L11 Immunity to Bacteria

Question 1

Do bacteria and fungi enter cells typically?

Answer 1

No, pathogenic bacteria and fungi typically do not enter cells, with a few exceptions

Question 2

Where do bacteria and fungi generally reproduce?

Answer 2

They tend to reproduce on the surface of mucosa and in body fluids

Question 3

Name some bacteria which do enter cells and grow within our cells?

Answer 3

• Salmonella enterica
• Mycobacterium tuberculosis (TB)
• Mycobacterium leprae (Leprosy)
• Listeria monocytogenes (food poisoning)
• Brucella abortus (can trigger abortion in cows)

Question 4

Give a brief description of how TB reproduces within our cells?

Answer 4

M. tuberculosis infects residential macrophages of the lung, the macrophages attempt to phagocytose the M. tuberculosis.
Hypersensitivity response results, formation of hard nodules in the lung called tubercles

Question 5

what is it called when pathogenic bacteria enters the blood?

Answer 5

Sepsis

Question 6

is gram positive bacteria or gram negative bacteria more commonly associated with sepsis?

Answer 6

gram negative bacteria

Question 7

Name a group of people susceptible to TB infection

Answer 7

HIV patients who are not on HAART anti-viral treatments

Question 8

What is the course of treatment for TB infection?

Answer 8

Antibiotic treatment: Isoniazid along with Rifampicin, Pyrazinamide, Ethambutol

Question 9

Describe immunity to Gram negative bacteria

Answer 9

Gram negative bacteria, like H. pylori, are susceptible to lysis by the complement system via peptidoglycan degradation by lysozyme.

Question 10

Which type of B cell releases antibodies?

Answer 10

plasma B cell

Question 11

Describe the neutralisation carried out by antibodies?

Answer 11

The antibody coats the bacteria bound to the antigen recognised by that antibody, promotes its opsonisation, and Fc mediated removal by phagocytes follows

Question 12

Describe opsonization

Answer 12

Tagging of foreign pathogens to alert the immune system’s phagocytes to phagosytose

Question 13

List characteristics of the cell wall of a gram-positive bacteria

Answer 13

thick layer of peptidoglycan

proteins, carbohydrates and lipoproteins sticking out (techoic acid, lipotechoic acid)

Question 14

describe the appearance of gram negative cell wall

Answer 14

two layers: inner cytoplasmic layer is the lipid bilayer, outer layer is mainly LPS with carbohydrates attached
two layers separated by a thin layer of peptidoglycan

Question 15

what do mycobacterium have in their cell walls which make them unique to gram positive and negative bacteria?

Answer 15

long fatty acids, mycolic acids

Question 16

function of mycolic acids in the cell wall of mycobacterium?

Answer 16

they are free radical scavengers which repell phagocytosis, phagocytes cannot get a proper grip on the mycobacterium

Question 17

Toll-Like Receptors and their dimers, list whether they are hetero or homodimers.

Answer 17

TLR1 heterodimer with TLR2
TLR2 heterodimer with TLR6
TLR4 homodimer
TLR5 is a single molecule which recognizes flagella

Question 18

what is the name of the receptors within the cytoplasm which monitor intracellular bacteria levels in the event that bacteria enters the cell?

Answer 18

NOD1 and NOD2

Question 19

Which immune cells have pathogen recognition receptors on their surface?

Answer 19

macrophages and dendritic cells. sometimes on epithelial cells.

Question 20

what receptor type usually identifies and prevents a bacterium from entering a cell?

Answer 20

Toll-like receptors

Question 21

list general barriers to pathogens

Answer 21

skin, fatty acids, lysozyme, acid, commensal bacteria

Question 22

role of lactoferrin?

Answer 22

Lactoferrin binds iron, which is required for bacterial growth and reproduction. It reduces iron to help stop the growth of bacteria.

Question 23

role of secretory IgA

Answer 23

• provides protection of mucosal surfaces

- prevents new/subsequent luminal invasion by the same pathogen

Question 24

function of mannosyl-fucose receptors

Answer 24

they bind sugars on the surface of microbes

Question 25

CD14 receptor role

Answer 25

remove microbes coated in serum protein, LPS binding protein which binds LPS

Question 26

What do Fc receptors bind to?

Answer 26

These receptors bind to antibodies which are bound to the pathogen (like IgG, IgM, IgA)

Question 27

what is the function of complement receptor CR1/CD35?

Answer 27

Binds complement coated microbes

Question 28

Which immunoglobulin antibodies can bind and activate complement?

Answer 28

IgM, IgG1, IgG3

Question 29

Describe phagosome to phagolysosome transition in relation to cationic proteins and lysosomal enzymes in bacterial killing

Answer 29

Cationic proteins work best at alkaline pH, which is in the phagosome. These are active at this stage. Lysosomal proteins are active when the phagosome fuses with the lysosome to form the phagolysosome. This has an acidic pH, which is optimal for the function of the lysosomal enzymes.

Question 30

What do reactive oxygen intermediates do in relation to killing pathogens by phagocytosis?

Answer 30

They attack amino acid side-chains, which are prominent features of enzyme active sites, which will prevent binding.

Question 31

give examples of reactive oxygen intermediates

Answer 31

H2O2, nitrogen derivatives

Question 32

How can M. tuberculosis and certain other pathogens survive phagocytosis?

Answer 32

They secrete anti-chemotactic factors, which inhibit the formation of the phagolysosome. The bacterium remains in the phagosome because it can survive the alkaline pH.

Question 33

What enzyme does M. tuberculosis produce to evade phagocytosis?

Answer 33

Catalase - this enzyme breaks down H2O2 into water and oxygen. It can also inhibit cytokine receptors and inhibit MHC Class processing. Bacteria must be killed by antibiotics as the immune system cannot usurp the effects.

Question 34

Which component of Streptococcus pneumoniae enables evasion of phagocytosis?

Answer 34

Its capsule

Question 35

what factors make an individual at higher risk of developing sepsis

Answer 35

young age, old age, immunosuppressive diseases like AIDS, cancer, immunosuppressive medications, diabetes, alcohol abuse, indwelling catheters.

Question 36

Give a description of sepsis

Answer 36

• Circulatory collapse, disseminated intravascular coagulation (micro-thrombi formation)
• Neutrophil-endothelial cell adhesion
• Activation of complement and clotting cascades, which will lead to the formation of the micro-thrombi
• Massive vasodilation occurs, loss of plasma volume, shock
• Shock caused by drop in BP, quickly will lead to organ failure

Question 37

intervention and its justification in sepsis

Answer 37

noradrenaline: vasopressor which will constrict blood vessels to raise blood pressure.

Question 38

What are some new therapies for sepsis?

Answer 38

• LPS removal via polymyxin B hemoperfusion

- Anti-TNFα mAbs

Question 39

What triggers the ‘Cytokine Storm’ in sepsis and what are the components of the storm?

Answer 39

LPS triggers the storm

This storm involves IL-6, TNFα and IL-1 secreted by monocytes

Question 40

which immune cells are predominantly involved in fungi immunity?

Answer 40

neutrophils, macrophages and Dendritic cells

Question 41

Describe Dectin-1

Answer 41

Binds β-glucan on surface of Candida albicans

Question 42

what is superficial mycosis?

Answer 42

dermatophytes, on non-living keratinised skin, hair, nails. (dry layer)
ringworm, tinea capitas (hair loss).

Question 43

respiratory mysosis

Answer 43

histoplasmosis, mainly infects lungs, a soil fungus.

Question 44

What is candidiasis?

Answer 44

Normally, Candida albicans is a commensal fungus. However, if its levels are uncontrolled it causes superficial infections of mucus membranes in mouth or vagina → candidiasis