autoimmunity Flashcards
What type of immune response is not present in any type of autoimmunity?
no IgE mediated responses
What is autoimmunity?
adaptive immunity specific for self-antigens
The cause of many autoimmune diseases are not known but what are the 3 main types that are known?
break down in the self-tolerance mechanisms of immune system
some mediated by Abs, others by T cells
some initiated by response to pathogens (molecular mimicry)
What are the simlarities of Type II autoimmunity and type II hypersensitivity?
mediated by Abs
specific for cell surface/ECM
What are the similarities of type III autoimmunity and type III hypersensitivity?
mediated by Abs
caused by immine complexes
What are the similarities of type IV autoimmunity and Type IV hypersensitivity?
mediated by T cells
What are mechanisms that contribute to immunological self-tolerance?
- negative selection in bone marrow and thymus
- expressionof tissue-specific proteins in thymus
- no lymphocyte access to some tissues
- suppression of autoimmune responses by Treg cells
- induction of anergy in autoreactive B and T cells
What is autoimmune hemolytic anemia?
a disease that is caused by Ab (IgG or IgM) specific for surface antigens of erythrocytes
What can autoimmune hemolytic anemia result in?
activation of classical complement pathway
can result in uptake of opsonized RBC by phagocytes (in spleen) bearin either complement or Fc receptors
both result in RBC destruction
How would you detect autoimmune hemolytic anemia?
Direct Coomb’s hemagglutination assasys detect auto-Abs bound to patient’s RBCs
What is autoimmune (idiopathic) thrombocytopenic purpura?
1) IgG mediated inhibition of an enzyme responsible for cleavage of von Willdebrand factor (vWF)
vWF links platelets and blood vessels with clots
2) caused by platelet specific auto-Abs in IgG
What can cause autoimmune thrombocytopenic purpura?
caused by platelet specific auto-Abs in IgG
How would you diagnose a patient with autoimmune thrombocytopenic purpura?
observation of microangioplastic hemolytic anemia
low platelet counts
presence of schistocytes (broken RBCs)
How would you treat autoimmune thrombocytopenic purpura?
plasmapheresis (exchange transfusion) with plasma from healthy donors
rutiximab
RhoGam
steroids
splenectomy
infusion of gamma globulin
What is good pasture’s syndrome?
Ab specific for type IV collaen which lines basement membranes thru-out the body
In good pasture’s syndrome, what initiates the response and what are the results?
Ab initiates inflammatory response
kidney damage results
How is goodpasture’s syndrome treated?
plasma exchange and anti-inflammatory drugs
What is schleroderma?
inflammatory destruction of vascular endothelial cells of arterioles and smooth muscle cells
IgG mediated
many times replacement with collagen and other fibrous materials
Other than vascular endothelial cells what else can be affected by schleroderma?
kidneys, blood vessels, liver, brain
What are the symptoms of schleroderma?
localized or systemic symmetrical skin thickening
hard, smooth ivory colored areas of hardened skin
Rh factor not required for disease
How would you diagnose a person with schleroderma?
presence of anti-nuclear Abs
anti-topoisomerase Abs
anti-centromere Abs (IgGs)
How would you treat someone with schleroderma?
no known cure or standard treatment
drugs can be given to increase the blood flow to extremities
What causes acute rheumatic fever?
caused by Abs that are produced during response to bacterial infection (group A streptococcus pyogenes)
What is a common result of acute rheumatic fever?
bacteria specific Abs cross react with heart tissue (molecular mimicry)
What Abs can be associated with rheumatic fever?
IgM or IgG
What are the results of acute rheumatic fever?
inflammation causes heart valve scarring and/or myocarditis
What is pemphigus vulgaris?
autoimmune condition mediated by IgG specific for 2 proteins
this results in the loss of cohesion in keratinocytes in the epidermis
What are the symptoms and diagnostic tools for pemphigus vulgaris?
Sx: painful chronic blistering of skin
Dx tools: punch biopsy of lesion followed by immunofleuorescent staining (IgG4 Ab considered pathogenic)
How would you treat pemphigus vulgaris?
corticosteroids and other anti-inflammatory drugs
rituximab (CD20 specific Ab; B cell surface marker)
What are the autoimmune diseases the thyroid gland?
Hashimoto’s throiditis
Graves’ disease
subacute thyroiditis
idiopathic hypothryoidism
What are the autoimmune diseeases of islets of langerhans (pancreas)?
type I diabetes
type II diabetes
What is the autoimmune disease of the adrenal gland?
addison’s disease
What is an antagonist wrt autoimmune disease?
molecule that binds to receptor, preventing its interaction with its specific ligand
What is an agonist wrt autoimmune disease?
molecule that binds to a receptor, triggering the receptor as if it is interacting with its specific ligand
What causes Grave’s disease?
caused by Abs that bind to the thyroid stimulating hormone (TSH) receptor
What is the result of Graves’ disease? why?
agonist=> Ab mimics the binding of TSH to TSH receptor
results in overproduction of thyroid hormone
What are the symptoms of Grave’s disease?
- heat intolerance
- nervousness
- irritability
- warm moist skin
- weight loss
- enlargement of thyroid
- bulging eye syndrome
- characteristic stare (muscle eye inflammation)
Would you expect the child of a pregnant woman that suffers from Goodpasture’s syndrome or Grave’s disease to have the disease?
yes
it is IgG Abs that cause the disease and are transported into fetal circulation via the brambell receptor
Of the child born of the mother with the graves or goodpasture disease, would the child suffer their entire lifetime?
No
once maternal Abs have been removed from fetal circulation then the child will no longer suffer symptoms of the disease
possible the child willone day make an autoimmune response to the TSH receptor though
How is myasthenia gravis mediated? What are symptoms?
mediated by antibodies specific for actylcholine receptors on mucle cells
generalized muscle weakness throughout the body especially the face and eyelids
What is the mechanism of action for myasthenia gravis? what type of antibody is it (agonist or antagonist)?
Ab binding to Ach receptors causes receptors to be endocytosed and degraded
loss of receptors leaves muscles less sensitive to neuronal stimulation
ANTAGONIST autoAb
How would you treat myasthenia gravis?
anti-inflammatory drugs
alternative Tx=> pyridostigmine => inhibit cholinesterase (to allow Ach to stay around longer to compete for binding)
What is the Ab for Subacute bacterial endocarditis? and how is it initiated?
IgG mediated inflammation of endocardium
inflammation is initiated by Abs taht bind to microbes that have colonized damaged heart valves
typically, A patient will only develop subacute bacterial endocarditis when?
if they have already suffered damage to their heart valves
In subacute bacterial endocarditis, what mediated the inflammation?
phagocytes that recognize opsonized bacteria (IgG, complement opsonins)
anaphylatoxins produced also promote inflammation
Describe mixed essential cryoglobulinemia
characterized by production of cryoglobulins
What are cryoglobulins?
immunoglobulins that become insoluble at reduced temperature
sometimes, only light chains (Bence Jones proteins)
When are cryoglobulins most-often produced?
by patients that have a B cell proliferative disorder (multiple myeloma or Waldenstrom macroglobulinemia)
Mixed essential cryoglobulinemia is a condition that is common with what type of infection?
common sequelae to infection with hepatitis C infection
What mediates sytemic lupus erythematosis?
mediated by autoantibodies specific for many self macromolecules
What is the mechanism of action for systemic lupus erythematosis? what is the result?
- Abs bind to cell surface components
- initiate inflammation
- leads to tissue destruction
Result=>
- damaged cells release soluble macromolecules
- immune complexes form and are deposited in blood vessels, kidneys, joints (further inflammation)
What are some common symptoms and genetics involved in SLE?
lupus = wolf => characteristic facial rash
most common in women (asian/African) = 1/500
severity highly variable
Describe the action of CD4 in the priming response for SLE
CD4 T cells specific for 1 epitope of macromolecular complex can provide help to B cells specific for other accessible epitopes of the complex
Describe the priming response in SLE with a B cell
A B cell that internalizes a macromolecular complex can present antigens to T cells specific for any of the proteins of the complex
What organ structure is generally affected with SLE?
glomerulus of kidney
