Flashcards in Host Infection Deck (29)
What are physical/mechanical barriers to infection?
Anatomical - physical barrier, skin
pH - inhibits growth
Flushing and peristalsis - physically removes, tears, saliva, mucous (also a physical barrier)
Host microbiota - competitively inhibits growth
What are innate immune responses to infection?
Non-specific, does not result in immunological memory, no priming
Mucosa contains both innate and adaptive cells at site of infection
Activated by PAMPs and DAMPs
All cells bear some capacity to mount an innate immune response (Cytokine production, Inflammation, Cell surveillance)
What are the major components of the innate immune system?
Pattern recognition receptors - cell membrane markers etc.
NK cell activity
Plasmacytoid DCs - subset of dendritic cells produce antimicrobial cytokines instead of presenting antigens.
Polymorphonuclear leukocytes (PMNs) - granulocytes, component of white blood cells. Neutrophils, eosinophils, basophils etc.
What are the major features of the adaptive immune response?
Specific, involves complex developmental processes, involves priming of naive cells, results in immunological memory
Professional antigen presenting cells (APCs) sample the periphery and migrate through lymph
Activated by antigen presentation on MHC
B cells (mainly produce antibodies) T cells (remove and regulate with cytokines)
Takes longer than innate (hours to days vs. days to weeks)
What are involved in the adaptive immune system?
Specialized APCs in specialized sites
Major processes during an adaptive immune response (Antibody production, Cell cytotoxicity, memory generation)
Major components of the innate immune system (APCs, T cells, B cells)
What is common about complement and antibody activation?
Opsonization of antigens/pathogens leading to phagocytosis and pathogen destruction
NK cells are activated by both (changes in surgace MHC expression etc)
NK cells activate multiple components of both (IFN gamma production, inflammatory cytokine production etc)
Dendritic cells have both innate and adaptive immune functions
What are characteristics of passive immunity?
Transfer of active immune mediators to a host
maternal transfer - milk (Pathogens can also be transferred e.g. HIV)
artificial transfer - antitoxins, antiserum, antivenom
provides protection against antigen
does not provide memory - antibody half life is days to weeks, it is transient
What are characteristics of active immunity?
The production of active immune mediators within a host
Innate and adaptive (humoral and cellular)
Provides protection against antigen
Provides immune memory
What are the general patterns of innate antibacterial immunity?
Innate: PAMPs active TLRs adn NLRs leading to activation of NFkB transcription factor, inflammation, antigen presentation (cell wall components, flagellin, modified DNA)
Bacteria activate antimicrobial peptides leading to bacterial cell wall destruction
Bacteria activate the complement cascade leading to phagocytosis
What are general patterns of adaptive antibacterial immunity?
Processing of extracellular antigens leads to activation of a largely humoral response (antibody mediated)
Th17 cells and antibodies promote clearance of extracellular bacteria
Th1 cells promote clearance of intracellular bacteria
What are factors that adaptive immunological memory and sterilizing immunity depends on?
Pathogen specific factors (breadth and duration of antigen presenation, pathogen evasion mechanisms, host immune competency)
What are patterns of antibacterial immunity in bacteremia?
Blood glucose levels generally decrease - bacteria is using it
blood protein levels relatively normal - Bacteria also producing protein?
Neutrophilia may be an indicator of bacterial infection
What are patterns of antibacterial immunity in CNS infection (meningitis/encephalitis etc)
CSF glucose levels generally decrease
CSF protein levels relatively normal
Neutrophilia may be an indicator of bacterial infection
What are patterns of antibacterial immunity in bacteria who evade phagocytosis?
Granuloma formation leads to immune mediated damage - centre becomes necrotic
Ie mycobacterial disease (TB, leprosy)
Also a feature of some fungal infections
What are the general patterns of innate antiviral immunity?
PAMPs activate TLRs, NLRs, and RLRs leading to activation of NFkB transcription factor, inflammation, antigen presentation (dsRNA, Non-self RNA)
Many viruses alter MHC expression, leading to recognition and destruction by NK cells
Type 1 IFNs are responsible for the induction of an antiviral state in affected cells (inhibition of viral gene expression, apoptosis of infected cells, promotion of antigen presentation etc)
What are the general patterns of adaptive antiviral immunity?
Processing of intracellular antigens leads to activation of a largely cellular response (T cell mediated)
Th1 cells promote cellular cytotoxicity and clearance of viral infected cells
What does adaptive antiviral immunological memory and sterilizing immunity depend on?
Breadth and duration of presentation
pathogen evasion mechanisms
host immune competency
What are the general patterns of immunity in viremia?
Blood glucose levels relatively normal - use same amount as host cell would just hijacked for viral proteins
Blood protein levels generally increase - producing large amount of viral proteins as replicating within a cell
WBC numbers generally increase - not neutrophil predominate, no one granulocyte predominates
What are the general patterns in antiviral immunity in a CNS infection? Meningitis/encephalitis etc
CSF glucose levels relatively normal
CSF protein levels generally increase
WBC numbers generally increase
Same as viremia serological markers
What are the general patterns of innate antifungal immunity
PAMPs activate TLRs and Ctype lectins leading to activation of NFkB transcription factor, inflammation, antigen presentation (Mannosylated cell wall proteins, B-glucan, chitin)
COmplement activation leads to opsonization of pathogen
Phagocytosis by neutrophils, macrophages and DCs are an important part of antifungal immunity
What are the general patterns of adaptive antifungal immunity?
TH1 cells promote cellular cytotoxicity and clearance of fungally infected cells INFgamma and IL12
Potential role for Th17 cells in antifungal immunity
TH2 cells generally thought to promote fungal susceptibility rather than promote clearance
Neutrophilia may be indicative of fungal infection
What are the general patterns of innate antiparasitic immunity?
TLRs NLRs Ctype lectins scavenger receptors and other antimicrobial peptides recognize parasite compounds leading to activation of inflammatory pathways and immunological protection
(Cell surface markers)
Phagocytosis by macrophages and neutrophils aids in clearance of parasite
What are the general patterns of adaptive immunity against parasites?
TH2 cells associated with helminthic and other protozoan infections, may promote progression of non protozoan infection
TH1 cells and IFN gamma are important sources
B cells and antibodies
Species dependent activation of adaptive immunological responses
Eosinophilia may be indicative of helminthic infection or other parasitic infection
What are evasion strategies used by microbes?
At all levels of host response to infection
alteration of MHC expression
Degradation of host antimicrobial components
Utilization of host immune functions
What is molecular mimicry?
Infection produces a protein that looks like host protein
What is a soluble ligand/receptor response?
Sequesters a molecule of interest from doing what it is supposed to do
Competitively inhibits a host cell ligand or receptor (also molecular mimicry)
What is degradation of host antimicrobial components?
When infection breaks down molecules of the host immune system
What is an example of a microbe that utilizes the host immune function?
Activation of immune response propagates infection