Flashcards in Immunity to infectious Disease and Vaccines Deck (79):
Why is immunity to infectious disease important?
1/3 of world (and US) deaths from ID, immune response necessary for survival, increased number or antibiotic resistant B, increase crowding and travel allows exposure to evolving viruses
What parts of the immune system are activated from virus infection in order?
very early/immediate: innate immune response IFN and cytokines, next NK cells mobilize to infection site, there is recognition of viral antigens, day 4-6 adaptive immune response (CD8 cells), followed by Ab production, develop memory, then can get anti-host pathologic effects (too vigorous response)
How des the body first recognize a viral infection?
RIG-1 receptor in infected cell, recognize viral dsRNA, or toll like receptors (TLR 3,7,8,9) recognize dsRNA, vsRNA, CpG DNA
Once viral infection is recognized, how is the innate immune system activated?
IFN regulatory factor and NfkB activated in dendritic cell, which stimulates secretion of INF alpha and beta and inflammatory cytokines (TNFa, IL6, IL12)
How does IFN alpha and Beta induce a cell into an anti-viral state?
translation of protein kinase R-> block eukaryotic initiation factor 2a activating BCL2 and caspase->apoptosis, 2,5-oligoadenylate cyclase Synthetase-> activate Rnase L-> degrades vRNA, and Mx protein-> blocks viral transcription
What cells in the immune system does IFN alpha and Beta activate?
dendritic cells, macrophages, NK cells T and B cells
Once activated by IFN alpha and Beta, what do dendritic cells and macrophages do during viral infection?
"garbage collectors", phagocytosis, Ag presentation, release of cytokines, kill virus infected cells
Once activated by IFN alpha and IL-12, what do NK cells do during viral infection?
cytotoxic to virus infected cells, produce IFN-gamma to activate adaptive immune system, shut down virus replication in cells, buys time for adaptive immune response
How does the adaptive immune system recognize virus or viral infected cells?
Viral Ag on EC surface(membrane or capsid AG on infected cells, viral structural proteins inserted in host membrane); Ab also recognize viral surface Ag on virion
What are the primary and secondary responses of adaptive immune system? what role does each play?
1- T cell, leads to resolution of infection; 2- Ab response, contributes to recovery from infection
In the primary T cell response what activates CD4+ cells and what do they do? Be specific for different kinds.
Both activated by IL-12 and IFN-gamma, TH1- produce IL2 to activate macrophage, induce T (CD8) and NK cell activation and proliferation, promote B cell production if Ig; TH2- provide help for B cell activation, differentiation, production of Ab, also activate eosinophils
In the primary T cell response what activates CD8+ cells and what do they do?
activated by IL-2 (from CD4+) cytotoxic to infected host cells, produce IFN-gamma and TNF which inhibit viral replication; principle surveillance (peptide and MHC class I)- direct killing by perforin and granzymes or activation of FAS ligand-> apoptosis
What is the course of Ab production in viral infection?
CD4+ help viral antigen specific B cells in lymph node- proliferate, clonal expansion, differentiation, somatic hypermutation occurs and selection for highest affinity B cells producing Ab to become plasma cell and migrate to bone marrow
Once made what does Ab against viral Ag do with extracellular virions?
binds extracellular virus and either prevents entry to host cell and/or enhance phagocytosis and mediates opsonization of viral particles (IgM, IgG and IgA)
Describe the features of antibody dependent cell cytotoxicity (ADCC).
Ab binds viral antigen on EC surface, activation of complement= lysis of infected cell
What role does immunologic memory play in viral infections?
preformed Ab, memory T cells and B cells can rapidly expand and differentiate into effector cells (much quicker and stronger response), reason behind viral vaccines (mom can pass to baby- Ab)
What are some examples of anti-host effects of virus in impairing the immune system?
immune evasion, avoidance of recognition, inhibit humoral immunity, inflammatory response, immunosuppression of host, infection of host immune cells (shut down or down regulate IFN and cytokine production)
How can viruses evade the immune system?
antigenic drift and shift (HIV and Flu), molecular mimicry (steal some of host genome so recognized as self)
How can viruses avoid recognition by immune system?
latent infection, replicate in "privileged" sites in host like CNS (very little to no immune activity), impair recognition by reducing MHC expression on infected cells
What are the pathologic consequences of the immune response induced by viral infection?
excessive cytokine production (cytokine storm), antiviral Ab form immune complexes causing disease, or virus specific T cells cause host damage
What are the consequences and some viral examples of excessive cytokine production?
acute respiratory distress (ARDS) seen with Flu A H5N1, H1N1 and Sars, usually mid-range of age, immune competent; in Ebola-> cytokine and damage to endothelial cells (infected)-> loss of vascular integrity, hemorrhage and vasomotor collapse may occur
When immune complexes are formed what condition can ensue with immune complex disease?
When virus specific T cells cause host cell damage, what else can happen? Viral examples?
induce autoimmunity; Hep B, Coxsacki B virus (islet B cells), and enterovirus-> anticardiomyocyte CD8 cells
What is the general immune response to bacterial and fungi?
induce inflammatory responses, produce cytotoxic endotoxins (LPS) or exotoxins (diphtheria toxin), recognition of B by PAMPs and recognized host TLR
What are the features of the innate immune response?
chemotaxis: C3a and C5a recruit phagocytic cells, following complement activation via alternate path, phagocytes (Macrophage and Neutrophils) engulf and destroy bacteria
What are the adaptive effector response to bacterial infection?
CD4+ T cells produce- IFN gamma and TNF to activate macrophage and induce inflammation, IL-4,5,6 induce Ab formation
What specific CD4+ T cell is important in resisting bacterial infection? Cytokines produced?
TH17 producing IL-17 (recruits neutrophils) and IL-22
What role do CD8+ T cells in bacterial infection response?
intracellular organism killed by killing the infected cell (very important in reponse to TB), secretes IFN-gamma to activate macrophages (kill infected B cells)
What are the Ab dependent anti-bacterial defenses?
neutralize toxins- Ab to toxin binds to toxin blocking binding of microbes to cellular receptors, increased opsonization and phagocytosis, activate and efficient targeting of complement
What are the bacterial defenses against host response to infection?
encapsulation, evade complement activation, kill phagocytes before ingestion, resistance to phagocytosis, phagosome-lysome fusion and lysosomal killing, intracellular microbes, can survive in phagocytes
What are the immunopathological reactions induced by bacteria?
excessive cytokine release (endotoxin septicemic shock, TSS) due to LPS from gram (-) bacteria; and superantigen of massive cytokine release (TSS) of staphylococcal toxin
What are the four major categories of fungi?
superficial mycoses, subcutaneous mycoses, respiratory mycoses, and candida albicans
What is the immune response to fungi?
primarily innate- neutrophils and macrophages for killing fungi; T cell response protective including CD4+ Th1 (delayed type hypersensitivity) and Th17
What are the general features of immunity to protozoa and worms?
complicated life style, complex relationship with host and immune system, poor immune response to chronic infections, immune evasion by antigenic variation (very efficient), no in vitro culture system (don't understand replication well)
What are the features of innate immune response to protozoa and worms?
PRRs on phagocytes recognize PAMPs on parasite, TLR 2,9,11, classic PRR: collectins, lectins, scavenger receptor, complement receptors CR3
What role do the various phagocytic cells play in protozoa and worm infections?
macrophage- smaller parasites, neturophils- clean up damage, eosinophils- responsible for helminthes IL-5 required, association with IgE, Mast cells control GI helminths
What is the adaptive immune response for T cells to protozoa and worms?
T cell- fund. to control infection and confer protection, Cytokines- Th1: IFN-gamma, TNF alpha, IL-2 and Th2: IL3,4,5,6,9,10,13;
What is the adaptive immune response for B cells to protozoa and worms?
B cells produce: IgM, IgG-activate complement, neutralize attachment, enhance phagocytosis, ADCC IgE: binds mast cell and basophils sensitizing tem to parasite Ag
What are the various immunologic escape mechanisms of protozoa and worms?
resist destruction by complement, intracellular parasites resistant to oxygen metabolites and lysosomal enzymes, hyper antigen variation, hide from and interfere with immune response
prevent disease, limit infection, and allow rapid recovery from infection (decrease morbidity and mortality), large economic, public health, social value, possibility to eradicate disease, required by law to attend school
What are the general concepts behind vaccination?
specific immunological memory using less virulent form of microbe (or toxin) induce long lasting protection, develop rapid, vigorous, specific, protective response (neutralizing Ab and long lived memory B and T cell clones [CD8 and 4]), safe adjuvant to enhance response
What is herd immunity?
vaccinated individuals prevent spread of infection in population, unvaccinated and community protected by vaccinated individuals, important for immune depressed (Pregnant, HIV, Cancer drugs), infants before vaccination and individuals refusing
What is passive immunity? Examples?
preformed Ab produced by humans or animals to treat infections (temporary protection), fetus and infants (IgG and IgA), specific gamma globulin (HepA, HepB, tetanus, snake bites, rabbies), monoclonal Ab (Zmapp to Ebola), and pooled human Ig
What are the features of active immunization?
immunity developed by own immune response (long lasting protection), natural disease exposure or vaccine
What makes an effective vaccine?
need a good antigen (live or attenuated, intact non-living, subcellular fragments, toxoids, recombinant DNA-based), good protocol, use of adjuvants, induce appropriate immunity, Th1 v Th2, Ab vs T cells
What is important in a live or attenuated viral vaccine?
viral replication, good cellular and humoral response, safety is very important because of chance of reversion to virulence;
Give an example of a successful vaccine.
vaccinia (cow pox) replicates but does not cause disease and induce good response to variola (small pox); elimination of one of the most terrible epidemics in history
What are some other live attenuated viral vaccines?
polio (Sabin, OPV, good IgA rep. in gut, never reach brain), Measles, Mumps, Rubella, Yellow Fever 17D, Varicella-zoster, live rotovirus, and flu mist
What are some features of inactivated viral vaccines?
killed or inactivated, need large amounts/multiple injections to induce immunity, usually develop IgG Ab, poor T cell response, protection not lifelong, need to give boosters
What are the features of the polio vaccine?
salk inactivated Polio vaccine (IPV) instead of OPV, use Alum (aluminum salts) as adjuvant, inactivated
What are the features of the rabies vaccine?
first used by Pasteur from infected rabbit spinal cord given to veterinarians and post exposure pre-exposure to dogs and cats, rabies encephalitis 100% fatal, replicate 4-5 days in skin then goes to brain, inactivated
What are the features of influenza vaccine?
good Ab IgG to H and N antigens, poor T cell response recommended given annually, produced in eggs (cell culture alterative), trivalent and quadrivalent, standard dose is trivalent intradermal, inactivated
What are the features of hepatitis A vaccine?
grown in human diploid cells, formalin inactivated, aluminum hydroxide adjuvant attenuated live vaccine available in combo with Hep B
What are the features of Hep B surface Ag vaccine?
subunit viral vaccine, can't grow Hep B in culture, first obtained from serum of Hep B carriers, HbsAg gene inserted in yeast, safe effective vaccine give to all children may prevent HCC
What are the features of the HPV vaccine?
recombinant capsid proteins self assemble into virus-like particles (VLPs) no viral DNA anti-HPV neutralizing antibodies quadrivalent vaccine, with adjuvant for warts and for 70% of all cervical cancers only effective when given prior to infection
What are the features of bacterial vaccines?
bacteria very complex, many antigens, whole cel may provoke hypersensitivity, exotoxins (LPS) are highly inflammatory, toxic, can cause cell use cell wasll, capsular polysaccharides or toxins as Ag
What are the features of live attenuated bacterial vaccines?
induces subclinical infection and protective immunity, produces T and B cell response
What is bacilli clamett-guerin (BCG, micobacteria bovis) and what is it used for?
single pathogen responsible for most death and disease, cell wall induces potent DTH response (CD4+), most used vaccine in the world not used , efficacy as a tuberculosis vaccine depends on cross reaction with M tuberculosis
What are the features of typhoid vaccine?
live oral vaccine, strain Ty21a is LPS deficient, whole bacteria induces Ab and cell mediated immunity (70% effective)
What are the features of inactivated bacterial cells as vaccines?
whole bacteria or cell extracts, inactivated by heat or fromaldehyde, some toxicity
What are the features of the pertussis vaccine?
for whooping cough- devastating resp. disease esp. in kids, whole cell vaccine- effective with some swelling, fever, some cases convulsion and encephalopathy, use a cellular (aP)- small # proteins, less toxic and safer, doesn't work as well
What are the features of the cholera vaccine?
inactivated, injected to induce IgG but need IgA protection in gut, 50% effective
What are the features of the anthrax vaccine?
zoonotic disease 90% fatal if inhaled, inactivation cell-free culture filtrate of attenuated strain, contains protective antigen (animal workers, veterinarians, military personel, biowarfare and terrorist agent
What are the features of bacterial subunit vaccines?
eliminate problems with whole cell, use relevant antigens, less toxicity than whole B, disadvantages: require adjuvant, induces Ab response when long term, may require T cell mediated response (poor)
what are the features of the typhoid bacterial subunit vaccine?
Vi capsular polysaccharide, effective, low reactions, does not produce long term immunity
What are the features of the haemophilus influenza B?
conjugated with polyribosyribitol phosphate (PRP), induces T cell-B-cell cooperation, prevents meningitis in kids
What are the features of the meningococcus vaccine?
purified capsular polysacch. for over 55 years, meningococcal conjugate (diphtheria toxoid vaccine, MCV4 for kids)
What are the features of pneumococcal vaccine?
PPSV23 polyvalent capsular vaccine for adults (>65), Prevnar 13 valent pneumococcal polysacch. protein conjugate for kids and immunocompromised
What are the features of the Lyme disease vaccine?
vaccine available but recent data shows significant adverse effects, manufacturer removed vaccine
What are the features of toxoid vaccines?
chemically inactivated exotoxins, need multiple doses for good protection, IgG Ab
What are the features of diphtheria vaccine?
toxin lost ADP ribyltransferase activity, but still immunogenic
What are the features of tetanus vaccine?
chemical inactivation of neurotoxin, give to children with DTaP vaccine, should be repeated every 10 years
What are the general features of parasite vaccines?
none effective, eukaryotes difficult to treat or vaccinate as genome similar to vertebrates, immune response learned to evade immune response and rapid replication in host will allow escape variations to evade vaccine immunity,
what are the features of the malaria vaccine?
both intracellular and extracellular stages in host CD8 T cell immunity important for liver infection, RBC surface antigens shown protection peptide sequences for several Ag in one large peptide, RTS single surface protein from plasmodium sporozoite, killed
What are some new approaches for vaccine development?
DNA vaccines, need new adjuvants, proposed Ebola vaccines, need HIV
What are the features of DNA vaccines?
DNA plasmid incorporating appropriate gene for potential vaccine candidate injected into muscle, DNA codes for peptide presented to immune system, used in animals for 10 years
What are the proposed ebola vaccines?
NAID and GlaxoSmithKline NIH phase I clinical trial, use chimpanzee adenovirus vector with genes for surface glycoproteins, successful in monkeys but booster provides long lasting immunity
What is necessary for a future HIV vaccine?
must prevent T cell and macrophage infection, be effective against all variants, difficulty in tests with animal models