10. 11. Infection I & II

Question 1

What are the 6 classifications of infectious organisms?

Answer 1

• Bacteria
• Virus
• Protozoan
• Fungus
• Intracellular bacteria
• Helminth

Question 2

Bacteria causes tissue injury by ... that aid ... and break down tissue (..., ... and .... Gram +ve bacteria also releases ... that inhibit cellular functions, including .... Gram -ve bacteria releases ... (LPS = ...), which have detrimental effects on cell function. Bacteria can initiate ....

Answer 2

Bacteria causes tissue injury by releasing enzymes that aid invasion and break down tissue (collagenase, coagulase and hyaluronidase. Gram +ve bacteria also releases exotoxins that inhibit cellular functions, including phagocytosis. Gram -ve bacteria releases endotoxins (LPS = lipopolysaccharides), which have detrimental effects on cell function. Bacteria can initiate later hypersensitivity response.

Question 3

Viruses produces ... that invade cells, and can evade .... Viruses replicate by using .... Cell damages result from ... of the cell membranes to release new .... Virus replication changes ... (MHC 1) and also invokes ... (NK and CD8+ cells, extracellular viral antigens). Intracellular virtual replication disrupts ... and therefore causes .... Some viruses can cause ..., causing ... and damage to surrounding tissues.

Answer 3

Viruses produces virions that invade cells, and can evade immune surveillance. Viruses replicate by using cell machinery. Cell damages result from rupturing of the cell membranes to release new virions. Virus replication changes cell's antigenic properties (MHC 1) and also invokes inflammatory/ immune response (NK and CD8+ cells, extracellular viral antigens). Intracellular virtual replication disrupts cell function and therefore causes cell death. Some viruses can cause unrestricted cell replication/ differentiation, causing neoplasia and damage to surrounding tissues.

Question 4

Similar to viruses, this pathogen enter cells in order to replicate in the cytoplasm →
...;
Protozoans, such as ... release enzymes, causing ... influx and cell lysis.
... causes excessive ... response. Both microorganisms try to avoid immune response through ...;
... can initiate excessive inflammatory and immune responses. There are also ... within the ... that can cause inflammation;
Fungi releases ... and provoke excessive immune response.

Answer 4

Similar to viruses, this pathogen enter cells in order to replicate in the cytoplasm →
Chlamydia;
Protozoans, such as Acanthamoeba release enzymes, causing calcium influx and cell lysis.
Toxoplasma causes excessive immune response. Both microorganisms try to avoid immune response through encystment;
Helminths can initiate excessive inflammatory and immune responses. There are also endosymbiotic bacteria within the helminth that can cause inflammation;
Fungi releases proteases and provoke excessive immune response.

Question 5

Most bacteria cannot penetrate an intact corneal/ conjunctival surface, but which bacteria can? And how?

Answer 5

Pseudomonas aeruginosa releases proteases that can slowly penetrate the epithelium in 3 hours. Breakage in the epithelium promotes adhesion and invasion.
Endotoxins released can also affect epithelial tight junctions. With sufficient bacterial load, toxins can provoke inflammatory response and epithelial damage, this increases bacterial access, particularly in the conjunctiva.

Question 6

What are the innate immune receptor and cells involved in innate immunity?

Answer 6

Toll-like receptors and Corneal dendritic cells

Question 7

What action of the bacteria causes inflammatory responses and continued tissue damages?

Answer 7

Bacterial replication in the stroma and continual release of exotoxins damages epithelium and causes inflammatory responses. Neutrophil enzymes can also cause further tissue damage.

Question 8

Name a long term complication resulting from acute infectious keratitis.

Answer 8

Loss of sensory nerves in the cornea, corneal scarring as a result of ulceration/ perforation.

Question 9

Contact lens wear increases susceptibility with .... Contact lenses causes tear film to become immobile, therefore prevents bacteria from being .... Contact lenses causes ... of the corneal epithelium, therefore disrupts the ... and promotes ... to epithelium. Overnight contact lens wear ..., therefore promote a ... environment.

Answer 9

Contact lens wear increases susceptibility with ocular bacterial infection. Contact lenses causes tear film to become immobile, therefore prevents bacteria from being swept away by the lids. Contact lenses causes chronic mild hypoxia of the corneal epithelium, therefore disrupts the homeostatsis and promotes bacterial adhesion to epithelium. Overnight contact lens wear alters tear levels of pro-inflammatory cytokines, therefore promote a pro-inflammatory environment.

Question 10

Extended wear CLs stimulates ... migration to ... cornea. These are ..., so if infection occurs, ... will become more agressive than normal ... response. Therefore damage is more extreme. Placing a contact lens on a healthy cornea can cause a ... of T cells.

Answer 10

Extended wear CLs stimulates Langerhans cell migration to central cornea. These are antigen presenting cells, so if infection occurs, inflammation will become more agressive than normal neutrophils response. Therefore damage is more extreme. Placing a contact lens on a healthy cornea can cause a loss of a number of T cells.

Question 11

Chronic dry eyes induces .... The accelerated cell death causes ... and improves .... Reduced tears results in reduced ....

Answer 11

Chronic dry eyes induces epithelial apoptosis. The accelerated cell death causes epithelial erosion and improves bacterial adhesion. Reduced tears results in reduced antibacterial activity.

Question 12

WIth an intact cornea and normal tear film, ... for bacteria is insufficient for ....
In a compromised cornea, bacteria can adhere and replicate, allowing release of ... and ..., breaks down the corneal barrier further. Bacterial proliferation occurs in the .... Injured epithelial cells release .... Early neutrophil ... from limbal vessels and anterior uvea. Release of ... and .... Later chemotaxis of ... from limbus. Corneal ... can occur if not treated soon.

Answer 12

WIth an intact cornea and normal tear film, adhesion time for bacteria is insufficient for invasion.
In a compromised cornea, bacteria can adhere and replicate, allowing release of toxins and enzymes, breaks down the corneal barrier further. Bacterial proliferation occurs in the corneal stroma. Injured epithelial cells release interleukins. Early neutrophil chemotaxis from limbal vessels and anterior uvea. Release of proteases and reactive oxygen species. Later chemotaxis of lymphocytes from limbus. Corneal perforation can occur if not treated soon.

Question 13

What are the clinical signs of protozoal infections?

Answer 13

Extreme pain

Question 14

Acanthamoeba is a ... and exist as two different forms: ... (motile form) or ... (cellulose wall). They can evade the ... and .... They undergo ...., and thus can go undetected. Acanthamoeba can form .... in the ... for .... They preferentially attacks ..., therefore causes .... They causes the formation of ... made out of mostly ....

Answer 14

Acanthamoeba is a protozoa and exist as two different forms: trophozoites (motile form) or encysted (cellulose wall). They can evade the immune system and anti-amoebal drugs. They undergo dormancy, and thus can go undetected. Acanthamoeba can form cysts in the corneal stroma for protection. They preferentially attacks corneal nerves, therefore causes pain. They causes the formation of perineural/ radial infiltrates made out of mostly neutrophils.

Question 15

The intracellular bacterium ... causes trachoma, which is the world’s most common .... Trachoma can manifest as an aggressive .... This bacterium also causes ..., but with less aggressive presentations. Infective particles are transmitted by .... They can form ... in host cells, which then grows to form .... This bacterium triggers ... involving ... and ... T cells. These responses causes formation of ... or ....

Answer 15

The intracellular bacterium Chlamydia causes trachoma, which is the world’s most common infective blindness. Trachoma can manifest as an aggressive keratoconjunctivitis. This bacterium also causes sexually-transmitted adult inclusion conjunctivitis, but with less aggressive presentations. Infective particles are transmitted by flies or sexual interactions. They can form small elementary inclusion bodies in host cells, which then grows to form large intial bodies. This bacterium triggers marked cellular immune responses involving CD4+ and CD8+ T cells. These responses causes formation of follicular hyperplasia of tarsal conjunctiva or follicular infiltrates of bulbar/ limbal conjunctiva.

Question 16

Fungi which most commonly infect the eyes are yeast ... and filamentary fungus .... Fungal infections is most common ... with vegetative matter, ... and in ... individuals. ... are the most common cell type in intial fungal infection. Once fungal infection takes hold, it spreads ... and many other cell types are recruited. Chronic fungal infections will become ... with time. ... can occur if fungal infection persist in the cornea for extended period of time.

Answer 16

Fungi which most commonly infect the eyes are yeast Candida and filamentary fungus Aspergillus. Fungal infections is most common post trauma with vegetative matter, post surgery and in immunocompromised individuals. Neutrophils are the most common cell type in intial fungal infection. Once fungal infection takes hold, it spreads extremely rapidly and many other cell types are recruited. Chronic fungal infections will become granulomatous with time. Corneal perforation can occur if fungal infection persist in the cornea for extended period of time.

Question 17

During a viral infection, ... fuse with ... and enters via .... Virions then ..., enter the nucleus for .... In the nucleus, ... are made and then released.

Answer 17

During a viral infection, virions fuse with cell membrane and enters via endocytosis. Virions then uncoat, enter the nucleus for replication. In the nucleus, new viral proteins are made and then released.

Question 18

What are the pathological consequences of a viral infection?

Answer 18

• Changes directly in host cell: virus damages or kills host cell; persistence of viral infection without cell injury; cell transformation, unchecked division causing neoplasia
• Host tissue reaction to cell changes and extracellular virus → innate system inflammation
• Host immune response → adaptive system also to virus and host cell changes

Question 19

What are the 5 possible effects of a virus on target cells?

Answer 19

• No effect/ Latency
• Cell death
• Cell fusion
• Formation of inclusion bodies
• Cell proliferation

Question 20

What are the two initial possibilities in a viral infection? What happens if the virus is not eliminated following initial exposure?

Answer 20

Initially, virus either cause effects only at the site of entry (e.g. Influenza), or cause systemic effects from the site of entry (e.g. poliomyelitis). Initial contact will usually result in an acute infection. If virus is not eliminated, it can have 4 different effects:
• Latent infection (HSV)
• Chronic infection (Hep B)
• Persistnet/ slow infection (HIV)
• Oncogenic (papilloma virus)

Question 21

Name the 11 common viruses that cause ocular pathologies.

Answer 21

• Herpes Simplex Virus (keratitis)
• Varicella Zoster Virus (keratitis)
• Adenovirus (conjunctivitis)
• Cytomegalovirus (retinitis)
• Human immune-deficiency virus
• Papilloma virus (conjunctival/ lid tumours)
• Poxvirus (Molluscum contagiosum lid lesion)
• Measles (keratitis)
• Epsein-Barr virus (retinitis)
• Rubella (congenital cataract)
• SARS-CoV-2 (conjunctivits, uveitis, optic neuritis)

Question 22

Recurrent ocular HSV infection can cause ..., ... or be associated with acquired .... HSV tends to affect the ... the most. Similar to Varicellar zoster virus, HSV also infect and spread via the ... nerve. Primary HSV infection appears as ... near the ..., which is close to sensory nerve ... and ... branches. HSV travels to the ... and remain .... Virus can become reactivatted by ..., ... or .... When infecting the cornea, HSV travels down to the ...l, because they are closest to the .... This activates the ... response. HSV virions enter cells, replcaite and cause .... Earliest clinical signs invovle epithelial ..., which later develops into .... Virions can accomulate at the apical surface of the corneal epithelium, which allow for the possiblity of ....

Answer 22

Recurrent ocular HSV infection can cause keratitis, uveitis or be associated with acquired Horner's syndrome. HSV tends to affect the corneal epithelium the most. Similar to Varicellar zoster virus, HSV also infect and spread via the CN5 Trigeminal nerve. Primary HSV infection appears as cold sores near the corner of the mouth, which is close to sensory nerve V2 and V3 branches. HSV travels to the trigeminal ganglion and remain dormant. Virus can become reactivatted by colds, sunlight or menstration. When infecting the cornea, HSV travels down to the basal epithelial cell, because they are closest to the trigeminal ganglion. This activates the innate immune response. HSV virions enter cells, replcaite and cause cell degeneration. Earliest clinical signs invovle epithelial cysts, which later develops into patent/ geographic ulcers. Virions can accomulate at the apical surface of the corneal epithelium, which allow for the possiblity of viral transmission through tears.

Question 23

Stromal ... can result from HSV infection. Clinically it can appear as ... or as .... Studies have suggested that infiltrates largely consist of .... The actual cause is not clearly known, but could be due to ... causing normal cell-mediated response, cell-mediated response to ... (autoimmune), naive T cell become activated by ... (bystander hypothesis). This condition is often ... and involve the ....

Answer 23

Stromal keratitis can result from HSV infection. Clinically it can appear as mild anterior cellular infiltrate or as necrotising stromal degeneration. Studies have suggested that infiltrates largely consist of CD4+ T cells. The actual cause is not clearly known, but could be due to residual viral antigen causing normal cell-mediated response, cell-mediated response to autoantigen (autoimmune), naive T cell become activated by sensitised T cells (bystander hypothesis). This condition is often recurrent and involve the stroma.

Question 24

Disciform keratitis/... is a result of recurrent HSV keratitis. This involves .... Inflammatory cells accumulates on ..., which causes formation of ....... may form, causing corneal opacities. Viral antigen can be found in endothelial cells, which drives cell-mediated inflammation.

Answer 24

Disciform keratitis/endothelitis is a result of recurrent HSV keratitis. This involves anteior chamber inflammation/ anteiror uveitis. Inflammatory cells accumulates on endothelium, which causes formation of keratic precipitates. Acute stromal oedema may form, causing corneal opacities. Viral antigen can be found in endothelial cells, which drives cell-mediated inflammation.

Question 25

Give an example of where a virus causes cell division.

Answer 25

Human papilloma virus expresses certain oncoproteins while replicating in a cell nucleus. These oncoproteins stimulate cells to divide infinitely, bypassing programmed stops of normal cellular division processes.

Question 26

How many % of the world population are infected with HSV?

Answer 26

60-90% of world population is infected with Herpes Simplex virus