Immunity to Infectious Diseases-2 Flashcards
(38 cards)
1
Q
What are viruses composed of?
A
- small segments of nucleic acid with a protein/ lipoprotein coat
- enter host cells through specific cell-surface receptors
2
Q
What is a feature of viral genome replication?
A
- virus enters cell > diverts machinery to replicate itself
- for some viruses, genome replication is error-prone > mutations
> mutants with survival/ immune evasion strategies can arise
3
Q
What are the innate immune effectors that eliminate many viruses?
A
- complement activation
- antimicrobial peptides
- recognition of viral PAMPs (dsRNA) by PRRs > PRR signaling > type I interferons (IFN-α/ IFN-β)/ inflammasome assembly/ NK cell activation
4
Q
What is the antiviral response induced by interferons?
A
- IFN-α/ IFN-β bind to and dimerize IFNAR
- this recruits and activates JAK1/ TYK2
- JAK1/ TYK2 bind and phosphorylate STAT1/ STAT2
- STAT1/ STAT2 dimerize/ enter nucleus/ stimulate antiviral proteins
> PKR/ 2’,5-oligo-A-synthetase/ Mx proteins/ IFIT proteins
5
Q
What are the 4 antiviral IFN-stimulated genes?
> important for inhibiting viral replication
A
- PKR > binds viral dsRNA/ inhibits activity of elf2α > inhibits translation
- 2’5’-oligo-A-synthetase > activates RNase L > degrades viral/ cellular mRNA
- Mx proteins > form ring-like structures > inhibit virus replication
- IFIT proteins >bind to viral RNA/ elF3 > inhibits translation
6
Q
What role do antibodies have in viral infections?
A
- many viruses are neutralized by antibodies
- antibodies specific for viral surface antigens > block spread/ secondary infection
- surface IgA/ circulating IgG are most protective > primary response
7
Q
What are neutralizing antibodies?
A
- antibodies that bind to key viral structures in a way that interferes with their ability to attach to host cells (prevent attachment)
8
Q
What antibodies are produced during a primary response when virions are recognized in extracellular spaces?
A
- surface/ mucosal IgA
- circulating IgG
9
Q
What are 4 mechanisms of viral neutralization by antibodies after viral attachment to host cells?
A
- bind to epitopes that mediate fusion of viral envelope/ plasma membrane > block viral penetration
- complement-mediated lysis of enveloped virus
- agglutination of viral particles/ opsonization > Fc/ C3b receptor-mediated phagocytosis of virions
- some antibodies bound to infected target cells can trigger ADCC by NK cells
10
Q
What is the #1 mechanism for eliminating viral infections?
A
- cell-mediated immunity is required once viral genome is integrated into host chromosomal DNA
11
Q
What are the mechanisms of antiviral cell-mediated immunity?
A
- both CD8+ Tc/ CD4+ TH1 cells required
- TH1 cells produce IL-2/ IFN-γ/ TNF-α
> IFN-γ induces antiviral state in nearby cells/ activates NK cells
> IL-2 activates CTL precursors/ NK cells - TH1 cells license pAPCs for cross-presentation > activate naive CD8+ T cells
12
Q
What is the timing of virus-specific CTL activity?
A
- arises within 3-4 days of viral infection
- peaks by 7-10 days
- virions usually eliminated in those first 7-10 days
- virus-specific memory CD8+ T cells > future antiviral protection
13
Q
What is required for the activation of naive Tc cells by exogenous antigens?
A
- DC licensing by TH cells
> DCs internalize/ process/ present antigen to CD4+ TH cells via MHC II (exogenous pathway)
> activates cells through CD40/ CD40L engagement - DC cross-presentation
> activated TH cells serve as bridge to activate CD8+ CTLs
> provide IL-2/ license DCs to cross-present internalized antigen via MHC I
14
Q
What 4 strategies do viruses employ to evade host immune defences?
A
- evade action of IFNα/ IFNβ
- inhibit antigen presentation by infected host cells
- change surface antigens
- cause immunosuppression
15
Q
How does EBV evade the immune system?
A
- produces protein homologous to IL-10 > immunosuppression
- protein suppresses cytokine production by TH1 cells > inhibits antiviral inflammatory response
16
Q
What are 2 examples of viruses that inhibit antigen presentation by infected host cells? (to evade host defence mechanisms)
A
- HSV produces protein that inhibits TAP (ER)
- adenovirus/ cytomegalovirus > reduce MHC I expression
17
Q
What is the difference in antibody production during primary/ secondary responses to viruses?
A
- Primary Response- activation of naive B cells > production of antibodies specific to epitopes on pathogen
- Secondary Response (to variant of pathogen)- reactivation of memory B cells > pathogen eradication
- Original antigenic sin > presence of preformed antibodies inhibits primary response to pathogen > memory B cells not naive B cells
18
Q
What is original antigenic sin?
A
- Fc regions of antibodies bound to surface of pathogen bind to FcRs on naive B cells > inhibit them from responding to new epitopes
- no immune response is mounted to each new epitope during subsequent exposures to pathogen until pathogen expresses a significant # of unique epitopes/ memory cells can no longer eradicate pathogen
19
Q
What does the level of host defence to bacterial infection depend on?
A
- # of organisms entering and their virulence
- low inocula/ virulence > phagocytes/ nonspecific innate defenses
- larger inocula/ greater virulence > antigen-specific adaptive responses
20
Q
What is the main mechanism of immunity to extracellular bacteria?
A
- mainly humoral immune response > antibodies
- opsonization > antibodies bind to bacterial surface antigens/ act as opsonins
- complement activation > C3b opsonin/ MAC/ C3a, C5a anaphylatoxins/ chemotactic factors for neutrophils/ macrophages
- neutralization > antibody binds to bacterial toxin/ neutralizes it
21
Q
What are the 4 primary steps in most bacterial infections?
- host defence mechanisms act at each of these steps > bacteria have evolved to evade
A
- attachment to host cells
- proliferation of bacterium
- invasion of host tissue
- toxin-induced damage to host cells (some cases)
22
Q
What are some examples of strategies bacteria have evolved to evade host defence mechanisms?
A
- inhibition of phagocytosis
- surviving within phagocytic cells ex) block phagosome/ lysosome fusion
23
Q
What are the 2 main types of parasites?
A
- Protozoan > unicellular
- Metozoan > helminths/ worms (multicellular)
24
Q
What are some features of protozoan parasites?
A
- unicellular eukaryotes
- many progress through multiple antigenic forms/ locations during life cycle in host > most enter intracellular in at least one life cycle stage
- in bloodstream/ gut/ interstitial fluid > humoral immunity is most effective; however, these stages are very transient/ evasion strategies
- in intracellular life stages > cell-mediated immunity required; however, these are short stops in parasite life cycle
25
What is the #1 parasitic cause of death worldwide?
- protozoan parasite
Plasmodium > Malaria
- poor degree of immunity to infection (evades immune system)
26
What 4 strategies does Plasmodium (protozoan parasite) have to evade the immune system/ cause malaria?
- changes in surface molecules > continual changes in antigens seen by immune system
- intracellular phases of life cycle > reduces degree of immune activation/ allows organism to multiple shielded from attack
- short time circulation in blood at most accessible stage
- sloughing off its surface antigens > antibodies ineffective
27
Apart from malaria (plasmodium), what are 2 other diseases caused by protozoan parasites?
- African sleeping sickness
> causative trypanosome protozoans evade immune system > up to 1000 variants of protein coat to outrun immune response
- Leishmaniasis
> TH1 response limits pathology/ TH2 response leads to progressive disease
28
What are some features of metazoan parasites (helminths/ worms)?
- exclusively extracellular > too big to enter intracellular
- poor immune reactivity > do not multiply within host
- too big for phagocytosis > expulsion is best approach
> not opsonization/ digestion response
29
What is the immune response to metazoan parasites (helminths/ worms)?
- TH2 response > ILC-2s/ IL-4/ TH2/ IgE
- IgE > mast cell degranulation/ histamine release > muscle contractions and mucus production > diarrhea/ vomiting/ coughing (expulsion)
30
What controls most fungal infections?
Innate immunity
- phagocytosis by neutrophils
- commensal organisms control growth of pathogens
- fungal cell wall PAMPs (6-glucans/ mannans/ chitin) recognized by PRRs > complement activation/ phagocytosis
31
What strategies have fungi evolved to evade innate immune responses?
- produce capsule > block PRR binding
- fungi-induced expulsion from macrophages after phagocytosis
32
What is an example of a fungus?
Cryptococcus neoformans (C. neoformans)
33
What is the difference between primary/ opportunistic virulence?
> fungal infections
- Primary > inherently virulent/ infects healthy hosts
- Opportunistic > low virulence/ infects immunocompromised hosts
34
What mechanism of adaptive immunity controls fungal pathogens?
- cell-mediated rather than humoral
35
What is the difference between emerging/ re-emerging infectious diseases?
- Emerging > arisen/ increased in human population in past 2 decades
- Re-Emerging > formerly rare (under control) but have recently begun to resurge
36
What are examples of emerging/ re-emerging infectious diseases?
- Emerging > SARS/ Zika
- Re-Emerging > Tuberculosis/ Measles/ Whooping cough/ Diptheria
37
Why are there re-emerging infectious diseases?
- development of drug resistance
- acquisition of new virulence factors
- environmental changes > enhance transmission rates
- immunosuppressive conditions > AIDS > tuberculosis
- human contact with wild animals > ebola
- laxity in vaccination program adherence > diptheria/ whooping cough/ measles
38
What is the culprit for more than 1/3 of all AIDS-associated fatalities?
Tuberculosis
