Day 2.3 Immuno Flashcards Preview

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Flashcards in Day 2.3 Immuno Deck (122):
1

What HPS types are Ab-mediated?

Type I
Type II
Type III
(Type IV is Tcell mediated)

2

How are Type II and Type III different in terms of Ab?

Type II has Ab against self. This induces macrophages to eat the self and causes tsu dmg.
Type III has Ab against non-self, and it's the Ab-Ag complex that gets deposited into tissues. This induces macrophages to eat the complexes and cause dmg.
In both cases, the dmg is due to macrophages.
Note: Some disorders which feature Type III and Type IV HPS have anti-self Ab. Just bc there is anti-self Ab doesn't mean the rxn will be Type II.
But, all Type II rxns are mediated by anti-self Ab.

3

How long does it take for...
Type I HPS?
Type III?
Type IV?

Type I = 15 min
Type III = 5-12 hrs
Type IV = 24-48 hrs (delayed)

4

Type I HPS

Anaphylactic and atopic.
Free Ag cross-links IgE on presensitized mast cells and basophils- these degranulate and rls vasoactive amines that act at post-capillary venules (histamine).
Causes edema.
Rapid

5

How do you test for Type I HPS?

Scratch test (scratch back and put Ag there, wait for 15 min to see well-defined wheal and flare.

6

What is wheal and flare?

Wheal = hive
Flare = red

7

Examples of Type I HPS

Anaphylaxis: bee sting, food/drug allergy
Allergic/Atopic: rhinitis, hay fever, eczema*, hives, asthma
Even tho eczema is Tcell mediated, it is a Type I bc it's fast!

8

Type II HPS

Antibody mediated- IgM, IgG bind to fixed Ag on "enemy cell" (which is actually self!), leading to lysis by complement, or to phagocytosis.
Cy-2-toxic.
Ab and complement lead to MAC.
Dz is usually specific to the tsu/site where Ag is found

9

What are the 3 mechanisms of a Type II HPS rxn?

1. Ab opsonize cells or activate complement
2. Ab recruit neutrophils and macrophages that incite tsu dmg
3. Ab bind to normal cellular receptors and interfere w functioning.

10

What is the test for Type II HPS?

Coombs (direct and indirect)
Use a known marker that binds to Ab to see if the Ab are there.

11

What is a direct Coombs test?

Anti-Ig antibody is added to the patient's RBC agglutinate to see if RBCs are coated with Ig.

12

What is an indirect Coombs test?

Normal RBCs are added to the patient's serum agglutinate to see if the serum has anti-RBC surface Ig

13

Ex of Type II HPS rxn

Auto-immune hemolytic anemia
Pernicious anemia
ITP (Ab against plts)
Erythroblastosis fetalis (Rh incompatibility)
Acute hemolytic txfsn rxns (wrong blood type)
Rheumatic Fever
Goodpasture's synd (vasculitis)
Bullbous pemphigold
Pemphigus vulgaris
Graves' dz (Ab against TSH receptor- stim the receptor --> hyperthyroidism)
Myasthenia Gravis (Ab against Ach receptor)

14

Type II HPS: What is pernicious anemia?

Have Ab against intrinsic factor (IF) so Vit B12 can't be absorbed in the ilieum.
B12 deficiency (neurologic problems)

15

Type II HPS: What is erythroblastosis fetalis?

Maternal Ab to a fetal RBC Ag. (Fetus is Rh+ but mom is Rh-, so mom makes Ab against fetus since it's "foreign").
Neonate has:
anemia d/t hemolysis of fetal RBC by maternal Ab
jaundice (Hb was broken down, so excess bilirubin --> jaund)
Hydrop fetalis (generalized fetal edema- fluid in lungs, peritoneum, tsus)
IU death.

16

Rh- moms don't have Rh-D on the surface of the blood cells. When should they get anti-Rh-D Ig?

28 weeks (bc fetus can be born after this time)
Any traumatic event in which mom might be exposed to fetal RBC (ex: MVA)
W/in 3 days of delivery
Abortion or miscarriage

17

For which pregnancies will the mom's anti-Rh Ab have an effect?

All pregnancies after the 1st one. (Incl if the first one ended in abortion/miscarriage).
The Ab develop in the 1st pregnancy, but are not in lg enough quantity to cause harm until 2nd pregnancy.

18

Type II HPS:
What is bullous pemphigoid and pemphigus vulgaris?

Bullous pemphigoid = Ab against hemidesmosomes
Pemphigus vulagaris = Ab against desmosomes / desmoglien
Both of these are Ab against epithelium, so they manifest in skin.

19

Type III HPS

Ab against non-self Ag, form Ag-Ab immune complexes and get deposited into tsu.
Ag-Ab (IgG) complexes activate complement, which attracts neutrophils.
Neutrophils rls lysosomal enz.
Imagine immune complex as 3 things stuck together: Ag-Ab-complement
5-12 hrs

20

What are 2 special kinds of Type III HPS?

Serum sickness
Arthus reaction

21

What is the mechanism of serum sickness?

Type III immune complex dz in which Ab to foreign proteins are produced (takes 5 days). Immune complexes form and are deposited in membranes, where they fix complement and cause dmg to the tsu.
In past before Abx, gave lots of Ab to the dz, so it would mk complexes and deposit in vessel walls (so, "serum" sickness). Now, it's usually caused by drugs.

22

Symptoms of serum sickness?

Type III immune complex dz.
Fever, urticaria, arthralgias, proteinuria (and glomerulonephritis), and lymphadenopathy.
Occurs 5-10 days after Ag exposure, bc Ab to the Ag have to be produced.

23

What is the mechanism of Arthus reaction?

Type III HPS, local, sub-acute, Ab-mediated.
Intradermal injection of Ag (eg tetanus vaccine) induces Ab, which form Ag-Ab complexes in skin.
Test for it w. immunofluroescent staining.

24

Symptoms of Arthus rxn?

Type III HPS
Edema, necrosis, activation of complement.
5-12 hrs after intradermal injection of Ag.

25

Ex of Type III HPS

SLE
Rheumatoid arthritis
Polyarteritis nodosa
Post-strep glomerularnephritis
Serum sickness
Arthus rxn
HPS pneumonia (farmer's lung)
Can be assoc'd with vasculitis and systemic manefestations

26

Type IV HPS

Delayed, T-cell mediated.
Sensitized Tcells encounter Ag and then rls lymphokines which lead to macrophage activation.
No Ab are involved.
24-48 hrs.
Bc it's cell mediated, it is not transferable by serum.
Test: patch test (e.g. PPD for TB)

27

What are the 4 T's of Type IV HPS?

T-lymphocytes (Tcell mediated)
Transplant rejections
TB skin tests
Touching (contact dermatitis)

28

Mnemonic for HPS rxns: ACID

ACID:
Anaphylactic and Atopic = Type I
Cytotoxic (Ab-mediated) = Type II
Immune complex = Type III
Delayed (Tcell mediated) = Type IV

29

Ex of Type IV HPS

DM Type I
MS
Guillian-Barre Synd
Hashimoto's Thyroiditis
Graft v Host dz
PPD (test for M. TB)
Contact dermatitis

30

What are ex of contact dermatitis (Type IV delayed HPS)

Poison ivy, oak
Nickel allergy- watch, belt buckle, sandal buckle

31

Anti-nuclear Ab (ANA)

SLE
but also many other things:
Sjorgrens
Scleorderma
Polymyositis
Dermatomyositis
Rheumatoid arthritis
Juvenile arthritis
MCTD

32

Anti-dsDNA, Anti-Smith

Specific for SLE
dsDNA = even more specific for renal dz in SLE

33

Anti-histone

Drug-induced lupus

34

Anti-IgG (Rhematoid Factor)

Rhematoid Arthritis.
This is IgM Ab attacking IgG

35

Anti-centromere

CREST Scleroderma

36

Anti-Scl70 (Anti-DNA topoisomerase I)

Diffuse Scleroderma

37

Anti-mitochondrial

Primary biliary cirrhosis

38

Anti-gliadin, Anit-endomysial

Celiac dz (malabs syndrome where villi of gut are severely atrophied)
Gliadin - component of wheat

39

Anti-basement mbr

Goodpasture's synd (renal dz, lung dz)

40

Anti-desmoglien

Pemphigus vulgaris

41

Anti-microsomal, anti-thyroglobulin

Hashimoto's thyroiditis

42

Anti-Jo-1

Polymyositis
Dermatomyositis

43

Anti-SSA (Anti-Ro)

Sjogren's
SLE

44

Anti-SSB (Anti-La)

Sjogren's
SLE

45

Anti-U1 RNP (ribonucleoprotein)

MCTD (mixed CT dz)

46

Anti-smooth muscle

Autoimmune hepatitis

47

Anti-glutamate decarboxylase (Anti-glutamic acid decarboxylase)

DM Type I

48

c-ANCA (Anti-neutrophil cytoplasmic An)

Wegener's granulmatosis

49

p-ANCA

Vasculitis:
microscopic polyangitis
Chrug-Strauss

50

mpo-ANCA (myeloperoxidase)

Pauci-immune crescentic glomerulonephritis

51

Anti-TSH receptor

Graves' Dz (HYPERthyroidism- the receptor is stimulated)

52

Anti-ACh receptor

Myasthenia Gravis

53

Illnesses with elevated ESR

Polymyalgia rhenmatica
Temporal arthritis
Disease activity in RA and SLE
Infection, Inflammation, Malignancy
Osteoarthritis- infection of bone, can be subclinical. if high ESR, increased suspicion; if not, can rule it out.

54

22q11 deletion syndromes

Due to aberrant devt of 3rd and 4th brachial pouches
CATCH-22:
Cleft palate
Abnormal facies
Thymic aplasia (--> Tcell deficiency)
Hypocalcemia (secondary to parathyroid aplasia)

DiGeorge = thymic, parathyroid, cardiac defects
Velocardiofacial syndrome = palate, facial, cardiac defects

55

Which immune deficiencies are B-cell disorders?

Bruton's agammaglobulinemia
Hyper-IgM Syndrome
Selective Ig deficiency
CVID- common variable immunodeficiency

56

Which immune deficiencies are T-cell disorders?

Thymic aplasia (DiGeorge)
IL-12 receptor deficiency
Hyper IgE Syndrome (Job)
Chronic mucocutaneous candidiasis

57

Which immune disorders are combined B-cell and T-cell disorders?

SCID - severe combined immunodeficiency
Ataxia-telangiectasia
Wiskott-Aldrich syndrome

58

Which immune disorders are due to phagocyte dysfunction?

Leukocyte adhesion deficiency (Type I)
Chediak-Higashi syndrome (MT fn)
Chronic granulomatous dz (NADPH oxidase deficiency)

59

Which immunodeficiencies are X-linked?

WBC:
Wiskott-Aldrich
Bruton's Agammaglobulinemia
Chronic Granuolmatous Dz (sometimes X-linked, not always)
Also one of the 3 types of Hyper-IgM Syndrome is X-linked (the type with no CD ligand)

60

What are the 3 types of Hyper-IgM syndrome?

Hyper-IgM = lots of IgM but low amts of other Ig's.
1. X-linked (no CD ligand)
2. Autosomal Recessive (no CD40)
3. NEMO deficiency

61

What is the defect in Bruton's agammaglobulinemia?

X-linked recessive, so moreso in Boys (one of the WBC X-linked)
Defect in BTK, a tyrosine kinase gene --> blocks Bcell differentiation and maturation --> low levels of all Ig's.

62

Px of Bruton's agammaglobulinemia

Recurrent bacterial infections after 6 months (decreased maternal IgG) due to opsonization defect.
Low levels of all Ig's so get lots of infections.

63

Labs for Bruton's agammaglobulinemia

Normal pro-B
Decreased maturation, # of B cells
Decreased Ig of all classes

64

Defect in Hyper-IgM syndrome

Defective CD40L on Thelper cells --> inability of B cells to class switch because need CD40-CD40L binding to signal it. So, all Ig's are stuck as IgM

65

Px of Hyper IgM syndrome

Severe pyogenic infections early in life.

66

Labs for Hyper IgM

Lots of IgM
very low IgG, IgA, IgE
No CD40L on flow cytometry for Tcells

67

Defect in Selective Ig Deficiency

Defect in isotype switching --> deficiency in a specific class of immunoglobulins. (Can be any, but IgA deficiency most common)

68

Px of Selective Ig Deficiency

Most pts are healthy, may not know.
Sinus/lung infections
Milk allergies and diarrhea
Assocd w atopy (allergy predisposition), asthma
Imp: Anaphylaxis on exposure to blood products with IgA.
Occurs in 1/600 pts of European descent

69

Labs for Selective Ig Deficiency

IgA deficiency is most common.
Failure to mature into plasma cells.
Decreased secretory IgA.

70

Defect in CVID (common variable immunodeficiency)

Defect in B cell maturation.
D/t many causes

71

Px of CVID

Can by acquired in 20s-30s
Increased risk of autoimmune dz, lymphoma, sinopulmonary infections.

72

Labs for CVID

Normal number of B cells but decreased plasma cells and Ig

73

Defect in DiGeorge Syndrome (thymic aplasia)

22q11 deletion
failure to develop 3rd and 4th brachial pouches

74

Px DiGeorge

No Thymus - no mature Tcells = recurrent viral, protozoal, fungal infections
No Parathyroid - no PTH - low Ca2+ = tetany
Congenital heart and great vessel defects
Facial abn - cleft palate, low ears, smooth phitrum, micrognathia (chin)

75

Labs DiGeorge

No thymus, parathyroid, so decreased T cells, decreased PTH, decreased Ca2+
No thymic shadow on CXR

76

What are the 2 signs for low Ca2+?

Chovstek's sign- tap cheek- when facial nerve is tapped, facial muscles will contract (tetany)
Trosseau's sign- Carpal spasm when tighten BP cuff (tetany)

77

Defect, Px, Labs in IL-12 receptor deficiency

Defect: Decreased Th1 response
Px: Disseminated mycobacterial infections
Labs: Decreased IFN-gamma (bc Th1 are not secreting it)

78

Defect in Job's Syndrome (Hyper IgE)

Th cells fail to produce IFN-gamma
So PMNs (neutrophils) don't respond to chemotactic stimuli (C5a, LTB4, IL-8)

79

Px of Job's syndrome (IgE)

Triad:
Eczema
Recurrent cold abscesses (S. aureus)
Course facial features: broad nose, frontal bossing of forehead, deep eyes, doughy skin.
Also can have retained primary teeth- 2 rows of teeth!
Job was FATED:
Facies
Abcesses (cold- noninflamed)
Teeth retained
E (hyper-IgE)
Dermatologic (eczema)

80

What is the defect, Px, and Rx for chronic mucocutaneous Candidiasis?

Defect: Tcell dysfn
Px:
C. albicans infections of skin and mucous mbr
Rx: Ketoconazole (anti-fungal)

81

What is the defect in SCID?

Defect is in early stem cell differentiation (No Bcells, Tcells)
Can be caused by >7 diff gene defects.
Most common:
Adenosine deaminase deficiency (purine salvage pathway)
Defective IL-2 receptor (X-linked defect)
Failure to synth MHC-II Ag
Only defense is NK cells.

82

Px of SCID

Triad:
1. Recurrent infections- viral, bacterial, fungal, protozoal due to both B and T cell deficiency (chonic mucocutaneous candida, RSV, VZV, HSV, measles, flu, parainfluenza, PCP pneumonia)
2. Chronic diarrhea
3. FTT
Plus no thymus on CXR (like DiGeorge)

83

Rx for SCID

Bone marrow txplt (no allograft rejection)

84

Labs for SCID

Decreased IL-2R (decreased Tcell activation)
Increased adenine (toxic to B and T cells)- decreased dNTPs, decreased DNA synth.

85

What is ADA deficiency (Adenosine deaminase)

ADA converts Adenosine to Inosine in the purine salvage pathway.
Defective ADA means accumulation of deoxyadenosine, which leads to excess ATP and dATP. This causes imbalance in nucleotide pool, d/t fdbk inhibition of ribonucleotide reductase. This prevents DNA synth and therefore decreases lymphocyte count.
Mjr cause of SCID.

86

What is the defect in Ataxia-Telangiectasia?

Defect in DNA repair enz and IgA deficiency.

87

Px of Ataxia-Telangiectasia

Triad:
1. Cerebellar defects (ataxia) plus poor smooth pursuit of moving target w eyes
2. Spider angiomas (telangiectasia) when >5yo
3. IgA deficiency
Also have increased CA risk (lymphoma, acute leukemia) and radiatiion sensitivity (avoid xray)
Die at 25yo

88

If you see a 1 yo with poor smooth pursuit, how should you check for Ataxia-Telangiectasia?

Increased alpha-fetoprotein (in kids >8mo)

89

Defect in Wiskott-Aldrich syndrome

X-linked recessive (it's an x-linked Wbc)
Progressive deletion of Bcells and Tcells

90

Px of Wiscott-Aldrich

WAITER:
Wiscott
Aldrich
Immunodeficiency/Infection
Thrombocytopenic purpura
Eczema (unusual bc it's trunkal eczema)
Recurrent pyrogenic infections- no IgM against capsular bacteria

91

Labs for Wiscott-Aldrich

Low IgM
High IgA, IgE

92

Defect in Leukocyte Adhesion Deficiency (Type 1)

Defect in LFA-integrin protein (CD18) on phagocytes. This means phagocytes can't exit circulation. (Can't "integrate" into tsu's)

93

Px of Leukocyte adhesion deficiency (Type I)

Recurrent bacterial infections, absent pus formation
Delayed separation of umbilicus

94

Labs for Leukocyte adhesion deficiency (type 1)

Neutrophilia (high amt of neutrophils in blood)

95

Defect in Chediak-Higashi syndrome

Autosomal recessive
Defect in microtubular function with decreased phagocytosis
Defective LYST gene (lysosomal txprt)- can't get the enz which degrade things into the lysosomes.
Defective phagocyte lysosome- see giant cytoplasmic granules in PMNs (can engulf, but can't degrade once engulfed)

96

What is a PMN?

Polymorphonuclear Leukocytes (PMN, PML) aka granulocytes.
There are three types of granulocytes:
Neutrophils
Eosinophils
Basophils
All have granules and lobed nuclei.

97

Px of Chediak-Higashi

Triad:
Partial albinism
Recurrent respi and skin infections (esp pyogenic infections by Staph and Strep)
Neurologic disorders- peripheral neuropathy

98

Defect in Chronic Granulomatous Dz

NADPH oxidase deficiency. Therefore phagocytes can't generate ROS (e.g. superoxide and free radicals). Absent respiratory burst in neutrophils.

99

Px of Chronic Granulomatous Dz

Increase susceptibility to catalase+ organisms:
Staph (esp S. aureus)
E. coli
Klebsiella
Aspergillis
Candida

100

Dx of Chronic Granulomatous Dz

Nitroblue tetrazolium dye test is negative.
Normal phagocytes engulf NBT dye and oxidize it, turning it from yellow to blue-black.
Pts w CGD can't oxidize- so don't see blue-black color.

101

Rx for Chronic Granulomatous Dz

Prophylactic TMP-SMX (bactrin)
INF-gamma can also help.

102

Where is the thymus derived from embryologically?

The 3rd and 4th brachial pouches, which are ENDODERM.

103

What are the type of grafts (allo, auto, etc)

Autograft- from self
Syngeneic graft - from identical twin or clone
Allograft - from nonidentical pt of same species
Xenograft- from different species

104

What are the 4 types of txplt rejection?

Hyperacute
Acute
Chronic
Graft-vs-Host dz

105

What is Hyperacute rejection?

Ab-mediated (Type II HPS)
Due to presence of pre-formed anti-donor Ab in the txplt recipient.
W/in minutes after txplt

106

What is Acute rejection?

Tcell-mediated d/t Cytotoxic Tcells reacting against foreign MHCs.
Weeks after txplt.
Reversible with immunosuppressants

107

What immunosuppressants can reverse Acute Rejection?

Cyclosporine
OKT3

108

What is Chronic rejection?

Tcell and Ab-mediated vascular dmg (obliterative vascular fibrosis)
Months-years after txplnt, Irreversible
The non-self MHC-I is seen by Cytotoxic Tcells as self MHC-I which is presenting foreign Ag, so it attacks.
Take immunosuppresants after txplt to delay this.

109

What is Graft-vs-Host dz?

Grafted immunocompetent Tcells proliferate in the immunocompromised host and reject foreign (to them) cells- which are the host's cells.
Causes severe organ dysfn.
Mjr sympt: maculopapular rash, jaundice hepatosplenomegaly, diarrhea.

110

What does the Long Thoracic N innervate

Serratus Anterior
(scapular winging if lesioned)

111

What does the Suprascapular N. innervate?

Infraspinatus M (lateral rotator)
Supraspinatus M (1st 10degrees of arm abduction)

112

What does the Lateral Pectoral Nerve innervate?

Pectoralis Mjr M.

113

What does the Upper Subscapular N. innervate?

Subscapularis M. (medial rotator)

114

What does the Thoracodorsal nerve innervate?

Latissimus Dorsi M.

115

What does the Lower Subscapular N. innervated?

Teres Mjr M. (medial rotator, extender, ADductor)

116

What does the Musculocutaneous N. innervate?

Flexor muscles:
Biceps brachii
Coracobrachialis
Brachialis

117

What does the Axillary N. innervate?

Deltoid m

118

What does the Radial N. innervate?

Extensors of forearm
Triceps

119

What does the Median nerve innervate?

Pronators.
Causes Pope's blessing, Ape hand

120

What does the Ulnar N innervate

Interosseous, Lumbricals
Causes claw hand

121

What is Cori's disease?

Deficiency in glycogen debranching enz.
Glycogen is stored in the liver. With debranching enz deficiency, it can't undergo glycogenolysis (glycogen breakdown) to turn it into glucose.
With no glucose except from diet, there is hypoglycemia.
This leads to FTT.

122

What is Von Gierke's Disease?

Glycogen storage disease- no glucose-6-phoshatase enz, so liver can't make glucose from glycogen or from gluconeogenesis