Lecture 14 - Su

Question 1

What is the principal function of the immune system?

Answer 1

Protect the host against pathogenic microbes.

Question 2

Where can the infections take place on the human body?

Answer 2

Skin
Resp tract
GI tract
Urogenital tract

Question 3

What are the three barriers to infection? Briefly describe each.

Answer 3

Physical/Chemical defences: skin, mucous, membranes, lysozyme in tears. Expulsion via coughing, sneezing, vomiting, and diarrhea.

Innate immunity: macrophages, neutrophils, eosinophils, basophils, monocytes, and the complement system.

Adaptive immunity: cellular and humoral immunity.

Question 4

What are the mechanical, chemical, and microbiological defences of the skin?

Answer 4

Mech: flow of fluid, sweat, sloughing of skin
Chem: sebum (fatty acids, lactic acid, lysozyme) and antimicrobial peptides (defencins)
Micro: Normal flora of the skin

Question 5

What are the mechanical, chemical, and microbiological defences of the GI tract?

Answer 5

Mech: flow of fluid, mucus, food, and saliva
Chem: acidity and enzymes (proteases) and antimicrobial peptides (defencins)
Micro: Normal flora of the GI tract

Question 6

What are the mechanical, chemical, and microbiological defences of the resp tract?

Answer 6

Mech: flow of fluid, mucus
Chem: lysozyme in nasal secretions and antimicrobial peptides (defencins)
Micro: Normal flora of the resp tract

Question 7

What are the mechanical, chemical, and microbiological defences of the urogenital tract?

Answer 7

Mech: flow of fluid, mucus, urine, sperm
Chem: acidity in vag secretions and spermine/zinc in semen and antimicrobial peptides (defencins)
Micro: Normal flora of the urogentract

Question 8

What are the mechanical, chemical, and microbiological defences of the eyes?

Answer 8

Mech: flow of fluid, tears
Chem: lysozyme in tears and antimicrobial peptides (defencins)
Micro: Normal flora of the eyes

Question 9

Briefly describe rates and amounts of virus production in acute infection.
Which viruses act like this?

Answer 9

High viral production at the beginning which is then cleared asap.
Rhinovirus, rotavirus, flu virus.

Question 10

Briefly describe rates and amounts of virus production in persistent infection.
Which viruses act like this?

Answer 10

Viral production amps up and remains high until host death.

Lymphocytic choriomeningitis virus

Question 11

Briefly describe rates and amounts of virus production in latent or reactivating infection.
Which viruses act like this?

Answer 11

Virus has high titre initially then is cleared with smaller or larger reactivations through time with high viral titres.
HSV

Question 12

Briefly describe rates and amounts of virus production in slow infection.
Which viruses act like this?

Answer 12

Virus has high titre at the beginning of the infection and then remains very low for a long while until it slowly grows and kills the host.
HIV
Measles

Question 13

What effect does a weak/absent innate/adaptive together functioning immune system have on HBV infection over years?

Answer 13

The virus will keep resurging over time with outbreaks.

Question 14

Define pathogen.

Answer 14

microbes capable of causing host damage.

Question 15

Name the key events that take place during the pathogenesis of infectious disease.

Answer 15

Entry of microbe
Invasion/colonization of host tissues
Evasion of host immunity
Tissue injury/functional impairment

Question 16

Name the general features of immunity to pathogens.

Answer 16

1. Defense via innate & specific immunity
2. Innate immune response determines nature of specific immune response.
3. Immune response can do so in specialized/different ways to combat effectively
4. Survival of pathogen in host critically influenced by evasion of immune system
5. Tissue injury/disease may be caused by the host response and not the pathogen itself.

Question 17

What is the primary route of infection?

Answer 17

Microbial adherence to epithelium, invasion of epithelial tissues, and local infection.

Question 18

How can the body protect against infection during primary infection?

Answer 18

normal flora and local chemical factors inhibit microbial growth. Phagocytes can be activated.
Wound healing induces antimicrobial peptides and complement pathway to destroy invaders.
Complement activation and DCs migrate to lymph nodes. Phagocyte activation. Cytokines and chemokines produced.

Question 19

how can the immune system protect the lymph node?

Answer 19

Pathogens are trapped and phagocytosed in the lymphoid tissue and the adaptive immunity is initiated by migrating DCs

Question 20

Where do extracellular infections generally enter?

Where are intracellular infections located?

Answer 20

Interstitial spaces, blood, lymph, and epithelial surfaces

cytoplasm and vesicles

Question 21

What kind of organisms infect interstitial spaces, blood, and lymph?

What kind of organisms infect epithelial surfaces?

Answer 21

Viruses, bacteria, fungi, worms

N. gonorrhoeae, Mycoplasma spp., Strep pneumoniae, V. cholorae, E. coli, H. pylori, C, albicans, etc.

Question 22

What kind of organisms infect the cytoplasm of a cell?

What kind of organisms infect cellular vesicles?

Answer 22

Viruses, protozoa, Rickettsia spp.

Salmonella, Y. pestis, Trypanosoma, etc.

Question 23

How does the body protect against organisms that infect...
Interstitial spaces, blood/lymph?
Epithelial surfaces?
Cytoplasm?
Vesicles?

Answer 23

Abs, complement, phagocytosis, neutralization

Abs (IgA), anti microb peptides

CTLs and NKs

T cell and NK cell dependent macrophage activation.

Question 24

What signalling pathway do most TLRs use?

Answer 24

NFkB

Question 25

What are the three ways to activate the complement pathways? Briefly describe the activation of each.

Answer 25

Classical: Ag-Ab complex driven Lectin: binding of mannose binding lectin Alternative: binding of C3b to cell surfaces on its own.

Question 26

What are the three outcomes of the complement pathway activation?

Answer 26

Inflammation Lysis of foreign cells (MAC) Opsonization (C3b)

Question 27

How do neutrophils kill microbes?

Answer 27

NETs

Question 28

What function can lipid mediators (protaglandins, leukotrienes) have on the immune system?

Answer 28

Recruitment and activation of monocytes and macrophages as well as migration and activation of DCs.

Question 29

What function can the release of preformed mediators like histamiine, heparin, TNF, etc. have on the immune system?

Answer 29

Recruit and activate T cells, neutrophils, basophils, and eosinophils. Phagocytosis/antimicrobial activity. Effects on epithelial cells' tight junction proteins.

Question 30

What effect can the production and release of cytokines, chemokines, and angiogenic/growth factors have on the immune system?

Answer 30

Degradation of endogenous toxic mediators as well as snake venom components.

Question 31

What effects do intracellular viral proteins have on a host cell that can cause disease?

Answer 31

``` Reduced host cell DNA, RNA, and protein synthesis. Viral inclusions. Metabolic derangements. Cell lysis or fusion. Neoplastic transformation. ```

Question 32

What are the principal mechanisms of innate immunity against viruses?

Answer 32

Physical and chemical barriers Inhibition of infection by type I IFNs NK cell-mediated killing of infected cells

Question 33

What is the adaptive immunity against viral infections mediated by?

Answer 33

Antibodies (block virus binding/entry CTLs (eliminate infection via killing infected cells)

Question 34

Define antigenic shift.

Answer 34

When RNA segments of a virus are exchanged between strains in a secondary host.

Question 35

Define antigenic drift.

Answer 35

When the RNA of a virus gradually changes over time due to mutations etc. during replication.

Question 36

H1N1 is a mixture of ______ and ______ strains created via _____.

Answer 36

``` Swine/avian/human and Eurasian avian/swine flu by Antigenic shift in pigs. ```

Question 37

How do viruses evade the host immunity?

Answer 37

Modulation of surface structure to avoid recognition Inhibition of phagocytosis Escape from phagosome Inhibition of phagosome/lysosome fusion Modulating signal tranduction, gene expression, and cell death Viral cytokines or soluble receptor homologs Inhibition of Ag presentation Viral latency

Question 38

How does HIV evade the immune system?

Answer 38

Antigenic variation Inhibition of Ag processing Infection of immunocompetent cells

Question 39

How does EBV evade the immune system/

Answer 39

Inhibition of Ag processing | Production of immunosuppressive cytokines

Question 40

How do extracellular bacteria cause disease? | What are the main principal mechanisms of this?

Answer 40

They induce inflammation which results in tissue destruction at site. Many bacteria produce endo/exotoxins. Complement activation, phagocytosis, and inflammatory response.

Question 41

At what is the immune response against extracellular bacteria aimed?

Answer 41

Eliminating the bacteria and neutralizing the effects of their toxins.

Question 42

What is the purpose of the complement system and phagocytes in the innate immune response against extracellular bacteria?

Answer 42

Complement: opsonization and enhanced phagocytosis as well as inflammatory stimulation and leukocyte activation. Phagocytes recognize bacteria with Fc surface receptors and complement receptors.

Question 43

How does the innate immune system cause inflammation as a result of extracellular bacteria?

Answer 43

TLRs activate phagocytes and stimulate engulfment. Phagocytes secrete cytokines which induce leukocyte infiltration. Inflammation can cause damage.

Question 44

How does the adaptive immunity resolve extracellular bacteria?

Answer 44

Humoral immunity with antibodies functions to block infection, eliminate microbes, neutralize toxins, and activate CD4+ helpter T cells.

Question 45

What are the main outcomes of adaptive immunity towards extracellular bacteria via B cells?

Answer 45

Antibodies: Neutralization Opsonization and Fc receptor-mediated phagocytosis Complement activation: Phagocytosis of C3b coated bacteria inflammation bacterial lysis

Question 46

What are the main outcomes of adaptive immunity towards extracellular bacteria via T cells?

Answer 46

``` Inflammation (various cytokines) Antibody response (IFNgamma) Macrophage activation (IL17, TNF) ```

Question 47

Briefly describe the premise for immune evasion via sequential DNA rearrangements of microbial antigens.

Answer 47

There may be many inactive genes capable of expressing a gene but only one site for expression so that they can change the expression to evade the immune system at will.

Question 48

How must the body get rid of intracellular bacteria?

Answer 48

They have to use cell-mediated immunity.

Question 49

What is Nod1? What is the result of its activation? How is it activated?

Answer 49

Nod1 binds LPS which also causes Nod1 to be oligomerized and activate the NFkB pathway. Activated epithelium secretes CXCL8 which recruits neutrophils. It is activated via intracellular infection.

Question 50

How does the innate immune system respond to intracellular bacteria? Using what cytokines?

Answer 50

Phagocytes and NK cells | IL-12 and IFN gamma

Question 51

What is the major protective immune response against intracellular bacteria?

Answer 51

T cell mediated immunity

Question 52

Briefly describe how T cells function in the adaptive immunity to rid the body of intracellular bacteria/pathogens.

Answer 52

Phagocytosed bacteria in the cell are processed and expressed on MHC II molecules for CD4+ T cells to view. CD4+ T cells release IFN gamma back to the phagocyte. MHC I is able to present to CD8+ CTLs which are able to kill the infected cell.

Question 53

What are some of the mechanisms of immune evasion by intracellular bacteria?

Answer 53

Inhibition of phagolysosome formation Inactivation of reactive oxygen and nitrogen species Disruption of phagosome membrane and escape into the cytoplasm

Question 54

How is fungi recognized by DCs? | What effector cells does this stimulate?

Answer 54

Mincle (FcRgamma) TLR2 Dectin-1, and -2 (CLRs) Th1 and Th17 cells

Question 55

Which cells provide the best protection against fungal infections and why?

Answer 55

CD4+ T cells that make IFNgamma (Th1) or IL-17 (Th17). These function by using neutrophils and macrophages for killing the fungus.