immunity and infection

Question 1

infectious diseases

Answer 1

1) 1/3 disease burden is due to infectious diseases
2) viruses, fungal, bacterial, parasites

Question 2

immunity to infection

Answer 2

1) immune system protects from pathogen and cancer
2) most pathogens do not overcome this
- surface barriers
- immune system
3) few potential pathogens cause diseasep

Question 3

physical and physiological barrier

Answer 3

1) saliva and skin
- lysozyme breaks down proteoglycan in cell wall

Question 4

disease caused by pathogens

Answer 4

1) can damage directly
- exotoxin damage surfaces of host cell
2) indirectly
- via immune response
- pro-inflammatory cytokines cause local symptoms
- epitopes can bind to heart tissue (complement mediated)
3) virus replication can destroy host cell

Question 5

immune responses are specific for different compartments

Answer 5

1) almost all pathogens have a extracellular stage, some have intracellular

Question 6

early immune response to infection

Answer 6

1) preexisting molecules like complement
- inflammation

Question 7

cooperation between innate and adaptive

Answer 7

1) adaptive is activated after innate immune system
2) innate controls most infections, but need both branches to eliminate pathogens that cause disease

Question 8

stages in typical infections

Answer 8

1) pathogen reaches physical barrier
2) innate immunity contains the infection through inflammation
3) Ag captured in secondary lymphoid tissue stimulate adaptive immune response (Ag can also be carried by DC)
4) activated TH1 and CD8+ cells migrate to site of infection

Question 9

complement

Answer 9

1) C3 is first immediate immune defenders
2) C3 is hydrolyzed spontaneously at low rate => iC3
- alternative pathway

Question 10

alternative pathway

Answer 10

1) iC3 can recruit serum factor B, a substrate for protease factor D
2) alternative pathway is initiated and surface bounded C3b is produced
3) C3b fixation leads to alternative C3 convertase
4) binding of another C3b subunit leads to formation of alternative C5 convertase
5) C5a attracts phagocytes and inflammatory response
—
1) it is inhibited by complement control proteins (DAF, MCP, CR1)
2) pathogens lack these control proteins, and they also attract factor P which stabilized alternative C3 convertase

Question 11

other components of early response (4-96 hrs)

Answer 11

1) phagocytes
2) NK cells
3) interferon

Question 12

phagocytes

Answer 12

1) both macrophages and neutrophils are
2) recognize pathogens through DC14, TLR4 and scavenger receptors
3) receptors that simulate phagocytosis
- CR1, CR3 and CR4
4) have chemicals and enzymes that destroy pathogens in phagolysosomes

Question 13

macrophages

Answer 13

resident in most tissues and abundant in mucosal tissues
- long lived
2) antigen presentation
3) inflammatory mediators

Question 14

PMN

Answer 14

1) abundant in blood and rapidly recruited to any site with active complement
- short lived
2) reactive chemical species
3) antimicrobial peptides
4) antibacterial enzymes
5) NETs

Question 15

phagocytes and innate immunity

Answer 15

1) receptors are PAMPs
- LPS, teichoic acids, or G+ bacteria
2) PAMPs recognized by PRR
- TLR4 recognizes LPS

Question 16

PRR on macrophage

Answer 16

1) CD14
- binds LPS from gram negative bacteria
2) mannose receptor
- lectin binds to some bacteria and viruses
3) scavenger receptors
- heterogenous family of receptors
4) TLR4

Question 17

role of macrophages

Answer 17

1) PRR or complement stimulate macrophage
2) macrophages transcribe cytokine genes
- TNF alpha, IL06, IL1beta, IL-12, IL-8
3) APC

Question 17

TNFalpha

Answer 17

1) contain infections
2) local inflammation

Question 18

IL-8

Answer 18

1) attract neutrophils
2) local inflammation

Question 19

iL-12

Answer 19

NK cell activation

Question 20

fever and acute phase protein production

Answer 20

1) IL-1beta, TNFalpha, IL-6

Question 21

TNFalpha

Answer 21

1 )activates local vascular endothelium
- increase vascular permeability
- supply of complement
- more fluid drains to lymph nodes
2) primes phagocytes, activating oxidative burst
3) induces maturation of DCs
- via direct contact with PAMPs
- or being secreted by macrophage

Question 22

pyrogens produced by macrophages

Answer 22

1) IL-1beta, IL-6, TNF alpha make fever
- increase metabolism of muscle and fat cells
- over 10% increase in metabolic rate per degree celcius
2) fever inhibits pathogen replication
3) stimulates adaptive immunity

Question 23

acute phase response

Answer 23

1) IL-1 beta, IL-6, and TNFalpha stimulate this in the liver
- massive increase in MBL and CRP in liver
- MBL and CRP are PRR
- both can activate complement
2) CRP binds to phosphocholine group of LPS
- can bind C1q (classical complement pathway)
3) MBL activates lectin pathway

Question 24

CRP and MBL

Answer 24

1) activate Complement and behave as opsonins 2) CRP is a marker for inflammation in clinics

Question 25

septic shock

Answer 25

1) bacterial infection of blood causes septic shock via endotoxins such as LPS - lading to massive secretion of TNFalpha - dilation of blood vessels and leakage of fluid into tissues - failure of vital organs (kidneys, heart, lungs) due to low blood supply 2) over 100k deaths per year in US

Question 26

PMN

Answer 26

1) short lived and focused on killing 2) most abundant WBC 3) circulate in blood and go to infected area due to release of CXCL8, N-fMet, C5a - interactions between cell adhesion molecules (selectins, LFA-1, ICAM1) 4) die in few hours and make pus

Question 27

PMN phagocytose and kill bacteria

Answer 27

1) PMN have CR, FcR and receptors for bacterial sugars 2) PMN have many granules with antimicrobial toxins (PMN are more aggressive than macrophages) 3) DNA nets

Question 28

INF

Answer 28

1) type II - INFgamma 2) type I - IFNalpha and IFN beta - activate NK cells 3) limit viral infection in early phase - have direct and indirect effects

Question 29

type I INF

Answer 29

1) activate endonuclease that degrade RNA 2) phosphorylation and inactivation of initiation factor eIF-2 (inhibit protein synthesis) 3) inhibit viral replication, activate NK, enhance Ag presentation

Question 30

type II IFN

Answer 30

1) activate macrophages 2) activate enzymes that degrade essential AA - host cell can survive temporarily without but bacteria cannot replicate

Question 31

NK cells

Answer 31

1) cytotoxic lymphocytes but do not express CD8+ 2) do not express TCR or make Ig 2) circulating lymphocytes in blood that go to infection site because of pro-inflammatory cytokines

Question 32

NK cells activation

Answer 32

1) activated before an infection, similar killing method to CD8+ - perforin, FasL, granzymes, and also secrete IFN gamma 2) activate by IFN alpha and beta, IL-12 3) early response to viral infection

Question 33

NK and viral infection

Answer 33

1) recruited by cytokines - IFN alpha/beta by infected cells - TNF alpha and IL-12 by macrophages at site of infection

Question 34

NK cell receptors

Answer 34

1) heterogenous set of activating and inhibitory receptors are expressed by different subpopulations of NK cells - recognize MHC-like molecules that reveal abnormal target cell - MIC-A and B which are expressed by stressed cells 2) some recognize MHC molecules that inhibit the NK - some viruses inhibit expression of MHC1

Question 35

NK recognize missing self

Answer 35

1) no MIC ligand - healthy cells - inhibitory receptors dominate 2) MIC ligand for NKG2D - expressed and will cause death - activating receptors dominate

Question 36

innate and adaptive immunity

Answer 36

1) innate controls many infections 2) innate sets stage for adaptive immunity 3)adaptive may be required for complete elimination of certain pathogens

Question 37

adaptive immune response

Answer 37

1) after 4 days 2) early response, DC stimulated by PAMPS carry antigens on MHC to lymph node 3) T cells (CD8+ and TH) recognize MHC peptide are activated 4) Ag specific B cells acquire Ag via surface IgM and present peptides via MHCII 5 )B cells presenting these are activated by cognate TH cells in lymph nodes

Question 38

primary immune response

Answer 38

1 )DC mature and migrate to lymph nodes under influence of chemokines 2) DC in lymph nodes secrete chemokines that attract naive T cells - CD4+ cells become TH2 or TH1 - activated T helper and CD8+ cells migrate to site of infection - TH2 cells stimulate specific B cells in lymph nodes

Question 39

secondary immune response

Answer 39

1) protective immunity - B and T cells activated - inhibit 2ndary infection shortly after primary infection 2) memory cells can be activated rapidly years after first exposure to antigen

Question 40

secondary vs primary antibody responses

Answer 40

1) unimmunized - low affinity of Ab - somatic hypermutation - IgM>IgG 2) immunized - high affinity - high hypermutation - IgG, IgA, IgE

Question 41

immunological memory

Answer 41

1) ability of immune system to respond more rapidly an effectively to a pathogen that has been encountered previously - reflects the preexistence of clonally expanded population of Ag-specific lymphocytes 2) memory due to a small but persistent population of memory cells that is independent of the continued persistence of the original antigen - most memory cells in resting state

Question 42

memory cells production

Answer 42

1) memory T cells can survive in the absence of MHC peptide stimulation

Question 43

immune response to infection

Answer 43

1) adaptive responses begin after 4 days 2) protective immunity provided temporarily 3) memory cells are activated faster in subsequence infections

Question 44

vaccines

Answer 44

1) memory B and T cells can allow you to respond to the pathogen 2) most provide lifelong protection - live, attenuated, inactivated, recombinant, peptide, anti-idiotype, naked DNA, RNA