10: Immune mechanisms in infection š Flashcards
Describe how an infection is controlled by the immune system
Where are PRRs (of the innate immune system) located?
in plasma membrane: lectin - fungal polysaccharides, TLRs - bacterial cell wall lipids
cytosolic: NLR - bacterial peptidoglycan, RLR - viral RNA, CDS - microbial DNA
endosomal: TLR - microbial DNA/RNA
Name Pattern Recognition Molecules of the innate immune system
Pentraxins - ex. CRP
Collectins - ex. MBL
Ficolins - ex. Ficolin
Complement - ex. complement proteins
all located in the plasma, Collectins also in Alveoli
What are the possible ways to fight extracellular bacteria (ex. Staph. aureus)
- innate humoral response: complement system -> lysis of bacteria
- adaptive immune response: B cells -> ABs to neutralise and opsonise (than phagocytosis or complement activation) bacteria
remember: complement system connects innate and adaptive immunity (alternative pathway)
What are the local and systematic effects of cytokines in response to infection?
local: inflammation; TNF and IL-1 increase endothelial permeability and activate Leukocytes , IL-1 and IL-6 attract more cell
systemic protective: TNF, IL-1 and IL-6 in brain cause fever, TNF, IL-1 and IL-6 in bone marrow increase Leukocyte production, IL-1 and IL-6 in liver activate acute phase proteins
systemic pathologic: TNF can cause pathologic abnormalities that lead to septic shock, etc.
What is polyclonal activation of T cells?
antigen independent stimulation of T cells by bacterial superantigens (ex. Staph. aureus) leading to cytokine storm
polyclonal activation is the specific activation of a VĪ²-chain at the TCR
What are the possible ways to fight intracellular bacteria (ex. Listeria m.)?
- innate immune response: phagocytes and NK cells, it normally only controls the growth of bacteria
- adaptive immune response: cellular based -> phagocytosis by Th1 activated macrophages
activation of macrophages is induced by IFN-Ī³
the response is enhanced killing of phagocytoses bacteria, increases expression of molecules for T cell activation and secretion of inflammatory cytokines
If bacteria can survive phagosomes and escape into cytoplasm CD8+ T cells will kill the infected macrophages
What are mechanisms by bacteria to evade the immune system?
- sialylation of LPS
- change of surface antigens
- decoy membrane blebs
- IgA proteases
- pili variants
What are the possible ways to fight fungi?
CLRs are the PRRs often sensing Dectin-1/2 and Mannose
Th17 cells are major T cell subset group to activate Neutrophils and induce production of antimicrobial peptides
What are the possible ways to fight viruses?
TLRs 1-9, RLRs and CDSs are the PRRs for viruses
innate immune response:
- cGAS catalysis cGMP/ cAMP from GTP/ATP activating STING which induces IFN gene expression and by that warning neighbor cells
- NK cells kill infected cells or activate macrophages to clear phagocytosed virus
adaptive immune response:
- AB secretion to neutralise virus
- CD8+ T cells killing infected cells
What are possible immune evasion tactics by viruses?
- genetic recombination (antigen shift), ex. Influenza
- inhibit antigen processing: 1. no proteasomal activity, 2. inhibition of MHC synthesis (HSV, CMV)
What are the possible ways to fight parasites (ex Leishmania major)?
innate immune response:
- complement activation -> opsonisation by C3, a) phagocytosis by macrophage, b) MAC formation
adaptive immune response:
- Th1 T cells activate macrophages further -> infection clearance
- Th2 T cells inhibiting the macrophage activation -> no infection clearance
complex helminths are often eliminated by IgE and eosinophils
What are possible immune evasion tactics by parasites?
- antigenic variation (trypanosomes, plasmodium)
- antigenic shedding (Entamoeba)
- acquired complement resistance (Schistosoma)
- inhibition of immune system (Filaria)
