Tolerance, Autoimmunity and AI disorders Flashcards
true or false: self-recognition/tolerance is a critical process
true (duh)
Failure to recognize self antigens results in what type of disease?
autoimmune diseases
Immune responses require what two mechanisms to happen?
APC presentation of foreign Ag and signal from MHC molecule on host’s cells
Define Tolerance
Lack of immune response to self antigens
A major mechanism of self-tolerance (autoreactivty) is the elimination of what cells?
Elimination of self-reactive immature lymphocytes
Failures of tolerance can result in what abnormalities?
- autoimmune reaction to self-Ag
- hypersensitivity
- autoinflammatory disorders
B cells undergo two selection processes during maturation. Briefly describe the main focuses of these stages.
Positive selection: signals for survival
Negative selection: T cells in thymus that lack self-MHC are eliminated (must go through this selection before achieving immunocompetence)
Peripheral tolerance: process of negative selection in periph lymph tissues and prim lymph tissues
True or false: T cells dont show a marked difference in tolerance at different stages of maturation
true
What are the three pathways recognized for T cell tolerance?
Clonal abortion
functional deletion
t cell suppression
What organ is responsible for deleting autoreactive t cells that have potential to cause autoimmune diseases?
Thymus
What are the four pathways of B cell tolerance?
clonal abortion
clonal exhaustion
functional deletion
Ab-forming cell blockade
True or false: potential for autoimmunity is constantly present in immunocompetent individuals
true
What are some focuses of genetic factors in autoimmunity?
- Focuses on common allelic variants (not mutations)
- familial aggregates common
- tendency for more than one autoimmune disease to occur in same individual
- more frequent in women
What are some factors that influence the development of autoimmunity?
Pt age (incidence increases with age (peak at 60-70yrs))
Exogenous factors (UV, drugs, virus, chronic infectious disease)
What are the three major phases of Autoimmune disease?
Initiation (genetic predisposition/environ triggers)
Propagation (cytokines,epitope spreading)
Resolution (cell intrinsic/extrinsic)
What is included in Antibodies to Antinuclear AB? (ANAs)
DNA, histones and nonhistone protein ab
What is the hallmark of autoimmune diseases?
tissue injury caused by T lymph or ab reactivity to self
What is the role of the innate system in tissue injury?
neuts and macros are recruited to sites of ischemic injury
Macrophages release proinflam mediators and initiate programs to help in clearance of dead tissue/repair (may be detrimental if chronic)
What cells contribute substantially to multiple autoimmune disorders?
B cells
What are some characteristic of Organ-specific autoimmune diseases?
- Produced by T cells or Ab restricted to one organ
- lesions produced by tissue damage and autoantibodies limited to one organ
- Examples: Type I diabetes, MS, thyroid
What are characteristics of Organ-nonspecific autoimmunity?
- systemic autoimm disease caused by - circulation of Ab or imm complexes and affects multiple organs
- lesions and autoab not confined to one organ
- Examples: SLE, RA
What is the characterization of midspectrum disorders?
localized lesions in a single organ and by organ-nonspecific autoantibodies
Cardiovascular disorders: what are some key factors about vasculitis?
- primary immune disorder of blood vessels
- circulation of immune complexes
- inflam lesions of blood vessels produce injury or necrosis of blood vessel wall
- Ab to endothelial cells may also contribute to vasculopathy
Cardiovascular disorders: what are some key factors about carditis?
- Primary imm disorder of the heart
- reaction of cardio myocytes to imm injury
caused by a variety of conditions (Rheumatic fever, lyme, cardiac transplant rejection)
An autoimmune disease characterized by the infiltration of the heart by macrophages and lymphocytes is called what?
Idiopathic myocarditis
Collagen vascular disorders: Progressive systemic sclerosis (scleroderma) key facts?
- collagen vascular disease of unknown cause
- Chronic multisystem causes thickening of skin
- initial symptoms in 3rd decade of life, slow progression
- 40-90% have ANAs
Collagen vascular disorders: what as some key factors about Eosinophilia-myalgia syndrome?
- caused by exposure to L-tryptophan
- pt develop severe myalgia
- more than 50% develop scleroderma like manifestations
Endocrine gland disorders: Thyroid disease key factors?
spectrum is very broad
Two major forms:
Chronic autoimmune thryroiditis and Graves disease (Shout out)
What are the basic factors of Lymphoid (Hashimoto) chronic thyroditis?
- exact cause unknown, more common in women (30-50)
- mode of inheritence unknown (possible genetic)
- hypothyroidism - late sequela of thyroiditis
can have coexistence of Graves and Hashimotos
What is the first Ab discovered against the thyroid in Hashimotos?
Thyroglobulin
What is thyroid microsome?
Ab against thyroid microsomes, antithyroid microsomal antibodies and TPO abs (Low titers correlate with thyroid involvement)
What Ag is directed against colloid proteins and is present in 50% of pt with subacute thyroditis?
Second colloid Antigen (CA2 ag)
What Ab are found in pt with goiter or hypothyroidism?
T4 and T3 (thyronine and triiodothyronine)
True or false: In hashimotos there is an increased TSH, decreased T4 and T3 and anti-TPO ab present
true
What is the diagnostic eval of Hashimotos?
fine needle aspirate of thyroid, infiltration of lymphs
True or false: Graves disease has high TSH and low T4 levels
False: Graves has low TSH and elevated free T4 levels
What receptor differentiates between graves and toxic nodular goiter?
TSH receptor Ab (TRAb)
What causes insulin-dependent diabetes mellitus?
imm destruction of B cells in pancreatic islets, requires exogenous insulin (CD4+ T cells responsible for imm response)
Pt with T1D have these types of antiboidies…
Insulin autoantibodies (IAAs)
Glutamic acid decarboxylase (GAD)
Islet cell antigen 2 (IA-2)
Fast facts about Latent autoimmune diabetes in Adults
found in pt >35 yrs old
frequently misdiagnosed as T2D
progress more rapidly to insulin dependence than T2D pt
Dysfunction of these organs can cause which diseases?
Adrenal gland
Pituitary gland
Parathyroid gland
Polyglandular syndromes
adrenal glands - addisons disease
pituitary - sheenhan syndrom
parathyroid - idiopathic hypoparathyroidism
polyglandular - mulitple organs involved
Women with unexplained infertility often have what kind of Ab?
smooth muscle ab, ANA and antiphospholipid Ab, Antisperm
Chronic inflam disease of unknown cause that affects lacrimal, salivary and other excretory glands is called what?
Sjogren Synrome
More common in women
( funfact: phonetically this is pronounced S-ee-yorg-ren from my limited swedish language knowledge)
The secondary form of Sjorgen syndrome is associated with what other disorders?
RA and connective tissue disorders
Atropic Gastritis is the chronic inflammation of what? what is its characteristics?
inflammation of gastric muscosa
AutoAb to gastric parietal cells, proton pump ATPase, and intrinsic factor
Always accompanies pernicious anemia
What disorder is classified as a megaloblastic anemia and is caused by a deficiency of vitamin B12?
pernicious anemia
What kind of staining pattern is this?
ANAs most frequent stain pattern is homogenous
What are the 4 groups of Autoimmune hemolytic anemia?
warm- reactive (most common)
cold reactive (<20%)
paroxysmal cold hemoglobinuria (rare)
drug-induced hemolysis
What are 4 neuromuscular disorders?
ALS
Guillain-barre syndrom (inflam plyneuropathies)
Myasthenia gravis
Ms (most common demyelnating disease of CNS)
What are three common forms of Multiple sclerosis?
Primary progressive
secondary
progressive relapse (most common)
What are two skeletal muscle disorders?
polymyositis and dermatomyositis
what are 4 skin disorders?
discoid lupus
bullous pemphigoid
pemhigus group
dematitis gerpetiformis
