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Flashcards in #1 immunology Deck (103):
1

delayed separation of the umbilical cord

leukocyte adhesion deficiency
-- along w/ poor wound healing, recurrent skin infections w/o pus, and gingivitis / periodonitis.

autosomal recessive, deficiency of CD18, needed for INTEGRIN formation

2

steps for leukocyte exiting blood stream

1. margination: increased vascular leakage --> hemoconcentration, decreased wall shear stress, improved contact of neutrophils w/ endothelial lining

2. rolling - loose binding of sialylated carbohydrate groups (sialyl lewis X or PSGL-1 to L-selectin on neutrophils or E-selectin/P-selectin on endothelial cells

3. activation - sense chemokine, will be able to bind

3. tight adhesion and crawling - CD18 beta 2 integrins (Mac-1 and LFA-1) to intercellular adhesion molecule-1 (ICAM-1) on endothelial cells

4. transmigration - PECAM-1, peripheral intercellular junctions of endothelial cells

3

myeloperoxidase deficiency

similar to chronic granulomatous disease (NADPH deficiency), but since MPO is missing, can't kill catalase + or catase - microbes (while NADPH def, can kill catalse - )

4

alpha-2 globulins (name 3)

haptoglobin, ceruloplasmin, alpha-2 macroglobulins.

- haptoglobin -- scavenger molecule for hemoglobin released from RBC in hemolysis
- ceruloplasmin -- serum carrier protein for Copper ions, decreased in Wilson's disease

5

anterior mediastinal mass in graves patient

thymus abnormalities, (eg thymoma, thymic hyperplasia)

6

polymyositis clinical presentation & implicated pathophys

autoimmune disease w/ symmetric proximal muscle weakness (CD8+ lymphocyte mediated damage)

7

eosinophilic infiltration of skeletal muscle

eosinophilic myositis, rare disorder associated w/ parasitic infxn. present w/ myalgia

8

IL-2 (aldesleukin) mechanism of action against tumor cells and therapeutic use

IL-2 anti-tumor effect by increasing T cell and NK activity.

immunotherapy for metastatic melanoma and renal cell carcinoma

9

alemtuzumab

anti CD-52, used for treatment of chronic lymphocytic leukemia. initiates direct cytotoxic effect

10

what agent increases MHC I and II presentation?

IFN gamma

11

describe serum sickness

most serum sickness is now caused by drugs acting as haptens

type III hypersensitivity rxn
-- fever, urticaria (hives), arthralgia, glomerulonephritis, lymphadenopathy 5-10 days after exposure to antigen. can have fibrinoid necrosis and neutrophil infiltration of arteries

decrease C3 (immune complex + complement)

sulfonamides can cause this

12

graft vs. host disease commonly occurs after [3]

1. allogeneic bone marrow transplantation
2. transplantation of organs rich in lymphocytes (like liver)
3. transfusion of non-irradiated blood

skin, liver, and GI tract commonly affected

acute gvhd -- 1 wk post transplant

13

distinguish (1) sarcoidosis (2) hypersensitivity pneumonitis (3) lymphocytic interstitial pneumonitis (AIDS)

(1) sarcoidosis
high CD4:CD8 T cell ratio (5:1 to 20:1)
(2) hypersensitivity pneumonitis
decreased CD4:CD8 ratio
(3) lymphocytic interstitial pneumonitis (AIDS)
decreased CD4:CD8 ratio

look in bronchoalveolar lavage

14

CD8+ T cell predominance in bronchoalveolar lavage fluid

lung transplant patient w/ bronchiolitis obliterans due to chronic rejection

15

CD22+

immunological marker for ALL

16

CD14+

monocyte macrophage lineage

17

CD7+

multi-chain complex T cell marker

18

Henoch-Schonlein purpura (HSP)

palpable skin lesion
abdominal pain
arthralgia
renal involvement

antigen exposure (bacterial / viral infxn) preceedig

deposition of IgA immune complexes

19

delayed hypersensitivity occurs against which organisms

intracellular: m. tuberculosis and fungi. mediated by activated macrophages that form granulomata

most common vasculitis in 3-10 y/o

20

recurrent mycobacterial or salmonella infxn? rx?

IL-12 receptor deficiency; ultimately have decrease IFN-gamma

macrophages infected w/ mycobacteria make IL12 --> stimulates T cells and NK cells to make IFN-gamma.

rx: lifelong treatment w/ antimycobacterial antibiotics.

21

X-linked agammaglobulinemia

X-linked recessive; Brutons
defect in BTK tyrosine kinase, no B cell maturation

recurrent bacterial and enteroviral infxn after 6 months

small lymph nodes / tonsils

susceptible to lower respiratory infxn and giardia

22

C3 deficiency

- recurrent pyogenic sinus and respiratory tract infections
- increased type III hypersensitivity (b/c C3 helps clear immune complexes)

23

symptoms of staphylococcal scalded skin syndrome (exfoliatin exotoxin)

- Nikolsky sign (skin slipping off w/ gentle pressure)
- epidermal necrolysis
- fever
- pain w/ skin rash

protease cleaves desmoglein in desmosomes

24

langerhans cells

- stellar cells w/ intracytoplasmic "tennis-shaped" Birbeck granules on EM
- a form of dendritic cell (t cell interaction)
-

25

Kupffer cells

macrophage-derived cells in liver, compose part of reticuloendothelial system
- lie in hepatic sinusoids

26

Merkel cells

neuroendocrine cells of the basal layer of the epidermis, role in touch.
- associated w/ rare but highly malignant Merkel cell carcinoma

27

Melanocytes

neural crest cells, migrate to basal layer of epidermis
- dendritic processes that intercalate between cells of epidermis
- deliver pigment-laden melanosomes to keratinocytes

darkening of skin does NOT mean more melanocytes. it means more MELANIN PRODUCTION

28

- (negative) nitroblue tetrazolium test on neutrophils

NADPH oxidase deficiency (chronic granulomatous disease) recurrent infxn w/ PLACESS NK
psuedomonas, listeria, aspergillus, candida, e. coli, s. aureus, serratia

X-linked

29

cytochrome C oxidase deficiency

rare autosomal recessive disease, causes mitochondrial dysfunction

symptoms: weakness, hypotonia, and encephalopathy

30

pyruvate kinase deficiency

common cause of hemolytic anemia caused by enzyme deficiency

31

adenosine deaminase deficiency

primary cause of SCID. autosomal recessive. profound deficiency of both B and T lymphocytes

32

define severe asthma. what is a novel treatment strategy?

severe asthma: needing ORAL steroids. symptoms throughout the day, nighttime symptoms daily, symptoms w/ limited activity, frequent exacerbations requiring ORAL STEROIDS, evidence of decreased lung function on pulmonary function tests, frequent use of short-acting beta-agonists

resistant to inhaled steroids & beta-agonists. NEED ORAL STEROIDS.

omalizumab (IgG1 against IgE) effective for moderate-to-severe persistent asthma (igE mediated)

33

use of H1 blockers

even though histamine is a bronchoconstrictor, we don't use H1 blockers in asthma.

treatment for chronic urticaria and allergic symptoms and sleep aid (if first generation)

34

bortezomib

proteasome inhibitor treatment for multiple myeloma and waldenstrom macroglobulinemia

35

embryological structure that fails to develop with digeorge

3rd-4th pharyngeal pouch (thymus and parathyroids)

36

clinical presentation of diGeorge (2)

- tetany (hypocalcemia; parathyroid gland aplasia
- recurrent viral/fungal infxn

37

2nd branchial cleft (pharyngeal groove)

obliterated in normal human development. persistence = formation of branchial cleft cyst at angle of mandible

38

3rd branchial arch

tissues innervated by CN9 (stylopharngeus muscle, portions of hyoid, posterior 1/3 of tongue

39

4th branchial arch

tissue innervated by superior laryngeal branch of CN X, inclu most of the muscles of the soft palate and pharynx. also posterior 1/3rd of tongue

notable exceptions: tensor veli palatini muscle (CN V: 1st arch) and stylopharyngeus (CN IX: 3rd arch)

40

septum transversum

mesodermally-dervived tissue that extends ventral to gut tube from umbilicus to pericardium. gives rise to myoblasts that form diaphragm and exists as a vestige of central tendon of diaphragm

liver grows into the septum transversum as an outpouching of the embryonal forgut

41

why does too MUCH IgA increase risk for disseminated infection?

IgA fixation prevents IgM / IgG fixation. only IgM and IgG can fix complement to kill bacteria

42

hypersensitivity pneumonitis produces serum IgG Abs which ppt what antigen?

actinomyces species antigen. type III hypersensitivity, deposition in vessel walls

43

pathogenesis of contact dermatitis

repeated binding of small foreign molecules (haptens) applied to the skin surface to proteins on the surfaces of cutaneous cells. Langerhan cells bound to hapten + protein migrate to lymph node and generate circulating Th1 memory cell. upon cutaneous reexposure of hapten, Th! cells release inflammatory cytokines at site of exposure

type IV hypersensitivity

44

atopic dermatitis

chronic, pruitic, eczematous skin condition that almost always begins in childhood, uncertain pathogenesis, can, but need not be type I

45

candida extract injection tests for..

intact T-lymphocyte fxn, if an induration forms
(will have + candida extract injection in Bruton's agammaglobulinemia)

46

how does adenosine deaminase deficiency lead to SCID

needed for purine metabolism. adenosine -> inosine for elimination. adenosine accumulation is toxic, leads to death of T and B lymphocytes

47

xanthine oxidase

responsible for the formation of uric acid from hyoxanthine and xanthine. essential as final step of purine degradation.

inhibited by allopurinol.

deficiency --> low uric acid level of serum & renal calculi due to relative insolubility of xanthine at urine pH

48

transport of tetanospasmin (toxin produced by C. tetani) and pathogenesis of tetanus

retrograde axonal transport into CNS.

tetanospasmin heavy chain binds ganglioside receptors on neuronal membranes, and light chain inhibits glycine and GABA release from inhibitory interneurons

-- lockjaw (masseter muscle spasm)
-- opisthotonos
-- dysphagia
-- risus sardonicus

vaccine -- formaldehyde inactivated tetanus toxin --> elicits humoral immunity

49

antimitochondrial antibodies

primary biliary cirrhosis

50

anti-nuclear antibodies

nonspecific in many connective tissue disorders

51

anti-centromere antibodies

CREST

52

anti-phospholipid antibodies

SLE and antiphospholipid antibody syndrome

53

antiphospholipid antibody syndrome presentation

hypercoagulability, paradoxical PTT prolongation, recurrent miscarriages (spontaneous abortions)

54

antibodies against DS-DNA

specific for SLE

55

extrinsic pathway of apoptosis (FAS mediated)

- Fas receptors aggregate and reveal death domain for Fas-associated death domain (FADD)
- receptor-bound FADD stimulates activation of caspcase 8&10 (initiators) that begin an activation cascade culminating in activation of executioner caspase (3&6).

--> cleavage of DNA, fragmentation of nucleus, organelle autodigestion, plasma membrane blebbing

56

describe the role of Fas and FasL on T-lymphocytes (along w/ activation-induced death)

Fas receptor on T-lymphocytes play an impt role in cancer and autoimmune disorders

activated T lymphocytes express Fas L.

initial clonal expansion, activated T-lymphocytes are resistant to Fas-induced apoptosis. become more sensitive w/ progressive stimulation

activation induced death: in the presence of stimulating self-antigens, activated T-lymphocytes eventually undergo apoptosis

57

deficiency of Fas or Fas-L

impaired activation-induced death of self-reactive T cells --> autoimmune disease

58

describe anergy vs. activation-induced death

state of prolonged unresponsiveness that occurs in T-lymphocytes as a form of immune tolerance. when self-reactive T cells bind to MHC w/o costimulation signal (CD28 w/ B7)

activation induced death: self-reactive T lymphocyte undergoes apoptosis

59

loading of MHC I

cytoplasmic proteins are degraded in proteasome, transported into rough ER, loaded into MHC I, sent to cell surface via Golgi

60

deficient DNA repair enzymes in Ataxia-telangectasia (ATM) is characterized by...

DNA hypersensitivty to ionizing radiation, but not UV

61

deficient DNA repair enzymes in xeroderma pigmentosum is characterized by...

DNA hypersensitivity to UV radiation (premature skin aging, increased risk of skin cancer: malignant melanoma and squamous cell carcinoma)

62

deficient DNA repair enzymes in Fanconi anemia is characterized by..

hypersensitivity of DNA to cross-linking agents

63

deficient DNA repair enzymes in Bloom syndrome is characterized by...

generalized chromosomal instability, increased susceptibility to neoplasms

64

deficient DNA repair enzymes in hereditary nonpolyposis colorectal cancer is characterized by...

defect in DNA mismatch enzymes. increased susceptibility to colon cancer

65

ataxia telangiectasia

AR, defect in DNA-repair genes. hypersensitive to ionizing radiation. cerebellar ataxia, oculocutaneous telangiectasias, repeated sinopulmonary infections, increased incidence of malignancy

66

which two things have posterior column involvement

vitamin B12 deficiency & syphilis

67

what types of antigens can be presenting on MHC class I

viruses, tumor proteins, endogenous

68

describe conjugate vaccine? name some protein carriers.

polysacch + diptheria toxoid
-- induce immunity against encapsulated bacteria (s. pneumoniae, n. meningitidis, h. flu)
- protein needed to stimulate T cell response

protein carriers: mutant nontoxic diptheria toxin, n. meningitidis outer membrane protein complex, tetanus toxoid

69

pertussis vaccine

acellular, contains purified components of Bordetella pertussis and detoxified pertussis toxin

70

hepatitis B vaccine

purified inactivated HBsAg obtained from yeast through recombinant DNA technology

71

varicella vaccine

live attenuated varicella virions

72

BCG vaccine

live attenuated vaccine obtained from a strain of Mycobacterium bovis. used in young children to immunize against TB

73

describe the two polio vaccines

Sabin oral polio vaccine (OPV) --> live attenuated virions
Salk inactivated polio vaccine (IPV) --> inactivated (killed) virions

only IPV is approved for use in US

74

T-cell maturation:
arrive to thymus as?
1. positive selection 2. negative selection

arrive as double negative Pro-T cells in subcapsular zone. then, TCR beta gene rearrangement occurs w/ simultaneous expression of CD4 and CD8

1. positive selection: can bind to MHC (thymic cortical epithelial cells)
2. negative selection: binds to MHC + self antigen OR binds to MHC too strongly (thymic medullary epithelial and dendritic cells)

75

what is affinity maturation? in which cell types does it occur?

enhaving the hypervariable region binding affinity. occurs after initial binding of antigen to membrane bound immunoglobulin on naive B lymphocyte and subsequent migration of that B-lymphocyte to a lymph node.

within the germinal center, affinity maturation is accomplished by the process of somatic hypermutation, DNA coding for the immunoglobulin variable region is mutated randomly at a very high rate.

does NOT occur in T-lymphocyte maturation

76

TCR DNA rearrangement

10^15 diff possible antigen binding sites, similar to immunoglobulin gene rearrangement in that it involves VDJC regions of TCR gene & processes of junctional flexibility & P-region nucleotide addition, alternative joining of genes, mult peptides combining to form receptor

has an a and b protein segment

77

when is the complement binding site on IgM Ab revealed

C1 binding site revealed only after antigen binding

78

what is the Fab region of the Ab also known as?

complementarity-determining region

79

Fc binding site of the Ab also serves as..

binding site for J chain of immunoglobulins in dimer (IgA) or pentameric (IgM) forms

80

can C1 binding to 1 Ab stimulate classical cascade?

no, need at least 2 Ab

81

who kills cells w/ decreased or absent MHC class I proteins?

NK cells; do not directly LYSE cell. instead, granzyme and perforins stimulate apoptosis

82

NK cell marker? activated by?

CD 16 or CD 56. activated by IFN-gamma and IL-12

83

eosinophil functions (2) what do their granules contain

1. parasite defense. bound by free IgE when enters. binds IgE Fc on eosinophil. release major basic protein and other enzymes from granules (macrophages and NK cells also rely on ADCC)
2. regulation of hypersensitivity reactions. granules have histaminase (degrades histamine, reduce severity of atopy). granules also have leukotrienes and peroxidases that facilitate inflammation

84

lymph node anatomy: 4 major pieces. what is contained in each?

capsule, subcapsular sinus, cortex & paracortex, medulla & medullary sinuses

cortex: germinal follicles, B cells
paracortex: T lymphocytes and DC

subcapsular sinus (surround cortex: direct communication w/ afferent lymphatic vessels and cortical sinuses that line trabeculae

85

what portion of the lymph node is enlarged during viral infections

paracortex

86

describe primary and secondary follicles in lymph nodes

primary: dense and dormant
secondary: pale germinal center w/ proliferating B cells and follicular dendritic cells

87

medullary cords in lymph nodes contain (3 cells)? medullary sinuses (2 cells)

medullary cord: B cells, plasma cells, macrophages
medullary sinus: reticular cells and macrophages

88

what region of lymph node is in direct communication w/ affterent lymphatic vessels and cortical sinuses that line trabecuae

subcapsular sinus.

cortical sinus continuous w/ medullary sinus and single efferent lymphatic drain from hilum

89

what does bradykinin do?

vasodilation, increased vascular permeability, stimulation of nonvascular smooth muscle contraction, mediates pain

90

what do C3a, C4a, C5a do?

inflammatory anaphylotoxins that trigger histamine release from mast cells --> vasodilation and enhanced vascular permeability

C5a recruits and activates neutrophils, monocytes, eosinophils, and basophils

C3a recruits and activates eosinophils and basophils, not neutrophils

91

leukotriene C4, D4, E4 triggers which 3 things?

vasoconstriction, vascular permeability, bronchospasm
think -- constricts a lot of things

92

leukotriene B4 & leukotriene precursor 5-HETE

stimulate neutrophil migration to site of inflammation

93

neutrophilic chemtactic agents (5)

IL8, n-formylated peptides, leukotriene B4, 5-HETE, complement C5a

94

Wiskott-Aldrich syndrome 3 cardinal features? main pathophysiology? Rx?

-eczema
-recurrent infections
-thrombocytopenia

X-linked
WATER mnemonic
problem w/ actin cytoskeleton rearrangement & tethering of membrane proteins

rx: HLA-matched bone marrow transplant

95

triad of hemolytic uremic syndrome

- thrombocytopenia
- microangiopathic hemolytic anemia
- acute renal failure

96

Chediak-Higashi
1. gene defect
2. inheritance
3. clinical presentation

autosomal recessive

defect in LYST lysosomal trafficking regulator gene

microtubule dysfxn in phagosome-lysosome fusion

Bleeding and Bruising
oculocutaneous Albinism
Leukopenia
Infxn w/ staph & strep
peripheral Neuropathy

97

poison ivy, poison oak, poison suman cause..

all produce common allergenic substance known as urushiol. 50% of individuals are sensitized. pruritic, erythematous, excoriation

delayed type IV hypersensitivity

98

what would we see on muscle biopsy of a patient w/ polymyositis? serum?

MHC I class overexpression on sarcolemma and CD8+ T cell infiltration.

serum, see increased creatinine kinase and anti-jo-1 antibodies

99

symptoms of polymyalgia rheumatica

bilateral stiffness of the shoulder and pelvic girdle muscles, fever, weight loss, increased ESR. association w/ temporal arteritis

100

ankylosing spondylitis -- (1) affected joints (2) demographic (3) common presentation (4) associated w/ MHC

chronic inflammatory disorder of sacroiliac joints and axial skeleton.

erosions, sclerosis, narrowing, and ultimately fusion.

spine x-ray --> bamboo spine, fused vertebrae

affects young & middle aged men, presents most commonly w/ morning stiffness and lower back pain. last 30 min and improves w/ exercise.

associated w/ HLA B-27 (PAIR - seronegative spondyloarthropathies

101

where is the secretory piece of IgA made?

epithelial cells, all other components made by plasma cells

102

when does the fetal thymus (derived from bone marrow) begin in gestation? when are mature naive T cells released into circulation?

begin in 9th wk of gestation, mature cells not realized until 16th week at earliest

103

what is the best way to prevent neonatal tetanus?

ensure that all pregnant women have been vaccinated w/ tetanus toxoid. allows IgG antitoxin Abs to cross placenta