infection Flashcards
Mendelian susceptibility to mycobacterial disease (MSMD)
defects in IFNgamma and IL12 pathway -> impaired production of / impaired response to IFNgamma
leads to increased susceptibility to mycobacteria
immunodeficiencies predisposing to mycobacterial infection (6)
congenital: MSMD, NEMO, ectodysplasia w hyper IgM (impaired NFkB signalling)
acquired: HIV, anti-TNF antibodies
maturational i.e. immune system immature as child
mechanism of genetic predisposition to invasive pneumococcal disease (IPD)
IRAK4-MyD88 mutation-> loss of TLR function (except TLR3) -> loss of TNF and IL-1beta signalling
TLRs crucial in protection against invasive infections by pyogenic bacteria
mechanism of genetic predisposition to herpes simplex encephalitis
Unc93b1 / TRIF mutation -> loss of normal TLR3 signalling -> loss of IFN
dsRNA (e.g. HSV1) -> TLR3 (important in protection against viral infection)
innate immunity: physical and chemical barriers
Physical barrier: skin, cilia of respiratory tract
Chemical barrier: lysozymes/defensins in mucosal secretions, pH of stomach/vagina (↑oestrogen in pregnancy → ↑lactobacillus → further ↓pH)
which cytokines are anti-inflammatory and which are pro (8)
pro-inflammatory: IL-12, IL-8, TNF-α, IFN-γ, IL-1
anti-inflammatory: IL-10, IL-4
IL-5 is mixed
cytotoxic T cells vs helper T cells
both CD3+
Cytotoxic T cells (CD8+)
1. destroy cells containing intracellular pathogens (virus)
2. recognise targets by binding to antigen-MHC class 1
T helper cells (CD4 +)
1. assist other leukocytes w immune response
2. activated when presented w antigen by MHC class 2
a. Th1 → activation of cytotoxic cells (regulated by IFN-γ)
b. Th2 → maturation of B cells into plasma cells
MHC class I vs II
MHC class I (HLA A, B and C)
- present on all nucleated cells (i.e. not RBCs)
- presents epitopes (of non-self) to cytotoxic T cells (CD8+) → apoptosis (if recognised) ∴ kills cell which contains intracellular pathogen
MHC class II (HLA DP, DM, DOA, DOB, DQ, DR)
- expressed on APCs (B cells, macrophages, dendritic cells)
- take up antigen, process and present part of antigen as epitope on APC’s surface within MHC class II molecule
- bind to naïve T helper cells Th0 (CD4 cells) → activation depending on local environment and cytokines produced by APC ∴ can aid cell death (Th1, Th17), antibody production (Th2), or immune tolerance (T-reg)
active vs passive immunity
Passive immunity: immunoglobulins directly given
Active immunity: small part of antigen given → activates immune response
central vs peripheral tolerance
Central tolerance: destruction of self-reactive T or B cells before they enter circulation
Peripheral tolerance: destruction/control of any self-reactive T or B cells which do enter circulation
signals required for adaptive immune response activation (3)
- Antigen recognition
- Co-stimulation
- Cytokine release
risk factors for non-tuberculous mycobacterial infection (4)
rarely causes disease in immunocompetent hosts
- Immunodeficiency; primary/acquired e.g. immunodeficiency (HIV)
- Central venous catheters
- Solid and hematopoietic stem cell transplant → disseminated disease (due to strong immunosuppression)
- Cystic fibrosis and Mendelian susceptibility to mycobacterial disease (MSMD)
timeline of TB infection
- Innate response: macrophages, neutrophils engulf bacteria
- Acquired response: bacteria become contained within granulomas
- Latent infection: bacteria reside within granulomas in non-replicating state
Can survive in this way for entire lifetime; may be completely asymptomatic
1/3 population are latently infected - Reactivation of disease can occur
Immunocompromised pts: acquired response insufficient → primary active TB disease (fever, night sweats, weight loss)
immune response to TB
- Macrophages:
a. Activated by Mtb binding to PRRs
b. Phagocytosis of bacteria and fusion with lysomes
c. Growth inhibition and killing by NO - Formation of granulomas; multi-nucleated giant cells
T cells surround and hold structure together, enclosing mycobacterium
TB evasion of host immune defences (4)
- Genotypic/phenotypic diversity between strains
- Resistance to microbiocidal mechanisms in phagocytic cells e.g. NO
- Subversion of intracellular pathway: inhibition of phagosome maturation, phagosome-lysosome fusion and/or acidification
- Subvert induction of pro-inflammatory cytokines
diagnostic tests for TB (6)
- tuberculin skin test (Mantoux)
- culture for acid-fast bacilli
- IGRAs (interferon-gamma release assays)
- Microscopic observation drug susceptibility testing (MODS)
- GeneXpert
- Lipoarabinomannan (LAM)
tuberculin skin test
how it works
advs + disadvs (2)
Intradermal injection of tuberculin (containing >200 Mtb Ags) into forearm
If prev exposure to Mtb, inflammation (redness, swelling) will occur due to primed T cells in immune system
1. Poor specificity; does not distinguish between active TB disease, latent TB infection, BCG and environmental mycobacteria
2. Poor sensitivity; can be falsely negative in early infection, immunocompromised
culture for acid-fast bacilli
how it works
advs + disadvs (2)
Using sputum, gastric washings or bronchioalveolar lavage (difficult to obtain in children)
Mycobacteria have mycolic acid in cell wall ∴ take up carbol-fuschin stain (pink) and resist decolourisation w acidified alcohol
1. Culture takes 4-6 weeks
2. Children are often paucibacillary (numbers of bacteria too low)
interferon-gamma release assays
how it works
advs + disadvs (4)
Measures host immune response to mycobacterial antigens
- More specific than tuberculin, but does not distinguish between infection and disease
- Technically challenging
- Expensive
- Venepuncture required; difficult for children
Microscopic observation drug susceptibility testing (MODS)
how it works
advs + disadvs (4)
Sputum: decontaminated → culture in broth (8-15 days) → inverted light microscope
- Sensitive
- High specificity
- Low cost
- Can determine antibiotic susceptibility at the same time
lipoarabinomannan testing for TB
how it works
advs + disadvs (2)
Based on identification of LAM in cell wall of mycobacterium tuberculosis
Secreted in urine; test uses lateral flow dipstick
1. 30 minutes
2. Poor sensitivity in children
differences to consider when treating children for TB (vs adults) (5)
- Most drug studies done in adults ∴ little evidence for what is effective for children
- Dose adjustment needed frequently due to growth
- Compliance issues
- Often treat w/o culture confirmed diagnosis
- Metabolism and excretion differs from adults due to large liver to body ratio
life cycle of HIV (7)
- Virion attaches to CD4 receptor and CCR5/CXCR4 co-receptor
- Virion fuses w human cell membrane releasing viral content
- Reverse transcription of viral RNA into dsRNA
- Viral DNA integrated into human genome
- Human machinery hijacked for replication
- Assembly and repackaging: capsid of virion cleaved by protease
- Viral release
HIV timeline of infection
which cells does it infect + consequences of this
- HIV targets and causes depletion of CD4 T cells →
a. ↓CD4 priming of B cells for Ab production
b. ↓recruitment of CD8+ CTL which destroy infected cells
c. Eventual decline in CD4 T cells → ↑viral → AIDS - HIV also infects macrophages (which are also targeted by TB)
clinical features of HIV (6) + AIDS (5)
- Respiratory disease
- Encephalopathy
- GI symptoms & wasting
- Recurrent URTI’s
- Recurrent oral thrush
- Hepato-splenomegally / lymphadenopathy
AIDS: - Pneumocystis pneumonia (pneumocystis jiroveci)
- HIV
- Encephalopathy
- Cytomegalovirus
- Multisystem abscess: submandibular abscess, severe wasting, developmental delay
paediatric HIV diagnosis
- HIV DNA PCR or HIV viral load (RNA) < 18 months
2. HIV Ab > 18 months; can be done after mother’s Abs have depleted
management of paediatric HIV (4)
- Start combination ART as soon as possible, before any symptoms (earlier ART → better long term outcomes incl. growth and neurocognitive outcomes)
- Protect from opportunistic infections e.g. PCP, CMV, mycobacteria etc.
- Protect CNS from HIV
- Work w mother to convince her of need to look after own health as well as baby’s
antiretrovirals (4) + recommended combination
Usually start w 2 nucleoside RTIs and 1 other class
1. Fusion inhibitors e.g. efurvitide / maraviroc
2. Nucleosides RTIs e.g. ZDV
or Non-NRTIs e.g. nevirapine
(Target reverse transcription of RNA → DNA)
3. Integrase inhibitors e.g. raltegravir
4. Protease inhibitors e.g. lopinavir, darunavir (inhibit cleavage of polypeptides and assembly)
disadvantages of ART (5)
- Lifelong ART
- Toxicity
- development of resistance
- expensive
- Does not cure HIV, as viral genome integrated into host cells; leaves latent reservoir that can still be reactivated and cause disease
Difference in quality of life w eradication vs remission; no longer HIV infectious, no need for viral load monitoring
future strategies for HIV Tx (2)
- Therapeutic HIV vaccination
- Introduce HIV resistant cells
a. Transfuse cells without CCR5 (co-receptor for HIV T-cell binding)
b. Bone marrow or cord blood transplantation
how does HIV increase susceptibility to TB (3)
- Depletion of T cells → ↓INFγ → ↑risk of latent TB reactivation and susceptibility to new infection
- Upregulation of Mtb entry receptor CD14 on macrophage
- Loss of macrophage oxidative burst capacity
how does TB increase susceptibility to HIV (3)
- ↑expression of HIV co-receptors CXCR4 and CCR5
- Mtb survives in dendritic cells and compromises antigen-presenting function
- Enhances HIV replication in the lung and infected T cells and macrophages
prevention of HIV-TB co-infection
- Use rapid test GeneXpert for diagnosis of TB in HIV pts
- If TB contact, prioritise HIV pts for TB evaluation
- Infection control for TB
- Isoniazid preventative therapy for HIV pts in areas w high TB prevalence
what is immune reconstitution inflammatory syndrome
risk factors
treatment
Characterized by transient severe inflammation and immunopathology directed at opportunistic infections (not HIV or TB) shortly after initiating ART
1. Rapid restoration of CD4 T cells leading to exaggerated immune responses
2. Short interval between initiation of TB drug and ART
a. Early ART → risk of IRIS
b. Deferred ART → risk of HIV disease progression
c. Choice dependent on severity of disease and CD4 count
3. Dissemination of TB to extrapulmonary sites (higher antigen load)
Treat w prednisolone
differences in how RNA and DNA viruses escape immune recognition
RNA viruses escape immune response by mutating so that no longer recognised by T/B cells
DNA viruses enter host cells and shut down host immune response
how can viruses be classified
- family, genus
- RNA vs DNA
- enveloped vs non-enveloped
- infection type
lytic vs non-lytic viral replication
- Lytic: build-up of viruses in cell until cell bursts and viruses released (usually RNA virus strategy as needs to be done rapidly)
- Non-lytic: produce smaller numbers of viruses by envelopment and spread from cell to cell
how do viruses cause disease (3)
- Direct pathology e.g. smallpox, ebola
a. Lesions caused by viruses killing cells
b. Ebola destroys cells lining blood vessels → haemorrhage and mortality - Immunopathology: damage done by immune response
- Oncogenesis: viruses prevent apoptosis e.g. HPV, EBV (infects and prevents apoptosis of WBCs)
antigenic drift (2) vs antigenic shift (4)
antigenic drift: minor changes, point mutations, slow process
antigenic shift:
1. multiple alterations in antigenic makeup
2. Reassortment of genome segments
3. Rapid process
4. Associated w pandemic outbreaks e.g. H1N1
coat proteins of influenza (2)
- Haemagglutinin (H): gets virus into cells (15 subtypes)
2. Neuraminidase (N): gets virus out of cells (9 subtypes)
prevention of flu (6)
- Good hygiene
- Vaccination of man or vectors
- Animal slaughter (zoonotic): impractical, unethical?
- Quarantine
- Anti-virals e.g. M2 inhibitor rimantidine
- Anti-inflammatory drugs
what is immunopathology
evidence
Immune response sometimes outweighs what is needed to clear infection
Infection and inflammation can inhibit lung function (i.e. prevent gas exchange)
Evidence
1. T cell response correlates w peak of symptomatic disease (rather than viral load)
2. SCID mice do not get acute disease after infection (as they are immunodeficient)
timing of giving anti-TNF in viral infections
- early: TNF boosts immune response to control pathogen
2. late: TNF increases immunopathology
phenotype vs endotype in chronic airway infection
- Phenotype
Set of observable characteristics of an individual resulting from the interaction of its genotype with the environment
e.g. airway phenotype of chronic bacterial infection is stereotypical: mucus, neutrophils and their products leading to host tissue damage
Chronic, non-specific treatment e.g. ABx, airway clearance - Endotype
Subtype of condition; defined by distinct functional/pathobiological mechanism
Possibility of targeted, specific treatment
what are pili + functions (4)
Thin, flexible filaments that protrude from bacterial surface
- Mediation of communication between bacterial cells
- Attachment to human epithelial cells
- Uptake of exogenous DNA
- “Motility”: from protraction and retraction of pilus
adaptation of neisseria meningitidis to host environment (4)
- Capsule and LPS inhibit action of immune factors
a. Vogel et al. (1996): capsule deficient → rats able to clear infection
b. Unencapsulated meningococci very rarely isolated from disease patients compared to carriers - Mimicry: Binding of fHbp and NspA to human factor H (prevents complement attack against self) → evades immune recognition
- Extensive variation
a. Antigenic: allows escape from immune recognition (capsules can change type)
b. Phase: may confer characteristic that helps escape immune recognition e.g. reduced production of particular protein
Selection: host immune system then destroys all bacteria except one w this characteristic - Meningococcus has proteins that can bind to and release iron from complexes so that it can be used
life cycle of HCV
- Virus binds to cell surface receptors and enters cell
- No reverse transcription or integration into human genome; virus embeds itself in ER and replicates
- Hijacks golgi mechanisms of lipid exporting from cells ∴ produces lipid droplet w virus inside ∴ can evade recognition by immune system
how does HCV evade the host immune response (4)
- Variation in genome/protein structure
- ER vesicles as site of RNA replication
- NS5A inhibits interferon responses
- NS3 inhibits cell monitoring of virus molecules
HCV transmission (2)
- Blood-blood contact
a. Transfusion of blood products/transplants
b. Contaminated needles/instruments
c. Cultural practices: ritual scarification, circumcision, body piercing, etc.
d. Sexual transmission rare (< 2%) - Children also become infected via mother-to-child transmission
a. Healthy placenta is usually good barrier to transmission of viruses, but can become damaged during childbirth
b. 5% transmission, 15-20% in HIV+ mothers
HCV presentation (6)
- Cirrhosis
- Hepatocellular carcinoma
- Ascites, portal hypertension, oesophageal varices → haematemesis
HCV drugs (3)
Direct acting antivirals (DAAs)
1. NS3/4A protease inhibitors
2. NS5A inhibitors: block replication complex formation, assembly and release
3. NS5B nucleoside (e.g. ribavirin)/non-nucleoside polymerase inhibitors
All oral, short-duration, once daily, low-toxicity
None of the new drugs are yet licensed for children or for pregnant women
malaria life cycle (8)
- Mosquito saliva infects human w malaria parasite (sporozoites) → bloodstream
- Enters liver cells via Kuffpfer cells and multiplies → newly formed parasites adapted to invade RBCs (merozoites)
- Parasite (trophozoite) hides from immune recognition in RBCs and multiply
- Gametocytes are formed
- Infected RBCs stick to vessel walls and burst releasing more parasites
- Only pregnant mosquitoes drink blood from humans
- When blood from humans cools, plasmodium forms eggs and sperm
- Cysts form on outer lining of mosquito stomach, which produce more parasites and infest salivary glands
pathophysiology of malaria (4)
- Invasion and destruction of RBCs and liver cells
- Infected blood cells destroyed in spleen
- Sequestration of infected cells in small blood vessels
→ obstructed blood flow in most tissues e.g. brain, lung (→ respiratory distress), adipose tissue, retina, rectal mucosa, placenta - Inflammation endothelial dysfunction
clinical features of uncomplicated (4) and severe malaria (3)
Uncomplicated malaria 1. Fever 2. Rigors 3. Headache 4. Lethargy Severe malaria (mostly in children and pregnant women) 1. Coma 2. Fits 3. Severe anaemia
outcomes of malaria in pregnancy
maternal (4) / fetal (4)
maternal 1. anaemia 2. mortality 3. cerebral malaria 4. severe malaria fetal 1. IUGR 2. abortion 3. stillbirth 4. preterm delivery
how can recurrent malaria occur (3)
- Recrudescence; incomplete clearance
depends on pharmacodynamic/pharmacokinetic relationship - Relapse: from re-emergence of blood stage from hypnozoites (latent form of parasite in liver; hidden from immune detection)
P. vivax and P. ovale only - Re-infection
malaria diagnosis (4); advs + disadvs
- “Clinical”/presumptive diagnosis
- Microscopy
advs: quantitative, can differentiate species
disadvs: requires equipment, supplies, training, maintenance of expertise, operator dependent, can be time-consuming - Rapid diagnostic tests (antigen based)
advs: easy to use, sensitive and specific, quick (20 minutes), cheap
disadvs: not quantitative, antigen deletions in malaria increasing ∴ not detected by test - PCR: research and surveillance only
malaria treatment
Previously quinine used, but resistance developed
Artemisinins currently most effective; resistance beginning to occur in last few years
Currently no vaccine
immature immune system of neonates (8)
- Takes time for immune system to adapt after birth
- Antibodies; in babies: no contact w infectious agents → no Ab production ∴ fully reliant on maternal transfer of Abs
But no guarantee maternal Ab present to the infecting organism
Greatest transfer of Ab across placenta during 3rd trimester
Ab not replenished by baby’s immune system ∴ levels decline - Less effective complement and neutrophils
- Immature skin and mucosal surfaces to provide barrier
- Fewer APCs
- Excessive inflammation (too much TNF, IL1beta, IL6)
- Too many IL17, Tregs + IL10 (inflammation turned off prematurely)
- Prematurity → immune system even more immature and ineffective
pathogenesis of group B strep in neonates (2)
- inhalation at delivery → lungs → sepsis or pneumonia
- chorioamnionitis
Majority of disease occurs within the first 24 hours after birth
how does group B strep evade the immune response
surface proteins expression is upregulated/downregulated dependent on environment ∴ difficult to develop vaccines
factors affect vaccination response in infants (6)
- Maternal antibodies may interfere w infant responses
- Epigenetics: maternal lifestyle can affect fetal immune system
- Genetic determinants control early phase of vaccine Ab response
- Environment predominantly influences Ab persistence and avidity maturation
- Vaccination timing
- Co-infections e.g. HIV: lower Ab response to primary vaccines (HiB, DTaP, PCV)
primary vs secondary immunodeficiency
- Primary immunodeficiency = inherited/genetic disorder that affects the immune system
Rare diseases w heightened susceptibility to infections from childhood onwards
e.g. Severe combined immunodeficiency (SCID) - Secondary/acquired Immunodeficiency = compromised immune system due to environmental factors
e.g. HIV, burns, medication
life cycle of HSV1
- Primary infection: virus enters through epithelial cell → dendrite → remains latent in ganglion
If infected, never eradicate from system i.e. live with for life - Recurrent infection: reactivation of virus, travels down axon → same epithelial area affected
primary immunodeficiency: deficiencies of immune pathways lead to? 1. T cells 2. B cells 3. complement 4. neutrophils
- T cell defects → susceptibility to intracellular pathogens e.g. Di George syndrome
- B cell defects → susceptibility to extracellular pathogens e.g. X-linked agammaglobulinaemia
- Complement defects → susceptibility to bacterial infection, especially N. meningitis
- Neutrophil defects → susceptibility to pyogenic bacterial infection e.g. chronic granulomatous disease
pneumococcus virulence factors (6)
- Capsule (most important): evasion of phagocytosis; inhibits host defence mechanisms e.g. complement and antibodies
- Autolysin: enzyme that breaks down peptidoglycan matrix allowing growth, cell division and transformation
- IgA1 protease: enzyme that cleaves IgA allowing crossing of mucous membranes
- Pneumolysin: cholesterol-dependent pore forming cytotoxin; inhibits ciliary beating and disrupts epithelial cells
- Haemolysin: lyses RBCs by destroying cell membrane
- Hydrogen peroxide: damages epithelial monolayer, facilitating access to blood
pathogenesis of pneumococcus
- Colonisation: usually resides in upper respiratory tract asymptomatically
60% of children are carriers of pneumococcus - Bacteria can migrate and infect middle ear or lungs
- Can cross alveolar barrier causing bacteraemia, which can lead to meningitis
mechanism of penicillin resistance
Transformation: when bacteria lyse, naked DNA released
Free DNA can be endocytosed by another nearby bacterium, and integrated into own genome
Pure polysaccharide vaccines vs polysaccharide-protein conjugate vaccines (4)
Pure polysaccharide vaccine
1. Antibody production
2. Lack of memory
3. Poor response in children
4. Little effect on pathogen transmission
Polysaccharide-protein conjugate vaccine
Presence of protein leads to recruitment of T helper cells →
1. High affinity antibody production
2. Memory
3. Better response in children
4. Reuced pathogen carriage leading to herd immunity
how does reverse vaccinology work?
- Collect blood from disease affected pts
- Monoclone every antibody from population
- Screen every antibody against pt isolate
- Antibodies found to be positive against pathogen → functional assay to confirm whether antibody will kill pathogen
- Proteomics used to determine which surface protein antibody recognises
- Can use this antigen to design new vaccine
effect of delivery on microbiome of newborn (3)
Vaginal delivery → microbiome similar to vagina
Caesarean delivery → microbiome similar to mother’s skin
Prematurity → delayed colonisation → decreased microbiotal diversity
effects of ebola on immune system (7)
- Infects dendritic cells → inhibits production of anti-inflammatory cytokines
- Prevents stimulation of CD4 and CD8 T cells
- Causes premature apoptosis of T cells
- Invades monocytes and macrophages
a. Stimulates production of pro-inflammatory cytokines
b. Inhibits production of anti-inflammatory cytokines - Direct viral invasion of hepatocytes and renal cells → organ failure
a. Gross hepatic failure → coagulation abnormalities → haemorrhage - Proinflammatory cytokines → endothelial leakage → petechial rash
- Neutrophils activate and degranulate → fever, malaise, muscle aches, pains, GI symptoms
→ poor overall immune response: increasing viraemia → ↑damage to organs → multiorgan failure and death
single-tagged mutagenesis
- Known transposons used to mutate and inactivate particular virulence genes
- Animal exposure to pathogen
- Output pool isolated after infection compared to input pool
a. Strains not seen in output pool lost virulence due to mutation
b. This virulence factor can be targeted therapeutically
in vitro models of lung tissues (3)
Transwells: used to mimic lung epithelium
- Can also produce air-liquid interface using device → production of mucous & differentiation (as in respiratory epithelia)
- Can also place endothelial cells beneath epithelial layer and study infection across both layers
- Can use vacuum to simulate breathing
comparison of sequencing methods (3)
- Sanger sequencing; late 1970s
High accuracy, expensive, time-consuming - Single-molecule real-time sequencing (Pacific Bio); late 2000s
a. Long read length: need combination of long and short reads to sequence genome (more difficult to match short reads to genome due to repeat sequences and repetitive DNA)
b. High error rate - Illumina; late 2000s
High yield; cost/base. short read length
how does nanopore gene sequencing work
- DNA attached to enzyme, docks on nanopore
- Single strand passes through pore, each base passing through is recorded
- Easy → instant analysis
- Can be used to rapidly identify causative organism of infection
16s rRNA; what is it?
uses in PID research
• Component of the small prokaryotic ribosomal subunit (30S)
• Present in all bacteria (vital for survival)
○ Conserved regions used to detect bacteria
○ Variable regions used to identify which family of bacteria
Uses:
1. Determine composition of bacteria across body sites and assess potential effects of flora on disease
2. Identify agents causing/associated w disease; by sequencing isolate RNA from infected pts
e.g. Neonatal Microbiota Study: identified ↑C perfringens in NEC → earlier onset, more severe disease, ↑mortality
Allows development of targeted Tx
how do DNA microarrays work
- Series of nucleic acid targets immobilised on a solid substrate
- Samples to be identified are washed over
- Complementary sequences ‘stick’ or hybridise to each other
- Quantify gene expression by fluorescence or colour
- Allows measurement of expression levels of large numbers of genes simultaneously
- Can compare differences in DNA sequence between individuals
examples of DNA microarray uses in PID research (4)
- Used in GWAS to identify SNPs, which can be genetic determinant of disease
- Used in combination w 16s rRNA to identify bacteria
- Identify biomarkers of paediatric diseases that are difficult to diagnose
→ fast, reliable, cheap, point-of-care tests for developing countries - Immunopathology of host response to pathogens
what is transcriptomics
Identifies total mRNA in cell or organism
○ Up/downregulated genes in health/disease
○ Allows monitoring of changes across whole genome simultaneously
uses of transcriptomics in PID research (2)
- Identifying new biomarkers
○ Infection causes changes in gene expression
○ Can measure expression level of all genes in cells from bloods and compare between patients to determine if suitable biomarker
○ Similar pathogens w similar clinical presentations will still have differing gene expression - Identification of virulence factors
○ Can look at chromosome position of genes; virulence factors clustered in one area due to horizontal gene transmission
SCID ; what is it
2 genetic causes
Lack of Y chain development required for T cell development and multiple IL receptors
- X-linked mutation
- Rag1/2 deficiency → failure of VDJ rearrangement for IgM production, failure of TCR synthesis
Loss of normal B and T cell function → ↑susceptibility to many infections
