Immune evasion Flashcards
What are the three preformed antimicrobial agents?
Interferons
Complement
Opsonin
What is the innate immune system?
Non-antigen specific, functions on the basis of recognising pathogenic and molecular patterns.
There is no immunological memory conferred through this system.
What are PAMPs?
Diverse set of microbial molecules, whereby general structural and biochemical patterns are shared through pathogen recognition receptors.
Which type of receptors detect PAMPs?
Pathogen recognition receptors (PRR)
Which type of transmembrane proteins located on leukocytes recognise conserves molecules through bacterial structures and viral structures?
Toll-like receptors
What are the examples of bacterial PAMPs? (4)
Flagellum (protein flagellin)
Lipopolysaccharide (Endotoxin)
Peptidoglycan
Glycolipids
What are the examples of viral PAMPs? (3)
Glycoproteins Double stranded (ds) DNA Single stranded (ss) DNA
What type of bacteria is S.aureus?
Gram positive, coagulase and catalase positive
Which type of coagulase bacteria is s.aureus?
Coagulase positive
What is the structure of s.aureus?
Consists of polysaccharide capsule, cell protein A, has catalase, coagulase proteins embedded within coat.
What is the function of the polysaccharide capsule within s.aureus?
Protective against phagocytes
What is protein A?
Clumping factor proteins, mediates adherence of bacteria to host tissues.
What is the function of catalase?
Protects the bacterium from peroxides produced by neutrophils and macrophages
What is the function of coagulase?
Converts fibrinogen to insoluble fibrin resulting in clot formation, protects from phagocytosis
Which enzymes secreted by s.aureus stimulate tissue destruction?
Lipases, nucleases and hyaluronidase
Which cytotoxins lyses erythrocytes, neutrophils, macrophages and host cells?
Cytotoxin, alpha, beta, delta, gamma and leucocidin
Which type of toxins are heat stable and acid-resistant?
Enterotoxins
Which type of toxins cause scalded skin syndrome?
Exfoliative toxins A and B
What is scalded skin syndrome?
The superficial layers of skin peel off
What is a pyogenic?
Pus forming
What two groups of diseases are formed from s.aureus?
Localised pyogenic diseases
Systemic diseases
What are localised pyogenic diseases?
Diseases characterised by tissue destruction mediated by hydrolytic enzymes and cytotoxins
What types of antigens do toxins behave as?
Superantigens
What type of disease is impetigo?
Pyogenic disease; localised skin infection characterised by pus-filled vesicles on a erythematous base.
What type of disease is pneumonia?
Pyogenic
Abscess formation in the lungs, secondary infection succeeding viral infections of the respiratory tract.
What type of pyogenic disease concerns hair follicles?
Folliculitis.
What type of disease are furuncle and carbuncles?
Large pus filled skin nodules progress deeper skin layers and spread into circulation.
Which S.areus pyogenic disease is associated with abscess formation in the lungs?
Pneumonia
What is osteomyelitis?
Bone degradation, primarily in highly vascularized areas of long bones
What is septic arthritis?
Infection of joint regions characterized by a swollen reddened join with an accumulation of pus
What are the three main toxin-mediated diseases of s.aureus?
Toxic shock syndrome
Food poisoning
Scalded skin syndrome
Why does food poisoning occur with s.aueus?
Consumption of heat-stable enterotoxin contamination results in the onset of severe vomiting, diarrhea, and stomach cramps
What is scalded skin syndrome?
Localised infections produce the toxin that traverses into circulation and causes outermost skin layer to blister and peel off
What is toxic shock syndrome?
Produced toxin that affects multiple organs, characterised by fever, hypotension, and a diffuse , macular, erythematous rash.
Which protein molecule assists with pathogen recognition for neutrophils & phagocytes?
Complement
How does s.aureus evade antibodies?
Contains polysaccharide capsule on cell surface membrane, resulting in masking the antigenic structures, preventing detection by the innate immune and adaptive immune components (complement and antibodies)
Capsule enhances microbial virulence
SpA secretion binds onto fc regions of antibodies
Antibody degradation
Antigenic variability
Which s.aureus protein binds to the respective Fc region expressed on antibodies?
SpA
What does SpA surface protein do?
Inhibits opsonization, and thereby preventing neutrophil detection of S.aureus (Associated Fc receptor cannot bind to unavailable Fc region)
Which immunoglobulin does SSL10 bind on the Fc region to?
IgG
Which antibody region does SSL10 bind onto?
Fc region of igG
What is the mechanism of SSL10?
Binds to fc region of IgG, prevents the Fc receptors on neutrophils from detecting igG, on the surface of S.aureus obviating neutrophil binding
How are antibodies degraded by S.aureus?
Extracellular proteases are secreted resulting in the hydrolytic cleavage of antibodies
Enzymes: zinc-dependent metalloproteases aureolysin, cyteine proteases
Serine proteases
How does antigenic variability confer antibody evasion?
Antigenic modification of cell surface membrane proteins prevents the binding mechanism of complement & opsonin due to structural incompatibility
Which complement complex is formed which stimulates cell destruction?
Membrane attack complex (MAC)
Which complement behaves as an opsonin?
C3b
What is C3a?
An anaphylatoxin that promotes inflammation
What does activated C3 do to cell membranes?
Triggers lytic pathway and damages plasma membranes of cells
What effect does C5a have?
Attracts macrophages, and neutrophils –> Activates mast cells
How is the classical complement cascade activated?
The antibody-antigen complex binds to C1
What are three components of C1?
CIq, C1R, and C1s
What does C3 convertase do?
Splits C3 into C3b and C3a (Activates mast cells, the release of histamine)
Which protein factors are involved with the alternative complement pathway?
Factor, B,D,H, and I, interacts with each, and with C3b, forms C3 convertase, C3bBb activates C3
What is c3 convertase?
C3bBb
What are the stages of the alternative complement pathway?
Initiation, the formation of c3 convertase, formation of c5 convertase, and MAC formation
Which s.aureus inhibitor protein binds to C3bBb?
SCIN
What does SCIN do?
Binds to C3bBb and inhibits the formation of C3 convertase and c5 convertase
Therefore this prevents the deposition of C3b (opsonin) , and c5a formation
Which protein prevents the binding of factor B to c3?
eFb (Extracellular fibrinogen binding protein)
This mechanism inhibits c3 processing
Which s.aureus peptide inhibits MAC formation?
SSL7
Which complement protein does SSL7 bind to
C5
What is the function of C5?
C5b consists of essential binding sites for the continuation of the cascade to synthesise and activate further complements in the pathway to generate the cytolytic complex (MAC)
What does SSL7 do?
Inhibit MAC formation
What effect does proteases have on complement?
Hydrolytically cleaves the complement protein inhibiting opsonization and MAC formation
What does factor H do?
Presented on the bacterial surface inhibits the action of C3B (opsonin cannot bind)
What granules are neutrophil receptors found in?
Azurophillic and gelatinase granules
What are pathogen recognition receptors?
Receptors directly detect microbial products & structures resulting in neutrophil priming or activation
Which receptors detect conserved microbial structures?
Toll-like receptors
How are microbial carbohydrates detected?
CLECs (C-type lectins)
How are formulated peptides detected?
Detected by Formyl-peptide receptors
G-coupled protein receptor results in extracellular signaling upon cognate ligand binding. FPR 1 key regulator in inflammation
What are fc receptors?
Fc receptors associate to complimentary fC regions of immunoglobulin opsonin antibodies that are attached to pathogens.
Complement receptors detect complement opsonin
What are ITAMs?
Immunoreceptor tyrosine based activation motif
ITAM signalling is required for the differentiation and function of B & T cells in adaptive immunity, and regulates the function of innate immune cells
What are the innate immune cells?
Macrophages, Nk cells, neutrophils and dendritic cells
What are the 6 immune receptors?
Cytokin receptors Chemoattractant LAIR SIGLEC LILR CEACAM
What are activator receptors?
Enhances immune cell activity
What are inhibitory receptors?
Suppresses immune cell activity
Which protein inhibits the chemotaxis of neutrophils and monocytes?
CHIPs
What is the full name for CHIPs?
Chemotaxis inhibitory protein of staphylococcus aureus
Which receptor does CHIPs bind onto?
C5aR and FPR
What effect does CHIPs have on neutrophils?
CHIPs blocked binding actions of C5Ar, therefore this means that the receptor sites are not activated, and neutrophils subsequently do not migrate to the sites of infectons, and do not become activated through C5aR or FPR 1
Which receptors do FLIPr bind onto?
Fc y receptors
What effect does FLIPr have?
Binding onto Fc Y receptors prevents the detection of IgG opsonized bacteria
What effect does SSL5 have?
Inhibits Fc alpha receptors, thereby reducing antibody-mediated phagocytosis and prevents s aureus destruction
How does s.aureus evade neutrophils using antagonists?
Receptor antagonists bind and inhibits the function of activatory receptors
What does SPIN do?
Inhibits the effects of mitochondrials
What are the four main mechanisms of neutrophil evasion?
Inhibit chemotaxis
Inhibit detection of bacteria
Kill neutrophils
Stimulate inhibitory receptors
