Immuno 17 Flashcards
What is autoimmunity?
adaptive immunity that is specific for self-determinants.
What is an antagonist in the sense of autoimmunity?
An antibody that binds to a cell surface receptor, thereby preventing its function
What is an agonist in the sense of autoimmunity?
an antibody that binds to a cell surface receptor in a way that mimics the binding of the actual ligand to the receptor
How do autoimmune diseases arise?
through breakdown of the negative selection processes that remove self-reactive B cells and T cells from the lymphocyte repertoire
What are some body functions that help prevent autoimmunity?
1) Negative selection in bone marrow and thymus via AIRE
2) Restricting lymphocyte accèss from certain sites (e.g. eyes and testes)
3) Tregs
What are some common Type II autoimmunity disorders?
1) Autoimmune hemolytic anemia
2) Autoimmune thrombocytopenia purpura
3) Goodpasture’s syndrome
4) Pemphigus vulgaris
5) Graves disease
6) Myasthenia graves
7) Type 2 diabetes
8) Hypoglycemia
What is autoimmune hemolytic anemia?
a condition that results from priming of an acquired antibody response to surface determinants of RBCs. These responses are mediated primarily by IgG, but some IgM will also be produced and can participate.
When this response is made, the antibodies bind to RBCs and become ligands for complement component C1q. Once C1 binds, the classical complement pathway becomes activated, resulting in deposition of C3b on RBCs as well as direct lysis of RBCs by abundant membrane attack complex formation. Opsonized RBCs are taken up and destroyed by phagocytes (via CR1) that recognize complement and IgG opsonins in the spleen.
How can autoimmune hemolytic anemia be verified?
a direct Coomb’s assay (direct antiglobulin test)
How would you treat autoimmune hemolytic anemia?
corticosteroids
What is Autoimmune (Idiopathic) Thrombocytopenic Purpura?
IgG-mediated inhibition of an enzyme responsible for cleavage of von Willdebrand factor (vWF)
OR IgG specific for gpII:IIIa on platelet surface
What happens when vMF is not cleaved?
excessive platelet adhesion occurs, partially occluding small blood vessels. As RBCs pass thru the partially obstructed vessels, they are damaged (microangioplastic hemolytic anemia)
What else occurs in Autoimmune Thrombocytopenia Purpura?
In addition, excessive platelet adherence results in damage to kidneys, liver, and even the brain, as well as platelet depletion from the circulation.
Reduced platelet numbers reduce the ability of the host to produce clots, so these patients also develop purpura (bruising).
How is diagnosis of ATP perfomed?
Treatment?
Diagnosis: observation of microangioplastic hemolytic anemia.
Treatment: plasma exchange (plasmapheresis) with plasma from healthy donors.
What is Goodpasture’s syndrome?
a condition caused by an IgG response to the α-chain of type- IV collagen (lines basement membranes all over the body)
What does IgG binding to type IV collagen result in?
Once antibodies bind, inflammation mediated by the classical complement cascade (and then the alternative pathway) and phagocytes causes tissue damage.
What tissues are most affected by Goodpastures?
The most important tissue damage is in the kidneys, resulting in progressive kidney dysfunction and culminating in glomerulonephritis.
25% of ALL kidney failure can be attributed to damage caused by the immune system
What are some common symptoms of Goodpasture’s disease?
loss of appetite, weakness, fatigue, progressive loss of kidney function
How do diagnose Goodpasture’s?
Treatment?
measurement of glomerular basement membrane-specific antibodies (anti-GBM)
Treatment: plasma exchange and with anti-inflammatory drugs
What is Schleroderma?
an IgG-mediated autoimmune disease that results in damage to the vascular endothelium of arteriole and smooth muscle cells that results in replacement of damaged tissue with collagen that results in skin thickening and hardening.
What other tissues besides skin are impact by Scleroderma?
kidneys, blood vessels, liver, and brain
What are the common symptoms of Scleroderma?
localized or systemic skin thickening: hard, smooth, ivory colored areas of hardened skin
What are the symptoms of Scleroderma mediated by?
ANA (anti-nuclear Abs), ATA (anti-topoisomerase Abs), and ACA (anti-centromere Abs), all IgGs.
diagnosis is via presence of any of these
What is the treatment of Scleroderma?
no standard treatment, but most include drugs that increase blood flow to extremities
What are the two forms of Scleroderma?
1) Limited scleroderma or CREST syndrome
2) Diffuse scleroderma
What is CREST syndrome characterized by?
Involves production of anti-centromere antibodies. This form is milder, and skin thickening is less widespread, typically confined to fingers, hands, and face and slowly developing
What is Acute Rheumatic Fever caused by?
an autoimmune condition that results from molecular mimicry. A normal IgG response to group A Streptococcus pyogenes (GAS) infection cross reacts with normal host tissue.
There are streptococcal envelope components that are very similar to determinants that are expressed on cardiac tissue. Typically, several weeks after a GAS infection (in some patients), damage to the heart is mediated by cross-reactive IgG, and the resulting inflammatory response (myocarditis) becomes symptomatic due to scarring of heart valves
not a memory response
What are the symptoms of Acute rheumatic fever?
chest pain, shortness of breath, fever, joint pain
What is acute rheumatic fever “acute” in nature?
since T cells do not recognize the streptococcal surface antigens, B cells cannot be fully activated; therefore, no immunological memory results and the autoimmune disease is transient
mainly an IgM response, not a memory response
What is Pemphigus vulgaris?
autoimmune condition mediated by IgG specific for 2 proteins (desmoglein 1 and 3); results in loss of cohesion in
keratinocytes in the epidermis
What are the symptoms of Pemphigus vulgaris?
painful chronic skin blistering
How is diagnosis of Pemphigus vulgaris performed?
immunofluorescent staining to identify IgG4 AB bound to tissue from a punch biopsy
What is the treatment for Pemphigus vulgaris?
corticosteroids and ritiximab (CD20-specific mAb)
What is Grave’s disease?
an autoimmune condition in which thyroid stimulating hormone receptor (TSH receptor)-specific IgG antibodies cause over-production of thyroid hormone because they act as receptor agonists of TSH
What are some of the symptoms caused by Grave’s disease?
bulging eye syndrome (with a characteristic stare) is hallmark; also: enlarged thyroid, heat intolerance, nervousness, irritability, weight loss, and moist skin
How does normal thyroid functioning occur?
When thyroid hormone does not need to be produced, thyroglobulin is stored in the thyroid in an iodinated form.
When thyroid hormone is needed, the pituitary produces TSH that, in turn, binds to TSH receptors on the thyroid, resulting in secretion of active T3 and T4 thyroid hormones.
Grave’s disease targets this.
Is Grave’s disease hereditary?
No, but because Grave’s disease is an IgG-mediated autoimmune disease, a pregnant woman with the condition will pass these IgGs to the developing fetus, and the fetus will also suffer from the condition.
Following birth, the treatment for the child is plasma exchange (or plasmaphoresis) to remove the antibodies. Once the mother’s TSH-specific IgGs are removed from the child’s circulation, normal thyroid function will be restored.
What is Myasthenia Gravis caused by?
IgG antibodies bind to acetylcholine receptors, causing them to be endocytosed and destroyed (recycled). Over time, this results in depletion of acetylcholine receptors at neuromuscular junctions, making muscles less sensitive to neuronal stimulation. Patients with this condition experience progressive weakness due to muscle atrophy.
What are the common symptoms of Myasthenia gravis?
typically begin with facial muscles, and especially muscles of the eyes and eyelids. These patients often present with diplopia (double vision) and ptosis (sagging eyelids).
Over time, the condition progresses to generalized muscle weakness (worse in the evenings)
Approximately 10% of these patients also develop a thymoma (a tumor of the thymus that is either benign or malignant).
What is the treatment of Myasthenia gravis?
With immunosuppressive drugs (to prevent formation of autoantibodies), or a drug called pyridostigmine which inhibits cholinesterase (which degrades acetylcholine); longer-lived acetylcholine can better compete with autoantibodies for binding to acetylcholine receptors.
What is subacute bacterial endocarditis?
an autoimmune condition mediated by IgG that is made in response the the normal flora organism Streptococcus viridans that have colonized damaged heart valves. (Typically, this organism only colonizes heart valves that have already been damaged (e.g. rheumatic fever, congenital condition, etc.)).*
When S. viridans has colonized heart valves, IgG specific for determinants of this bug bind to the bacteria, promoting recognition of the immune complex by phagocytes as well as initiation of the classical complement cascade. The inflammation that results causes further damage to the heart valves and myocardium.
This is considered an immune complex “hypersensitivity” or immune complex autoimmune disease because the inflammation results from recognition of immune complexes.
What is Mixed essential cryoglobulinemia?
an odd condition that is characterized by production of what are known as cryoglobulins.
What are cryoglobulins?
Cryoglobulins are immunoglobulins that become insoluble at reduced temperatures (sometimes they are only composed of light chains) and are similar to rheumatoid factor in that they have specificity for the Fc regions of antibodies and can cause immune complex disease.
