Hypersensitivities
Two types of antigens can cause immune complex mediated injury (Type III hypersensitivity):
________ antigens & _______ antigens
BONUS: Provide an example of each.
1. Exogenous antigen - Ex: post streptococcal glomerulonephritis
2. Endogenous antigen - Ex: SLE with self-antigens
Source: Dr. Somji's Hypersensitivity lecture (Slide 44)
A neonate is diagnosed with neonatal lupus. Name two autoimmune diseases that the mother may have.
- SLE & Sjogren's (anti-SSA/Ro and/or Anti-SSB/La) are big two!
- Mixed connective tissue disease, RA, Scleroderma, PAN, etc also possible
Source: Dr. Strauch's Clinical Manifestations of Immune Diseases (Slides 43 & 44)
_____ genes are associated with susceptibility to autoimmune diseases.
BONUS: True or False - Most autoimmune diseases can be attributed to one single gene.
HLA genes
FALSE!
source: Dr. Somji's Immunologic Deficiency Syndromes & Autoimmunity (Slide 71 & In Handout)
True or false: Most patients with a positive Lupus anti-coagulant do not have SLE.
TRUE
source: Dr. Strauch's Clinical Manifestation of Immune Disease lecture (Slide 36)
For whatever reason, some organs are spared in systemic autoimmune diseases:
1) Polyarteritis nodosa spares the _____.
2) Scleroderma typically spares the ______.
1) PAN spares the lungs
2) Scleroderma -> liver
*1-2% experience primary biliary cirrhosis*
Source: Anking
Which autoimmune disease is described by the destruction of islet cells via a cytotoxic CD8+ T-cell mediated mechanism?
What type of hypersensitivity reaction is this?
Type I Diabetes Mellitus
Type IV Sensitivity
Source: Dr. Somji's Hypersensitivity Lecture (Slide 73)
Match the autoimmune disease with its common demographic.
1) Scleroderma 2) Sjögren's syndrome 3) Goodpasture syndrome 4) RA 5) SLE 6) PAN
a) Young adult males
b) Middle-aged men
c) Middle-aged women & people of color
d) Middle-aged women (30-50 years old)
e) "Older" women (40-60 years old)
f) Women >65 years old
1) D
2) E
3) A
4) F
5) C
6) B
Source: Anking
One mechanism of autoimmune disease induction includes microorganisms expressing antigens that have amino acid sequences similar to self-antigens, which may result in the activation of self-reactive lymphocytes. This is known as ____________.
Molecular mimicry
Source: Somji's Immunologic Deficiency Syndromes and Autoimmunity Lecture (Slide 73 & In Handout)
While patients with SLE may test positive for ANA, anti-dsDNA, and anti-Smith antibodies using a(n) __________ (type of lab/test), drug-induced lupus will likely only test positive for ANA.
What antibody has a higher incidence in patients with drug-induced lupus?
1) Indirect Coombs test
2) anti-histone antibody
- drug-induced presents very similarly to SLE & can be caused by a wide variety of drugs including hydralazine, isoniazid, and procainamine
Source: Dr. Strauch's Clinical Manifestations of Immune Diseases (Slide 42)
Rheumatoid arthritis and SLE may cause anti-factor __ (#) antibodies, resulting in acquired hemophilia type ___.
Acquired Hemophilia (A)
Source: Anking
What are the two types of type IV hypersensitivity reactions?
hint: cell type(s)
1. Direct cell cytotoxicity - CD8+ cytotoxic T cells kill targeted cells
*Ex: Multiple sclerosis*
2. T-cell mediated inflammation (Delayed type hypersensitivity (DTH) - effector CD4+ T cells recognize antigen & release inflammation-inducing cytokines.
*primarily involves mononuclear phagocytes & lymphocytes. Ex: tuberculin reaction)
Source: Dr. Somji's Hypersensitivity Lecture (Slide 58, 59, 69)
Sjögren's syndrome can be a primary condition (sicca syndrome). However, it can also be a secondary syndrome due to another autoimmune condition, especially __________.
Rheumatoid Arthritis
Source: Anking
Infections may induce certain autoimmune diseases. This occurs due to the up-regulation of __________ & __________ on antigen presenting cells during infection.
hint: broad-term
co-stimulatory and MHC molecules
Source: Dr. Somji's Immunologic Deficiency Syndromes and Autoimmunity Handout
If an autoimmune hemolytic anemia is on your differential diagnosis list, name 3 tests you might order to further investigate:
1. peripheral blood smear -> ex: spherocytes in WAIHA
2. indirect bilirubin -> increased in AIHA
3. lactate dehydrogenase -> increased in hemolytic anemias
4. serum haptoglobin -> decreased w/ intravascular hemolysis (CAIHA (rarely))
5. direct Coombs' test -> looking for Ab or C on patient RBC. DIAGNOSTIC for AIHA
6. indirect Coombs' test -> looking for antibodies in serum or plasma (not RBC)
Source: Dr. Strauch's Hemolytic Anemia & Coagulation Disorder lecture (Slides 46-56)
Some carcinomas, like _________ carcinoma, are associated with local deposits of amyloid.
(As opposed to something like multiple myeloma, which is associated with widespread deposits of amyloid).
Medullary thyroid carcinoma
*Strauch told us to star this! Did you?!*
Source: Dr. Strauch's Clinical Manifestations of Immune Diseases
Autoimmune hemolytic anemia is an example of a type ____ sensitivity reaction. AIHA can be divided into two types: Cold AIHA & Warm AIHA.
What are distinguishing features of each on a peripheral blood smear?
1) Type II Hypersensitivity
2a) Cold AIHA - agglutination of RBCs
*Usually extravascular, can be intra- if severe*
-C3 positive on direct Coombs test*
2b) Warm AIHA - abundant spherocytes
*Always extravascular*
- IgG typically +, C3 + or - on a direct Coombs test
Sources: Dr. Somji's Hypersensitivity lecture & Dr. Strauch's Hemolytic Anemia & Coagulation Disorders (Slides 48-55)
A 50 year old female patient presents with a rash around their eyes, muscle weakness, and generalized fatigue. On physical exam you notice the patient has pelvic girdle weakness and the skin on their knuckles appears irritated. However the patient is adamant that it's because of the dry winter weather. Labs come back with elevated CK.
Ben convinces you that you need a muscle biopsy. 1)Will you see intramuscular inclusion bodies?
This is dermatomyositis! (periorbital rash, proximal muscle weakness, and papules on knuckles).
NO you will not see intramuscular inclusion bodies.
-dermato has CD4+ lymph infiltrate closer to skin (perimysium), while polymyositis has CD8+lymph in endomysium (and usually no skin findings)
*CK elevation rules out polymyalgia rheumatica*
Source: Anking
Systemic Lupus Erythematosus is a well-known example of an autoimmune disease that's mechanism of induction involves the activation of ___clonal expansion of ________.
POLYclonal expansion of B CELLS
- polyclonal = produced by or involves cells that come from two or more cells with different genetic make-up
- "In addition, formation of new antigens in damaged tissue. Release of sequestered self-antigens."
Source: Dr. Somji's Immunologic Deficiency Syndromes and Autoimmunity Lecture
D-dimers are a result of the splitting of_____, and it's used to check for _______.
1) cross-linked fibrin (NOT fibrinogen)
2) blood clots
Source: Anking
The most commonly used initial monotherapy in rheumatoid arthritis is _______, which works by inhibiting the enzyme ________, subsequently increases levels of ______ (an inhibitor of inflammation).
BONUS: Toxicity effects will be decreased by supplementing with _______.
1) Methotrexate (a non-biological DMARD)
2) Inhibits dihydrofolate reductase
3) Increases adenosine
BONUS: folic acid 1mg/day
Source: Dr. Claren's Anti-inflammatory Agents lecture (Slides 37-39)
Result: Positive immunofluorescense at the dermal epidermal junction with granular and patchy deposits noted.
Which hypersensitivity type is consistent with this description?
BONUS: Which hypersensitivity would be indicated by linear distribution of immunofluorescence?
Type THREE hypersensitivity
- the granular character is consistent with immune complex deposition. Could indicate lupus (Lupus band test).
BONUS: Type II (Example - Goodpasture syndrome). "Paint the basement floor"
Source: Dr. Strauch's Immunopathology Path Application lecture (Slide 31)
A 32-year-old woman with a hx of Raynaud's phenomenon presents to a gastroenterologist's office for slowly progressive dysphagia over the course of a year. Physical exam reveals thickening of the skin on the face and hands, subcutaneous calcium deposits in the fingers, and multiple telangiectasias. What is most likely related to this patient's dysphagia?
A) impaired relaxation of the lower esophageal sphincter
B) fibrosis and atrophy of the esophagus
C) esophageal neoplasm
D) loss of elasticity of the upper esophageal sphincter
E) cirrhosis with esophageal varices
B. Fibrosis and atrophy of the esophagus
this is CREST (calcinosis, Raynaud's, esophageal dysfunction secondary to fibrosis and atrophy, scleroderma, and telangiectasias.
CREST is also known as limited cutaneous systemic sclerosis.
Source: Board Vitals (moderate difficulty)
Infection with Streptococcus pyogenes (or other group A strep species) can cause rheumatic fever.
Rheumatic fever is a rare autoimmune disease that is induced by expression of large amounts of ______ (virulence factor), which induces large amounts of Ig___. These antibodies can confuse host cell's for viral particles, resulting in an autoimmune response.
BONUS: What type of hypersensitivity is this?
BONUS BONUS: If this patient were to require an anti-coagulant medication, would warfarin or a DOAC be indicated?
1. M protein
2. IgG
- Attacked host cells tend to be cardiac cells but inflammation can also present in the joints, skin, and other organs.
BONUS: Type II (This is molecular mimicry)
Source: Dr. Somji's Immunologic Deficiency Syndromes and Autoimmunity lecture (Slide 74).
BONUS BONUS: Warfarin!
*Typically: warfarin -> mechanical heart valves & DOACs for native heart valves BUT rheumatic heart disease and mitral stenosis are exceptions.
Source: Claren's Thrombolytics & Anticoagulants Part 2 Lecture (21:48min)
1. What autoimmune factor may be elevated in a patient with infective endocarditis?
2. This factor is an autoantibody of what isotype?
1. Rheumatoid factor
2. IgM (against the Fc portion of IgG)
Source: Anking
A pregnant woman at 25 wks gestation presents to the ED with vaginal bleeding & lower abdominal pain. Vital signs are BP: 88/52mmHg, HR: 122bpm. A bedside ultrasound reveals placental abruption. Labs indicate low Hb, low platelets, elevated PT and PTT, and elevated indirect bilirubin. A peripheral blood smear reveals many schistocytes. Which of the following is responsible for these abnormalities?
A) Formation of anti-GpIIb/IIIa antibodies
B) Deficiency of ADAMTS13
C) Release of bacterial toxin
D) Release of tissue factor
E) Decrease in von Willebrand factor
This patient has DIC due to placental abruption. The microangiopathic hemolytic anemia of DIC results from the widespread activation of clotting due to:
- D) tissue factor activation!
Source: Board Vitals (This question was hard sorry!)