Host Defense

Question 1

What are the general principles of Host Defense

Answer 1

Host Defense = Innate + adaptive immunity to eliminate microbes

Five Types: Extracellular/Intracellular bacteria, Fungi, viruses, parasites

Question 2

Describe the most effective immune response to Extracellular bacteria

Answer 2

Innate:
–> Phagocytosis,
–> Alternative Complement pathway - bacterial cell wall components can activate complement to lyse or opsonize bacteria (doesn’t require antibody)
Adaptive:
–> Humoral immunity
** IgG opsonizes + toxin-specific antibodies neutralize
** IgM and IgG activate classical complement to lyse

Question 3

describe how extracellular bacteria evade immunity

Answer 3

Polysaccharide capsule

• -> resist phagocytosis
• -> inhibit alternative pathway complement activation

Genetic variation of surface antigens:
–> one step ahead of antigen-specific antibodies

Question 4

What are the deleterious effects of Extracellular bacteria of the immune response

Answer 4

Septic shock:
–> bacteria induce macrophages to release tumor necrosis factor and IL-1

Bacterial toxins = superantigens

• -> super antigens bind to class II MHC proteins on antigen presenting cells and to T cells, causing T cell activation
• -> Many T cells activated causes large amounts of cytokines which leads to septic shock-like conditions

Question 5

Describe Rhematic fever

Answer 5

Cross-reactive antibodies induced by streptococcal M-protein causes binding to sarcolemma proteins in heart which leads to carditis

Question 6

Describe Poststreptococcal glomerulonephritis

Answer 6

Infection with streptococci –> antibodies that form immune complexes with bacterial antigen –> lodge kidney –> nephritis

Question 7

Define the general principles of intracellular bacteria

Answer 7

• -> survive/multiply in macrophages
• -> inaccessible to circulating antibodies
• -> strategies that allow them to thrive in phagocytic cells

Question 8

Describe the innate response to Intracellular bacteria

Answer 8

innate:
- -> ineffective - bacteria not killed when ingested
- -> NKC activated by macrophage via IL-12 which causes NKC to produce IFN-gamma to activate macrophages

Question 9

Describe the adaptive immunity to intracellular bacteria

Answer 9

DTH-like (type IV) reaction:

• -TH1 cells become activated → release interferon- → activated macrophages may eliminate bacteria
• -Organisms may persist in the body for extended periods of time
• -If so, activated macrophages may surround microbes to form a granuloma to prevent spread (walls off bacteria so it cannot spread

Question 10

How do intracellular bacteria evade immunity

Answer 10

Mycobacterium –> inhibits fusion of phagosomes and lysosomes + may scavenge reactive oxygen intermediates to prevent bacterial killing

Listeria monocytogenes –> disrupts phagosome (escapes into cytosol)
–> CTL’s generated if the bacteria escape from phagosomes into cytosol or if bacterial antigens transported into cytosol (MHC Class II)

Question 11

What are the deleterious effects of the intracellular bacteria

Answer 11

Granuloma formation may severely compromise tissue function:

–> devastating if infected tissue is the lungs

Question 12

Define the general principles of virus immunity

Answer 12

Viruses - obligate intracellular microbes that pirate host cell’s machinery
–> many viruses lyse host cells

Question 13

Describe the innate response to viruses

Answer 13

Type 1 IFN = alpha and beta interferons

• -> cause up regulate the expression of class I MHC
• -> activate NK cells

NK cells lyse virus-infected cells early in infections:

• -> Most viruses down regulate class I MHC expression
• -> released from normal state of inhibition by absence of class I MHC
• -> activity enhanced by interferons

Question 14

Describe the adaptive immunity to viruses

Answer 14

Humoral immunity IMPORTANT EARLY IF ANTIBODIES PRESENT:

• -> prevent virus from binding to a target host cell
• -> opsonize virus to enhance phagocytosis
• -> Activate complement to lyse viral envelopes

CTL’s

• -> principle immune component during ESTABLISHED virus infections
• -> Virus antigen processed/presented on Class I MHC, therefore CTL’s are the form of immunity most effective against viruses

Question 15

Describe how Viruses evade immunity.

Answer 15

Viruses can alter antigens in several mech.

• -> HIV = Error-prone reverse transcriptase causes point mutations and leads to antigenic variability
• -> Influenza reassortants produce antigenic alterations
• -> viruses prevent class I MHC expression
• -> HIV infects/kills CD4+ T cells, thereby preventing immune response

Question 16

describe the deleterious effects of virus immune response

Answer 16

CTL’s may mediate pathologic lesions in some viral disease states:

• -> hepatitis B virus infection induces CTL response that destroys liver
• -> Some viruses express proteins with homology for host cell proteins.

Question 17

Describe innate immunity response to Fungi

Answer 17

Neutrophils are the main mediators of innate immunity

• -> phagocytosis – lysosomal enzymes + reactive oxygen intermediates
• -> NEUTROPENIC individuals highly susceptible to fungal infections

Question 18

Describe adaptive immunity response to fungi

Answer 18

Th1-mediated immunity = MOST IMPORTANT

• -> cryptococcus neoformans eliminated by CTL’s
• -> Granuloma formation

Question 19

describe innate immunity response to parasites

Answer 19

Macrophages phagocytize protozoa –> many organisms resistant to killing (may even replicate)

Question 20

Describe adaptive immunity response to parasites

Answer 20

Protozoa that survive within macrophages = CD4+ T lymphocytes –> interferon-gamma –> activates macrophages

Plasmodium –> Th1-mediated CTL’s (antibodies too, but not as effective)

Helminthic infestations (worms) –> IgE + eosinophils during ADCC (Th2 immunity)

Question 21

describe the effector mechanisms used for optimal response

Answer 21

Antibody against intracellular bacteria would be INEFFECTIVE

CTL response against extracellular bacteria would be INEFFECTIVE

Question 22

What are some of the negative consequences to immune response

Answer 22

Some tissue injury result from immune response:

–> overzealous immune response may result in injury to host tissue