Infection overview Flashcards
What elements must you consider when a patient presents with an infection?
- Host
- Environment
- Pathogen
always consider pathogen last
According to Dr. Ahmadi, what about the HOST is most important to consider?
Immune competent or immune compromised
According to Dr. Ahmadi, what about the ENVIRONMENT is most important to consider?
Port of entry, community or hospital acquired
According to Dr. Ahmadi, what about the PATHOGEN is most important to consider?
MOA, pathogenicity, virulence
Patient with liver disease presents for routine exam. According to Dr. A, what should you consider and why?
Possibility of occult infection. Research shows 2/3 of those w/chronic liver disease have an occult infection.
3 types of immune compromised states
- Primary immune deficiency
- Secondary or acquired immune deficiency
- Autoimmune disease
Examples of primary immune deficiency
Neonate, elderly
Examples of secondary immune deficience
AIDS, chemotherapy, relative immune deficiency (DM, cancer, poor nutrition state)
Autoimmune disease Dr. A mentions in relation to immune deficiency
SLE
What is surprising about SLE in relation to immune deficiency?
Although they have hyperactive immune systems, they’re not good at offering protection
Image: what does the pathogen want to in the body?
Attach → proliferate → avoid phagocytes → damage host via either toxins or invasion
Image: what do abs do to attempt to stop the pathogen at the attachment level?
Attachment: abs attach to fimbriae, lipoteichoic acids, and some capsules
Image: what do abs do to attempt to stop the pathogen at proliferation level?
Proliferation: a) Abs trigger complement-mediated damage to gram neg outer lipid bilayers, b) Abs block transport mechanisms & receptors (e.g., iron chelating compounds)
Image: what do abs do to attempt to stop the pathogen at the phagocyte avoidance level?
Avoidance of phagocytes: a) Abs to M proteins and capsules give opsonization via Fc and C3 receptors, b) Abs neutralize immunorepellents
Image: what do abs do to attempt to stop the pathogen at the host damage level?
Toxins: Abs neutralize toxins
Invasion: Abs neutralize spreading factors, enzymes (e.g., hyaluronidase
What type of organisms are those with B Cell deficiencies at risk for?
Encapsulated organisms, e.g., Streptococcus pneumoniae, Hemophilus influenzae
What organism is the most common cause of community acquired pneumonia?
Streptococcus pneumoniae
What types of infections are people with B cell deficiencies prone to?
Pneumonia, Sepsis, Infections of Sinuses, Ears and GI tracts
What types of infections are people with T cell deficiencies prone to?
Fungal, viral, and intracellular bacterial infections – e.g., chronic mucocutaneous candidiasis alerts you to T cell deficiency
Classic intracellular organism frequently seen, even in immune competent
Mycoplasma – chain coughing w/no other presenting symptoms
Syndrome that commonly causes T Cell deficiency
DiGeorge Syndrome: partial or complete absence of T cell immunity; lack of thymus; region of the developing embryo that is affected controls the development of the face, parts of the brain, the thymus, the parathyroid glands, the heart and the aorta.
Syndrome that leads to combined T and B deficiency
- Wiskott-Aldrich syndrome
- Normal IgA and IgG but very low IgM (so ACUTE phase is most problemetic)
What type of infections are those with Wiskott-Aldrich syndrome prone to?
Prone to infections with Encapsulated Bacteria
- Pseudomonas, Strep, H. Influ,
Conditions that leads to combined T and B cell deficiency
- RAG-1 or RAG-2 deficiency
- Bare lymphocyte deficiency
- MHC class I and II deficiency
- Wiskott-Aldrich syndrome
- Ataxia-telangiectasia (AT)
RAG-1 or RAG-2 deficiency: what does RAG stand for?
Recombinant activating gene
RAG-1 or RAG-2 deficiency: signs and symptoms
- No symptoms are detected during pregnancy, birth and within the first few weeks of life.
- The clinical signs are characterized by chronic respiratory disease, recurrent acute pneumonia, therapy-resistant mucocutaneous candidiasis, eczematous dermatitis and systemic bacterial infections.
Effect of recurrent infections and chronic enteritis of RAG-1 and RAG-2 deficiencies
- a therapy-resistant growth failure. Intracellular parasites (Listeria, Legionella), viruses (EBV) and cytomegaloviruses (CMV) cause lethal complications.
- All SCID children die within few months if they are not provided with haematopoietic stem cells.
Physical Exam of RAG deficient patient reveals…
unusual infections and a characteristic absence of lymphatic organs. In most cases cervical lymph nodes and tonsils are undetectable.
What type of person does listeria tend to infect?
Those at extremes of age. Classic intracellular organism
Types of complement deficiency
- C3 deficiency
- Mannose-binding lectin (MBL) deficiency
- Properdin deficiency – terminal part of pathway
- Factor I and factor H deficiency
- C9 deficiency – terminal part of pathway
What type of infection do phagocyte deficiencies tend to lead to?
Gram positive infections
What is Chédiak-Higashi syndrome?
- Defect in Cytoplasmic Granules (microtubule polymerization)
- Associated With Oculocutaneous albinism
Clinical signs of Chédiak-Higashi syndrome?
Mild coagulopathy, Hepatosplenomegaly
Recurrent Gram Positive infections Skin and Respiratory tract
Diagnosis of of Chédiak-Higashi syndrome?
Neutrophils with giant lysosomes,
Pancytopenia
Treatment of of Chédiak-Higashi syndrome?
Daily Bactrim, Daily ascorbic acid
Seen in Severe congenital neutropenia
Cyclic neutropenia
What is myeloperoxidase deficiency ?
NADPH Oxidase Deficiency
myeloperoxidase deficiency and candidiasis
Only DM patients get Candidiasis
What is Chronic granulomatous disease?
Mutation in NADPH complex, can not produce H2O2
Clinical characteristics of chronic granulomatous disease
Severe Pneumonias, Tumor like granuloma in the lungs, skin, bones
Treatments For Immune Deficiencies
- Gamma-globulin therapy
- Transplantation or transfusion
- Treatment with soluble immune mediators
- Gene therapy
Normal microbiome
- symbiotic relationship between humans and microorganisms
- skin, mouth, GI tract, respiratory tract, genital tract
Explain symbiotic relationship with the microbiome in the gut
- normal bacterial microbiome of human gut is provided w/nutrients from ingested food & in exchange
- produce enzymes that facilitate digestion of complex molecules
- produce antibacterial factors (baceriocins, colicins) to prevent colonization by pathogens
- produce usable metabolites metabolites (e.g., vit K, B)
True pathogens vs opportunistic microorganisms
- Opportunistic microorganisms cause disease only in immune compromised state
- True pathogens find a way to circumvent individual’s defences (usually d/t # of organisms, not immune competence)
How is homeostasis maintained w/normal microbiome?
- Physical integrity of skin/gut (breach –> local infections, sepsis, etc)
- Immune & inflammatory systems (compromised immune –> opportunistic infections)
- BUT this relationship can be breached by injury. Leave normal site and go cause infection
Stages of infection (pathogen perspective)
- Colonization
- Invasion
- Multiplication
- Spread
How does colonization work?
(stages of infection)
- Microorganism finds its way from reservoir to individual
- After deposition, stabilizes adherence to tissue through specific surface receptors (thus difficult to removal by mechanical factors, e.g. by coughing)
- Specificity of adherence limits infection locations – e.g., cold virus to respiratory tract
- Adherence often through pili on bacteria (rod-like projections), but many other methods – complement receptors, AA sequence in fibronectin, etc.
Biofilm
Consist of mixed species of microorganisms, e.g., bacteria, fungi, viruses – often grow together to increase chance of survival. Play a role in recurrent and persistent infections
Colonization: types of reservoirs
- Animal reservoirs
- contaminated materials (direct exposure)
- Human
- Horizontal transmission
- Vertical transmission
Colonization: animal reservoirs
- Direct contact (e.g., rabies bite)
- Vectors (insects)
- Mechanical vectors (passive: housefly)
- Biologic vectors (bites/stings: fleas, lice, mosquitos)
Colonization: direct exposure to contaminated materials
- Fecal-oral (salmonella, cholera, hep A, polio, rotavirus)
- Soil (tetanus)
Colonization: human-human horizontal transmission
- Droplets (respiratory – common cold, flu, strep throat, bact meningitis)
- Physical contact (sex, blood, wounds – STIs, hep B, CMV, HSV, warts)
- Airborne transmission (rare – SARS, TB, norovirus, smallpox)
Colonization: human-human vertical transmission
- Mother-child placenta (treponoma pallidum, listeria monocytogenes, CMV, toxoplasma gondii)
- Mother-child birth canal (GBS, E coli, chlamydia, gonorrhoeae, hep B, HIV, C. albicans)
- Mother-child breast milk (S. aureus)
How does invasion work?
(stages of infection)
After colonization, find way to penetrate tissues & evade nonspecific and specific defenses (inflammation & immunity)
How does multiplication work?
(stages of infection)
- Human tissue is warm & nutrient filled = most microorganisms can rapidly multiply
- Viruses: replicate w/in cells
- Bacteria: some intracellular and replicate in macrophages and other cells
- Immune response takes 3-5 days. If can divide faster, more effective and fatal (cholera, some group A strep, GBS)
How does spread work?
(stages of infection)
- Relies on virulence factors (e.g., adhesion molecules, toxins, protection against inflammatory & immune systems)
- localized w/o spread to other regions (cholera)
- Or highly invasive – lymphatics, blood, internal organs
Stages of infection (individual perspective)
- Incubation period
- Prodromal stage
- Invasion period
- Convalescence (or, less commonly fatal or latent)
Mechanism of action
How organism damages tissue
Infectivity
Ability of pathogen to invade & multiply in host
Pathogenicity
Organisms potential to cause disease
Virulence
Capacity of pathogen to cause severe disease
Immunogenicity
- Capacity of pathogen to cause significant immune reaction
- e.g. Staph aureus, while waiting for echo, you can get rheumatoid factor (if no RA). Sensitive not specific.
Toxigenicity
- Toxin production capacity, influences virulence
- e.g., 2 strains of e coli w/differing toxigenicity. One releases toxins, the other not
Endemic classification
Relatively high, but constant, rates of infection in a particular population
Epidemic classification
Number of new infections in a particular population greatly exceed number usually observed
Pandemic
Epidemic that spreads over a large area, such as continent or worldwide
Pathogen defense mechanisms
- Surface coats
- Antigenic variation
Examples of antigenic variation
- Mutation
- Antigenic drift
- Recombination
- Antigenic shift
- Gene switching
- “hypermutable gene”
Gene switching: which is the most concerning hypermutable gene?
Pseudomonas
