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79 Cards in this Set
- Front
- Back
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so an autoimmune is when we attack self, what is an immunodeficiency
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absebce of failure of immune system
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what is the main thing we see with immunodeficiencies
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recurrent infections
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what are some general things we see with a B cell deficiency (humoral)
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lots of polygenic bacterial infections in the airway and gut.ear infections, parasites, extracellular bugs
deficiency in IgA stuff, and ALL ig are decreased tonsils may look small |
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do we see reduced DTH with B or T deficit
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T
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in general what do we see with T deficiency
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normal or reduced Ig
decreased DTH (type 4, T cell dependent) *lots of opprotunistic infections |
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ppl who get lots of recurrent pyogenic infections have a deficit inwhat (pnemonia, ear infection, sinusitus)
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humoral
ear, pnemonia, sinus, paraiste, giardia in git, polio in gut |
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we see increased parasitic infections with B or T defect
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B
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other than B cells what other htings are affected with HUMORAL immunodeficiency
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anything in the humor (fluid)
cytokines, compliment, AB |
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ppl who are more susceptible to a virus may be deficit in T or B
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T
intracellular bugs, opprotunistic infections |
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are T cell dificits usually isolated
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not really, T cells are needed to have a good B cell response so we often see dificits in B when we have deficits in T
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when might we see oral thrush
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candidiasis seen in mouth of ppl with decreased T
HIV pts |
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what is a primary immuno deficiency
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genetic problem
developmental (embryonic) defect 1. Defect in WBC maturation, function. Compliment deficit |
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is a compliment defect T or B. Primary or secondary
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B (humoral)
primary |
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what are hte primary immuno deficiencies we talked about that cause caused by defects in WBC maturation (8)
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1. DiGerorge:
2. XLA 3. TAP 4. X linked SCIDS 5. ADA SCIDS 6. RAG 7. JAK3 8. Bare lymphocyte |
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what are the primary immunodeficiencies that are caused by defects in the WBC
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1. X linked Hyper IgM
2. CGD 3. LAD1 4. CHS 5. WAS 6. HIES 7. AT |
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what are the defects, 1 or 2. B or T
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1 B
C protein deficiency C1 Inh deficiency DAF nad CD59 deficiency |
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what can cause a 2 immunodeficiency
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its aquired!
1. malnutrition 2. drug indiced (transient) 3. Cancer 4. Infections (HIVI |
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if you have an acquired immune deficiency is it 1 or 2
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2
malnutrition, drugs, cancer, infection |
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so primary immune deficiencies display a wide variety of sx. what is the common link of them all
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recall 1 oa a genetic or developmental deficit in WBC maturation or fx or a compliment deficiency
**ALL ALLOW MULTIPLE INFECTIONS |
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so infectrions are the hallmark of primary immune responses is this the only thing that goes on
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NOPE, and its often not the most importatn
assocaited with other PI: anemia, arthritis, autoimmune disease can also involve heart, GI, nervous system can retard growth, increase cancer risk |
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what are a few of the things tht can be associated with PI other than increased infections
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anemia, arthritis, autoimmune disease
heart, GI, nervous system slow growth, increase risk of cancer |
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PI are the result of what
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defects in lymphocyte maturation/activation/fx
defects in innate immunity (compliment) |
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what are some innnate PI
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1. CGD
2. leukocyte adhesion deficiency congenital agranulocytosis |
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what are some B cell PI
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1, common variable hypogammaglobulinemia
2. X linked agammaglobulimemia 3. X linked hyper IgM 4. Selective Immunoglobulin Deficiency |
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what are some examples of T cell PI
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1. De georgi
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what are some examples of SCIDS (B and T are deficient)
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1. reticular dysgensis
2. SCID 3. bare lymphocyte syndrome 4. wiskott Aldridch |
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what are the ten warning signs of PI
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1. eight+ new infections/year
2. 2+ sinus/year 3. 2 mo on antibiotic w/o help 4. 2+ pnemonia/year 5. dont gain weight 6. recurrent deep skin/abcesses 7. thrush after 1yo 8. IV antibiotics to clear infection 9. 2+ deep seated infections 10. family hx of PI **if 2 or more look into more tests |
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so what info do the 10 PI warning signs tell us
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if they have 2 or more there MAY be an immunodeficiency. look for more testing
8 new infections, 2 sinus/pnemonia, 2 mo on abiotics wo help, dont gain weight, deep skin infections, thrush, IV antibiotics needed, 2 deep seated infections, family hx |
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so if a kiddo has more than 8 new infections in a year that dont respond to antibiotics in 2 months and require IV antibiotics. what shuld you do?
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TESTS to check for PI
1. base line info: CBC, H&P 2. Ig titers. Boost and remeasure 3. DTH and phagocyte response (like TB tests to see if T cells work) 4. Specific tests |
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what are the 4 things you need to test if you think a kid has PI
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1. Get a baseline
2. Check Titers and see of they respond to a boost (chech AB) 3. Check DTH, like a TB test. Check phagocyte response (chect T) 4. SPecific tests |
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what is the mechanism of defect and the fx deficiency seen in chronic granulomatous disease
is this innate, T, B, combined |
mutation in phagocyte oxidase, cytochrome B558
phagocytes cant make ROS and so inflammation persists and granuloma forms INNATE |
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what is the mechanism of defect and fx deficit seen in Leukocyte Adhesion deficiency 1
is this innate, T, B, combined |
INNATE
mutation in B chain of B2 integrins **absent/deficient expression of B2 integrins causes defective leukocyte adhesion |
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what is the mechanism of deficit for leukocyte adhesion deficiceny 2. what is the fx defecit
is this innate, T or B |
mutation in E/P selectins ligand
leukocytes wont migrate into tissues. because lack of ligand innate |
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what is the mechanism of deficit and the fx deficit seen in a C3 difeicieny
innate, t, b, or TB |
mutation in C3
cant activate compliment cascade *innate |
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what happens with C2 or C4 deficeincy
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cant activate classical path, buildup of immune complexes and development of lupus like disease
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what is the mechanism of defect and functional defect in Chediak Higashi Syndrome
innate, T, b, TB |
mutation in a gene endocing a lysosomal trafficking regulatory protein
defective lysosomal fx in PMN, macro, dendritic cells. defective granule fx in NK INNATE |
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what is CHS
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deficit in LYST causes deficient intracellular protein trafficking of lysosomes and granules
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in what disease is LYST defective
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CHS
*LYST controls intracellular protein trafficking of lysosomes nad granules **impairs the lysosomes found in leukocytes nad platelets **impairs granules in PMN *inpairs menanosomes of melanocytes Pts ahve recurrent infections, partial oculocutaneous albianism, and infiltration of organs with non neoplastic lymphocytes |
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what are the cells affected by CHS
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leukocytes nad platelets have impaired lysosomes
PMN have impaired granules Melanocytes have impaired melanosomes **this all leads to albinism, infections. leukocyt infiltration in organs Deficit in LYST that monitors lysosomes and granules |
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what disease affects lysosome and granules, waht gene
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CHS
LYST gene **impairment of: 1. lysosomes of leukocytes/platelets 2. Grnaules of PMN 3. Melanosomes of Melanocytes **leads to recurrent infections, albinism, infiltration of lymphocytes into organs |
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what is CD132.
what happens when we ahve a deficiency in CD132 |
CD132 is a common g chain if several cytokine R
*CD132 deficit leads to deficit in IL2 Il4 IL7 IL15 RECEPTROS. important cytokines for lymphocyte maturation/activation leads to SCIDS: secere combined imminodeficiceny (B and T are affected) *ancoded on X chromoseom |
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a defiency is wht CD leads to a SCID that affects many IL receptors
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CD132
**cd1332 is a common g chain of IL2 IL4 IL7 IL15 RECEPTORS. this leads to deficits in plymhocyte activation./matureation NO T or NK, the B are non fx |
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what would cause IL2 4 7 15 Receptors to ALL be defective
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defectice in Cd132
**primary immunodeficiency **CD132 is a common g chain in all of these IL receptors No T or NK cells, B are deficient |
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what happens with ADA SCIDS
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ADA helps break nucleotides
**lymphocytes are most sensitive to ADA deficits. toxic metabolits build up and ALL Lymphocytes are lost |
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what immune cell is affected in ADA SCIDS
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ALL lymphocytes
**ADA is deficient and so toxic materia backs up, inhibit DNA synthesis |
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what happens with a deficiency in JAK3
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deficit in T and B
**cant signal either lymphycote |
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what happens with RAG deficienct
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NK is normal. B and T are bad
RAG is needed for TCR and BCR formation. No receptor no fx T or B cell |
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what happens when we have a SCID of T and B but NK are ok. its due to no BCR or TCR
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this is RAG deficiency
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in what kind of SCID would NK be normal
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RAG deficit
**RAG is used for TCR and AB/BCR |
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do immunodeficiency SYNDROMES inclue just the immune system
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Nope, multi systems involved nad usually both T and B are affected so they are caleld SCIDS
Ex: DiGeorge Ataxia Telangiectasia Wiskott Aldridch Syndrome Job syndrome: hyperIgE |
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WAS (Wiskott Aldrich Syndrome)
is characterized by a genetic defects in... It is characterized by what 3 things, and why do we see thse defects |
WASp protein on the X chromosome. interferes with HSC growth and signaling
1. Bleeding: thrombocytopenia 2 Infections: decreased B/T. low IgM but increased IgG, IgA, IgE. 3. Eczema **increased rosk of AI and bone cancers |
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waht disease is characterized by Bleeding, Recurrent infections, decreased IgM, increased IgE/A/G and eczema
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WAS
**defect in the X linked WASp that has to do with HSC signaling and growth |
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waht disease is characterized by an X linked deficiency in the abilty of HSC to grow and signal
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WAS
WASp is the protein and it is characterized by 1. Thrombocytopenia 2. Recurrent Infections (Decreased IgM, Increased IgG/E/A) 3. Eczema |
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what is Ataxia Telangectasia?
what kind of genetic defect? what are clinical things seen |
Autosomal Recessive Defecit in ATM (this repairs DNA, when its broken we get non ranom 7:14 translocations thta occur)
*increased cancer rates, SCIDS 1. Abnormal Gait: cerebellar egeneration 2. Dilated BV in eyes/skin 3. Recurrent infections (Decreased IgG/E/A and increased IgM) |
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so one disease has Decreased IgM and Increased IgG/E/A and another has the total opposite
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WAS: decreased IgM, increased IgE/G/A
AT: increased IgM, Decreased IgE/G/A |
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what does ATM do, in what disease is it deficient, what do we see as a result of deficiency
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ATP repaires DNA
without it we have ineffectiant repair and we get 7:14 mutations. This comprimises humoral and CMI and increases rates of cancer 1. Abnormal Gait 2. Dilated BV in eye/skin 3. Recurrent Infection: Increased IgM, decreased IgE/A/G |
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what is hyper IgE, what genetic component is out of wack
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STAT3
**Decreased Phagocytic killing and activation --> decreased IL12 **no IL12 means that we cant get Th1 differentiation. Th2 builds up and we get LOTS of IgE |
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what PT is characterized by a lack of Th1
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hyper IgE, we have excess Th2 that secrete IgE
**this is because we have decreased phago, this means decreased IL12 and decreased Th1 differnetiation **characterized by DHT deficits, skin abcess, pnemonia, facial abnormalities |
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what does IL12 do? in what disease is it deficient
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IL12 from phago indice Th1,
defective in Job (hyper IgE) **no IL12 so no TH1, so we get LOTS of Th2. This makes IgE |
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what Pi is characterized by facial abnormalities, skin abcess, and pnemonia, also DHT deficit
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Job, Hyerp IgE
**STAT is efective so we have defective phago, this mean defective IL12, this means no TH1, this means high Th2, this means high IgE |
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what are teh 2 approaches to tx of PI
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1. Minimize/COntrol Infections
2. Replace the immune system with adoptive transfer or Genetic replacement like gene therapy or BMT |
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to tx PI we might replace the immine system. what are 2 ways this can be dome
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1. Adoptive Transfer: passive immunization with pooled gammaglobulin, exogenous administration of cytokines or enzymes
2. Genetic Replacement: gene therapy or BMT |
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what is DeGeorge Syndrome
whats broken, what clinical manifestatiosn do we see |
delete part of Ch 22, paryngeal arch defect
**NO thymus/Parathyroid -variable T cells -No T memory-decreased response to skin test AG -increased infections -HYPOcalcemia |
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if we have a break in chromosome 22 adn we see decreased T cell and hypocalcemia what PI are we thinking
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DiGeorge
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what is deficient in XLA, what do we see as a result
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a tryosine kinase that converts Pro B to PreB
**no Mature B cell! *low Ig, low B, normal T. Lots of infections, tonsils are barely detectable |
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what is the disease that is characterized by inability to make mature B but can make T
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XLA
**missing tyrosine kinase that makes Pre B, no mature B ever form lots of infections, things arent cleared by compliment, opsinization, etc |
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what is a TAP deficiency
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when we cant display AG in MHC I
**decrease CTL Activity |
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what can be the cause if we cant display AG on MHC I
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TAP deficiency
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what is hyper IgM
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Loose CD40L so we cant activate B cells in a T dependent manner
*we can make IgM w/o CD40L but none of the others can be made bc T dependent is required for class switching |
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what can cause the inability to class switch AB
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Hyper IgM
**loose CD40L so we dont have a 2 signal in T dependent B cell activation **cant class switch so we get HYPER IgM |
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what is CGD
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cells do not have the appropriate ROS so inflammatory mediators continue and we get granulomas
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what disease is caused by an inability to remove pathogens that have been ingested due to defective ROS
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CGD
**the pathogen persists and so we get chornic inflammation that leads to CGD |
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what causes LAD 1
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problem with B2 integrin (CD18) and so inflammatory cells cant get to the tissues
*we see recurrent infectinos |
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what is the complimnt deficiency C1Inh
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C1 is always active ad so we have lots of C3a and C5a making anaphylatoxins so we get angioedema
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what disease that is characterized angioedema, what causes it
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C1Inh
**C1 inhibitor is broken so C1 is always on and so C3a and C5a are always on, thes are anaphylatoxins that cause angioedema |
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what happens with a DAF CD59 deficiency
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excess compliment activation on RBC surface
*hemolytic thrombosis and venous thrombossu |
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a deficiency in what leads to excess comlpiment activation that results in hemolytic anemia nad venous thrombosus
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DAF
CD59 |
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defects in TCR complex signaling are due to deficiency in what
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MHC II
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so mutations where lead to x linked nad autosomal hyper IgM
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Autosomal: AID mutations
X Linked: CD40 Ligand |
