13 Background to the infectious diseases

Question 1

What are steps successful microbe must make to cause infection?

Answer 1

Attachment + entry

Multiply

Spread in body

Evade host defense

Shed from body

Cause damage to host - not strictly necessary, but for example diaarhoea/ nasal discharge required for transmission

Question 2

Host defense and microbe answer - how does this protect host, how does microbe evade, and give example

Mechanical barriers -
- Host secretions on skin

• Ciliary tract respiratory

Answer 2

• Host secretions on skin - microbe attaches to receptor molecule on host cell. Influenza, rhinovirus, chlamydia, gonococci
• Ciliary tract respiratory - interfere with ciliary activity. Bordetella pertussis, pneumococci, pseudomonas

Question 3

Host defense and microbe answer - how does this protect host, how does microbe evade, and give example

• Membranes as barriers

Answer 3

• traverse host cell membrane - fusion protein in viral envelope. Influenza, HIV
• enter cell by active penetration using enzymes. Trypanosomes, toxoplasma

Question 4

Host defense and microbe answer - , how does microbe evade, and give example

• Microbe ingested and killed by phagocyte

Answer 4

• inhibit phagocytosis - cell capsule. Pneumococci, treponema pallidum, haemophilus
• inhibit phagosome-lysosome fusion such as sulphatides of mycobacterium tuberculosis
• interfere signal transduction of macrophages. Toxoplasma
• resist killing, then multiply in phagocyte. Brucella, listeria, measles, dengue

Question 5

Host defense and microbe answer - how does this protect host, how does microbe evade, and give example

• Host molecules lactoferrin/ transferrin restrict availability of free iron needed by microbe

Answer 5

• microbes compete with host for iron, by have avidly binding iron proteins. Neisseria, E. Coli, pseudomonas

Question 6

Host defense and microbe answer - how does this protect host, how does microbe evade, and give example

• inactivate complement

Answer 6

• produce an elastase to inactivate complement. pseudomonas

- block C3b receptor to inhibit complement. Candida, toxoplasma, M protein of strep pyogenes

Question 7

Host defense and microbe answer - how does this protect host, how does microbe evade, and give example

• host produces interferons to inhibit virus replication

Answer 7

• induce poor interferon response. Core antigen of HBV supresses production. HBV, rotavirus
• insensitive to interferons by producing enzyme. Adenovirus

Question 8

Host defense and microbe answer - how does this protect host, how does microbe evade, and give example

• produces antibody

Answer 8

• destroy antibody with enzymes. Gonococci, haemophilus, streptococci
• displacy Fc receptor on microbial surface, so antibodies bind in upside-down position. Staphylococci protein A, trypanosomes, HSV, CMV

Question 9

Host defense and microbe answer - how does this protect host, how does microbe evade, and give example

• host produces antimicrobial cell-mediated response

Answer 9

• invade T cells and interfere with function. HIV binds to CD4 on T-helper cell
• induce regulatory T cells reduce immune response. Bordatella pertussis, TB, H. pylori, HIV

Question 10

Host defense and microbe answer - how does this protect host, how does microbe evade, and give example

• antimicrobial immune response recognises infected cells and destroys them

Answer 10

• viral antigens not synthesised. HSV in latent phase

- virus inhibits transport MHC class I to cell surface, avoiding recognition by CD8 T cells. CMV, adenovirus

Question 11

Host defense and microbe answer - how does this protect host, how does microbe evade, and give example

• effective immune response produced by identifying microbial antigens

Answer 11

• switch on different surface antigens. Trypanosomes, borrelia
• mutate antigen/ genetic recombination. Influenza, streptococci, gonococci

Question 12

What are routes of attachment and entry for infecting microbes?

Answer 12

• attach/ penetrate with specific attachment protines - most bacteria/ viruses
• arthropods
• skin wounds/ animal bites - clostridia, animal bites, pasteurella
• cannulas/ catheters

Question 13

What are Koch’s postulates that microbe causes specific diseases?

Koch stipulated this in 1890. Work done on anthrax, TB and cholera by discovering cause of disease. Founder of germ theory.

Grew bacteria on potato slices initially. His pupil Petri developed solid gelatin growth media petri dish

Answer 13

• microbe present in every case
• microbe isolated from diseased host in culture
• diseases reproduced when pure culture is introduced into non-diseases host
• micro can be recovered from experimentally infected host
• Not all microbes can be grown in culture (treponema, HBV, EBV etc) - so criteria revised by Evans 1976

Question 14

What is definition of sepsis?

Answer 14

Life-threatening organ dysfunction due dysregulated host immune response to infection

septic shock is lactate >2.0, or need for vasopressors to maintain MAP >65mmHg

Question 15

SIRS is no longer used for definition of sepsis, as too broad, and was often an appropriate response to infection.

What scoring system is now used?

Answer 15

Sequential Organ Failure Assessment (SOFA) - organ dysfunction defined as an increase of two points on SOFa score

Oxygen requirement
GCS
MAP
Platelets
Bilirubin
Creatinine

qSOFA screening score is screening test for sepsis. Defined as at least two of the following:

• altered GCS
• systolic BP <100mmHg
• RR >22

Increasing score associated with increase mortality