1. Host Defenses

Question 1

innate and adaptive immunity, if a microbe is causing disease it avoids the host immune response

Answer 1

general principles

Question 2

innate provides early defense with no memory and pathogens have resistance mechanisms, adaptive immunity is longer to develop and antigen specific, is the memory response, provides optimal type of immune response for a pathogen, evasion of immune reponse outcoe depends on whether microbial stategies can be countered by an immune response, deleterious effects of the immune response may result in injury to the host tissue of overactivated like lepromatous leprosy, viruses act as obligate intracellular microbes and pirate host cell machinery, many lyse host cells called cytopathic effect, successful virus infection involves viral entry into the organism, viral replication, spread, transmission, each stage contents with physical barriers and innate adaptive immunity

Answer 2

features of antimicrobial immunity

Answer 3

physical barriers

Question 4

skin and most microbes can’t cross intact skin due to keratinization, breaks, cuts, animal bites, insect vector punctures, and needle injection provide entry, alimentary tract has acid and proteolytic enymmes break down virsues, bile destroys lipids of enveloped viruses, and noneveloped viruses survive the bile, respiratory tract involves mucus which traps viruses and cilia which are transported to the throat, nasal turbinates impede virus entry down a narrow and complicated path, eyes and genitourinary tract have no major physical barriers

Answer 4

physical barriers

Question 5

hepatitis B and papillomavirus through minor breaks and cuts, rabies through animal bites, west nile viruses through mosquito bites, HIV/hepatitisB/hepatitisC by injection

Answer 5

skin infections

Question 6

herpes simplex 1 and epstein barr through the mouth, hepatitis A/rotavirus/poliovirus through the intestinal tract

Answer 6

alimentary tract infections

Question 7

adenovirus/rhinovirus through the upper respiratory tract and local disease, influenza and RSV through the lower respiratory tract and local disease, measles/mumps/rubella/varicella through local infection and systemic disease

Answer 7

respiratory tract infections

Question 8

adenovirus and enterovirus by direct contact

Answer 8

conjunctival infections

Question 9

hepatitis B/hepatitis C, herpes simplex 2, papillomavirus

Answer 9

genitourinary infections

Question 10

interferon a and B also called type I interferon, natural killer cells, and macrophages

Answer 10

innate immunity

Question 11

most viruses stimulate production of interferon a and b by infected host cells, inhibit viral replication in surrounding uninfected host cells, leukocytes produce interferon a, fibroblasts and other non-leukocytes produce interferon b

Answer 11

inteferons

Question 12

intereron binds to receptor increases protein kinase activity, is activated by dsDNA, phosphorylates eukaryotic initiation factor 2, inhibits viral protein synthesis, or increases 2’5’ oligo a synthetase, activations by dsDNA producing oligo A, activating RNAase L with degrades viral RNA

Answer 12

interferon mechanism of action

Question 13

lyse virus infected cells early in viral infection, many viruses decreased production of class I MHC to avoid lysis by CTL’s, are so natural killer cells are released from a normal state of inhibition by absence of class I MHC, natural killer cell activitiy is enhanced by the inferons, mediate antibody dependent cell mediated cytotoxicity and are activated by across linking of IgG Fc receptors, two killing mechanisms including apoptosis and perforin mediated osmotic death

Answer 13

natural killer cells in innate immunity

Question 14

antiviral effects are through production of TNF a and nitric oxide, interfere with virus replication, viruses that infect macrophages are cytomegalovirus, ebola virus, HIV, measles virus, rubella virus, traffics to many body sites, facilitates viral spread

Answer 14

macrophages in innate immunity

Question 15

virus infections are localized to mucosal site resulting in short lived protective immunity, systemic virus infections have long lived responses, humoral immunity is most important in early viral replication, present as result of previous infection or vaccination. plasma cells move to the bone marrow which is the major site of antibody production, memory B cells reside in lymph nodes and the spleen and upon reinfection will differentiate into plasma cells, antibody functions to prevent virus from binding a target host cell, opsonize virus to enhance phagocytosis, activate complement to lyse viral envelopes, facilitate ADCC by natural killer cells to lyse infected host cells, CD8+ CTLs are the principal protectie immunity during established virus infections, since endogenous antigen activates class I MHC, apoptotic and perforin mediated mechanisms are usedto kill, produce TNFa to interfere with virus replication, 1-2 weeks after virus infection CTL counts are massive, following virus elimination , CD8+ cells contract to 5%, remainging cells are long live memory cells, memory responses are measured as little as 1 day following reinfection since the same expansion and contraction occurs

Answer 15

adaptive immunity

Question 16

differences between T and B cell memory responses, memory T cells are quiescent until reactivated by antigen, B cell memory response increases production of serum antibody for potentially decades which wards off infection following exposure

Answer 16

memory response to viruses

Question 17

half life of serum immunoglobulin in 3 weeks or less, most plasma cells live only several days before dying, mechanisms for long term antibody levels lead to periodic re-exposure to a virus, asymptomatic chronic infection, long term expression of antigen on APC’s, and long lived plasma cells

Answer 17

adaptive immunity antibody response to viruses

Question 18

strategies include altering antigens through an reassortment of segmented RNA genomes, cytomegalovirus has decoy MHC molecules to inhibit natural killer cells preventing class I MHC mediated expression of viral peptides, HIV infects and kills CD4+ T cells which cripples the immune response, latent infections are present by neuron ifection with HSV and B cell infection by epstein barr virus, CNS is an immunologically priveleged site and is the ideal location for infections, immunologic tolerance of neonatally infected hepatitis B carriers occus because virus specific T cells are clonally deletd in the thymus due to virus antigen

Answer 18

evasion of immunity

Question 19

cytotoxic lymphocytes can cause pathology rather than direct virus damage including cytotoxic t lymphocytes which destroy liver tissue in hepatitis B infection, as a comparison immunodeficiency individuals don’t have liver damage, chronic viral infection leads to immune complex disease which deposts in the kidney which is the major site affected in the glomeruli and arterioles, some viruses may express proteins having homology with normal tissue otherwise known as molecular mimicry

Answer 19

deleterious effects of the host immune response

Question 20

listeria monocytogenes and mycobacterial survive/multiple in macrophages which makes them inaccessible to circulating antibodies, other important members are mycobacterium leprea in leprosy and chalmydia trachomatis in trachoma, >600 million humans have diseases cause by intracellular bacteria

Answer 20

general principles

Question 21

ineffective against intracellular bacterial and are not readily killed once ingested, natural killer cells are activated by macrophage produced IL-12 which produces interferon gamma and activates macrophages which are more efficiency killers, interferon Y induces production of nitric oxide which is a highly reactive antimicrobacterial agent, some intracellualr bacteria may be killed but adaptive immunity is generally required for infection

Answer 21

innate immunity

Question 22

mediated by a delayed type hypersensitivity like reaction, T cells become activated, interferon Y gamma is released, macrophages are activated and eliminate bacteria, some mycobacteria can persist in the body for extended periods of time by granuloma formation, granulomas are a Th1 mediated response triggered by release of IL-12 by macrophages after microbial invasion, remember that Il-4 steers the immune response towards Th2 immunity, granulomas impair bacterial replication by activating macrophages and thus inhibiting bacterial growth through nitric oxide production, encapsulate bacteria through fibrosis and calification, decreased nutrient and oxygen supply as a result of tissue necrosis, some pathogens are not killed so breakdown of the granuloma releases bacteria for systemic dissemination, exposed to M tuberculosis leading to 90% eradication of the organism or containment within the granuloma, CTL’s generated against bacteria escape from phagosomes into the host cell cytosol or if bacterial antigens are transported into the cytosol, bacterial peptides will be processed/expressed on class I MHC to activate CTL’s

Answer 22

adaptive immunity

Question 23

mycobacterium inhibits fusion of phagosomes and lysosomes, may scavenge reactive oxygen intermediates to prevent bacterial killing, listeria monocytogenes disrupts phagosome of macrophages and escapes into the cytosol, also can spread from cell to cell without coming in contact with extracellular host mechanisms

Answer 23

evasion of immunity

Question 24

granuloma formation may severely compromise normal tissue, mycobacterium leprae can cause tuberculoid or lepromatous leprosy, tuberculoid leprosy is Th1 mediated leading to granuloma formation and few detectable bacilli, lepromatous leprosy is Th2 mediated but there are many bacilli in the lesions, it is unclear how inapproaprate Th2 mediated immune responses are generated, Th1 responses inhibit Th2 responses, important because vaccines work by Th2 response which can suppress leprosy’s Th1 response

Answer 24

deleterious effects of the immune response