins, it will cross-react through molecular mimicry

30. Inappropriate expression of class II MHC
in insulin-dependent diabetes mellitus (IDDM) healthy beta cells do not express class II MHC
same for thyroid acinar cells
an inappropriate expression sensitizes T cells to peptides derived from the beta cells or thyroid cells

31. Treatment of autoimmune disease
Treatments are aimed at reducing symptoms
They provide nonspecific suppression of the immune response
does not differentiate between good and bad
Use immunosuppressive drugs
i.e., corticosteroids, azathioprine and cyclophamide
patients at greater risk for infections or cancer

32. Assignment Read Chapter 21, Immunodeficiency Diseases
Review question 3 (pg 521)