Week 9 Pathology - Infectious Disease

Question 1

What are the mechanisms of immune evasion by microbes?

Answer 1

1. Antigen variation
2. Resistance to innate immune defences
3. Impairment of effective T cell antimicrobial responses by specific and non specific immune suppression

Question 2

What are some examples of antigen variation?

Answer 2

1. High mutation rate due to low fidelity of viral RNA polymerase (HIV, influenza)
2. Genetic reassortment (influenza, rotavirus)
3. Gene recombination to alter surface antigen expression (Neisseria, malaria)
4. Large diversity of serotypes (rhinovirus, pneumococcal)

Question 3

What are some examples of resistance to innate immune defences?

Answer 3

1. Production of surface molecules that resist action of innate anti-microbial peptides/inactive/downregulate effect
2. Production of proteins that kill phagocytes/prevent migration, diminish oxidative burst

Question 4

What are some examples of impairment of T cell responses by specific and non specific immune suppression?

Answer 4

1. Binding/altering MHC 1 molecules (HSV, EBV, CMV)
2. Making MHC II homologues which act as inhibitors of NK cells
3. Herpesviruses can target MHC II molecules for degradation, impairing antigen presentation to CD4+ T cells

Question 5

What is the difference between endotoxins and exotoxins?

Answer 5

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

Question 6

What is an example of an endotoxin?

Answer 6

LPS - important player in septic shock, DIC, ARDS through cytokine induction

Question 7

What are examples of exotoxins?

Answer 7

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

Question 8

What is suppurative inflammation?

Answer 8

Reaction to acute tissue damage, increased vascular permeability and leukocyte infiltration - predominantly mediated through neutrophils, causing liquefactive necrosis and abscess formation

Question 9

What is mononuclear/granulomatous inflammation?

Answer 9

Diffuse, mononuclear interstitial infiltrates in context of chronic inflammation, usually evoked by intracellular pathogens/viruses

Question 10

What is cytopathic-cytoproliferative inflammation?

Answer 10

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)

Question 11

What are examples of organisms that cause necrosis?

Answer 11

Clostridium perfringens, Entamoeba histolytica
Caused by secretion of toxins, causing rapid and severe tissue damage, generally few inflammatory cells present

Question 12

What are the 2 major stages of HSV infection?

Answer 12

Acute and latent infection

Question 13

What are the different categories of herpesviruses?

Answer 13

alpha group: HSV 1, HSV 2, VZV
beta: CMV, HHV 6, HHV 7
gamma: EBV, KSH/HHV-8

Question 14

What is the pathogenesis of herpes simplex infection?

Answer 14

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

Question 15

What are some common clinical manifestations of S. aureus infection?

Answer 15

Skin infection/abscess, pneumonia, IE, joint infections, osteomyelitis, toxic shock, food poisoning

Question 16

What opportunistic infections does S. epidermidis cause?

Answer 16

Catheter related infections, IE in valvular disease/IVDU

Question 17

What is the most common clinical manifestation of S. saprophyticus?

Answer 17

UTI

Question 18

What are virulence factors associated with S.aureus?

Answer 18

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

Question 19

Describe pathogenesis of measles:

Answer 19

Transmitted respiratory droplets, initial replication within upper respiratory epithelia and spread to lymphoid tissue –> systemic dissemination

Question 20

What’s the clinical presentation of measles?

Answer 20

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

Question 21

What hypersensitivity reaction is involved in TB?

Answer 21

Type IV

Question 22

What are the major steps in the pathogenesis of tuberculosis?

Answer 22

1. Entry into macrophages
2. Replication within macrophages: evasion of usual phagosome production
3. Th1 response: presentation of antigens to T cells
4. Th1 mediated macrophage activation and killing of bacteria (via production of IFN-gamma)
5. Granulomatous inflammation and tissue damage: Th1 response causes formation of granulomas and caseous necrosis

Question 23

What is primary tuberculosis?

Answer 23

Lobar consolidation (Ghon focus) , hilarious adenopathy, pleural effusions, flu like symptoms

Question 24

What is secondary tuberculosis?

Answer 24

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

Question 25

What is the most frequent presentation of extra-pulmonary tuberculosis?

Answer 25

Lymphadenitis

Question 26

What’s the causative organism in syphilis?

Answer 26

Treponema pallidum, gram -ve spirochete

Question 27

How does syphilis evade immune responses?

Answer 27

TrpK protein on outer membrane, accumulates structural diversity during course of infection through gene recombination to create antigenic variation

Question 28

What is the classic pathological finding that is present in all stages of syphilis?

Answer 28

Proliferative endarteritis affecting small vessels

Question 29

Describe primary syphilis:

Answer 29

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

Question 30

Describe secondary syphilis:

Answer 30

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

Question 31

What are the 3 manifestations of tertiary syphilis?

Answer 31

Cardiovascular syphilis: aortitis and aneurysm of proximal aorta
Neurosyphilis: 10% of untreated cases,
Benign tertiary syphilis: characterised by ‘gammas’ (nodules related to delayed hypersensitivity)

Question 32

What is the life cycle of HIV?

Answer 32

1. HIV infects cells by targeting CD4 molecule as receptor, ‘selective tropism’ for CD4 cells (monocytes, macrophages, dendritic cells) –> requires co-receptors
2. 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)
3. 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

Question 33

What are suggested mechanisms of CD4 cell death in HIV infection?

Answer 33

1. Plasma membrane permeability due to budding viruses
2. Virus replication interfering with regular protein synthesis
3. Activation induced apoptosis

Question 34

What are the mechanisms by which HIV escapes host immune response?

Answer 34

Antigenic variation
Proviral latency
Sequestration into immune privileged sites (CNS, genital tract, lymphoid tissue)

Question 35

What are the 3 major stages of HIV infection?

Answer 35

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