Host-Pathogen Interaction And The Innate Immune System

Front 1

What are the 4 types of microbes that cause infections disease in man?

Back 1

Bacteria
Viruses
Fungi
Parasites - protozoa, worms

Front 2

What are 5 features of prokaryotes that distinguish them from eukaryotes?

Back 2

1. Lack a nucleus
2. Have a cell wall consisting of peptidoglycan
3. Single chromosome
4. 70s ribosomes
5. Can be round, rod-shaped, or spiral

Front 3

How are bacteria classified based on their stain?

What does the stain result from?

Back 3

Gram-positive (purple) or Gram-negative (pink)

Results from differential thickness of the peptidoglycan in the cell wall

Front 4

What do gram-negative bacterial cell walls contain?

What does it do?

Back 4

Lipopolysaccharide (LPS or endotoxin)

Stimulates the innate immune responses through TLR4

Front 5

What do lipoproteins stimulate?

Back 5

Stimulate the innate immune system through TLR2

Front 6

What do Gram positive cocci form?

Where are they located and what can they do?

Back 6

Can form capsules (polysaccharide polymers)

External to bacterial cell wall, can make organism resistant to certain immune mechanisms like complement lysis, phagocytosis

Front 7

What are 4 examples of toxin-producing bacterial diseases?

Back 7

Cholera
Tetanus
Diphtheria
Toxic Shock

Front 8

What happens in cholera?

Back 8

Bacteria in gut lumen produces toxin --> causes massive diarrhea

Front 9

What happens in tetanus?

Back 9

Bacteria --> potent neurotoxin, too small amount to produce an inflammatory response

Front 10

What happens in Diphtheria?

Back 10

Bacteria transmitted via respiratory secretions --> makes toxin in throat --> kills epithelial cells --> pseudomembrane of dead cells --> swells airway

Front 11

What happens in toxic shock?

Back 11

Superantigens stimulate T cells --> massive release of inflammatory mediators --> toxic shock

Front 12

How can the humoral response help destroy a bacterial infection? (3)

Back 12

Antibodies --> kill pathogens by targeting complement lytic components, neutralize exotoxins, enhance phagocytosis of encapsulated bacteria

Front 13

How can the cellular response help mediate a bacterial infection?

Back 13

Activate myeloid lineage cells --> enhance capacity to kill pathogens

Front 14

What is the general life cycle of a virus?

Back 14

Attach to host via specific receptors --> host internalizes virus --> uncoating --> replication of viral genetic material and synth of mRNA --> synth of viral proteins --> virus self-assembles and releases

Front 15

What is uncoating of a virus?

Back 15

When the virus separates its nucleic acid from its protective protein shell

Occurs after it has been internalized by the host

Front 16

What does it mean that viruses are 'obligate intracellular parasites'?

Back 16

They are incapable of replicating in the absence of a host cell and its biosynthetic machinery

Front 17

What are viruses made up of?

Back 17

1. Nucleic acid genetic material
2. Protein capsid
3. In some cases, outer envelope derived from host plasma membrane

Front 18

What are 3 methods for viruses to avoid intracellular destruction in lysosomes?

Back 18

1. Inhibit biochemical processes in the phagosome
2. Inhibit phagolysosomal fusion
3. Exit the phagosome to enter the cytoplasm or nucleus for replication

Front 19

What is cellular tropism?

Back 19

Each specific virus infects only a narrow range of eukaryotic host cells

Front 20

What is viral latency?

What are 3 examples?

Back 20

Viruses persist in the host indefinitely

1. Herpes in nucleus as an episomal element
2. Hepatitic C in hepatocytes
3. HIV - DNA integrated into host cell chromosome

Front 21

How does the role of the humoral response (antibodies) in viral infection differ if the virus is outside the cell vs. inside the cell?

Back 21

Antibodies can neutralize extracellular virus

Once cell is infected, elimination of infection is cell-mediated in concert with antibodies

Front 22

What are 2 differences between fungi and human cells?

Back 22

1. Presence of carbohydrate polymer cell wall
2. Presence of surrounding matrix of mannoproteins or mannans

Front 23

What are mannoproteins?

Significance in fungi?

Back 23

Conjugates of peptides with long mannose polymers

Stimulate innate immunity through Toll-like receptors, targets for nonspecific phagocytosis through mannose binding lectin (a scavenger receptor)

Front 24

What are 2 morphological forms of fungi?
At what temperature do they grow?

Back 24

Yeast - 25 deg
Molds - 37 deg

Front 25

What are yeasts? How do they reproduce?

Moulds?

Back 25

Yeast = single celled, reproduce by budding

Moulds = complex filamentous form

Front 26

What are dimorphic fungi?

What types of diseases are these implicated in?

Back 26

Fungi that can transition between yeast and mould


Cause endemic mycoses

Front 27

Where in the host do fungi grow?

Back 27

Extracellularly inside the host

Some can grow in phagocytic cells

Front 28

What is Candida?

What are 4 instances in which the Candida can become pathogenic?

Back 28

Yeast in our mucosal surfaces, opportunistic pathogens

1. Antibiotics reduce the amount of normal flora, allowing overgrowth of the yeast
2. Chemo reduces neutrophil count --> reduced host defense
3. AIDS
4. Specific immunodeficiency syndromes

Front 29

What is Cryptococcus neoformans?

What does it have that makes it virulent?

Back 29

Species of yeast that, when inhaled, causes pneumonia

It has a polysaccharide capsule that inhibits effective phagocytosis by neutrophils and macrophages

Front 30

What is histoplasma capsulatum?

Back 30

Mould in soil, yeast in host, can avoid killing by macrophages and proliferate in patients with defects in cell-mediated immunity

Front 31

What is aspergillus?

Back 31

Mould that can cause infection when inhaled by cancer patients with low numbers of leukocytes and macrophages

Front 32

What are 4 categories of single celled parasites?

Back 32

Amebas, Ciliates, Sporozoans, Flagellates

Front 33

What are some characteristics of multicellular parasites?

Helminths in particular?

Back 33

Worms that have complex life cycles, multiple hosts

Helminths have invasive phases where eggs, larva, or adult worms migrate through the vertebrate host

Front 34

What are the 4 roles of the innate immune response?

Back 34

1. Prevent infection of sterile tissues
2. Detect infections in sterile tissues when they occur
3. Mount an immediate, generic response
4. Transport antigens to lymph nodes --> initiate adaptive response

Front 35

What are 3 ways for bacteria to cross mechanical barriers?

Back 35

1. Microscopic trauma --> invasions by skin bacteria
2. Major trauma --> Implantation of soil or mouth bacteria (bites)
3. Introduced by arthropod vectors (bug bites)

Front 36

What are 5 non-immunological barriers to infection (besides mechanical barriers)?

Back 36

1. Normal bacteria flora can keep pathogens from colonizing or overgrowing
2. Mechanical methods like intestinal peristalsis or urine
3. Cough/gag reflexes prevent aspiration of mouth contents into lungs
4. Mucociliary removal of respiratory secretions and foreign matter
5. Low gastric pH

Front 37

What is the first stage of the immune response?

3 steps?

Back 37

Phagocytosis

1. Bacteria attaches to cell surface of macrophage --> engulfed into endosomic vesicle
2. Phagosome is acidified
3. Phagosome fuses with lysosome --> releases enzymes that kill bacteria

Front 38

What is the second stage of the innate immune response?

What are its 3 functions?

Back 38

Inflammation

1. Deliver effector molecules and cells to the site of infection
2. Induce blood clotting --> physical barrier to infection
3. Repair damaged tissue

Front 39

How is the inflammatory response initiated?

Back 39

Secretion of a variety of cytokines and chemokines by macrophages

Front 40

What are the 3 local responses to the release of pro-inflammatory cytokines?

Back 40

1. Increase vascular permeability, activate vascular endothelium to express cell adhesion molecules to localize immune cells (IL-1B, TNF-a)

2. Activate lymphocytes and immune cells at site of infection (IL-6, IL-12)

3. Recruit neutrophils, basophils, T cells via chemotaxis (CLC8)

Front 41

What is the general result of releasing pro-inflammatory cytokines to the site of infection?

Back 41

Flood area with cells and proteins, sequester the infected area

Front 42

What are neutrophils?

What are they replaced by?

Back 42

Phagocytic, short-lived members of the myeloid lineage

Replaced by monocytes, which eventually differentiate into macrophages

Front 43

What are the local effects of IL-1B? (4)

Back 43

1. Activates vascular endothelium
2. Activates lymphocytes
3. Local tissue destruction
4. Increases access of effector cells

Front 44

What are the systemic effects of IL-1B? (2)

Back 44

1. Fever
2. Production of IL-6

Front 45

What are the local effects of TNF-a?

Back 45

Activates vascular endothelium and increases permeability --> increased entry of IgG, complement and cells to tissues and increased fluid drainage to lymph nodes

Front 46

What are the systemic effects of TNF-a? (3)

Back 46

1. Fever
2. Mobilization of metabolites
3. Shock

Front 47

What are the local effects of IL-6?

Back 47

Lymphocyte activation and increased antibody production

Front 48

What are the systemic effects of IL-6?

Back 48

Fever
Induces acute-phase protein production by hepatocytes

Front 49

What are the local effects of CXCL8?

Back 49

Chemotactic factor recruits neutrophils, basophils, and T cells to site of infection

Front 50

What are the local effects of IL-12?

Back 50

Activates NK cells, induces the differentiation of cD4 T cells into TH1 cells

Front 51

What are the effects of IL-1B/IL-6/TNF-a on the liver?

Back 51

Acute phase proteins --> activation of complement opsonization

Front 52

What are the effects of IL-1B/IL-6/TNF-a on the Bone marrow endothelium?

Back 52

Neutrophil mobilization --> phagocytosis

Front 53

What are the effects of IL-1B/IL-6/TNF-a on the Hypothalamus?

Back 53

Increased body temp --> decreased viral and bacterial replication, increased antigen processing, increased specific immune response

Front 54

What are the effects of IL-1B/IL-6/TNF-a on fat and muscle?

Back 54

Protein and energy mobilization --> Increased body temp --> decreased viral and bacterial replication, increased antigen processing, increased specific immune response

Front 55

What are the effects of IL-1B/IL-6/TNF-a on dendritic cells?

Back 55

TNFa stimulates migration to lymph nodes and maturation --> initiation of adaptive immune response

Front 56

How do cells in the innate immune system sense the presence of pathogenic microbes?

Back 56

Pathogen-associated molecular patterns (PAMPs) on microbes bind to receptors called Pattern Recognition receptors (PRRs)

Front 57

What is mannose-binding lectin (MBL)?

Back 57

a soluble, complex lectin in the innate immune system that binds mannose and fucose carbohydrate residues on bacterial cell walls

Front 58

What is the structure of MBL?

How does this determine its function?

Back 58

2-6 clusters of carbohydrate-recognition domains, within which are clusters of carb-binding sites

MBL binds when mannose and fucose residues are spaced correctly on the bacterial cell wall

Front 59

What do the TLR family of receptors do?

Back 59

PRR receptors that sense the presence of extracellular microbial pathogens and initiate an innate immune response --> triggers secretion of the inflammatory cytokines and chemokines

Front 60

How are the 10 TLR genes able to recognize PAMPs on most pathogenic microbes?

Back 60

TLR receptors detect components that are common to Gram neg. bacteria, gram pos. bacteria, mycobacteria, yeast, and nucleic acids that are unique to viruses or viral genomes

Front 61

What happens when a TLR receptor binds a PAMP?

Back 61

Recruitment of adaptor proteins --> recruitment and activation of protein kinases --> activation of transcription factors --> gene transcription --> expression of inflammatory cytokines, chemokines, endothelial adhesion molecules, co-stimulatory molecules, antiviral cytokines

Front 62

What are the most common pathogens in the common cold?

How do they act?

Back 62

Rhinoviruses, Coronavirus

Act by attaching to cells in the nasopharynx via ICAM-1 (adhesion molecule) --> replicates in cells of the nasopharyx --> sets up a localized infection within upper respiratory tract

Front 63

How are viruses sensed by the innate immune system?

Back 63

PRR sensors RIG-1 and MDA-5 (expressed in cytoplasm of most cells) bind to viral dsRNA (replication intermediate) --> IRF3 and IRF7 transcription factors to nucleus --> Type I interferons made

Front 64

Where do NK cells develop? What do they respond to?

Back 64

Develop in bone marrow

Respond to type I interferons

Front 65

What are the 4 effects of the release of type I interferons by a virus-infected cell?

Back 65

IFN-a and IFN-b -->
1. Induce resistance to viral replication in all cells
2. Increase MHC class I expression and antigen presentation in all cells
3. Activate dendritic cells and macrophages
4. Activate NK cells to kill virus-infected cells (primary response)

Front 66

How do NK cells sense a virus-infected cell?

Why did this adaptation come about?

Back 66

Virus-infected cells fail to express normal levels of MHC class I molecules

Viruses developed decreased MHC class I surface molecules to avoid detection by CD8+ T cells; as a result, the body developed NK cells

Front 67

What do NK cells have on their surface that allows them to initiate lysis of cells with abnormal characteristics?

Back 67

Inhibitory and activating receptors

The balance of inhibitory/activating receptors that are activated when a given NK cell binds a cell determines the activity of the NK cell

Front 68

How are NK cells recruited to virus-infected cells?

Back 68

Type I interferons released --> activate resident macrophages --> secrete cytokines --> mix of cytokines recruits NK cells

Front 69

What are 4 elements of the immune response that help individuals recover from a viral infection?

Back 69

1. Type I interferon
2. NK cell activation
3. CD8 T cells that specifically recognize virally infected cells
4. B cells-mediated production of antibodies against mature viral particles

Front 70

TLR receptors that bind to Bacterial triacylated lipopeptides?

Back 70

TLR 1 and 2

Front 71

TLR receptors of bacterial peptidoglycan, lipoprotein, liptechoic acid, viral hemagglutinin

Back 71

TLR 2

Front 72

TLR receptor of Gram neg. bacterial LPS, fungal mannans, parasitic phospholipids, viral envelope proteins, host heat shock proteins

Back 72

TLR 4

Front 73

TLR Receptor of bacterial flagellin

Back 73

TLR 5

Front 74

TLR receptor of bacterial diacylated lipopeptides and lipotechoic acid

Back 74

TLR 2 and 6

Front 75

TLR 3 binds?

Back 75

Viral DS RNA

Front 76

TLR 7 binds?

Back 76

Viral ss RNA

Front 77

TLR8 binds?

Back 77

Viral ss RNA

Front 78

TLR 9 binds?

Back 78

Viral and bacterial unmethylated cpG DNA