#1 immunology Flashcards
1
Q
delayed separation of the umbilical cord
A
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
Q
steps for leukocyte exiting blood stream
A
- margination: increased vascular leakage –> hemoconcentration, decreased wall shear stress, improved contact of neutrophils w/ endothelial lining
- 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
- activation - sense chemokine, will be able to bind
- tight adhesion and crawling - CD18 beta 2 integrins (Mac-1 and LFA-1) to intercellular adhesion molecule-1 (ICAM-1) on endothelial cells
- transmigration - PECAM-1, peripheral intercellular junctions of endothelial cells
3
Q
myeloperoxidase deficiency
A
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
Q
alpha-2 globulins (name 3)
A
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
Q
anterior mediastinal mass in graves patient
A
thymus abnormalities, (eg thymoma, thymic hyperplasia)
6
Q
polymyositis clinical presentation & implicated pathophys
A
autoimmune disease w/ symmetric proximal muscle weakness (CD8+ lymphocyte mediated damage)
7
Q
eosinophilic infiltration of skeletal muscle
A
eosinophilic myositis, rare disorder associated w/ parasitic infxn. present w/ myalgia
8
Q
IL-2 (aldesleukin) mechanism of action against tumor cells and therapeutic use
A
IL-2 anti-tumor effect by increasing T cell and NK activity.
immunotherapy for metastatic melanoma and renal cell carcinoma
9
Q
alemtuzumab
A
anti CD-52, used for treatment of chronic lymphocytic leukemia. initiates direct cytotoxic effect
10
Q
what agent increases MHC I and II presentation?
A
IFN gamma
11
Q
describe serum sickness
A
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
Q
graft vs. host disease commonly occurs after [3]
A
- allogeneic bone marrow transplantation
- transplantation of organs rich in lymphocytes (like liver)
- transfusion of non-irradiated blood
skin, liver, and GI tract commonly affected
acute gvhd – 1 wk post transplant
13
Q
distinguish (1) sarcoidosis (2) hypersensitivity pneumonitis (3) lymphocytic interstitial pneumonitis (AIDS)
A
(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
Q
CD8+ T cell predominance in bronchoalveolar lavage fluid
A
lung transplant patient w/ bronchiolitis obliterans due to chronic rejection
15
Q
CD22+
A
immunological marker for ALL
16
Q
CD14+
A
monocyte macrophage lineage
17
Q
CD7+
A
multi-chain complex T cell marker
18
Q
Henoch-Schonlein purpura (HSP)
A
palpable skin lesion
abdominal pain
arthralgia
renal involvement
antigen exposure (bacterial / viral infxn) preceedig
deposition of IgA immune complexes
19
Q
delayed hypersensitivity occurs against which organisms
A
intracellular: m. tuberculosis and fungi. mediated by activated macrophages that form granulomata
most common vasculitis in 3-10 y/o
20
Q
recurrent mycobacterial or salmonella infxn? rx?
A
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
Q
X-linked agammaglobulinemia
A
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
Q
C3 deficiency
A
- recurrent pyogenic sinus and respiratory tract infections
- increased type III hypersensitivity (b/c C3 helps clear immune complexes)
23
Q
symptoms of staphylococcal scalded skin syndrome (exfoliatin exotoxin)
A
- Nikolsky sign (skin slipping off w/ gentle pressure)
- epidermal necrolysis
- fever
- pain w/ skin rash
protease cleaves desmoglein in desmosomes
24
Q
langerhans cells
A
- 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
