Antibacterial Responses

Question 1

What is an infection?

Answer 1

Interaction between pathogen and host

Question 2

What are the key steps in infection?

Answer 2

Entry of pathogen, invasion and colonisation of host tissue, evasion of immunity and tissue damage

Question 3

Why can some bacteria not be cleared by immune system?

Answer 3

bacteria establishes latent or persistent infection

Question 4

What is the first line of defense?

Answer 4

Innate / barriers

Question 5

What are the 3 categories of innate first line of defense? + examples of each

Answer 5

Mechanical - flow of fluid (mucus, cilia)
Chemical - (sebum, acidity, lysozymes) + AMPs (defensins)
Microbiological - (normal flora)

Question 6

What do defensins do?

Answer 6

Released into extracellular environment and kill microbes by penetrating microbial membranes and disrupting their integrity

Question 7

Why is microbiota important apart from innate / barrier function?

Answer 7

Protect against unwanted immune response

Question 8

What types of defensins are there?

Answer 8

alpha defesin and beta defensin

Question 9

Which cell secrete alpha defensins?

Answer 9

Neutrophils and paneth cells

Question 10

Which cells secrete beta defensins?

Answer 10

Broad range of epithelial cells esp in resp tract, skin and urogenital tract

Question 11

What happens if initial barriers are crossed by pathogens?

Answer 11

Complement activation by microbial cell wall components

Complement is the PRR

Question 12

When is the alternative pathway activated?

Answer 12

• specific PAMPs on bacteria cell walls (lipopolysaccharides)
  Complement (PRR) recongises LPS in peptidoglycan to activate the pathway

Question 13

When is the lectin pathway activated?

Answer 13

Complement (PRR) recognises mannose on surface of bacteria

Question 14

When is the classical complement pathway activated?

Answer 14

Activated by antibodies and antigen binding

Question 15

What is the indirect effect of complement pathways?

Answer 15

1) Induce inflammation, recruit inflammatory cells

2) Enhance phagocytosis via opsonisation

Question 16

What is the direct effect of activated complement pathway?

Answer 16

Complement mediated cytolysis

Complement forms complex (polymersiation of complement) and punches holes in bacteria for lysis

Question 17

Which type of microbes do complements usually work against?

Answer 17

Extracellular bacteria

Question 18

How does complement make phagocytosis more efficient?

Answer 18

C3B (complement) decorates microbe targetting for phagocytosis

Question 19

How does complement induce inflammation and how does this help in a bacterial infection?

Answer 19

C3B and C5A complement pathway induce inflammatory process which brings in more antibacterial neutrophils which destroy bacteria

Question 20

Why do decorates microbes (with complement) enhance phagocytosis?

Answer 20

Phagocytes (macrophages) have lots of complement receptors (e.g. CR3 NOT TLRs) which detect the complement and takes up the bacteria indirectly (since receptor is specific to complement not bacteria allowing more efficient internalisation of bacteria for lysis

Question 21

What are the 2 ways macrophages detect bacteria for phagocytosis?

Answer 21

TLRs (type of PRR) detect PAMPs (bacterial component directly) and takes up bacteria
Complement receptors detect complement (that has bound to bacteria) and takes up bacteria

Question 22

Are PRRs complement receptors?

Answer 22

No since complement receptors do not detect PAMPs.

Question 23

What receptors can be found on phagocytes?

Answer 23

PRRs - TLRs, scavenger receptors
Receptors for defensins
CR3, CR1 (complement receptors)

Question 24

Where are TLRs found?

Answer 24

Phagocytic cells - on surface as well as intracellular (therefore can detect intracellular bacteria too)

Question 25

What happens when PRR and PAMPs interact?

Answer 25

Phagocytosis (engulf) and cytokine production (initiation of inflammatory response)

Question 26

How is an inflammatory response inititated?

Answer 26

Resident cells detect infection and produce chemokines and cytokines that increase endothelial permeability allowing circulating cell to infiltrate and be recruited to site of infection

Question 27

Which cells infiltrate to area of infection in inflammation?

Answer 27

Neuttophils, monocytes and specific lymphocytes

Question 28

What other chemical are released during an inflammatory response apart from chemokines and cytokines?

Answer 28

Local cells e.g. mast cells release histamine and prostaglandins

Question 29

Neutrophils recruited early in inflammatory process. What do neutrophils do?

Answer 29

Phagocytosis and degranaultion of granules - intracellular killing of bacteria Kill bacteria phagocytosing bacteria - NEUTROPHILS EXTRACELLULAR TRAPS (NETS

Question 30

What is the role of antibodies?

Answer 30

Neutralise bacterial tocins Trigger classical complement pathway by binding IgM to bacteria surface Opsonisation - coat bacteria with antibody for phagocytosis

Question 31

What response is antibodies involved in?

Answer 31

Humoral response

Question 32

How do bacterial toxins disrupt normal function of host cells and how do antibodies do toxin neutralisation using this?

Answer 32

Bacterial toxin must bind to receptor to be internalised (endocytosis) with the receptor and disrupt function when the toxin is released from the receptor. Antibodies bind to receptor to block toxin binding to receptor

Question 33

What are the two methods of antibody opsonisation?

Answer 33

Only Antibodies coat pathogen entirely or they can bind alongside complement also binding to pathogen aiding in uptake for phagocytosis (both antibody and complement can be recognised by phagocyte)

Question 34

Step by step, explain the complement cascade?

Answer 34

Pentameric IgM bound to surface of bacterium binds to a complement component to initiate classical pathway of complement activation Causes bacterial surface to be covered with C3B which faciliates phagocytosis

Question 35

Why are only certain types of immunoglobulins involved in opsonisation for phagocytosis?

Answer 35

Diff Ig's have diff anit-microbial properties IgM in opsonisation with C3B complement IgG for neutralisation of bacterial toxin

Question 35

Why are only certain types of immunoglobulins involved in opsonisation for phagocytosis?

Answer 35

Diff Ig's have diff anit-microbial properties IgM in opsonisation with C3B complement IgG for neutralisation of bacterial toxin

Question 36

What events does an adaptive immune response lead to?

Answer 36

Inflammation and bacterial eradication (humoral by B cell and cellular by T cells)

Question 37

Where do dendritic cells present antigens?

Answer 37

Extracellular bacteria taken up and dendritic cells travel to present them to T cells in secondary lymphoid organs e.g. lymph nodes

Question 38

What are the 2 types of Th cells and what does each do? how does each come about

Answer 38

T cell activated and differentiates after encountering pathogen / antigen on APCs Th1 - antibacterial response Th2 - (indirect) activate B cells to produce antibodies

Question 39

How do micobacterium tuberculosis hide in humans?

Answer 39

They hide inside macrophages

Question 40

What is the purpose of cytokines in the innate response vs adaptive response?

Answer 40

Innate - Activate more immmune cell e.g NK cells | Adaptive - differentiate T cells into Th1 or Th2

Question 41

What do CD4 helper T cells do?

Answer 41

Recognise peptide antigen complex and enhance phagocytosis of extracellular pathogens by activating macrophages

Question 42

How do cells deal with intracellular bacteria?

Answer 42

Processed and presents antigen via MHC 2 molecules. If helper T cells