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House Clinical Pathology > Autoimmunity > Flashcards

Autoimmunity Flashcards

1
Q

Autoimmunity is defined as ___________ against __________

A

an immune response

self (autologous) antigens.

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2
Q

Autoimmunity

• It is a condition that occurs when the immune system ________ ———- _____________________

A

mistakenly attacks and destroys healthy body tissue.

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3
Q

LAYERS OF SELF-TOLERANCE

Type of tolerance

A

Central tolerance
Antigen segregation
Peripheral anergy
Regulatory cells
Cytokine deviation
Clonal exhaustion

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4
Q

LAYERS OF SELF-TOLERANCE

Type of tolerance; mechanism ; Site of action

Central tolerance
Antigen segregation
Peripheral anergy

A

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

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5
Q

LAYERS OF SELF-TOLERANCE

Type of tolerance; mechanism ; Site of action

Regulatory cells
Cytokine deviation
Clonal exhaustion

A

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

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6
Q

AutoImmunity can affect any organ/ organ system in the body.

T/F

A

T

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7
Q

Auto imunity can be classified into clusters that are either________ or _______

A

organ-specific or systemic

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8
Q

Organ-specific autoimmune diseases

________________
________ syndrome
_____________
_____ disease, _______ thyroiditis, Vitiligo, myasthenia gravis

A

Type I diabetes mellitus

Goodpasture’s

Multiple sclerosis

Grave’s; Hashimoto’s

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9
Q

Systemic autoimmune diseases

___________
_____________
__________(SLE)
polymyositis
____________ syndrome

A

Rheumatoid arthritis
Scleroderma
Systemic lupus erythematosus

primary Sjögren’s

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10
Q

CAUSES OF AUTOIMMUNITY

•The principal factors in the development of autoimmunity are:

_______________ of _________

____________ such as _______

A

The inheritance of susceptibility genes

Environmental triggers; infections

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11
Q

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.

A
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12
Q

GENES AND AUTOIMMUNITY

• The concept that a single gene mutation leads to a single autoimmune disease is the _______, not the ______.

A

EXCEPTION

rule

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13
Q

GENES AND AUTOIMMUNITY

autoimmune diseases are generally classified as (simple or complex?) diseases

With reason

A

Complex

as there is no single “pinpoint-able” gene.

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14
Q

Most autoimmune diseases are ______genic, _____genous and ______factorial.

A

polygenic

Hetero

multi

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15
Q

EXCEPTIONS TO THE RULE: SIMPLE GENETIC AUTOIMMUNE DISEASES

Disease : Gene: mechanism

APS

IPEX

ALPS

A

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

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16
Q

Full meaning

APS-1

IPEX

ALPS

A

Autoimmune polyglandular syndrome type 1

Immunodysregulation, polyendocrinopathy, enteropathy, X-linked

autoimmune lymphoproliferative syndrome

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17
Q

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

A

B27

B27

DR2

DR2

DR3

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18
Q

EFFECT OF ENVIRONMENT

• Pathogens, drugs, hormones and toxins are just a few of the ways that the environment can trigger autoimmunity.

T/F

A

T

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19
Q

MAIN EXAMPLES OF MOLECULAR MIMICRY BETWEEN A PATHOGEN AND AUTO-IMMUNE DISEASE

List 7

A

Chagas’ cardiomyopathy

Rheumatic fever

Myasthenia gravis

Multiple sclerosis

Guillan-Barre
Type 1- diabetes mellitus

Systemic lupus erythematosus

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20
Q

MAIN EXAMPLES OF MOLECULAR MIMICRY BETWEEN A PATHOGEN AND AUTO-IMMUNE DISEASE

Disease : pathogens

Chagas’ cardiomyopathy

Rheumatic fever

A

Trypanosoma cruzi

Streptoccocus pyogens

21
Q

MIMICRY BETWEEN A PATHOGEN AND AUTO-IMMUNE DISEASE

Myasthenia gravis

Multiple sclerosis

A

Herpes virus, Hemophilus influenza

Corona, measles, mumps, EBV, herpes

22
Q

MIMICRY BETWEEN A PATHOGEN AND AUTO-IMMUNE DISEASE

Guillan-Barre

Type 1- diabetes mellitus

Systemic lupus erythematosus

A

Campylobacter jejuni

Coxsackivirus B, rotaviruses, herpes, hepatitis C, rhinohantaretroviral

EBV pneumococcal polysaccharide.

23
Q

DRUGS AND TOXINS

Pronestyl (drug prescribed for the treatment of _____________)

Drug induced _______

A

abnormal heart rhythms

lupus

24
Q

DRUGS AND TOXINS

Toxins

Example: ______ syndrome

Occurred in ____ in ______ after people ate contaminated ________

Affected people developed a unique illness marked by ________,______, and _______

A

toxic oil

Spain; 1981; olive oil

lung disease, eosinophilia and excessive IgE

25
Q

HORMONES
• (Males or Females?) are much more likely to develop autoimmune illness

A

Females

26
Q

HORMONES
• Rise in hormones associated with pregnancy may even cause _________

A

abortion of the fetus

27
Q

HORMONES

•__________ and _______ are both autoimmune in nature

A

Endometriosis and preeclampsia

28
Q

• A defect in any arm of the immune system can trigger autoimmunity

T/F

A

T

29
Q

COMPLEMENT DEFICIENCIES

CD59 OR CD55
________________
 Autoimmune __________________
Autoimmune ___________
________________

A

Paroxysmal nocturnal hemoglobinuria

hemolytic anemia

thrombocytopenia

Lupus lymphopenia

30
Q

COMPLEMENT DEFICIENCIES

Deficiencies in the ______ complement pathway renders a person more likely to develop immune complex diseases

 _______
___

A

classical

SLE

RA

31
Q

THE COMPLEMENT SEE-SAW

• The complement system is a mediator in both the ________ and _______ of immune complex diseases

A

pathogenesis and prevention

32
Q

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

A

functioning in moderation against pathogens

inflammation

cellular damage

33
Q

It is (easy or hard?) to classify autoimmunity as strictly a B cell or T cell mediated disease

With reason

A

Hard

as multiple arms of the immune system are involved.

34
Q

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 _____________________________.

A

progressive weakness

muscle control

produce antibodies that attack nicotinic acetylcholine receptors.

35
Q

B CELL DISEASE OR T CELL DISEASE?

Diabetes can be classified as a “T cell disease” as the T cells _____________________________.

A

attack and destroy pancreatic beta cells

36
Q

SYSTEMIC LUPUS ERYTHEMATOSUS

This is an autoimmune disease in which organs and cells undergo damage mediated by tissue-binding ___________ and __________.

A

autoantibodies and immune complexes

37
Q

SYSTEMIC LUPUS ERYTHEMATOSUS

______% of patients are women of child-bearing age, though people of _____ sexes, ____ ages and ____ ethnic groups are susceptible.

A

90; both; all; all

38
Q

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.

A

mistaken for other diseases

differential diagnosis

39
Q

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

A

greater than or equal to 4

40
Q

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

A

innate; dendritic; immune complexes

RNA/protein self- antigens

activation thresholds of adaptive immunity

Ineffective

clearance of apoptotic cells and of immune complexes

41
Q

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.

A

ANA

95

42
Q

RHEUMATOID ARTHRITIS

Rheumatoid arthritis (RA) is a/an (acute or chronic?) multisystem disease of __________ cause.

A

Chronic

unknown

43
Q

RHEUMATOID ARTHRITIS

Although there are a variety of systemic manifestations, the characteristic feature of established RA is persistent inflammatory _______, usually involving ____________ in a ________ distribution.

A

synovitis; peripheral joints

symmetric

44
Q

RHEUMATOID ARTHRITIS

The potential of the synovial inflammation to cause __________ and __________ and subsequent changes in joint integrity is the hallmark of the disease.

A

cartilage
damage and bone erosion

45
Q

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)

A

B lymphocytes

HLA-DR4; MHC Class II; TPN22

vascular

IgGFc; rheumatoid factors

citrullinated peptides

46
Q

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

A

Four

47
Q

No tests are specific for diagnosing RA

T/F

A

T

48
Q

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.

A

autoantibodies; Fc; IgG

49
Q

GENERAL TREATMENT OPTIONS

• Anti-inflammatory drugs (_______,_______)

• Immunosuppresant drugs (________)

• Radiation

• Cell Blocking Reagents (______,_________)

• Cytokine Blocking Reagents

A

NSAIDS, corticosteroids

Methotrexate

Rituxan, Teplizumab

House Clinical Pathology (45 decks)

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