immunodeficiencies Flashcards
X-linked agamma globulinemia ( brutuns disease)
failure of mature of precursor B cell due to failure to make Light chain due to defective BTK gene
what is the clinical presention of Brutuns disease
1- Loss of mature B cells symptomatic at 6 months
2- recurrent Respiratory bacterial infection due to loss of opsonization by encapsulated bacteria causing sinusitis, PNA and artheritis
3- GI pathogen infection due to loss of IgA
4- absence of mature B cell CD19, CD20 and BCR
5- underdevelloped germinal center and absence of Ab
Common Varible immunodeficiency CVID
Defective B cell maturation, and loss of plasma cells
normal B cell count but absence of Ab usually IgG and sometimes IgA and IgM
High frequency of RA, PA and lymphomas
X-linked Severe combined immunodeficincy SCID
loss of CMI,HMI and NK responses but primarly a T cell problem
X-linked due mutation in y subunit of IL2R
loss of thymic shadow and loss of germinal center
clinical presentaion of X-linked SCID
Thrust, bacteria, viral and fungal infection
diaper rash and failure to thrive in kids
Autosomal recessive SCID causes
- Mutation in RAG1 and RAG2 causing no T and B cell maturation involved in VDJ recombination
2- PNP mutation
3-ADA deficincy causinf increase in dATP inhibiting ribonucleatide reductase causing B and T dysfucntion and decrease DNA synthesis and increase in purines
4- Mut in JAK3
5- Digeorge syndrome
DIgeorge syndrome
Failure of 3rd and 4th pharyngeal puch to form due to deletion of 22q11 chromosome
T cell deficincy
clinical presentation of Digeorge syndrome
Loss of thymus
loss of parathyroid G
congental heart defect
no thymic shadow and face abnormalities
underdeveloped paracortex in LN and periarterolar seet in sleen and it may cause SCID
what is the difference between Brutuns disease and CVID
CVID has later onset of symptoms 20-45 years and CVID can afect femlaes as well but brutuns is xlinked
Ataxia telangiectasia
B cell deficincy
Autosomal recessive defective ATM gene on chromosme 11involved in DNA repair
it will cause ataxia and telagiectasiasis due to dialated capilary vessels on skin and iincrease infections and malignancies
begins with gait and balance problems
Cerebellar atrophy ( Ataxia)
Resp infection due to low IgA and IgG
Hyper-IgM syndrome
Class swithcing disorder due to failuer of CD40-CD40L interaction s B cell can make only IgM
due to defecitve CD40L and is mostly Xlinked
Clincal rpesentation of Hyper IgM syndrome
Pneumonia, sinusitis, ottis media and pneumocysitits Jirovici due to defective Tdep macrophage activitiy
- (IMP) DECREASE HMI AGAINST INTRACELLULAR BACTERIA
Wiskott-aldrich syndrome
X linked disorder in WAS gene making defective in WAS protien which is needed fro T cell cytoskeltion and form immunogenic synapase
Causing high IgE and IgA causing eczema
Clinical presention of Wskott aldrich syndrome
male infant, 6m old, eczema and blleding and petechiae due to low plateltles and recurrrent ifnection
LFA deficincy type 1
innate immunity problem
defective neutrophil migrateion due to mutated in genes encoding intergirns or signaling molecules
autosomall recessive defecitve CD18 (LFA1) forming B2 subunit of integrins
clinical presention of LFA deficncy type 1
Recurrent bacterial infections, neutrophilia and WBCs especially PMNs cant migrate
LFA type 2 deficincy
DEfective lleukocyte rolling and migration due to absent eukocyte Ligandto E selectins and mutation in GDP-Fructiose transporter 1
Chediak Higashi syndome
innate immune disorder
failure of phagolysosome formations due to mutation in LYST gene causing micortubule dysfunction
Clinical presention of CHediak higashi syndrome
Oculocutanous albinism due to microtubule dysfunction
severe neuro impairment due to peripheral neuropathy
recurrent bacterial infection
Chronic granulomatous disease (CGD)
Xlinked innate immunity isorder
chrachterized by accumlation of macrophages
loss of function of NADPH xoidase which produce ROS ( Respiratory burst)
caused by Staph auerus, pseudomonas and asperigillus
Catalase + bacteria which can break down H2O2 wil cause recurrent infection but catalase - bacteria the macrophage can use their H2O2
Bare lymphocyte syndrome
defective activation of T cell due to No mHC2 expression due to mutation in the TF factor
cause loss of CD4 T cells
Loss of Th1 response increasing nontb mycobacterial infection
defective of Th17 response increaseing funal and bacterial ifnection
Hemophagcytic lymphohistocytosis
defective T cell activation
systemic activation of immune cells by infection
Tc and NK cant kill viruse ifnected cells due to mutation in genes encoding perferons and protiens envolved in granule exocytosis
causes presistant infection and increase INFy by T cell and NK increasing macrophage activity ingesting RBCsc
clinical presentation of HLH
cytopenia
hepatospleenomegaly due to immune cell infiltration
maculopapular rash
triggered by EBV, lymphoma, SLE and chediak higashi and X linked lymphoprofilerative disease
Causes of acuqired immuno deficincies
HIV –> dec CD4 Th cell response
radiation and chemotherapy –> Dec BM percursor
Immune supression for grafts
metastasis adn leukemiia–> reduce site of leukocyte development
protien calorie malnutrion –> dec maturation
removal of spleen –> Dec phagocytosis of microbes
HIV infection mechanism
gp120 binds to cd4 and CXCR4 and CCR5 on CD4, Dc and macrophages
RNA release viral proteases
DNA copy. ofviral RNA by reverse transcriptase
DNA integration by viral integrase
ACute HIV syndrome
Early HIV infection causinf mild acute illness, fever, maalise and the virus can go latency
Latecy HIV infection
progressive loss of CD4 T cells and less than 200 is diagnositic of HIV
Clincla aids clincal presention
1- Increase viral, bacterial and fungal infection due to weak T cell immunity and Dec T cell dependent ab response
2- reactivation of latent viruses like CMV, EBV due to dec CTL due to decrease Th function
3- B cell lymphoma, kaposi sacroma
4- wastic syndrome
5- Dementia due to ifneciton of microglial cells in brain ( macrophages)
why is immune system defective against HIV
High mutatio in Gp120
inhibit of MHC1
P23 viral protien overcome inhibiteffects of host cells
Tat proomtoe cell cycle arrest
Vpu promtoe CD4 degradtion
nef protien decreae CD4. MHC and block apoptosis
Elite controllers of HIV
HLA-B57, HLA-B27 protective of HIV effecitnly in presenting HIV
Resistaant HIV people
32 pair deletion polymorphism causinf resistnat to HIV infection
