Week 9 Pathology - Infectious Disease Flashcards
What are the mechanisms of immune evasion by microbes?
- Antigen variation
- Resistance to innate immune defences
- Impairment of effective T cell antimicrobial responses by specific and non specific immune suppression
What are some examples of antigen variation?
- High mutation rate due to low fidelity of viral RNA polymerase (HIV, influenza)
- Genetic reassortment (influenza, rotavirus)
- Gene recombination to alter surface antigen expression (Neisseria, malaria)
- Large diversity of serotypes (rhinovirus, pneumococcal)
What are some examples of resistance to innate immune defences?
- Production of surface molecules that resist action of innate anti-microbial peptides/inactive/downregulate effect
- Production of proteins that kill phagocytes/prevent migration, diminish oxidative burst
What are some examples of impairment of T cell responses by specific and non specific immune suppression?
- Binding/altering MHC 1 molecules (HSV, EBV, CMV)
- Making MHC II homologues which act as inhibitors of NK cells
- Herpesviruses can target MHC II molecules for degradation, impairing antigen presentation to CD4+ T cells
What is the difference between endotoxins and exotoxins?
Endotoxins are components of bacterial cell wall which mediate immune/inflammatory response, contributing to illness
Exotoxins are secreted proteins from microbes which cause cellular injury
What is an example of an endotoxin?
LPS - important player in septic shock, DIC, ARDS through cytokine induction
What are examples of exotoxins?
Enzymes - coagulases, proteases (i.e. S. aureus, exfoliative protease cleaves keratinocytes intracellular binding)
Toxins that alter intracellular signally (Anthrax toxin)
Superantigens - stimulate large number of T cells binding to TCR –> massive T cell proliferation and cytokine release, capillary leakage, shock (S. aureus, S. progenies)
Neurotoxins - clostridium botulinum and retain, inhibit release of neurotransmitters and cause tetanus
What is suppurative inflammation?
Reaction to acute tissue damage, increased vascular permeability and leukocyte infiltration - predominantly mediated through neutrophils, causing liquefactive necrosis and abscess formation
What is mononuclear/granulomatous inflammation?
Diffuse, mononuclear interstitial infiltrates in context of chronic inflammation, usually evoked by intracellular pathogens/viruses
What is cytopathic-cytoproliferative inflammation?
Usually in response to viral infections, characterised by cell necrosis or cellular proliferation, typically with sparse inflammatory cells. May present as intracellular aggregates/inclusions. Often associated with epithelia cell proliferation (as in HPV genital warts)
What are examples of organisms that cause necrosis?
Clostridium perfringens, Entamoeba histolytica
Caused by secretion of toxins, causing rapid and severe tissue damage, generally few inflammatory cells present
What are the 2 major stages of HSV infection?
Acute and latent infection
What are the different categories of herpesviruses?
alpha group: HSV 1, HSV 2, VZV
beta: CMV, HHV 6, HHV 7
gamma: EBV, KSH/HHV-8
What is the pathogenesis of herpes simplex infection?
Replicate within the skin and mucous membranes (oropharynx and genitals), producing virions and causing vesicular lesions in the epidermis –> spread to sensory neurons, travelling along axon to cell bodies –> latency
What are some common clinical manifestations of S. aureus infection?
Skin infection/abscess, pneumonia, IE, joint infections, osteomyelitis, toxic shock, food poisoning
What opportunistic infections does S. epidermidis cause?
Catheter related infections, IE in valvular disease/IVDU
What is the most common clinical manifestation of S. saprophyticus?
UTI
What are virulence factors associated with S.aureus?
Surface receptors for fibrinogen, fibronectin to bind to host endothelial cells
Polysaccharide capsule allows organise to adhere to artificial materials and resist host phagocytosis
Express surface protein A, which binds to Fc portion on antibodies and escape antibody mediated killing
Describe pathogenesis of measles:
Transmitted respiratory droplets, initial replication within upper respiratory epithelia and spread to lymphoid tissue –> systemic dissemination
What’s the clinical presentation of measles?
T cell mediated immunity often leads to hypersensitivity reaction IV to infected skin cells –> leads to classic measles rash (starts face first, then trunk and proximal limbs
3 C’s: cough, coryza, conjunctivitis
What hypersensitivity reaction is involved in TB?
Type IV
What are the major steps in the pathogenesis of tuberculosis?
- Entry into macrophages
- Replication within macrophages: evasion of usual phagosome production
- Th1 response: presentation of antigens to T cells
- Th1 mediated macrophage activation and killing of bacteria (via production of IFN-gamma)
- Granulomatous inflammation and tissue damage: Th1 response causes formation of granulomas and caseous necrosis
What is primary tuberculosis?
Lobar consolidation (Ghon focus) , hilarious adenopathy, pleural effusions, flu like symptoms
What is secondary tuberculosis?
Classically involves apex of the upper lobes of lung/s associated with cavitating lesions
Generally will have classic symptoms of weight loss, night sweats, anorexia, malaise, fever
What is the most frequent presentation of extra-pulmonary tuberculosis?
Lymphadenitis
What’s the causative organism in syphilis?
Treponema pallidum, gram -ve spirochete
How does syphilis evade immune responses?
TrpK protein on outer membrane, accumulates structural diversity during course of infection through gene recombination to create antigenic variation
What is the classic pathological finding that is present in all stages of syphilis?
Proliferative endarteritis affecting small vessels
Describe primary syphilis:
3 weeks post infection, formation of raised, red chancre, at the site of treponema invasion - painless, and heals with/without treatment - full of spirochetes which then spread throughout body via haematological and lymphatic spread
Describe secondary syphilis:
Painless, superficial lesions of the skin and mucosal surfaces 2-10 weeks post primary chancre in 75% untreated people. Often associated “B” symptoms in this phase, lasting several weeks before entering latent phase
What are the 3 manifestations of tertiary syphilis?
Cardiovascular syphilis: aortitis and aneurysm of proximal aorta
Neurosyphilis: 10% of untreated cases,
Benign tertiary syphilis: characterised by ‘gammas’ (nodules related to delayed hypersensitivity)
What is the life cycle of HIV?
- HIV infects cells by targeting CD4 molecule as receptor, ‘selective tropism’ for CD4 cells (monocytes, macrophages, dendritic cells) –> requires co-receptors
- RNA genome of virus undergoes reverse transcription, making double stranded complementary DNA, which circularises and becomes incorporated into host genome (DNA can then be latent or be transcribed and cause formation of virions)
- Completion of viral life cycle after cell activation –> gene up regulation and transcription of of genes encoding the virus –> viral budding from cell membrane –> death of infected cells, greater viral loads
What are suggested mechanisms of CD4 cell death in HIV infection?
- Plasma membrane permeability due to budding viruses
- Virus replication interfering with regular protein synthesis
- Activation induced apoptosis
What are the mechanisms by which HIV escapes host immune response?
Antigenic variation
Proviral latency
Sequestration into immune privileged sites (CNS, genital tract, lymphoid tissue)
What are the 3 major stages of HIV infection?
Active: CD4 >500, initial 4-8 weeks, sharp initial rise in plasma HIV RNA load
Latency: CD4 200 -500, occurs over 10 years
AIDS: CD4 < 200, progression to opportunistic infections, malignancy, neurological symptoms
