Immunology Flashcards
What are secondary causes to consider when thinking of PID
Meds:
- steroids
- chemotherapy
- “natural”
Infections
- HIV
- TB
- Herpes group viruses
- Measles
Structural
- anatomic
- impaired membrane integrity
- immotile cilia
- CF
- indwelling cath
Malignancy:
- Hodgkin’s
- leukemia
- solid tumor
- myeloma
Other:
- diabetes
- renal insufficiency/dialysis
- hepatic insufficiency
- malnutrition
- GERD with aspiration
What is the most common category of PID?
Most common:
Humoral deficiencies: 65%
Combined deficiencies (cellular and humoral): 15% Phagocytic deficiencies: 10% Cellular deficiencies: 5% Complement deficiencies: 5%
What are the features of T cell Immune defects
Age: 2 - 6 mon
Bacteria: Gram + and -, mycobacteria
Virus: CMV, EBV, Paraflu
Fugi: Candida, PJP
Affected organs: Sinopulmonary, FTT, diarrhea
Associated features: Omenn syndrome, disease post -BCG or VZV vaccine
What are the features of B cell immune defects
Age: > 6 mon (after maternal Ig gone)
Bacteria: Encapsulated (strep, Hemophilus)
Viruses: Enterovirus in XLA
Fungi: Giardia, Cryptosporidium
Affected organs: sinopulmonary, GI, arthritis, meningoencephalitis
Associated features: Autoimmune, lymphoma
What are the features of phagocytic immune defects
Age: early onset
Bacteria: Staph, Pseud, Serratia
FungI: Candida, Aspergillus
Affected organs: Abscesses, mouth ulcers, osteo
Associated features: delayed cord separation, poor wound healing
What are the features of complement immune defects
Age: any age
Bacteria: Pneumococcal, Meningococcal
Affected Organs: Septicemia, meningitis
Associated features: autoimmune
What are the 10 warning signs of Primary Immunodeficiency
- 4 or more new ear infections w/n 1 yr
- 2 or more serious sinus infections w/n 1 year
- 2 or more months on abx with little effect
- 2 or more pneumonias w/n 1 yr
- Failure of an infant to gain weight or grow normally
- Recurrent deep skin or organ abscesses
- Persistent thrush in mouth or fungal infections on skin
- Need for IV abx to clear infections
- 2 or more deep seated infections including septicemia
- A family hx of PI
Clues on History for a PID
Infection:
- number, frequency, age, severity
- unusual pathogens?
- treatment required? IV? hosp?
Autoimmunity:
- cytopenias
- colitis
- arthritis
Malignancy FTT Eczema - especially if refractory to txt Delayed separation of the umbilical cord Reactions to live viral vaccines Positive FHx: cosang, infantile deaths, affected maternal uncles
Clues on Physical for PID
FTT Dysmorphic Absent tonsils/CLN Scared TM Oral Thrush Lung disease (pneumonia, bronchiectasis) Splenomegaly Skin: fungal skin/nail infections, eczema, chronic warts/molluscum, abnormal nails
What do you expect on CBC for pts with PID
Lymphs
- increased in some malignant conditions
- reduced in many primary/secondary immune def.
Neuts
- increased in some phagocytic diseases
- Reduced in autoimmunity and BM failure
Eosinophils
-increased in atopic diseases
Platelets
- increased in inflammatory conditions
- reduced in autoimmunity and WAS
How do you do a Humoral Assessment
Look at number:
- Quantitative Ig levels (IgG, IgA, IgM, IgE)
- Lymphocyte subsets: evaluate B cell numbers (CD19+ cells)
Function:
- specific abs to antigen which the patient was exposed through vaccination or disease (diptheria, tetanus, measles, mumps, rubella, varicella, EBV, CMV, pnumococcal)
- Isohemagglutinin (IgM) to Blood group A or B
How do you do a Cellular Assessment
Number
- lymphocyte subsets
- evaluate CD4 and CD8 cells
Function:
- lymphocyte proliferation in response to mitogens and antigens (mitogen stimulation assay testing)
- Adenosine deaminase and purine nucleoside phosphorylase level
- T-cell receptor excision circles (TRECs)
How do you do a Phagocytic assessment
Number:
Neutrophil Counts
Function:
- Nitroblue tetrazolium test (NBT) or neutrophil oxidative burst index (NOBI)
- measurement of adhesion markers: CD11 and CD 18 (specialized testing)
How do you do a Complement Assessment
Number:
- C1 esterase inhibitor levels
- Specific complement levels
Function:
- Total hemolytic complement (CH50)
- alternative pathway (AH50)
- C1 esterase inhibitor function
List 3 types of Humoral (Antibody) Immune Deficiencies
- X-linked agammaglobulinemia (XLA)
- Common variable immune deficiency (CVID)
- Transient hypogammaglobulinemia of infancy
What is X-linked Agammaglobulinemia
- Absent B lymphocytes in peripheral blood
- No B cells = No lymphatic tissue!! (no LN or tonsils on PE)
- No immunoglobulin produced
What is the gender, age range of pts with XLA and what kind of infections do they get?
Gender - Male
Age: 6 - 24 months (when protective maternal IgG disappears
Infections: Sinopulmonary, OM, GI, arthritis, meningitis, sepsis. Encapsulated bacteria (S. pneumo, H. influ) and enteroviral meningoencephalitis
What lab features are seen in XLA
- absent B cells <2 % of lymphocytes
- absent IgG, IgA, IgM
- absent Abs to vaccines
How do you manage XLA
- Abx txt of infections
- IgG repacelment for life (monthly IV or wkly SC). Monitor trough IgG levels aim for lower limit
- follow PFT and CT chest - at risk for bronchiectasis
- genetic confirmation and gentic counselling
What is Common Variable Immunodeficiency. What are the clinical features
- most common humoral PID
- heterogenous disorder (variable)
- adults but also peak in first years of life
-presence of lymphatic tissue
Clinical Features:
- Autoimmunity:
- cytopenia, IBD/pangastritis, small bowel nodular lymphoidhyperplasia, arthritis, granulomas (lung, liver spleen skin), thyroiditis - Malignancy
- increased incidence of lymphoreticular and gastric malignancies - Recurrent infections
What kind of infections occur in CVID
recurrent bacterial and sinopulmonary infections:
-H. flu, S. pneumo = bronchietctasis and fibrosis in lungs
mycoplasma
enterovirus
giardiasis
How do you manage CVID
- similar to XLA
- Abx txt
- Immunoglobulin replacement for life
- Monitor for autoimmunity and malignancy
What are Combined Immune Deficiencies and list 6
Abnormalities in T and B cell development and function
(in some the humoral deficiency can be related to inability of T cells to instruct B cells)
- severe combined immunodeficiency (SCID)
- Wiskott-Aldrich Syndrome (WAS)
- Ataxia Telangiectasia (AT)
- Hyper-IgM syndrome
- X-linked Lymphoproliferative Disease
- Cartilage Hair Hypoplasia
What are the features of SCID
- present by 2 - 6 months of age (die by 1 yr unless txted)
- Medical emergency
- Persistent, recurrent, severe opportunistic infections: (bacterial, fungal and viral, sinopulmonary, oral thrush, chronic diarrhea)
- all lead to FTT
- absent LN and tonsils
What are the lab features of SCID
Number:
- lymphopenia
- severely reduced T cell numbers
- B and NK cell numbers can be low, normal or elevated
Function:
-low or absent T cell function
(lymphocyte proliferation in response to mitogens and antigens)
-absent Abs to vaccines
What is the management of SCID (6)
Treat and prevent infections:
- aggressive antimicrobial therapy
- Immunoglobulin replacement therapy
- PJP prophylaxis
- CMV negative irradiated blood products
- Strict protective isolation
Most important
-new immune system = BMT
Features of Wiskott-Aldrich Syndrome
X-linked condition with triad of:
- Thrombocytopenia
- Eczema
- Recurrent pyogenic infections in infancy
- Watery/blood diarrhea & petechiae in first months
- bacterial infection with encapsulated organism
What are the lab features of WAS
Number:
- Thrombocytopenia
- Low IgM, variable IgG, high IgA, high IgE
Function:
- poor ab response to vaccines
- decreased T cell function
Management of WAS
- Immunoglobulin replacement therapy
- Abx proph
- BMT
What are the features of Ataxia Telangiectasia (5)
- Autosomal Recessive
- Ataxia (cerebellar)
- starts around 18 months of age
- wheelchair by teenage years - Telangictasia
- prominent on face, conjunctiva, ear lobs
- appears at 2 - 4 yrs of age - Progressive neurodegeneration
- Immune deficiency
- not as clinically significant
- Can have recurrent sinopulmonary infections and bronchiectasis
Lab features of Ataxia Telangiectasia?
Number:
- increased AFP
- decreased T cell numbers
- Absent IgA in 80%
Function:
- decreased T cell function
- Can have poor Ab response to some vaccines
What investigation must you avoid with pts with AT
- avoid X-ray and CT
- cells have increased sensitivity to irradiation
How do you manage AT
- supportive, BMT not possible
- Immunoglobulin replacement therapy in those with demonstrated humoral deficiencies
- watch for malignancy: 15% may develop malignancy especially lymphoma
What are the features of DiGeorge Syndrome
-cellular deficiency
CATCH 22:
- cardiac defects, abnormal facial features, thymic hypoplasia, cleft palette and midline abnormalities, hypocalcemia, 22q.11 deletion (3rd & 4th pharyngeal pouch)
- FTT
- developmental delay
- Psychiatric issues (Schizophrenia)
What are the facial features of DiGeorge
- hooded eyelids
- bulbous nasal tip
- hypertelorism
- low set prominent posteriorly rotated ears
- notched pinnae
- reduced helix formation
- migrognathia
- short philtrum
- bifid uvula
- high arched palate
What are the Lab features of DiGeorge
Number:
-mildly reduced CD4+ and CD8+ T cells (improves with age)
Function:
- normal or mildly reduced T cell function
- may have poor Ab response to vaccines (uncommon)
Management of immune defects in DiGeorge
- most only have mild T cell deficiency which improves with age
- some have severe T cell deficiency (treat like SCID)
- blood products should be CMV neg and irradiated
- Should not receive live viral vaccines until immune competence demonstrated
List 3 Phagocytic Immune Deficiencies
Chronic Granulomatous Disease
Hyper IgE Syndrome (Job’s)
Leukocyte Adhesion Defects (LAD)
List 2 innate Immune Deficiencies
IRAK4 Deficiency
Mendelian susceptibility to myocbateria
What are the features of Chronic Granulomatous Disease
Defect in NADPH oxidase
-required for effective phagocytic killing of certain pathogens
65% X-linked
-remainder are AR
- recurrent bacterial and fungal infections since infancy
- Abscesses and granulomas (skin, LN, lung, liver, GI, GU with bladder obstruction)
- inflammation and colitis
What organisms are pts with CGD susceptible to? (6)
Catalase positive pathogens
- S. aureus
- Aspergillus
- Nocardia
- Serratia marcescens
- Burkholderia cepacia
- Salmonella
What are the lab features of CGD
Number:
normal or increased neutrophils
Function:
-Abnormal NOBI or NBT
What is the Management of CGD
- Aggressive abx for current infections
- Antibacterial and antifungal proph
- Anti-inflammatory txt (for colitis)
- BMT
- Genetic Counselling
What are the features of Hyper IgE Syndrome (Job’s) (6)
- AD mutation in STAT3 OR AR in Dock8
- Recurrent abscesses in skin, joint, lungs
- ‘cold boils’ (no pain, heat or erythema)
- S. aureus - Eczema
- Coarse facial features
- Delayed shedding of teeth
- Bone fractures, scoliosis, joint hyperlaxity
What is the management of Hyper IgE syndrome
- treat infections
- anti-staphylococcal prophylaxis (Cotrimoxazole)
What are the lab features of Hyper IgE Syndrome
Number:
- Very high IgE (> 20,000) (not required to be high to have hyper IgE)
- Eosinophilia
Function:
-can have poor antibody response to vaccines
What is the features of Leukocyte Adhesion Defects
-very rare
-deficiency in adhesion molecules:
Abnormal neutrophil migration and penetration into tissue
Neutrophils remain in the blood, unable to migrate to site of infection
-delayed separation of umbilical cord > 4 wks
-staphlococcal infections: dental gingivitis, intestinal
Laboratory Features of LAD
Number:
-Neutrophilia: Can be > 100,000 even when no infection
Function:
-absent surface adhesion molecules CD11 and CD18
What is the management for LAD
- Antibiotics
- Bone Marrow transplant
What are the defects in early (C1, C2 and C4) components
What are the defects in late (C5 - 9) components
C1, C2 , C4:
Rheumatic disease, lupus, infections rare
C5 - C9
invasive neisserial and pneumococcal infections
What is the management for complement deficiencies
- Abx prophylaxis
- Immunizations (meningococcal & pneumococcal)
What are the lab features of complement deficiencies
Number:
- normal C3, C4 (don’t send)
- measuring other specific complement levels only done in specialized labs
Function:
- Abnormal CH50 (total hemolytic complement)
- check if alternative pathway (AH50) if CH50 normal and still suspect complement deficiency
