all immuno II Flashcards
10 warning sign of PID
- 4+ ear infection within 1yr
- 2+ serious sinus infection within 1yr
- 2mo+ on ABX with little effect
- 2+ pneumonia within 1yr
- failure to thrive
- recurrent deep skin or organ abscess
- persistent thrush in mouth or fungal infection on skin
- need IV ABX to clear infection
- 2+ deep-seated infection including septicemia
- family hx of PID, consanguineous marriage แต่งงานในเครือญาติ
ส่วนนี้พัง ติดเชื้อไหนได้บ้าง บ้าง บ้าง
- phagocytic defect: catalase-positive bac
- C’ defect: recurrent neisseria infection (C’5-9 form membrane attack complex)
- defect of IFN gamma / IL-12 axis: mycobacterial disease, salmonella
- defect of TLR3: herpes simplex 1 encephalitis
- CARD9 mutation: invasive candidiasis
test ทั้งหลายยยยย
- test for B cell defect or Ab def
- screening: quantitative Ig (IgG IgA IgM IgE), specific Ab titers, natural Ab (e.g. isohemagglutinin), B cell number (CD19 or CD20)
- secondary test: IgG subclass, Ab response to vaccination
- test for T cell defect
- screening: CBC and differential, T cell number (CD3 CD4 CD8)
- secondary test: PHA stimulation
- test for NK cell defect — screening: NK cell count (CD3 CD16 CD56)
- test for phagocytic defect
- screening: CBC and differential, peripheral blood smear (ดู morphology)
- secondary test: DHR 123 test (กก hydrogen peroxide)
- test for C’ defect — screening: CH50 C3 C4
combined immunodeficiency: SCID, BLS
- SCID ∼ bubble boy
- x-linked: interleukin receptor common γ chain mutation, defect T cell mature due to lack of IL-7 signal (IL-2 4 7 9 15 21) / T cell ต่ำ, normal or increase B cell (บาง type ต่ำได้), reduce serum Ig
- RAG mutation: cause VDJ recombination defect / common in leaky SCID and omenn syndrome
- ADA def: accumulate adenosine and deoxyadenosine ทำให้เกิด deoxyadenosine triphosphate (dATP) which toxic to B and T cell
- s&s: LN not palpable, small thymus, unheal BCG scar และ suscept ต่อทุกเชื้อ
- investigation: TREC absent or low, low T B cell proliferative, cxr absence of thymic shadow, LN biopsy absence of germinal center
- note: ห้ามฉีด live atten, HSCT is recommend for long-term mx, ABX prophylaxis ดี, IVIG เดือนละแสน
- bare lymphocyte syndrome type II (CD4 def): โรคที่คล้ายกันแต่ไม่หนักเท่า SCID
immunodef with other abnormalities: WAS, digeorge
- wiskott-aldrich syndrome: microthrombocytopenia, T cell defect, low IgM, abnormal actin cytoskeleton organization, มี severe eczema ร่วมด้วย / WAS mutate / tx → severe bleed may consider splenectomy เพราะเปนแหล่งทำลาย plt, HSCT
- ataxia-telangiectasia
- Digeorge: no thymus, hypoPTH lead to hypocal มาด้วยชัก, saddle bridge nose, low set ear, cardiac anomaly (prognosis depend on cardiac severity เลยย) / chromosome 22q11.2
predominantly antibody defects ออกแน่
- x-linked agammaglobulinemia (bruton disease): bruton tyrosine kinase (BTK) mutate / B cell def lead to infect encapsulated bacteria (e.g. staph strep H.influ pneumococci) เพราะไม่มี Ab คอยช่วย opsonization & clearance
- common variable immunodeficiency (CVID) aka late onset hypogammaglobulinemia: B cell growth factor receptor mutation / reduced Ig lead to suscept to bac infection / may have ass disease e.g. polyarthritis, autoimmune disease, bronchiectasis, granulomatous disease, cancer / tx IVIG monthly, ABX prophylaxis
- selective IgA def: avoid blood transfusion or FFP that contain IgA bc pt will develop IgG and IgE against IgA and have anaphylaxis (ก็คนมันไม่เคยเห็น IgA นี่)
- IgG2 subgroup deficiency: suscept to encapsulated bac and polysaccharide Ag ทั้งมวล / often ass w IgA def and CVID
- transient hypogammaglobulinemia of infancy: low level of IgG โดยปกติเด็กจะสร้างเองได้ตอนอายุ 6mo แต่เด็กที่เป็นโรคนี้จะสร้างได้ ~18mo เพราะ immune พัฒนาช้าเฉย ๆ ระหว่างนั้นก็ให้ ABX วนไปตามอาการ เดะก็หายจ้า
- hyper IgM syndrome: มีหลาย type เลยย ~ x-linked defect in CD40L is most common, AICD def, CD40, defect in class switching / ซึ่งไทป์ x-link CD40L คือเอฟเฟคไปถึง fx ของ T cell, DC, macrophage ด้วยนา / investigation → neutropenia, LN biopsy lack of germinal center
phagocytic defect: chronic granulomatous disease (CGD)
- ขา 1 ตัว cell แย่เอง: NADPH oxidase complex defect → cant produce superoxide
- ขา 2 พวกเชื้อมันร้าย: พวก catalase positive neutralize hydrogen peroxide (H₂O₂) ที่ phagocyte พอสร้างได้น้อยนิด ทำให้พวกมันถูกกิน แต่ไม่ตาย :P
- recurrent intracellular bacterial and fungal infection
- infection w catalase positive “space & bluemoon” : S.aureus, Serratia spp., pseudomonas, aspergillus, candida, E.coli, enterobacter, burkholderia, listeria, mycobacterium, nocardia
- intracellular survival of bacteria lead to granuloma formation
- DHR 123 test: คนปกติจะสามารถ oxidize DHR 123 (ไร้แสง) to rhodamine 123 (fluorescence) after PMA stimulation which detected by flow cytometry
phenocopies of IEI
* common *
- called adult onset immunodef
- autoantibody against cytokine e.g. anti-IFN gamma / suscept to atyp mycobacterium, fungi
- if tx w anti-cytokine Ab like TNF alpha inh → worsen the disease เพราะทำให้ภูมิตกกว่าเดิม
autoinflammatory syndrome
ไม่เคยออกปะ55555
- defect of inflammasome e.g. NLRP3 NOD2 IL1RN
- อจยกตัวอย่างไทป์นึง: Familial Mediterranean Fever (FMF)
- MEFV gene mutation
- symptom: recurrent fever, abdominal pain, chest pain, arthritis
- pathogenesis: mutation lead to improper regulation of NLRP3 inflammasome, causing episodes of inflammation
developmental stage, host, asexual of toxoplasma
Developmental Stages
1. tachyzoites: rapidly dividing, acute infection, sensitive to drug, extracellular phase / infected by → congenital (transplacenta) or direct contact (blood transfusion)
2. bradyzoites: slow-dividing, latent infection, resistant, intracellular phase (in tissue cyst) / infected by undercooked meat, organ transplant
3. Oocysts: Infectious form in feces of definitive host (cats) / infected by → contam food or water
Host
1. DH: Cats (sexual reproduction in intestine)
2. IH: Humans/animals (asexual reproduction in tissues)
Asexual Multiplication
- Schizogony: Multiple rounds of nuclear division before cytokinesis.
- Endodyogeny: Internal budding; two daughter cells form within a mother cell.
- Endopolygeny: Multiple daughter cells form simultaneously inside the host cell
how toxoplasma invade cell and can survive
Invasion of Host Cell
1. Active invasion without disrupting host membrane.
2. Uses micronemes, rhoptries, and dense granules for entry and parasitophorous vacuole (PV) formation.
How Toxoplasma Survives in Macrophages
- preventing fusion of parasitophorous vacuole with lysosomes.
- inh nitric oxide production and host apoptosis
tachyzoite ↔ bradyzoite / genotype
Factors Affecting Tachyzoite ↔ Bradyzoite Conversion
- Stress, immune response, cytokines (e.g., IFN-γ) favor conversion to bradyzoites. (also heat shock, mitochondrial inh, pH สูงหรือต่ำไป)
- Immune suppression/reactivation promotes tachyzoite resurgence. คือภูมิต่ำเปน tachy
Genotypes
- Type I แย้: High virulence, severe disease (common in immunocompromised), rapid growth
- Type II: Most common in Europe, milder disease.
- Type III ดี: Mild disease, zoonotic origin (slow growth, low virulence, form cyst ง่ายสุด)
- Atypical strains: Severe congenital toxoplasmosis, outbreaks.
clinical manifest of toxoplasma
“favor site: CNS, eye, skeletal and cardiac”
- immunocompetent (80-90% asymp): asymptomatic or flu-like symptoms (fever, lymphadenopathy)
- immunocompromised: CNS toxoplasmosis: headache, seizures, multiple ring-enhancing lesions on imaging
- congenital toxoplasmosis: classic triad → hydrocephalus, intracranial calcifications, chorioretinitis.
- ocular toxoplasmosis: retinochoroiditis ∼ blurred vision, floaters, scarring
dx and tx of toxoplasma
Diagnosis
1. Specific Tests
- Impression smear: Detect tachyzoites in tissue.
- Histopathology: Identify cysts/tachyzoites in biopsy.
- PCR: Detect T. gondii nucleic acids in CSF or blood.
2. Serologic Tests
- Sabin-Feldman dye test: Gold standard; detects active infection. [ทำยาก มีที่ทำน้อย]
- Immunofluorescent antibody (IFA): Measures antibody response kinetics.
- ELISA: //ใน immunocompromise อาจตรวจไม่ขึ้น
- Detects IgG (chronic infection) and IgM (acute infection).
- Avidity test for IgG: Distinguishes recent from past infection.
- Western Blot: Confirms serological findings.
3. Suggestive Evidence
- X-ray: Cerebral calcifications.
- CT/MRI: Multiple ring-enhancing lesions in the brain.
Treatment
1. First-line: Trimethoprim + Sulfamethoxazole.
2. Alternative: Pyrimethamine + Sulfadiazine (with folinic acid)
basic info PCP
developmental stage
- trophic form: attaches to host alveoli, involved in asexual multiplication
- cyst form: thick-walled, contains intracystic bodies (sporozoites) that release infectious trophic forms, sexual reproduction
pneumocystis as an atypical fungus
- Lacks ergosterol (target of many antifungal drugs).
- Genetically related to fungi but has protozoa-like features.
- Obligate extracellular organism.
transmission & incubation period
- transmission: airborne, person-to-person
- incubation: wk to mo (varies by immune status)
PCP pathogenesis
Pathogenesis
1. pneumocystis attache to alveolar epithelial cells using glycoproteins //major surface glycoprotein
2. disrupts gas exchange via damage to alveolar-capillary barrier
3. causes alveolar inflam, with a foamy, proteinaceous exudate
4. leads to hypoxia due to impaired oxygen diffusion
Pneumocystis-Host cell interaction
- bind to Type I pneumocytes and evades host immune responses
- Recruits immune cells (macrophages, CD4+ T cells), causing inflammation.
- CD4+ T-cell depletion (e.g., HIV) results in unchecked proliferation.
HIV and non-HIV in PCP
- HIV: CD4+ count <200 / gradual onset / rare extrapulmonary PCP / fewer inflam response
- non-HIV immunosuppression: organ transplant, chemotherapy, corticosteroid use / rapid progress / extrapulmonary PCP is more common / severe inflam ทำให้ตายง่ายกว่า
clinical manifest in PCP
- pulmonary symptoms: progressive dyspnea, dry cough (non-productive), fever / sign → hypoxia disproportionate to radiographic findings
- extrapulmonary: affect liver, spleen, BM, skin, LN / rare ∼ seen in severely immunocompromised pt
PCP patho n radio
pathology
- alveolar spaces filled w foamy exudate containing organism //honeycomb pattern of alveolar exudate
- interstitial inflam and thickening
radiographic
- typical findings: diffuse, bilat interstitial infiltrate (ground-glass opacities)
- atypical findings: cavitation, nodules, pneumothorax, pleural effusion (less common)
lab dx PCP
- microscopy: detection of organisms in induced sputum, BAL (bronchoalveolar lavage), or tissue biopsy — using special stains such as Giemsa, Gomori methenamine silver (GMS), calcofluor white
- molecular tests: PCR for Pneumocystis jirovecii DNA (high sensitivity)
- Beta-D-glucan assay: Nonspecific fungal marker (elevated in PCP).
candidiasis (focus on disease)
- disease
- cutaneous candidiasis: satellite lesion ตามที่เคยเรียนใน integ
- oropharyngeal candidiasis: white plaque on mucous membrane
- angular cheilitis แผลที่มุมปาก
- esophageal candidiasis
- oropharyngeal-esophageal symptom: white patch, red or sore, pain while eat or swallow
- pathogenesis: higher fungal load → switch btw yeast to hyphae → hyphae induce cytokine (IL-1α and IL-6) → also 1β, macrophage which further stimulate TH17 cell
- virulence factor: adhesin → adherence to epith, fibronectin, biofilm establish / phenotype switching → conversion to more virulent form, evade host response
- risk factor: immunocompromise → HIV, T cell defect, aerosolized steroid use / hyposalivation → from drug like antipsychotic, sjogren, radio or chemotherapy / poor oral hygiene / denture → plaque on denture harbor C.albicans / missing teeth → กัดปากเปนแผล increase risk for angular cheilitis / smoke / ABX use / vitB12 or iron def
invasive candidiasis
- consisted of candidemia, deep-seated tissue candidiasis (เช่นตับม้าม)
- risk factor of invasive candidiasis: neutrophil abnormality / impair cutaneous barrier (burn) / immunocompromise → T cell deplete, transplant, solid neoplasm, granulocytopenia, corticosteroid, hematologic malig / impair gut wall integrity → abd surgery, chemo, recurrent intestinal perforate, ascites, mucositis, severe pancreatitis, parenteral nutrition / prolong IV cath / broad or multiple ABX
candidiasis investigation and tx
investigation
- wet mount: budding yeast w pseudohyphae
- อื่น ๆ: KOH/+-calcofluor white stain, gram stain, GMS, culture, microscopic morphology from cultured colonies
- ไว้แยก candida albicans & ตัวอื่น
- germ tube test / reynolds braude phenomenon
- chlamydoconidia/chlamydospore production: using cornmeal agar or glutinous rice agar for enhance chlamydospore formation
- CHROMagar
- automatic yeast biochem test
- serology: (1→3)-β-d-glucan (BG) which positive with candida fusarium trichosporon saccharomyces acremonium P.jiroveci
tx for
- oral candidiasis: ไม่หนักมากใช้ topical clotrimazole, miconazole, nystatin / เริ่มหนักใช้ oral fluconazole
- esophageal candidiasis: oral fluconazole (if refractory to fluco can be use itra or vori instead)
- invasive candidiasis: echinocandin**, fluco, isa, vori
cryptococcosis
- neoformans 🕊️/ gattii 🐨อันนี้คนปกติติดได้
- pathogenesis: inhale spore or yeast cell → pulmonary infect → crytococcal meningitis
- can harm many organ e.g. pulmonary, cutaneous, osseous, ocular, esp in CNS**
- risk factor: defective cell-mediated immunity pt, severe HIV, organ transplant, reticuloendothelial malig, corticosteroid tx
- C.neoformans vs C.gattii ขอพิมพ์แค่ neoformans ที่เหลือก้กลับด้านจ้า: main host → immucompromise / involve CNS>lung / less complication / suscept to fluconazole / tx response is good :)
- investigation: CNF analysis, india ink, CSF culture, cryptococcal Ag from blood or CSF
- pathophysio: trojan horse, transcytosis, paracellular crossing
- virulence factor: melanin, polysaccharide capsule
- tx (esp in HIV pt)
- induction phase: ampho B, flucytocine, fluconazole (มี 3 regimen แต่ยาที่ใช้วน ๆ แค่นี้)
- consolidation phase: fluco
- maintenance phase: fluco (lower dose)
talaromycosis 🐁🎋
- Talaromyces marneffei (Penicillium marneffei)
- transmission: breathing from bamboo rats and their burrows — “ภาคเหนือ โพรงป่าไผ่ หนูอ้น”
- clinical feature: fever, anemia, weight loss, skin lesion, lymphadenopathy
- dx
- direct examination (yeast form): wright stain, giemsa, GMS // finding → oval to elliptical, fission yeast w distinctive clear central septum, intracellular (in macrophage) or extracellular, may elongated as sausage-shaped
- culture (25°c mold form) use specimen from blood, scraping, pus, biopsy
- tx: induction phase → ampho B / consolidation phase or prophylaxis → itra
histoplasmosis 🦇
- ติดไม่ติด หนักไม่หนัก depend on host status and loading (ปริมาณเชื้อ)
- risk factor: immunocompromise ทั้งหลายย ~ infant, AIDS w CD4<150, immunosuppressive use, hematologic malig, solid organ transplant, pt who require TNF-anta
- progressive disseminated histoplasmosis
- after exposure → histoplasma may remain dormant and reactivation อาจเกิดได้หลังจากนั้นเปนปี ๆ
- symptom: acute → fever, worsen cough, weight loss, malaise, dyspnea / subacute → wide spectrum makkk in GI CNS บลา ๆ / chronic → constitutional symptoms
- favor adrenal gland — cause primary adrenal insuff ที่เจ๋งคือเวลาเจอ addison เลยควรเฉี่ยน infection cause ไว้ด้วย
- pathogenesis: inhale of micronidia mycelium → spread via lymphatic to RE system → incubation period vary makk depend on degree of host immune and inoculum size
- dx
- direct examination: tissue biopsy (from LN, BM..) wright stain , GMS // finding → oval, budding yeast, intracellular (in macrophage) or extracellular
- culture: blood or tissue culture
- tx: induction phase → ampho B / consolidation phase or prophylaxis → itra
symptom asper ไข้ไอหอบ
- allergic bronchopulmonary aspergillosis (ABPA): similar to asthma, wheezing, shortness of breath, cough
- aspergilloma (fungus ball): cough, coughing up blood, shortness of breath
- chronic pulmonary aspergillosis: เหมือนอันบนแต่ + weight loss, fatigue
- invasive aspergillosis: fever, chest pain, cough, coughing up blood, shortness of breath, other symptoms (when spread from lung to other parts e.g. crust at nasal septum)
host factor for invasive fungal infection
- recent hx of neutropenia (<500) for 10 days related to onset of fungal disease
- hematologic malig which active or remission in recent past (not AA)
- receipt allogenic stem cell transplant / solid organ transplant
- prolong using corticosteroid
- tx w other recognized T cell immunosuppressant e.g. cyclosporin, TNF-a inh
- tx w B-cell immunosuppressant e.g. BTK inh
- inherited severe immunodef (CGD, SCID) also CARD9, STAT3 defects
- aGVHD grade III or IV refractory to steroid tx
virulence factor (divided from pathogenesis)
- entry: thermotolerance, stress response, morphology
- adhesion: adhesin, biofilm, sialic acid
- acquire nutrient: extracellular enz, siderophore
- avoid host immune response: catalase (antioxidant enz), cell wall, melanin, dimorphism
- replicating: genetic adaptation, genomic plasticity, thermotolerance, stress response, biofilm
- disseminating (angioinvasion): adhesin, hydrolytic enz, phenotype switching
- transmitting (close contact, carrier, fomite): phenotype switching, its morpho, hydrolytic enz, stress response
- secondary metabolite: ราสร้าง ไม่มีประโยชน์กับมัน แต่มีโทษกับมนุด e.g. gliotoxin (induce host cell apoptosis, epith cell damage, inh phagocyte n oxidative burst, inh T-cell response)
- มันมี galactosaminogalactan (GAG) ทำให้เราไม่สามารถกำจัดเชื้อได้ เพราะมันบัง β-glucan, induce neutrophil apoptosis อี้ก
pathogenesis and host immune response of asper
pathogenesis มี 2 ขาหลัก ๆ (ก่อนหน้านั้นหายใจเอา conidia aka spore เข้าไป ละมันจะ invade สร้างความเสียหายไปเรื่อย ๆ)
- corticosteroid-induced immunosuppressant: PMN recruitment and tissue damage ตู้ม ๆ
- neutropenia: excessive hyphal growth and dissemination
host immune response
- น่าจำคือ dectin1 ของเราจับกับ β1,3-glucan ของมันได้ กระตุ้น innate ทำให้ cytokine รุม ๆๆ
dx invasive asper by EORTC2020 guideline
- host factor ขอไม่กล่าวซ้ำ ตามต้อกนั้น
- clinical feature: fever refractory to ABX / chest pain, hemoptysis, dyspnea / sinusitis w black necrotic lesions / CNS symptoms (seizures, focal deficits)
- imaging (CT): lung nodules w halo sign (early) / air-crescent sign (late phase) / cavitations or consolidation
- microbio: direct evidence → aspergillus in sterile site (e.g. lung biopsy) / indirect evidence → positive galactomannan (serum or BAL), positive β-D-glucan (serum)
- culture and histopatho: hyphae with acute-angle, septate branching / positive culture from sterile site or BAL fluid
category of dx: proven ข้อ 5 / probable ข้อ 1 2 4 / possible ข้อ 1 2
รวมมิตร asper อย่างละนิดละหน่อย
- morphology: vesicle ผลิต conidia (กลม ๆ ปลายสุด) เป็น asexual spore
- investigation
- KOH prep w calcoflour white stain from BAL คือสารนี้จะไปจับกับ chitin แล้วเรืองแสง
- culture ด้วย BAL อาจ false neg เพราะตรวจ non-invasive ไม่ได้ / EIA ใช้ดู galactomannan (GM), β-D-glucan (BDG) / PCR, real-time PCR แพง ไม่ใช่รูทีน
- tx: voriconazole (first-line), isavuconazole
clinical manifest (เน้น rhinocerebral mucormycosis)
- start w blood vss invasion → ischemia and arterial thrombosis → tissue infarc and necrosis
- clinical manifest depend on location of involvement: rhinocerebral disease, pulmonary disease, cutaneous disease which mostly following injury or burn, GI disease
pathogenesis mucor
- spore inhale or inoculate ที่ผิวหนัง
- ควรมี macrophage and neutrophil มาช่วยจัดการ แต่ถ้า prolong glucocorticoid using or neutropenia จะเอาเชื้อไม่อยู่
- neutrophil attack hyphal form & ยึดเหล็ก แต่ถ้า prolong glucocorticoid using or neutropenia or hypergly or iron overload เชื้อจะยังโตได้ เพราะเรากาก ;-;
- angioinvasive growth in tissue w hemorrhage, thrombosis, necrosis
- disseminate อะเฮือก
- pt w DKA: เชื้อจะ favor จมูก ปอด เพราะมี GRP78 (express มากขึ้นใน hypergly ซึ่งอยู่แถวจมูก) & CotH3 (fungal protein) พอจับกันก้เข้าเซลล์ invasive มันส์เลย
- immunocompromise: favor ที่ปอดอย่างเดียว เพราะ CotH3 ไปจับกับ α3β1 at alveoli
- อจไม่เน้นแต่อ.กรวลีเขียนไว้ FTR1 ช่วยหาเหล็กให้รา
host predisposing factor mucor
- neutropenia
- immunosuppressive tx
- hemato malig
- BM or solid organ transplant
- DM pt esp w ketoacidosis
- iron overload
- tx w deferoxamine (เพราะยาจับกับ free iron อยู่ แต่ mucor ไปขโมย iron มา ‘deferoxamine acts as a fungal siderophore’
