Autoimmunity Flashcards
Autoimmunity is defined as ___________ against __________
an immune response
self (autologous) antigens.
Autoimmunity
• It is a condition that occurs when the immune system ________ ———- _____________________
mistakenly attacks and destroys healthy body tissue.
LAYERS OF SELF-TOLERANCE
Type of tolerance
Central tolerance
Antigen segregation
Peripheral anergy
Regulatory cells
Cytokine deviation
Clonal exhaustion
LAYERS OF SELF-TOLERANCE
Type of tolerance; mechanism ; Site of action
Central tolerance
Antigen segregation
Peripheral anergy
Deletion and Editing; Thymus Bone marrow
Physical barrier to self- antigen access to lymphoid system; Peripheral organs (e.g. thyroid, pancreas)
Cellular inactivation by weak signaling without co-stimulus; Secondary lymphoid tissue
LAYERS OF SELF-TOLERANCE
Type of tolerance; mechanism ; Site of action
Regulatory cells
Cytokine deviation
Clonal exhaustion
Suppression by cytokines, intercellular signals; Secondary lymphoid tissue and sites of inflammation
Differentiation to TH2 cells, limiting inflammatory cytokine secretion; Secondary lymphoid tissue and sites of inflammation
Apoptosis post-activation; Secondary lymphoid
AutoImmunity can affect any organ/ organ system in the body.
T/F
T
Auto imunity can be classified into clusters that are either________ or _______
organ-specific or systemic
Organ-specific autoimmune diseases
________________
________ syndrome
_____________
_____ disease, _______ thyroiditis, Vitiligo, myasthenia gravis
Type I diabetes mellitus
Goodpasture’s
Multiple sclerosis
Grave’s; Hashimoto’s
Systemic autoimmune diseases
___________
_____________
__________(SLE)
polymyositis
____________ syndrome
Rheumatoid arthritis
Scleroderma
Systemic lupus erythematosus
primary Sjögren’s
CAUSES OF AUTOIMMUNITY
•The principal factors in the development of autoimmunity are:
_______________ of _________
____________ such as _______
The inheritance of susceptibility genes
Environmental triggers; infections
GENES AND AUTOIMMUNITY
• The concept that a single gene mutation leads to a single autoimmune disease is the EXCEPTION, not the rule.
• Because of this autoimmune diseases are generally classified as complex diseases as there is no single “pinpoint-able” gene.
• Most autoimmune diseases are polygenic, heterogenous and multifactorial.
GENES AND AUTOIMMUNITY
• The concept that a single gene mutation leads to a single autoimmune disease is the _______, not the ______.
EXCEPTION
rule
GENES AND AUTOIMMUNITY
autoimmune diseases are generally classified as (simple or complex?) diseases
With reason
Complex
as there is no single “pinpoint-able” gene.
Most autoimmune diseases are ______genic, _____genous and ______factorial.
polygenic
Hetero
multi
EXCEPTIONS TO THE RULE: SIMPLE GENETIC AUTOIMMUNE DISEASES
Disease : Gene: mechanism
APS
IPEX
ALPS
AIRE ; Decreased expression of self- antigens in the thymus, resulting in a defect in negative selection.
FOXP3; Decreased generation of regulatory T cells
FAS, FASL; Failure of apoptotic death of self-reactive T or B cells
Full meaning
APS-1
IPEX
ALPS
Autoimmune polyglandular syndrome type 1
Immunodysregulation, polyendocrinopathy, enteropathy, X-linked
autoimmune lymphoproliferative syndrome
COMPLEX DISEASE AND GENETICS
ASSOCIATIONS OF HLA SEROTYPE WITH SUSCEPTIBILITY TO AUTOIMMUNE
Disease: HLA ALLELE
Ankylosing spondylitis
Acute anterior uveitis
Goodpasture’s syndrome
Multiple sclerosis
Graves’ disease
B27
B27
DR2
DR2
DR3
EFFECT OF ENVIRONMENT
• Pathogens, drugs, hormones and toxins are just a few of the ways that the environment can trigger autoimmunity.
T/F
T
MAIN EXAMPLES OF MOLECULAR MIMICRY BETWEEN A PATHOGEN AND AUTO-IMMUNE DISEASE
List 7
Chagas’ cardiomyopathy
Rheumatic fever
Myasthenia gravis
Multiple sclerosis
Guillan-Barre
Type 1- diabetes mellitus
Systemic lupus erythematosus
MAIN EXAMPLES OF MOLECULAR MIMICRY BETWEEN A PATHOGEN AND AUTO-IMMUNE DISEASE
Disease : pathogens
Chagas’ cardiomyopathy
Rheumatic fever
Trypanosoma cruzi
Streptoccocus pyogens
MIMICRY BETWEEN A PATHOGEN AND AUTO-IMMUNE DISEASE
Myasthenia gravis
Multiple sclerosis
Herpes virus, Hemophilus influenza
Corona, measles, mumps, EBV, herpes
MIMICRY BETWEEN A PATHOGEN AND AUTO-IMMUNE DISEASE
Guillan-Barre
Type 1- diabetes mellitus
Systemic lupus erythematosus
Campylobacter jejuni
Coxsackivirus B, rotaviruses, herpes, hepatitis C, rhinohantaretroviral
EBV pneumococcal polysaccharide.
DRUGS AND TOXINS
Pronestyl (drug prescribed for the treatment of _____________)
Drug induced _______
abnormal heart rhythms
lupus
DRUGS AND TOXINS
Toxins
Example: ______ syndrome
Occurred in ____ in ______ after people ate contaminated ________
Affected people developed a unique illness marked by ________,______, and _______
toxic oil
Spain; 1981; olive oil
lung disease, eosinophilia and excessive IgE
HORMONES
• (Males or Females?) are much more likely to develop autoimmune illness
Females
HORMONES
• Rise in hormones associated with pregnancy may even cause _________
abortion of the fetus
HORMONES
•__________ and _______ are both autoimmune in nature
Endometriosis and preeclampsia
• A defect in any arm of the immune system can trigger autoimmunity
T/F
T
COMPLEMENT DEFICIENCIES
CD59 OR CD55
________________
Autoimmune __________________
Autoimmune ___________
________________
Paroxysmal nocturnal hemoglobinuria
hemolytic anemia
thrombocytopenia
Lupus lymphopenia
COMPLEMENT DEFICIENCIES
Deficiencies in the ______ complement pathway renders a person more likely to develop immune complex diseases
_______
___
classical
SLE
RA
THE COMPLEMENT SEE-SAW
• The complement system is a mediator in both the ________ and _______ of immune complex diseases
pathogenesis and prevention
THE COMPLEMENT SEE-SAW
• It has a protective effect when ————————————————- ; at the same time, the ———— promoted by complement activation can result in ____________ when not kept in check
functioning in moderation against pathogens
inflammation
cellular damage
It is (easy or hard?) to classify autoimmunity as strictly a B cell or T cell mediated disease
With reason
Hard
as multiple arms of the immune system are involved.
B CELL DISEASE OR T CELL DISEASE?
For instance, myasthenia gravis, a disease marked by _________ and loss of __________ can be classified as a “B cell disease” as B cells _____________________________.
progressive weakness
muscle control
produce antibodies that attack nicotinic acetylcholine receptors.
B CELL DISEASE OR T CELL DISEASE?
Diabetes can be classified as a “T cell disease” as the T cells _____________________________.
attack and destroy pancreatic beta cells
SYSTEMIC LUPUS ERYTHEMATOSUS
This is an autoimmune disease in which organs and cells undergo damage mediated by tissue-binding ___________ and __________.
autoantibodies and immune complexes
SYSTEMIC LUPUS ERYTHEMATOSUS
______% of patients are women of child-bearing age, though people of _____ sexes, ____ ages and ____ ethnic groups are susceptible.
90; both; all; all
SYSTEMIC LUPUS ERYTHEMATOSUS
Many organs and organ systems can be affected in patients with SLE and it is often ____________________.
A ___________________ thus must be made to diagnose SLE.
mistaken for other diseases
differential diagnosis
SIGNS AND SYMPTOMS
Malar rash
Discoid rash
Photosensitivity
Oral ulcers
Arthritis
Serositis
Renal disorders
Neurologic disorders: seizures or psychosis
Hemtological disorders
Immunologic disorders
Antinuclear antibodies
If ____________________ of these criteria, well documented are present at any time in a patient’s history, the diagnosis is likely to be SLE
greater than or equal to 4
PATHOGENESIS
Activation of _____ immunity (_______ cells) by CpG DNA, DNA in _________ and RNA in __________________
Lowered _________ of ________ cells (antigen-specific T and B lymphocytes)
___________ regulatory and inhibitory CD4+ and CD8+ T cells
Reduced ________ of __________ and _________, thus allowing inflammation and disease to develop as these
innate; dendritic; immune complexes
RNA/protein self- antigens
activation thresholds of adaptive immunity
Ineffective
clearance of apoptotic cells and of immune complexes
LABORATORY TESTS
• Laboratory tests serve to establish or rule out the diagnosis, to follow the course of the disease, particularly to suggest that a flare is occurring or organ damage is developing; and to identify adverse effects of therapies
• Diagnostically, the most important autoantibodies to detect are ____ since the test is positive in >_____ % of patients.
ANA
95
RHEUMATOID ARTHRITIS
Rheumatoid arthritis (RA) is a/an (acute or chronic?) multisystem disease of __________ cause.
Chronic
unknown
RHEUMATOID ARTHRITIS
Although there are a variety of systemic manifestations, the characteristic feature of established RA is persistent inflammatory _______, usually involving ____________ in a ________ distribution.
synovitis; peripheral joints
symmetric
RHEUMATOID ARTHRITIS
The potential of the synovial inflammation to cause __________ and __________ and subsequent changes in joint integrity is the hallmark of the disease.
cartilage
damage and bone erosion
PATHOPHYSIOLOGY of Rheumatic arthritis
No single trigger for RA has yet been found, though some studies have provided information that adds to our understanding of the disease:
oDepletion of ___________
oHaving the ______ gene and related allotypes of _______ and the ________
oThe pathogenesis of _______ disease of many types is linked to the disease
oThe presence of autoantibodies to ______, known as ____________ and antibodies to ___________________ (ACPA)
B lymphocytes
HLA-DR4; MHC Class II; TPN22
vascular
IgGFc; rheumatoid factors
citrullinated peptides
Signs and symptoms of rheumatic arthritis
Morning stiffness of the joints Arthritis of three or more joint areas Arthritis of hand joints
Symmetric arthritis
Rheumatoid nodules
Serum rheumatoid factor Radiographic changes
_______ of these seven criteria are required to classify a patient as having RA
Four
No tests are specific for diagnosing RA
T/F
T
LABORATORY TESTS
• However rheumatoid factors, which are ________ reactive with the ____ portion of _____ are found in more than 2/3rds of adults with RA and have classically been used to evaluate patients with RA.
autoantibodies; Fc; IgG
GENERAL TREATMENT OPTIONS
• Anti-inflammatory drugs (_______,_______)
• Immunosuppresant drugs (________)
• Radiation
• Cell Blocking Reagents (______,_________)
• Cytokine Blocking Reagents
NSAIDS, corticosteroids
Methotrexate
Rituxan, Teplizumab
