LEC 9: Failures of the Body's Defenses

Question 1

What are the mechanisms of evasion and subversion of

the immune system by pathogens?

Answer 1

1. Genetic Variation
2. Mutation and recombination
3. Hiding
4. Sabotaging immune defense mechanisms

Question 2

________ within a species can prevent long-term immunity

Answer 2

Genetic variation within a species can

prevent long-term immunity

Question 3

What are serotypes?

Answer 3

strains which differ in capsular polysaccharides

Question 4

Mutation allows influenza virus to escape immunity

Answer 4

Antigenic drift = point mutations in viral genes causing changes in the
structure of surface antigens → year to year antigenic differences in virus

Question 5

What is an epidemic?

Answer 5

outbreak of infectious disease that affects many individuals in a population

Question 6

What is antigenic drift?

Answer 6

point mutations in viral genes causing changes in the

structure of surface antigens → year to year antigenic differences in virus

Question 7

Recombination gives viruses a

competitive advantage

Answer 7

Antigenic shift = reassortment of segmented genomes to radically change
surface antigen

Question 8

What is a pandemic?

Answer 8

outbreak of infectious disease that spreads worldwide

worldwide epidemic

Question 9

What is an antigenic shift?

Answer 9

reassortment of segmented genomes to radically change

surface antigen

Question 10

Influenza pandemics of the 20th century

Answer 10

1918: Spanish Flu
H1N1

1957: Asian Flu
H2N2

1968: Hong Kong Flu
H3N2

Question 11

Swine flu outbreak 2009

Answer 11

Influenza A H1N1 virus – hybrid of swine, avian, and human strains

~18,000 deaths, or 0.03% fatality rate (Spanish flu 3%)

some estimates as high as >200,000 deaths

Question 12

Severe acute respiratory syndrome (SARS) outbreak 2003

Answer 12

caused by bat coronavirus (coronavirus also causes the common cold)

Question 13

Middle East Respiratory Syndrome (MERS)

Answer 13

Novel coronavirus, hCoV-EMC has recently emerged

– first case in Jordan in April 2012

– reported in 22 countries – almost all cases linked to
Saudi Arabia

Question 14

Avian Influenza H5N1

Answer 14

“Bird Flu”

Question 15

Antigenic variation through gene

conversion in African trypanosomes

Answer 15

VSGs = variable surface glycoproteins

Question 16

Herpes viruses hide from the

immune response

Answer 16

viral latency = dormant state in which the virus does not replicate

Question 17

herpes simplex virus

Answer 17

– cold sores

Question 18

herpes varicella-zoster

Answer 18

chicken pox - shingles

Question 19

______ are favored site to hide.

Why?

Answer 19

Neurons are favored site to hide because they
express very small number of MHC class I
molecules

Question 20

Epstein-Barr virus (EBV) infects B cells

Answer 20

• binds to CR2 component of BCR co-receptor
complex

→ infected B cells proliferate and produce virus

→ stimulation and proliferation of EBV-specific T cells

→ infection controlled but small number of B cells latently infected

*Reactivation can lead to malignant transformation of B cells in some people

Question 21

Viruses have evolved the greatest variety of
mechanisms for evading immune defense
mechanisms

Answer 21

1. Inhibit humoral immunity
2. Inhibit inflammatory response
3. Suppress host immune response
4. Block antigen processing and presentation

Question 22

Ebola

Answer 22

first appeared in 1976 in Sudan & R. of Congo
• single-stranded RNA virus
• produces filamentous virions (family Filoviridae)
• attach to C-type lectins, integrins
• virus accumulates throughout body, specifically in
blood

illness characterized by fever, abdominal pain, blood in vomit/stool
→ rapid progression to death ~3 days

Average rate of fatality ~80%

Question 23

EBOV proteins interfere with

Answer 23

innate immune response

Question 24

Viruses can inhibit the immune response through

Answer 24

mimicry

Question 25

Subvert the immune response through interfering with

Answer 25

MHC class I

Question 26

Inherited Immunodeficiencies are caused by

Answer 26

dominant, recessive, or X-linked defects

Question 27

Primary immunodeficiency

Answer 27

inherited defects in genes for components of the immune system * dominant – inherit one functional, one dysfunctional allele * recessive – must inherit two defective alleles * X-linked – recessive defects in genes on the X chromosome

Question 28

Secondary immunodeficiency

Answer 28

not due to defective genes, but to environmental | factors such as immunosuppressive drugs

Question 29

Defects in ______ can result in | severe combined immunodeficiency (SCID)

Answer 29

Defects in T cell development can result in | severe combined immunodeficiency (SCID)

Question 30

Treatments for inherited immunodeficiencies

Answer 30

1. Injections of gamma globulin – antibody containing preparation made from the plasma of healthy blood donors 2. Bone marrow transplant 3. Somatic gene therapy – functional copy of defective gene introduced into stem cells isolated from patient bone marrow, then re-infused

Question 31

Acquired immune deficiency syndrome

Answer 31

(AIDS) Particularly prevalent in Africa

Question 32

Human Immunodeficiency Virus (HIV)

Answer 32

• HIV-1 principle cause of AIDS • HIV-2 less virulent, slower progression to AIDS → jumped from chimpanzee → jumped from sooty mangabey

Question 33

HIV infects

Answer 33

CD4 T cells, macrophages, and dendritic cells viral gp120 binds to CD4 on T cells, macrophages, and DCs PLUS co-receptor → HIV variants bind different co-receptors • ‘macrophage-tropic’ bind CCR5 on macrophages, DCs and CD4 T cells • ‘lymphocyte-tropic’ bind CXCR4 in activated CD4 T cells

Question 34

Progression to AIDS

Answer 34

often takes many years

Question 35

_______ of HIV makes treating infected patients a challenge

Answer 35

Rapid mutation Targets for drug treatment • viral reverse transcriptase • viral protease (cleaves viral polypeptides to enzymes and proteins) Drugs prevent further infection…BUT only temporarily → high rate of HIV mutation produces variants resistant to the action of drugs

Question 36

Combination therapy uses several antiviral drugs together

Answer 36

HAART = highly active anti-retroviral therapy • effective at reducing viral load and disease progression • prevents new infections from forming a provirus • rapid decline in viral load due to short lifetime of free virions and activated CD4 T cells Virus becomes undetectable, BUT not eradicated → stop taking meds, virus re-emerges

Question 37

Genetic deficiency of the CCR5 co-receptor | confers resistance to HIV infection

Answer 37

CCR5-∆32 – 32 nucleotide deletion causing altered reading frame and premature termination of translation → non-functional protein → present only in Caucasians, 10% heterozygous, 1% homozygous

Question 38

Broadly neutralizing antibodies | against HIV

Answer 38

~ 1:500 infected individuals make antibodies that neutralize a broad range of HIV-1 strains = broadly neutralizing antibodies elite neutralizer ``` recognize one of four epitopes of the envelope glycoprotein highly conserved regions of biological importance. e.g. CD4 binding site on gp120, gp41 ``` variable regions have high number of mutations – both insertions and deletions • mutations in framework region