Flashcards in #1 immunology Deck (103):
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
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
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 - )
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
anterior mediastinal mass in graves patient
thymus abnormalities, (eg thymoma, thymic hyperplasia)
polymyositis clinical presentation & implicated pathophys
autoimmune disease w/ symmetric proximal muscle weakness (CD8+ lymphocyte mediated damage)
eosinophilic infiltration of skeletal muscle
eosinophilic myositis, rare disorder associated w/ parasitic infxn. present w/ myalgia
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
anti CD-52, used for treatment of chronic lymphocytic leukemia. initiates direct cytotoxic effect
what agent increases MHC I and II presentation?
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
graft vs. host disease commonly occurs after 
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
distinguish (1) sarcoidosis (2) hypersensitivity pneumonitis (3) lymphocytic interstitial pneumonitis (AIDS)
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
CD8+ T cell predominance in bronchoalveolar lavage fluid
lung transplant patient w/ bronchiolitis obliterans due to chronic rejection
immunological marker for ALL
monocyte macrophage lineage
multi-chain complex T cell marker
Henoch-Schonlein purpura (HSP)
palpable skin lesion
antigen exposure (bacterial / viral infxn) preceedig
deposition of IgA immune complexes
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
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.
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
- recurrent pyogenic sinus and respiratory tract infections
- increased type III hypersensitivity (b/c C3 helps clear immune complexes)
symptoms of staphylococcal scalded skin syndrome (exfoliatin exotoxin)
- Nikolsky sign (skin slipping off w/ gentle pressure)
- epidermal necrolysis
- pain w/ skin rash
protease cleaves desmoglein in desmosomes
- stellar cells w/ intracytoplasmic "tennis-shaped" Birbeck granules on EM
- a form of dendritic cell (t cell interaction)
macrophage-derived cells in liver, compose part of reticuloendothelial system
- lie in hepatic sinusoids
neuroendocrine cells of the basal layer of the epidermis, role in touch.
- associated w/ rare but highly malignant Merkel cell carcinoma
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
- (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
cytochrome C oxidase deficiency
rare autosomal recessive disease, causes mitochondrial dysfunction
symptoms: weakness, hypotonia, and encephalopathy
pyruvate kinase deficiency
common cause of hemolytic anemia caused by enzyme deficiency
adenosine deaminase deficiency
primary cause of SCID. autosomal recessive. profound deficiency of both B and T lymphocytes
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)
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)
proteasome inhibitor treatment for multiple myeloma and waldenstrom macroglobulinemia
embryological structure that fails to develop with digeorge
3rd-4th pharyngeal pouch (thymus and parathyroids)
clinical presentation of diGeorge (2)
- tetany (hypocalcemia; parathyroid gland aplasia
- recurrent viral/fungal infxn
2nd branchial cleft (pharyngeal groove)
obliterated in normal human development. persistence = formation of branchial cleft cyst at angle of mandible
3rd branchial arch
tissues innervated by CN9 (stylopharngeus muscle, portions of hyoid, posterior 1/3 of tongue
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)
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
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
hypersensitivity pneumonitis produces serum IgG Abs which ppt what antigen?
actinomyces species antigen. type III hypersensitivity, deposition in vessel walls
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
chronic, pruitic, eczematous skin condition that almost always begins in childhood, uncertain pathogenesis, can, but need not be type I
candida extract injection tests for..
intact T-lymphocyte fxn, if an induration forms
(will have + candida extract injection in Bruton's agammaglobulinemia)
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
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
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)
-- risus sardonicus
vaccine -- formaldehyde inactivated tetanus toxin --> elicits humoral immunity
primary biliary cirrhosis
nonspecific in many connective tissue disorders
SLE and antiphospholipid antibody syndrome
antiphospholipid antibody syndrome presentation
hypercoagulability, paradoxical PTT prolongation, recurrent miscarriages (spontaneous abortions)
antibodies against DS-DNA
specific for SLE
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
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
deficiency of Fas or Fas-L
impaired activation-induced death of self-reactive T cells --> autoimmune disease
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
loading of MHC I
cytoplasmic proteins are degraded in proteasome, transported into rough ER, loaded into MHC I, sent to cell surface via Golgi
deficient DNA repair enzymes in Ataxia-telangectasia (ATM) is characterized by...
DNA hypersensitivty to ionizing radiation, but not UV
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)
deficient DNA repair enzymes in Fanconi anemia is characterized by..
hypersensitivity of DNA to cross-linking agents
deficient DNA repair enzymes in Bloom syndrome is characterized by...
generalized chromosomal instability, increased susceptibility to neoplasms
deficient DNA repair enzymes in hereditary nonpolyposis colorectal cancer is characterized by...
defect in DNA mismatch enzymes. increased susceptibility to colon cancer
AR, defect in DNA-repair genes. hypersensitive to ionizing radiation. cerebellar ataxia, oculocutaneous telangiectasias, repeated sinopulmonary infections, increased incidence of malignancy
which two things have posterior column involvement
vitamin B12 deficiency & syphilis
what types of antigens can be presenting on MHC class I
viruses, tumor proteins, endogenous
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
acellular, contains purified components of Bordetella pertussis and detoxified pertussis toxin
hepatitis B vaccine
purified inactivated HBsAg obtained from yeast through recombinant DNA technology
live attenuated varicella virions
live attenuated vaccine obtained from a strain of Mycobacterium bovis. used in young children to immunize against TB
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
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)
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
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
when is the complement binding site on IgM Ab revealed
C1 binding site revealed only after antigen binding
what is the Fab region of the Ab also known as?
Fc binding site of the Ab also serves as..
binding site for J chain of immunoglobulins in dimer (IgA) or pentameric (IgM) forms
can C1 binding to 1 Ab stimulate classical cascade?
no, need at least 2 Ab
who kills cells w/ decreased or absent MHC class I proteins?
NK cells; do not directly LYSE cell. instead, granzyme and perforins stimulate apoptosis
NK cell marker? activated by?
CD 16 or CD 56. activated by IFN-gamma and IL-12
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
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
what portion of the lymph node is enlarged during viral infections
describe primary and secondary follicles in lymph nodes
primary: dense and dormant
secondary: pale germinal center w/ proliferating B cells and follicular dendritic cells
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
what region of lymph node is in direct communication w/ affterent lymphatic vessels and cortical sinuses that line trabecuae
cortical sinus continuous w/ medullary sinus and single efferent lymphatic drain from hilum
what does bradykinin do?
vasodilation, increased vascular permeability, stimulation of nonvascular smooth muscle contraction, mediates pain
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
leukotriene C4, D4, E4 triggers which 3 things?
vasoconstriction, vascular permeability, bronchospasm
think -- constricts a lot of things
leukotriene B4 & leukotriene precursor 5-HETE
stimulate neutrophil migration to site of inflammation
neutrophilic chemtactic agents (5)
IL8, n-formylated peptides, leukotriene B4, 5-HETE, complement C5a
Wiskott-Aldrich syndrome 3 cardinal features? main pathophysiology? Rx?
problem w/ actin cytoskeleton rearrangement & tethering of membrane proteins
rx: HLA-matched bone marrow transplant
triad of hemolytic uremic syndrome
- microangiopathic hemolytic anemia
- acute renal failure
1. gene defect
3. clinical presentation
defect in LYST lysosomal trafficking regulator gene
microtubule dysfxn in phagosome-lysosome fusion
Bleeding and Bruising
Infxn w/ staph & strep
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
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
symptoms of polymyalgia rheumatica
bilateral stiffness of the shoulder and pelvic girdle muscles, fever, weight loss, increased ESR. association w/ temporal arteritis
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
where is the secretory piece of IgA made?
epithelial cells, all other components made by plasma cells
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