Antibacterial Responses

Question 1

General features of bacterial infections + immunity against bacteria
State features of a bacterial infection?

Answer 1

• Bacterial pathogens -> found in EC spaces with exceptions -> some diseases are caused via the toxins they produce
• Infection is an interaction between the pathogen + host
• Steps: entry, invasion + colonisation of host tissue, evasion of immunity, tissue damage

Question 2

Do all bacteria cause disease?

Answer 2

• No: microbiota: MOOs of specific environment -> mechanism of protection to infection both ecological and immunological
• Fact check: The intestine in a healthy adult contains about 10 14 essential bacteria • With about another 1012 on the skin

Question 3

State general features of immunity to bacteria?

Answer 3

• Defense: innate + adaptive immune system -> adaptation to specific bacteria
• Survival of bacteria -> dependent on ability to evade immunity -> Can lead to latent or persistant infection (microbe not cleared)
• defect in immunity -> increased susceptiability -> increased tissue damage

Question 4

Innate immunity to CF bacteria
Describe the components of the innate immune system (first line of defence)?

Answer 4

Mechanical (flow of fluid - e.g. mucus), chemical (enzymes, secretions + antimicrobiral peptides (defensins)) + microbiological (normal flora) -> various organs

Question 5

Describe anti-bacterial peptides defensins?

Answer 5

• Kill bacteria -> penetrate microbial membranes + disrupts integrity -> active against bacteria, fungi + enveloped OR non-enveloped viruses
• Two types -> alpha-defensins (secreted by neutrophils + Paneth cells) + B-defensins (secreted by respiratory tract, the skin + urogenital tract epithelial cells)

Question 6

Describe the complement system?

Answer 6

• Key effector function of the humoral response -> Serum + cell surface proteins (PRs) that interact with one another to generate products that eliminate extracellular bacteria -> activated via microbial cell wall components
• Pathways -> classical (antigen), Lectin (Mannose on surface of bacteria), alternative (LPS (G-ve), PG (G + ve)) -> functions

Question 7

Describe the functions of the complement system?

Answer 7

Macrophages -> increased levels of expression of complement receptors (CR1, CR3, CR4) -> bacteria binding to C3b (mainly) -> pathways -> Opsonization (-> phagocytosis), IF + lysis

Question 8

What detects the presence of bacteria on phagocyte and state an example?

Answer 8

• Pattern recognition receptors
• e.g. Toll-like receptors (surface or intracellular)
• Detects cell wall components

Question 9

Phagocytes
How is phagocytosis induced eventually leading to inflammation?

Answer 9

PAMP binding by PRs activates phagocyte -> Phagocytes ingest microbes, increase size + metabolic activity -> increased antimicrobial activity -> release of chemokines + cytokines -> IF

Question 10

Inflammation
What is the purpose of inflammation and what 2 factors are regulated between?

Answer 10

• Purpose -> change properties of endothelium -> allows cells e.g. leukocytes to move to site of damage
• Balance -> beneficial response + injurious process

Question 11

State the functions of neutrophil in bacteria infection?

Answer 11

Phagocytosis + Neutrophils -> degranulation of granules, oxidative burst + Neutrophils extracellular traps (NETS -> kills bacteria phagocytosing bacteria)

Question 12

Adaptive immunity to extracellular bacteria - Antibodies - humoral response
Describe the 3 functions of the Antibodies

Answer 12

• Neutralise bacterial toxins
• Trigger classical complement pathway by binding of IgM to bacterial surface
• Opsonisation; coating of bacteria with AB -> aids phagocytosis

Question 13

Describe how toxins are neutralised?

Answer 13

• Bacteria secrete protein toxins -> binds cell receptor -> disease caused via by disruption of function of host cell
• AB binds to these receptors blocking the toxin function

Question 14

Anti-bacterial qualities of lgs
Describe how the classical complement cascade is triggered?

Answer 14

Pentameric IgM binds antigen on bacterial surface -> IgM bound binds to a C1g -> initiates classical pathway -> cell surface is coated in C3b -> facilitates phagocytosis.

Question 15

State the anti-bacterial qualities of Igs?

Answer 15

• Neutralization, opsonization, complement system activation, sensitisation
• ingestion + destruction by phagocyte

Question 16

Inflammation
Describe the key responses involved within the adaptive immune response + what they lead to
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Answer 16

• Humoral + cellular -> IF + bacteria eradication
• Humoral response -> AB (neut. + op. -> Fc-receptor phagocytosis) + complement activation (phagocytosis of c3b-coated, IF + lysis)
• Cellular response -> DC uptake -> CD4+ Th cell -> IF. macrophage activation
  (- P + bacteiral killing), AB response

Question 17

Describe the role of dendritic cells in adaptive response?

Answer 17

• Antigen uptake -> presentation to T cells -> secondary lymphoid organs (e.g. lymph node) -> B cell activation

Question 18

Innate + adaptive immunity to Intracellular bacteria
Cellular response
How do some pathogens like mycobacterium tubercluosis adapt to survive?

Answer 18

• Adapt -> survive inside macrophages -> IC bacteria

Question 19

Briefly describe the time course of immunity to IC bacteria?

Answer 19

Same as EC bacteria

Question 20

CD4+ - CD8+ cooperation
Describe the role of MHC class II pathway in Extracellular infections?

Answer 20

The MHC class II pathway presents bacterial antigens derived from extracellular infections to CD4 TH cells -> macrophage activation -> increased phagocytosis of EC pathogens

Question 21

Describe the cooperation of CD4+ and CD8+ T cells during intracellular infections?

Answer 21

CD4+ T cell not effective solely in IC -> CD8+ Cytotoxic cells -> kill cell