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lipopolysaccharide (LPS)
- major inflammatory stimulus found in gram negative bacteria
- aka endotoxin
- elicits septic shock via TLR4
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gram staining
- gram +: purple
- gram -: pink
- based on thickness of peptidoglycan on cell wall
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bacteria lipoproteins signal through which receptor?
TLR2
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Composition of bacterial lipoprotein
diacylglycerol moiety bound to cysteine through thioester linkage
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4 Toxin producing bacterial diseases
- cholera (vibrio cholerae): bacteria stays in gut lumen and secretes toxins
- tetanus (clostridium tetani): secretes very low amounts of potent neurotoxin that's undetected by immune response
- diphtheria (corynebacterium diphtheria): transmitted via respiratory secretions, toxins kill epithelium and form pseudomembrane leading to airway swelling
- toxic shock (staphylococcus aureus): produces superantigens that activate many T cells to develop shock
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Viral life cycle
- attach to host surface receptor
- internalization in endocytic vesicle
- uncoating of protein shell
- nucleic acid is used to synthesize viral mRNA
- mRNA directs synthesis of viral proteins
- viral particle sself assemble and exits infected cell
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cellular tropism
each type of virus can only infect a narrow range of eukaryotic host cells
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Herpes simplex viruses
- infect neuronal cells
- exists in nucleus as an episomal element (plasmid-like)
- periodic release of virus results in recurrent outbreak
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2 major differences betwee human and fungal cells
- carbohydrate polymer cell wall
- surrounding matrix of manoproteins/mannans
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What are mannoproteins?
- conjugates of peptides with long polymers consisting of mainly mannose
- initiate immunity via TLR
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2 morphological forms of fungi
- Yeast: single cell, reproduce asexually via budding
- Mould: complex filamentous form
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Where do fungi grow?
- soil
- extracellulary inside host
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Candida cause disease under these 4 circumstances
- antibiotic treatment reduces normal bacterial flora
- chemotherapy reduce # of neutrophils
- AIDS
- other immunodeficient syndromes
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What disease is caused by cryptococcus neoformans?
- inhalation of this yeast causes pneumonia
- can cause meningitis in AIDS patients
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How does cryptococcus neoformans escape phagocytosis by neutrophils and macrophages?
polysaccharide capsules
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Defect in which part of the immune system is especially detremental in a histoplasma capsulatum infection?
- Cell mediated immunity
- this yeast can avoid killing and proliferate within macrophages, so they must be controlled by cell mediated immunity
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Characteristics of asperguillus
- opportunistic pathogen mould
- inhaled spores usually stay dormant unless host has low PML and macrophage counts
- causes pneumonia
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Disease caused by entamoeba histolytica
lives in the intestine, can cuause ulcers and bloody diarrhea
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What are helminths?
Worms
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Response and result to helminth infection
- local inflammation with plasma cells, eosinophils, and mast cells
- histamine release
- chronic inflammation may lead to fibrosis
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Disease caused by trypanosoma
African Sleeping Sickness
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TLR family receptors is part of the ___ immune system?
innate
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pathogen-associated molecular patterns (PAMPs)
innate immune system uses PAMPs to sense presence of pathogenic microbes
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pattern recognition receptors (PRRs)
receptors used by innate immune system to recognize PAMPs
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What is mannose-binding lectin (MLB)?
- soluble component of innate immune system
- targets bacteria for phagocytosis
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Mechanism of MBL action
- MBL= mannose binding lectin
- localizes on bacterial cell wall by binding specific spatial pattern of mannose and fructose residues
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2 most common causes cold
- Rhinoviruses (30%)
- Coronavirus (15%)
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Pathway of common cold infection
- viruses attach to nasopharynx via ICAM1
- viral replication within cell then spread to upper respiratory tract
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Timeline of common cold infections
Infection occurs 2-3d prior to development of symptoms, and usually resolves 7-10d later
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1st step of innate immune response to viral infection
activate type 1 interferons in infected cell
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RIG1 and MDA5 localization and function
- - PRR sensors that are expressed in cytoplasm/cytosol of most cells
- - recognizes dsRNA
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pathway of innate immune system in a viral infection
- PRR sensors (RIG1 and MDA5) recognize viral dsRNA
- activate transcription factors (IRF3, IRF7)
- initiate production of type 1 interferons
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4 pathways initated by tyep 1 interferon
- induce resistance to viral replication in all cells
- increase MHC class I expression and antigen presentation in all cells
- activate dendritic cells and macrophages
- activate NK cells to kill virus-infected cells
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Function of MHC class I molecules
enhance recognition and killing of virally infected cells by cytotoxic T cells
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Function of dendritic cells
promote initiation of adaptive resonse in local lymph nodes
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Function of macrophages
promote secretion of inflammatory cytokines
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What is the most immediate innate response to viral infection?
NK cell activation target production of virus by infected cell
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Development of NK cells (location, lineage)
- produced in bone marrow
- circulates in blood
- lymphoid
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What activates NK cells?
- type 1 interferon
- other macrophage-induced inflammatory cytokines
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How is NK cell killing regulated?
- NK cell inhibitory receptors block killing of cells with normal amoutns of MHC class I molecules
- downregulation of MHC class I molecules in virally infected cells will be lysed
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Basic responsibility of MHC class I molecules
presenting pieces of intracellular pathogens to CD8+ T cells
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Evolution of NK cells
- MHC class I molecules present intracellular pathogens to CD8+ T cells
- some viruses evolve to downregulate MHC class I molecules in infected host to evade CD8+ T cells
- innate immune system develops NK cells which lyse cells lacking MHC class I molecules
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4 primary responsibilities of the innate immune system
- prevent infections into sterile tissues
- detecting infections in sterile tissues
- mounting an immediate, nonspecific response to clear pathogen
- transporting antigens to lymph node to elicit adaptie response
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3 ways to breach simple mechanical barriers (epithelial tight junction)
- microscopic trauma
- major trauma
- introduced by arthropod vectors
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9 types of innate immune barriers
- epithelium with tight junction
- longitudinal air/fluid flow
- movement of mucus by cilia
- fatty acids
- low pH
- pepsin (enzyme)
- lysosozyme (salivary enzymes)
- defensins (antibacterial peptides)
- normal flora
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5 cellular processes of innate imune system
- phagocytosis
- inflammation
- recognition of extraellular pathogens
- recognition of intracellular (viral) infections
- recognition and kiling of viral infected cells by NK cells
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4 pro-inflammatory cytokines
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local and systematic effects of IL-1beta
- activate vascular endothelium
- activate lymphocytes
- local tissue destruction increases access of effector cells
systemic: fever, IL6 production
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local and systemic effects of TNF-alpha
- activate vascular endothelium and vascular permeability
- increases entry of IgG, complement and cells
- increases fluid drainage to lymph nodes
systemic: fever, shock, mobilize metabolites
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local and systematic effects of IL6
- lymphocyte activation
- increased antibody production
systematic:fever, acute phase protein production by hepatocytes
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effects of Cxcl8
chemotactic factor recruits neutrophils, basophils,a nd t cells to site of infection
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effects of IL12
- activates NK cells
- induces differentiation of CD4 T cells into Th1 cells
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Effects of IL1beta/IL6/TNF-alpha on LIVER
- acute phase proteins (mannose binding lectin)
- activation of complement opsonization
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Effects of IL1beta/IL6/TNF-alpha on BONE MARROW ENDOTHELIUM
- Neutrophil mobilization
- phagocytosis
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Effects of IL1beta/IL6/TNF-alpha on HYPOTHALAMUS
- increased body temperature
- decreased viral and bacterial replication
- increased antigen processing
- increased specific immune response
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Effects of IL1beta/IL6/TNF-alpha on FAT/MUSCLE
protein and energy mobilization to increase body temperature
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Effects of TNF-alpha on DENDRITIC CELLS
- migration to lymph nodes and maturation
- initiates adaptive immune response
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