Immunology Flashcards
X linked agammaglobulinema
Btk deficiency, pre B cell arrest
Presents 4-6mo, boys, 1:100,000
Absent B cells
Recurrent infections
-bacterial
-enteroviral
Absent lymphoid tissue
Ex IVIG
Drug reactions
Type 1- IgE mediated
Type 2- cytotoxic (haemolytic anemia secondary to ceohalosporin)
Type 3- immune complex ( serum sickness)
Type 4- delayed hypersensitivity ( cell mediated ; SJS/TEN ; rash)
Innate immune system
Cellular
- phagocytes (ROS by Resp burst and NAPDPH oxidase)
Neutrophils
eosinophils (IgE, helminth),
basophils (Mast cell, hypersens)
NK cells (IFN gamma) - cytotoxic to virus and tumor
- macrophages
Mediators between innate and adaptive
Dendritic cells (APC) NB in recognition by T lymphocytes via MHC2
Humoral
- Complement
Rapid response 0-4hours; not antigen specific
Innate immune system defects
CGD
LAD
TLR defects
Complement deficiencies
Leukocyte adhesion defect
Impaired adhesion of leukocytes to vascular endothelium
Delayed cord separation
Often high WCC
Severe necrotising bacterial infections (staph and GNB) but NO PUS
Oral/genital infections
Absent expression of CD18 and CD11 on flow cytometry
HSCT
3 types
- LAD1 most common, defect Beta chain of beta2 integrin
Chronic granulomatous disease
Defect in phagocyte NADPH oxidase
Most common type is Xlinked (g91phox deficiency)
Inheritance XL OR AR
Increase incidence Maori boys
Clinical
- recurrent severe infections with catalase positive organisms (mnemonic cats been places )
- Burkhokderia ; -nocardia - pasturella. ; - aspergillus
- Candida ; - E Coli - staph NB abscess; - serratia
Recurrent skin / GI infections - pneumonic, abscess, Supp adenitis, ON, bacteraemia or fungaemia Abscesses (skin, liver, lung) VEOIBD ; mimic IBD, form granulomas Adenopathy Hepatosplenomegaly
Inx
DHR or NBT
Rx Itraconazole fungal prophylaxis PCP prophy (cotrimox) IFN GAMMA HSCT
Mononoclonal AB targets
Omalizumab - IgE
Infliximab - TNF alpha inhibitor (binds to it and inhibits it’s activity)
Rituximab - CD20 (b cells)
Alemtuzumab(Campath) - CD52(mono/lymphocytes)
Mepolizumab- IL5
Anankira - IL1R antagonist
Toculizimab - Anti IL6
HLH
PRIMARY
SECONDARY
Diagnosis
- molecular
- Clinical (5/8 of below) Fever >38.5 Splenomegaly Cytopenia (2+cell line) Hypertroglyceridemia +/_ low fibrinogen Haemophagocytosis on BM LOW NK activity Ferritin >500 Elevated soluble CD25 ( IL2 receptor)
Adaptive immune system
B lymphocytes
T lymphocytes
Antigen specific
Amplification or response on re-exposure
Memory
CVID
1+
- susceptibility to infection
- autoimmune
- granulomatous disease
- unexplained polyclonal prolif
- affected family member with Ab deficiency
AND
Marked decrease IgA, IgG +/- IgM
Poor vaccine response, low memory B cells
Diagnosis >4
Secondary causes ruled out
No evidence T cell deficiency
B cell disorders
Antibody production defects
Present 4-6mo Recurrent sinopulmonary infections - encapsulated bacteria - parasites / fungi - giardia and cryptosporidium - enterovirus (esp in XLA)
THI
XLA
CVID
HyperIgm( intrinsic T cell defect)
- CD40ligand ; risk PCP
Vaccine response
- t dependent ( diphtheria, tetanus, PCV)
- t independent (polysaccharide conjugate, prevnar23
X linked hyperIgM
Mutation CD40 ligand gene
Intrinsic T cell defect (CD40L on activated T cell binds CD40 on b cellls)
No isotope switching
Low IgG and igA, High IgM
Abnormal vaccine response
Recurrent infection
Risk PCP (40% wo Rx)
Cryptosporidium ( risk Sclerosing cholangitis)
Giardia
Rx
IVIG
PCP Prophy
Avoid live vaccines and crypto
BMT (70% survival )
Selective IgA deficiency
Common 1/500
Low IgA, normal IgG and IgM
Increase risk mucosal infections (Resp/GI)
Assoc atopy and autoimmune
Risk anaphylaxis with blood products
IVIG no use
T Helper subsets
Th1: IFN gamma ; macrophage activation and IgG production; role in autoimmune
Th2: IL4,5,13; mast cell, IgE, eosinophil production
Role allergy and parasitic infection
Th17; IL17,22 ; neutrophil, monocytic inflammation, role autoimmunity
Which cytokines cases T cell proliferation
IL-2
Role prolif of memory and effector T cells
Maintenance Treg
SCID
Severe, fatal by 1yr Combined (humoral and adaptive) Immune def - low lymphocytes ( <3 under 3 months) - T cell deficiency
Present <3 mo with recurrent infections, FTT, diarrhoea, thrush; opportunistic infection ( PCP)
No thymus, no lymph tissue
Inx
Newborn screening ( tests for TREC)
Lymphocyte subsets
Lymph proliferation testing (PHA)
Most common(45%) is common gamma chain (T-B+NK-) which is XLinked mutation JAK3)
Rx Isolation Reduce CMV risk IVIG PCP and fungal prophy No live vaccines Caution transfusion ( cmv irradiated )
Rx
HSCT
MHC
MhC1- cytotoxic T (CD8)
MHC2- Helper T(CD4)
22q11 deletion ( DiGeorge)
Conotruncal cardiac defect (interrupted arch, Truncus, TOF) Thymic hypoplasia (lymphopenia) - complete (absent) vs partial Hypoparathyroid - low calcium Palatal defects Low IQ Increase risk schizophrenia Dysmorphic
Rx COmplete DGS
- BMT( Hla Match)
- thymus transplant
Wiskott Aldrich
X linked mutation (WASP deficiency)
Immune deficiency
Eczema
Small platelets
Increase autoimmunity
Ataxia telangiectasia
DNA repair defect
Immune defect Neuro defect ( cerbellar ataxia, chorea) Oculocutaneous telangiectasia
Low IgA
Higg AFP
ATM gene mutation
Chediak Hegashi
Immune defect
Neuro defect
Oculocutaneous albinism
Giant lysosomal granules in neutrophils
Mutation LYS7 gene
Rx HSCT
IPEX
Immune defect
Polyendocrinopathy
enteropathy
X linked
High eosinophils
Defect IL-12 and IFN gamma
Increase risk mycobacterium infection
HyperIgE
Eczema Recurrent skin infection Cold abscesses ( staph) Increase risk fungal infection ( low TH17) Lung pneumatocoeles( AD)
AD - Job syndrome, STAT3 mutation
- coarse facial features
- pneumatocoeles
- delayed shedding teeth
AR - Dock8 deficiency -autoimmune -no coarse facial features - delayed shedding primary dentition - marked viral skin infection (molluscum) Elevated IgE
