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Immunodeficiency and Serology
KYCOM Block 8
111
Immunology
Graduate
04/27/2013

Additional Immunology Flashcards

 


 

Cards

Term
what are the causes of secondary immunodeficiency (10)
Definition
T cell activity defect
immunosupressive therapy
spleen surgery/disease
nutrition/malnutrition
trauma
age
microbe infection
malignancy
biocehmical homeostasis imbalance
protein loss
Term
what are the types of immunosupressive therapy (5)
Definition
ctotoxic chemotherapy for malignancy
treatment of autoimmune disease
marrow albation prior to transplant
treatment of prophylaxis for solid organ transplant
immunosupressive drugs
Term
what are the immunosupressive drugs (4)
Definition
cyclosporine A and tacrolimus
corticosteroids
mnolclonial antibody to cytokine (TNF)
Term
what do cyclosporine A and tacrolimus do
Definition
block calcineurin protein which activates T cells
disrupts signal transduction
Term
what do corticosteroids do (3)
Definition
inhibit cytokine production, affect antigen presentation, reduce peripherial lymph nodes
Term
what does monoclonal antibodies to a cytokine do to the body
Definition
interleukin or receptor dysruption
Term
what does a splenectomy do to the immune system
Definition
reduced response to t independent antigens and to encapsulated bacteria
Term
what are the major areas of nutrition deficit that affect the immune system (9)
Definition
proteins, glutamine, iron, zinc, selenium, vitamin A, B6, C, E
Term
overall, what does changes does malnutrition cause in the immune system
Definition
decreased circulating T cells, increased NK cells, increased Ig levels but decreased response, less cells in lymph organs, increased incidence of infection
Term
what are the types of trauma that can dysrupt the immune system (3 + 3 subcategories)
Definition
mechanical, burn, enviromental (radiation: UV, chemotherapy, ionizing)
Term
what does mechanical trauma do to the immune system
Definition
increase inflammatory cytokines (IL-1, TNF)
Term
what do burns to do the immune system
Definition
barrier dysruption and serum protein leaking increases infection risk
Term
what are the types of radiation, what do they do the immune system (3)
Definition
UV: skin cancer, decrease lymphocytes, mast, and dendritic cells

chemotherapy: cytotoxic to rapidly dividing cells (like immune stem cells in marrow)

ionizing (x-ray, y-ray): impairs cell division (malignancy, mutation)
Term
what does HIV do to the immune system
Definition
infects CD4 and is cytotoxic
Term
what does measles do to the immune system (3), what usually causes death of these patients
Definition
T cell lymphopenia (deletion of T cell areas of spleen, nodes, decreased antibodies to to T cell infection)

CMI supression

interfere with signaling

death due to co-infections
Term
what does CMV do to the immune system
Definition
transporter associated with antigen processing (TAP) transfers antigen to the ER. this is prevented so MHC-1 never gets to surface
Term
what does herpes change in the immune system (2)
Definition
MHC-1 cannot get to the ER and is not displayed
reduced INFy production
Term
what does EBV do to the immune system
Definition
IL-10 analog inhibits Th1 development
Term
what bacteria (or categories of bacteria) cause immunosupression. what is their weapon (4)
Definition
S. aureus: superantigen PVL

gram negative: endotoxin causes spesis

gram positive cocci: toxin causes toxic shock

mycobacterium
Term
how does mycobacterium cause immunosupression (3)
Definition
interfere with phagolysome fusion to lysosome preventing phagocytosis of itself and other microbes

replicates in phagocytes

increased risk for secondary infection
Term
what are two categories of malignancy that cause immunosupression
Definition
leukemia and reduced Ig production
Term
what is leukemia
Definition
proliferation of abnormal cells leading to functional issues and crowding

cancer of immune system
Term
what are examples of reduged Ig production malignancies that cause immunosupression, give a brief description of them (4)
Definition
hodgkins disease: lymphoid tumor

chronic lymphocytic leukemia: B cell tumor

multiple myeloma: many monoclonial antibodies. marrow tumor

waldenstorm macroglobulinemia: lymphoplascytic lymphoma, increased IgM due to tumor in IgM secreting B cell
Term
what are two conditions that can cause biochemical homeostasis imbalance
Definition
diabetes mellitus and hepatic insufficiency / cirrhosis
Term
how does diabetes mellitus cause immunosupression (2)
Definition
reduced neutrophil killing ability due to fingal infection and hyperglycemia

bad peripherial circulation causes skin ulceration and reduced neutrophil delivery
Term
how does hepatic insufficiency / cirrhosis cause immunosupression (3)
Definition
serum protein issues

increased glycocorticoids cause immune dysfunction

blood shunting decreases kupffer cell exposure to blood
Term
what are disorers that cause protein loss
Definition
nephrotic syndrome (can come from immunosupressive drugs)

severe dermititis (proteins leak out of skin)

peritoneal dialysis across membrane (treatment for chronic renal disease)

enteropathy (leaking of proteins into GI lumen)
Term
what are the signs of a primary immunodeficiency (17)
Definition
mostly in kids
after exclusion of organ, allergy, asthma, anatomic abnormality
normal growth and development
healthy between episodes
quick response to treatment
recurent infection or abcess (especially GI, respiratory)
antibody therapy isnt working
unusual opportunistic infections
family history, especialy in males
structural abnormality
failure of infant to thribe
hepatosplenomeagly
malignancies
chronic thrush, rash, riarrhea
reduced lymphoid tissue
Term
what are the B cell primary deficiencies (4)
Definition
ataxia telangiectasia
burton's ammaglobulinemia
IgA defieicney
common variable immunodeficiency
Term
what are complement, cytokine, co-stimulatory, and signal transduction deficiencies (9)
Definition
hereditary angioneurotic edema
C2 deficiency
C3 activation defect
factor H or I defect
C3-C4 defect
C5-C9 defect
MAC attach interruption
INFy receptor defect
decay accelerating factor deficiency (CD59)
Term
what are phagocyte primary deficiencies (6)
Definition
CD18 mutation
leukocyte adhesion deficiency
congenital agranullocytosis
chronic granulomatous disease
chediak higashi syndrome
respiratory burst
Term
what are T cell primary deficiencies (15)
Definition
SCID
CD40/CD154 x-linked hyper IgM
wiskott aldrich syndrome
adenosine deaminase / purine nucleotide phosphorlyase defect
bare lymphocyte syndrome
thymus maturation disorders
stem cell disorders
surface receptor disorders
signal transduction disorders
diGeorge syndrome
RAG gene mutation
omen syndrome
IL-2 production or receptor issues
CD3 zeta defect
ZAP 70 phosphotyrosine kinase defect
Term
ataxia telangiectasia: inheritence, issue, symptoms
Definition
autosomal

cant repair DNA breaks in T and b cells, purkinje fiber movement issues in development and vision

loss of balance, widened capillaries, increased malignancy, retarted growth, immunodefects of superimmunoglobins
Term
what is the cause of x-linked (burton's) agammaglobulinemia (3)
Definition
defect in burtons protein tyrosine kinase (BTK) CD40

intracellular signal for pre B to pro B cell stopped, Ig reduced
Term
what are the effects of x-linked (burton's) agammaglobulinemia (2)
Definition
increased respiratory, meningitis, and GI infection, increased vulnerability to bacteria with polysaccharide capsules
Term
treatment of x-linked (burton's) agammaglobulinemia (2)
Definition
injection of gamma globulin or antibody from plasma of healthy donors
Term
what is the cause of an IgA deficiency
Definition
IgA precursor cell fails to mature due to 6 chromosome 14 deletion options

IgM and IgG normal
Term
what are the effects / symptoms of an IgA deficiency (2)
Definition
increased GI, respiratory infection, allergy, CNS disorders, autoimmune diseases

may produce anti-IgA antibody causes anaphylaxis
Term
what is the signs of common variable immunodeficiency (CVID) (3)
Definition
presents a little after birth because mom's IgG help
recurrent respiratory infection, low IgG
Term
what are general signs of a B cell primary deficiency (3)
Definition
resist many pathogens and treated by antibiotics for rest

bronchiectasis (loss of elasticity due to chronic inflammation), chronic lung disease

tissue damage due to treatment causing protease release from phagocytes and abcteria
Term
how are B cell primary deficiencies detected (4)
Definition
reduced Ig titer following vaccine
Ig quantitation
reduced B cell numbers
flow cytometry cell count for monclonial antibody to CD19
Term
what are the general signs of a complement,cytokine, co-stimulatory, or signal transduction primary deficiency (4)
Definition
increased alternate and mannose-lectin binding pathway, bacterial infection, autoimmune diseases due to inability to destory immune complexes, accumulation of immune complexes
Term
herditary angioneurotic edema: causse and effect
Definition
C1 inhibitor (C1INH) leaks and activates classic complement pathway

overproduction of vasoactive C2a causes edema and epiglottal swelling
Term
C3 activation defect: cause, effect
Definition
missing protein

decrease in phagocytosis, susceptibility to pyrogenic infections
Term
factor H or I defect effects
Definition
conversion of C3 to C3b is unchecked and C3 stock pile is depleted due to alternate pathway activation
decreased MAC attack
Term
what are the isgns of a C3-C4 defect
Definition
cant clear immune complexes because C3/4 attach to CR1 on RBC to capture complexes

inflammation, tissue damage
Term
what does C5-9 defect increase susceptability to
Definition
nisseria meningitis
Term
how is an interruption of the MAC attack immunodeficiency treated (2)
Definition
gamma globulin injections, GM-CSF injection to stimulate phagocyte differentation
Term
what is the cause and effects of decay accelerating factor (DAF CD59) deficiency
Definition
not protected from activating alternate pathway of complement activation
complement mediated lysis of RBC causes paroxymal nocturnal hemoglobinuria
Term
how are complement and cytokine disorders detected (5)
Definition
complement or regulator levels
analysis of components
opsonic index
cytokine levels
Ig levels
Term
mutation of BD18: inheritance, what it does to body, what disease it causes
Definition
autosomal recessive

codes for B subunit of leukocyte integrins (CR2, CR4, LFA-1) adhesion molecules

causes leukocyte adhesion deficiency
Term
what are the effects of leukocyte adhesion deficiency on the body (6)
Definition
phagocytes cannot leave blood and enter infection site

persistant infection, poor wound healing, gum inflammation, poor response to antibiotics

leathal without marrow transplant
Term
what is the cause of congrnital agranulocytosis
Definition
decreased GM-CSF causing decreased neutriphils and macrophages
Term
what is the cause of chronic granulomatous disease
Definition
phagocytes cant make superodixde radical due to mutation in NADPH oxidase enzyme (myeloperoxidase and G6PDH)
Term
what are the effects of chronic granulomatous disease (3)
Definition
chronic bacterial infection, granuloma, chediak-higashi syndrome
Term
what is the tretment for chronic granulomatous disease
Definition
antimicrovirals, gamma globulin, marrow transplant, gene transfer
Term
what is the cause of chediak-higashi syndrome (3)
Definition
defective CHS1 gene on 1q42043 causes deficiency or G6PDH or myeloperoxidase

phagocytosed material not delivered to the lysosome (poor granular trafficing) due to vesicle fusion defect (cytiskeleton proteis missing)
Term
what are the symptoms of chediak-higashi syndrome (6)
Definition
albnism, peripherial neuropathy, lysosomal granules, reduced chemotaxis and phagocytosis due to decreased neutrophils, increased pyogenic infection, decreased platelets causing bleeding disorders
Term
what causes respiratory burst (2)
Definition
high NO due to a NADPH oxidase enzyme deficiency reduces vascular tone and CO and contributes to the low BP of septic shock

high NO acts as messenger ot promots T cells causing chronic inflammation
Term
how is a phagocyte disorder detected
Definition
nutroblue tetraolium reaction: yellow to purple in presence of ROS

respiratory burst assay
Term
how is a respiratory bust assay done
Definition
WBC incubated with dihydrorhodamine and catalyase
stimulated with phorbol 12-myristase 13 acetate
dihydrprhydoamine oxidation or rhodamine by peroxidase causes green floursence
measured by flow cytometry
Term
what are some causes of SCID (8)
Definition
no T cell dependent antibody response or cell mediated immune response. B cell as a result are not fuctional

X chromosome gamma chain causes JAK3 kinase production which codes for cytokine receptors (IL-2, 3, 7, 9, 15) decreasing signal transduction

adenosine deaminase/purine nucleotide phosphorlyase defect

bare lymphocyte syndrome (HLA-II only)

stem cell disorders

RAG gene mutation

IL-2 production or receptor issues

CD3 zeta issues
Term
CD154/Cd40 x-linked hyper IgM: inheritance (2), defect (2)
Definition
autosomal dominant (sometimes recessive)
defects
cutidine deaminade (AID) defect.
CD40 on T cells is not activating B cells, B cells cant change to plasma cells
Term
signs of hyper IgM (11)
Definition
no specific antibodies made, only IgM
no hypermutations to make better antibodies
no memory cells
recurrent infection in respiratory and GI
anemia
lymphoma
autoimmunity
no germinal centers
no leukocytes increase in infection
neutropenia: blisters in mouth and throat
Term
hyper IgM treatment (3)
Definition
galla globulin, antibiotics, GM-CSF
Term
cause of wiskott aldrich syndrome
Definition
gene on X chromosome codes for WASP protein which reogranizes cytoskeleton before T cell delivers cytokines to B cell, macrophages, or target cells. impairs plateles and lymphocytes
Term
symptoms / effects of wiskott aldrich syndrome
Definition
thrombocytropenia, GI bleeding, respiratory infection, ecsemia, cancer, low polysaccharide antibody response (ABO antibodies)
Term
adenosine deaminase (ADA) or purine nucleotide phosphorlyase (PNP) defect: inheritance, defective process, cause of toxicity
Definition
autosomal recessive

enzymes in purine degration missing, causes nucleotide metabolites (dATP/dGTP) to build up and hurt developing T and B stem cells
Term
treatment of ADA/PNP deficiency (3)
Definition
RBC transfusion, RBC enzyme replacement, gene therapy (insertion of viral vector into patient T cells)
Term
what are the types of bare lymphocyte syndrome, what are common symptoms
Definition
HLA-I or HLA-II deficiency
Term
how does a HLA-II deficiency occur, what does this cause
Definition
CD4 cannot develop due to defect in transcription regulators for HLA-II (DP, DQ, DR)

transactivator CIITA and pomotor building protein RFX are the ones messed up

causes SCID
Term
how does HLA-I deficiency occur, what does this cause
Definition
gene to tapsin (TAP) peptide transporter is defective and delivery of peptides to ER where they would bind to make HLA-I is stopped

causes CD8 loss, NOT SCID
Term
what are the effects of DiGeorge (7)
Definition
CMi reduced allowing infection
T dependent antigen response in tact
cardiac, facial, thymus, cleft, hypocalcemia abnormalities
Term
what microbes infect people with DiGeorge syndrom (8)
Definition
mycobacteria, listeria, salmonella, viruses, CMV, attenuated vaccine, canidia, pneumocystitis carinii
Term
what are the causes of the symptoms of DiGeorge syndrome (4)
Definition
3rd and 4th pharyngeal pouches (for thymus, parotid, aorta and craniofacial) malformation

chromosome translocation

thymic aplasia

T cells dont mature enough to function
Term
what structures does a RAG gene mutation mess up (3)
Definition
TCR and BCR and editing of autoreactive receptors
Term
what is the cause of omen syndrome
Definition
less severe RAG geme mutations, partial activity
Term
what issues come from IL-2 production or receptor issues (3)
Definition
cant activate T cell

gamma chain issues

SCID
Term
explain what ZAP 70 and CD3 zeta normally do
Definition
CD3 transmits signals from TCR to cytoplasmic tyrosine kinase

CD3/CD4/CD8 signals combine to stimulate T cell functions

sometimes when zeta part of CD3 is used and ZAP 70 is stimulates

ZAP 70 initiates gene expression, secondary messengers, PKC, etc
Term
what are the effects of a CD3 zeta defect (3)
Definition
T cell development defective

SCID

signal transduction issues
Term
what are the effects of ZAP 70 phosphotyrosine kinase defect (2)
Definition
faulty interaction with CD3 zeta

poor CD8 development
Term
how are T cell disorders detected (4)
Definition
flow cytometry cell count for antibody to CD3, 4, 5, 16, 56

reduced CD3, 4, 8

reduced DTH to tuberculin, canidia, trichophytin, mumps

mitogen responses
Term
what are mitogen responses
Definition
acrivation and proliferation of lymphocytes to phytohemagglutinin, pokeweek, concanavalin A
Term
metagenomics: define, use
Definition
DNA sequencing of member organisms from samples in a non-biased manner, not targeting a specific species

not suitable for clinical setting, low sensitivity, time constraints, cost
might save lives in an outbreak where standard culture based tests dont exist
Term
what are the two ways to perform agglutination
Definition
hemagglutination, latex particle
Term
hemagglutination: process, example
Definition
antigen is on RBC and antibodies to surface antigen join RBC.

antigens include ABO, Rh, blood groups

example: inhibition for antibody to influenza
Term
explain how to test with a latex particle, give examples
Definition
latex particle is coated with antibodies and specimine is mixed in, cross linking of antibody causes visible agglutination

examples: Rh to IgM/IgG, HCG in urine, rotavirus in stool, influenza in throat swab
Term
how do you do an ELIZA test, what is a common example
Definition
need to know antibody

bind, wash, label, and read

rapid strep test
Term
explain how a rapid strep test works
Definition
S. pyogens cell wall antigen extracted from throat swab is added to antibody strip via capillary action.
bound antigen reacts with second enzyme labeled antibody to make a visible color
Term
explain how flow cytometry works
Definition
antibody tp surface molecule is tagged with flouresence
cell passes through laser light
excited dye is detected electronically
Term
how is a polyclonial antibody used for testing
Definition
antibody injected into suitable animal
variety of antibodies to different epitopes of antigen
Term
how is a monoclonial antibody used for testing
Definition
antibody to a single determinant
highly specific
Term
what does a stain tell us about a microbe
Definition
preliminary information: bacterial, fungi, parasite
Term
what does a culture tell us about a microbe
Definition
artificial, tissue, animal, bacterial, fulgal, viral
Term
what does a tissue culture tell us about a microbe, example
Definition
microbes change the tissue their in

viruses cause multinucleate cells in epithelium
Term
what does a serological culture tell us about a mcirobe
Definition
detects antigen or antibody
Term
from what categories can a microbe be identified using simple characteristics and biological properities
Definition
simple characteristics
biochemical properities
FA analysis of the cell wall
determining antibotic susceptibility
Mass Spec
Term
what are simple characteristics of microbes
Definition
gram reactions
morphology: rod, coccus, pairs, chains
anaerobic, aerobic
growth requirements (simple/fastidious)
Term
what are biochemical properities of microbes
Definition
enzymes made
oxidation or fermentation of sugars
substrates used for growth
Term
explain how a mass spec works
Definition
patterns of protein detected directly from bacteria

applied to metal plate, irridated with laser, matrix absorbs laser, vaporizes sample (ionization) giving it a charge, electric fields guide ions to flight mass spectrometer, ions separated according to mass charge ratio

quantity of each ion measured
Term
what are the disadvantages of antibody detection methods for diagnosis
Definition
must know antigen
retrospective: it takes 2-4 weeks for IgG to develop then sustain in infection
positive test only indicates contact with microbe at some point in time
IgM qithin 7-10 days of infection can be seen as active but later are inactive
Term
what can ELIZA test for
Definition
lyme disease, HIV
Term
what can western blod test for
Definition
confirm tests for lyme disease and HIV
Term
what can anti-streptolysin O test for
Definition
AGN, rheumatic fever
Term
how do you assess the host defense system
Definition
detect opsonic activity of complement
respiratory burst
nitroblue tetrazolium (NBT) test
lymphocyte testing via polyclonial stimulators
lymphocyte testing via surface molecules
ELiSPOT technique
using ability of Tc and NK to attack a target
Term
how do you detect opsonic activity of complement
Definition
measure serum sample ability to facilitate uptake microbal particle by phagocytes
Term
how does a nitroblue tetrazolium test work
Definition
assess ability of neutrophils to become phagocytitic and reduce molecular O2

NBT forms complex with heparin or fibrogen and neutrophils phagocytose them
dye is taken into neutrophils in substitute of O2
Term
how is a lymphocyte tested via surface molecules
Definition
immunoflourescent techniques
Term
ELISPOT technique
Definition
identify lymphocyte secreting antibodies (B cells) or cytokines (T cells)

secreted products are impregnated with antigen, secreted product is identified via ELIZA
Term
how are Tc and NK used to assess host defenses
Definition
make radioactive isotope with 51Cr and put it into damaged cells
have Tc cells eat them and release isotope
Term
what are examples of tests that use latex particles with antibodies
Definition
rapid strep test, flow cytometry, tissue antigen, antigen in clinical specimen
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