Antibacterial Responses Flashcards
General features of bacterial infections + immunity against bacteria
State features of a bacterial infection?
- 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
Do all bacteria cause disease?
- 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
State general features of immunity to bacteria?
- 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
Innate immunity to CF bacteria
Describe the components of the innate immune system (first line of defence)?
Mechanical (flow of fluid - e.g. mucus), chemical (enzymes, secretions + antimicrobiral peptides (defensins)) + microbiological (normal flora) -> various organs
Describe anti-bacterial peptides defensins?
- 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)
Describe the complement system?
- 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
Describe the functions of the complement system?
Macrophages -> increased levels of expression of complement receptors (CR1, CR3, CR4) -> bacteria binding to C3b (mainly) -> pathways -> Opsonization (-> phagocytosis), IF + lysis
What detects the presence of bacteria on phagocyte and state an example?
- Pattern recognition receptors
- e.g. Toll-like receptors (surface or intracellular)
- Detects cell wall components
Phagocytes
How is phagocytosis induced eventually leading to inflammation?
PAMP binding by PRs activates phagocyte -> Phagocytes ingest microbes, increase size + metabolic activity -> increased antimicrobial activity -> release of chemokines + cytokines -> IF
Inflammation
What is the purpose of inflammation and what 2 factors are regulated between?
- Purpose -> change properties of endothelium -> allows cells e.g. leukocytes to move to site of damage
- Balance -> beneficial response + injurious process
State the functions of neutrophil in bacteria infection?
Phagocytosis + Neutrophils -> degranulation of granules, oxidative burst + Neutrophils extracellular traps (NETS -> kills bacteria phagocytosing bacteria)
Adaptive immunity to extracellular bacteria - Antibodies - humoral response
Describe the 3 functions of the Antibodies
- Neutralise bacterial toxins
- Trigger classical complement pathway by binding of IgM to bacterial surface
- Opsonisation; coating of bacteria with AB -> aids phagocytosis
Describe how toxins are neutralised?
- 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
Anti-bacterial qualities of lgs
Describe how the classical complement cascade is triggered?
Pentameric IgM binds antigen on bacterial surface -> IgM bound binds to a C1g -> initiates classical pathway -> cell surface is coated in C3b -> facilitates phagocytosis.
State the anti-bacterial qualities of Igs?
- Neutralization, opsonization, complement system activation, sensitisation
- ingestion + destruction by phagocyte
Inflammation
Describe the key responses involved within the adaptive immune response + what they lead to
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- 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
Describe the role of dendritic cells in adaptive response?
- Antigen uptake -> presentation to T cells -> secondary lymphoid organs (e.g. lymph node) -> B cell activation
Innate + adaptive immunity to Intracellular bacteria
Cellular response
How do some pathogens like mycobacterium tubercluosis adapt to survive?
- Adapt -> survive inside macrophages -> IC bacteria
Briefly describe the time course of immunity to IC bacteria?
Same as EC bacteria
CD4+ - CD8+ cooperation
Describe the role of MHC class II pathway in Extracellular infections?
The MHC class II pathway presents bacterial antigens derived from extracellular infections to CD4 TH cells -> macrophage activation -> increased phagocytosis of EC pathogens
Describe the cooperation of CD4+ and CD8+ T cells during intracellular infections?
CD4+ T cell not effective solely in IC -> CD8+ Cytotoxic cells -> kill cell
