23 - Immune Responses to Bacteria Flashcards
Pathogenesis
- Attachment and colonisation to host tissue
- Invasion into deeper host tissue and production of toxins
- Growth and multiplication at site of invasion
What determines immune responses to pathogneic bacteria
Surface chemistry
What is active against peptidoglycan layer
Lysosomal enzymes and lysozymes
What is active against. the outer lipid bilayer of gram negative
Cationic proteins and complement
What are immune responses to pathogens determined by
-If intracellular or extracellular
- Mechanisms of pathogenicity
Direct mechanisms of tissue damage by pathogens
- Exotoxin production
- Endotoxin (e.g. LPS)
- Direct cytopathic effect
Indirect mechanisms of tissue damage by pathogens
- Immune complexes
- Anti host antibody
- Cell mediated immunity
Recognition of bacterial components
- Many PAMPS activate cells via TLRs and other PRRs
- TLR activation leads to expression of co stimulatory molecules on phagocytes and has important role in production of inflammatory cytokines
Nucleotide binding oligomerisation domain (NOD) like receptors
Recognise bacterial degradation product in the cytoplasm
Extracellular bacteria
- Replicate outside host cells (e.g. blood, connective tissue) and in tissue spaces
- Induce inflammation resulting in tissue injury at the site of infection and produce toxins
Immunity to extracellular bacteria
- Phagocytosis, complement activation, and the inflammatory response
- Humoral immunity is a major protective immune response against extracellular bacteria, and it functions to block infection, to eliminate the microbes, and to neutralise their toxins
Anaphylatoxin C5a
- Enhances the phagocytosis of microorganisms opsonised in an innate immune response
What are phagocytes attracted by
- Bacterial structural components
- Complement products such as C5a
- Locally released cytokines and chemokines derived from resident macrophages and epithelial cells
What is neutralisation mediated by
High affinity IgG, IgM, and IgA
What is opsonisation mediated by
IgG1 and IgG3
What is complement activation initated by
IgM, IgG1 and IgG3
Cell mediated immune responses to extracellular bacteria
- CD4 + helper T cells induce local inflammation, enhance the phagocytic and microbicidal activities of macrophages and neutrophils, and stimulate antibody production
- Th17 responses recruit neutrophils and monocytes and promote local inflammation at sites of bacterial infection
Intracellular bacteria
- Bacteria that are ingested by macrophages but able to survive and replicate within these cells
- some infect nonphagocytic cells
- Can be facultative or obligate intracellular bacteria
Immunity to intraceullar bacteria
- The innate immune response to intracellular bacteria is mediated mainly by phagocytes and NK cells
- The major protective immune response against intracellular bacteria is T cell–mediated recruitment and activation of phagocytes
Cytokines that mediate innate immune response to intracellular bacteria
Il-12 and IFN-γ
M1 macrophages
- Classically activated macrophages
- Microbicidal and inflammation
- induced to differentiate by IFN gamma and CD40L
M2 macrophages
- Alternatively activated macrophages
- Anti inflammatory effects, wound repair
IFN-γ and TNF-α, produced by Th1 cells, and CD40:CD40L interaction
Contribute to the recruitment of monocytes and granulocytes and
activate the anti-microbial activity of macrophages through phagosome maturation, production of reactive nitrogen intermediates and antigen presentation
Mechanisms used by bacteria to subvert the host immune system
- Inhibition of PAMP recognition
- Antigenic variation
- Inhibition of opsonisation
- Resistance to antimicrobial peptides
- Phagocytosis inhibitions
Mechanisms used by Neisseria
gonorrhoea to evade humoral immunity
- Fails to evoke a large antibody response
- Secretes an IgA protease to destroy antibody
- Membrane vesicles (blebs) are released (deplete antibody levels)
- Alter antigenic composition (e.g. LPS may be sialylated)
Th1 Effector functions in infections by intracellular bacteria
- Induce and activate M1 macrophages
- Induce apoptosis of bacteria laden macrophages
- Act on naive CD4 and CD8 cells to favour production of Th1
- Stimulate production of monocytes by bone marrow
- Acts on endothelium to enhance macrophage exit from blood vessel
- Produces CCL2, a chemoattractant for monocytes