Wh'Odilia? YOUdilia WHIINNNEEYYBURG Flashcards
Bacterial adherence is mediated by: (4)
pili, fimbrae, afimbrial adhesins, polysaccharide capsules
T/F: Antigenic variation in the surface structures of a pathogen is a form of immune evasion
TRUE: Allows pathogen to evade current specific immune responses by changing antigen being detected
T/F: Bacterial colonization of host mucosal surfaces by Shigella involves attachment and invasion
TRUE: contacts host surface and induces membrane ruffling –> internalization
T/F: NK cells are innate cells that engulf bacteria and kill them through release of granules containing perforin, granzymes and granulysin
FALSE: NK cells detect changes on cell surface of infected cells and kill infected host cells, not bacteria DIRECTLY
Phagocytosis:
Enhanced by opsonization
T/F: APC activate T and B lymphocytes
FALSE: APCs present antigens as peptides in MHC molecules recognised by T lymphocytes using T Cell receptors
CDF lymphocytes produce cytokines that help B to produce antibodies
B do not have a receptor that recognises MHC/peptide complexes presented on surface of APC and use antibody to recognise antigen
CD4 helper T cells
Provide help to B cells through CD40-CD40L interactions
Recognise MHC II
Mature into Th1 in lymphoid tissue
Do not express innate immune receptors
T/F: Antibodies are proteins that have multiple functions (3)
TRUE:
- Bind antigens through Fab fraction
- Bind complement using Fc fraction
- Bind to FcR through Fc fraction
CD4 helper 2 cells characterised by ability to produce:
IL4 and IL5
Leukocytes:
Stem cell:
- Common myeloid progenitor
a) Auxiliary cells: megakarocyte –> platelets, mast cell, basophil
b) Phagocytes: neutrophil, eosinophil, monocyte –>macrophage
c) dendritic cell - Common lymphoid progenitor:
a) NK cell
b) B cell –> Memory B, plasma
c) T cell –> effector T, Cytotoxic T, Memory T
PAMPS
Unique to microbes but shared within discrete taxonomic groups e.g. LPS
Recognised by special receptors of innate immune cells
TLR:
1&2, 2&6: surface lipoprotein 3: ds RNA 4: LPS 5: flagellin 7/8: ssRNA 9: CpG DNA 11: uropathogenic bacteria
NOD like receptors
Recognise peptidoglycan
Sensors of PAMPs and DAMPs
RIG like helicases
important in antiviral immunity
Collectins
proteins that bind carbohydrates
DAMPs
Can initiate and perpetuate immune response in noninfectious inflammatory response
Complement: (4)
- Opsonize
- mediate inflammatory responses
- activate B cell responses
- Kill through complement membrane attack
Cytokines: (2)
- Orchestrate immune responses
2. activate cells of adaptive immune system
Inflammasomes
Multiprotein oligomer: caspase 1, PYCARD, NALP and sometimes caspase 5(11)
Expressed in myeloid cells
Innate immune system
PROMOTES MATURATION OF INFLAMMATORY CYTOKINES IL1B, 1L-18
Shown to induce cell pyroptosis (programmed cell death associated with antimicrobial responses during inflammation)
NLRC4
Contains CARD domain + NBD + LRR to recruit procaspase-1 directly
Activated by bacteria e.g. Salmonella, legionella, pseudomonas
Inflammasome components:
NLR: sensor
NACHT: NLR oligomerisation
PYD: signal transduction, caspase recruitment
ASC domain: bridging or adaptor protein recruits pro-caspase 1
Activated Caspase 1 activates:
- preILb –> IL1b: promotes inflammation
2. IL18: +IL12 promotes IFNg production
NLRP3
Biggest inflammasome Activated by: 1. low intracellular potassium concentrations 2. viruses 3. N.gonorrhoeae 4. bacterial toxins 5. liposomes 6. crystallized endogenous molecules
Complement System:
- Classical pathway - antibody complexes
- Mannose-lectin pathway:
- Alternative: Pathogen surfaces bind C3b
Activation of complement system
c3 convertase –> c3 –> C3b –>C5b –>c5b binds C6,C7,C8,C9 –> membrane attack complex (lysis of bacteria)
C5a
Peptide mediator of inflammation, chemotaxis and B cell activation
Mast cells release vasodilator
Fever
Chemoattractant for neutrophils
Stimulates neutrophils to release oxygen radicals
Antibody isotypes
IgG & E: monomeric
IgA: dimeric, connected by J chain
IgM: pentameric, connected by J chain
Antibody roles:(4)
Neutralization
Opsonization
Complement activation
Agglutination
MHC
II: present to CD4, expressed by APCs
I: present to CD8, found on all cells
Treg
–> tGF-B: produces TGFb, IL10
Th1
Needs IFNy
IFNy: macrophage activation, cytotoxic T cell activation
TNFa: inflammation, cytotoxic T cell activation
IL2: Proliferation of Th1 cells
Th2
needs: IL4
IL4: antibody synthesis
IL5: eosinophil activation
IL10/13: downregulation of immune response
Th17
IL17, IL6, TNFa: inflammation
Vaccine
Antigens derived from bacteria/virus
Stimulates memory immune response
Non toxic or attenuated antigens that are injected, ingested, or inhaled to induce the specific protective host immune defences without having to go through the disease process
Antigen
substance that interacts with an antiboy
immunogen
antigen that elicits an immune response
Epitope
Part of the antigen that is recognised by the antibody
Continuous epitope
1 chain of peptides
Discontinuous epitope
Made up of different parts of a protein
Passive vaccination
Short term
Human Ig preparations from pooled human sera
Administering antibodies or antitoxins
Immediate line of specific defence - neutralize venoms
Active vaccination
Immune memory
Antibody responses
Design into CTL/Th responses - viral infections/TB
vaccine responses
prophylaxis: prevent infectious disease
therapeutic: cure existing infectious disease
anti-hormone: block physiology
Requirements for a vaccine
Safety
Efficacy
Stable
Affordable
Enhancing immunogenicity
correct type of immune response
adjuvants - increase immunogenicity (stimulate/modify immune system)
targeting innate immunity to activate adaptive immunity
target mucosal immunity e.g. cholera
Whooping cough
Bordatella pertussis -GN coccobacilus
Spread by aerosols
Toxins (pertussis toxin), adenylate cyclase, adhesin
Original whole cell vaccine tested in Kendrick test
Now given as triple antigen - pertussis, tetanus, diptheria
Incorporate virulence determinants - toxoids and adhesins
Tetanus vaccines
95% efficacy Need noninjectable Clostridium tetani - enviornment, can't erase Toxin-neutralizing antibodies Inhibits disease, not infection Antibody level need to be high enough
Haemophilus influenzae
Immunity develops 10-16 years old
Epiglottitis - rare but dangerous
Capsule inhibits C3b binding - bacteria evade phagocytosis
Uncontrolled growth –> septic shock –> cytokines act on blood vessls –> reduced blood pressure
Conjugate vaccines
Capsular antigens and help for b cell to isotype switch –> memory
Strep pneumoniae
GP diplococcus
Asymptomatic colonization URT
Invasive pneumococcal disease
Virulence factors - capsule, adhesins, pneumolysin
Strep vaccine
Polysaccharide (PS) -7
Protein conjugate vaccine (PCV) -13
Based on most common serotype in Australia
Herd immunity - reduced invasive pneumococcal in children and elderly
Less successful vaccines
No protective response: salmonellosis, cholera, TB (pre existing immunity?)
Side effects: rotavirus - intestinal blockage
Worsen disease: RSV, c.trachomatis
Enhancing immunogenicity of vaccines
Eliciting correct type of immune response: intracellular vs extracellular, multiple virulence factors, potential antigens difficult to identify
Target dendritic cells and innate immune sensing
Target mucosal immune systxem
New approaches to vaccines
Live attenuated: dliver >1 antigen, genetic mutations
Delivery route (oral, intranasal)
Naked DNA vaccines
Novel adjuvants
