number 4

Done by أبو عوضحسام

Corrected by عبدهللا زريقات

Doctor Sameer

Pathogenesis Terms

Endemic (متوطن): The disease is constantly present in a certain region (at a

fairly low level).

Epidemic: A rise in the number of people infected by the disease in a certain

region in a certain period of time.

Pandemic: When an epidemic infection reaches the entire world it becomes

“pandemic”.

Infectivity: The frequency with which an infection is transmitted when contact

between a virus and host occurs

Disease index: Number of people to develop the disease/Total number

infected

Prevalence: The total number of people infected with the disease at a certain

time.

Incidence: Number of new cases within a specific period of time (Percentage).

Virulence: Number of deaths by the disease / Total number of cases

What do Pathogens Try to Do?

➢ Pathogens infect their host (if the pathogen is a parasite then the word used is

“infest”).

➢ Pathogens ensure that they reproduce (progeny = offspring).

➢ Pathogens ensure that their progeny are transmitted to other hosts (to

continue their life cycles).

Routes of Viral Entry

Note: All the examples under this sub-heading are not to be memorized

.(إال إذا انت قطاعة)

Viruses can enter the body through three main methods:

1- Horizontal (Human to Human): Several mechanisms are possible:

i- Inhalation: The virus enters via the respiratory tract. E.g.

Rhinovirus (common cold), RSV (Respiratory Syncytial virus),

MMR (measles, mumps and rubella), VZV (Varicella zoster

virus).

ii- Ingestion: The virus enters via the gastrointestinal tract. E.g. Hepatitis

A, Rotavirus, Astroviruses, Caliciviruses.

iii- Inoculation: The virus eners via skin abrasions (جلد متآكل), mucous

membranes (e.g. sexual transmission), blood transfusion (the blood from

the donor may contain a virus and is then transmitted to the patient),

injections (e.g. shared syringes in drug abusers), organ transplants.

2- Vertical (Mother to Baby): Also three possible mechanisms:

i- Transplacental: E.g. CMV (Cytomegalovirus), Rubella, HIV.

ii- Delivery: E.g. Hepatitis B, Hepatitis C, HSV (Herpes Simplex

virus), HIV, HPV (Human papillomavirus).

iii- Breast Feeding: E.g. CMV, Hepatitis B, HIV.

3- Zoonotic (From Animals to Humans): Most parasitic infections

enter our bodies via this route. Again, three ways of zoonotic entry:

i- Animal Bite: E.g. Rabies (caused by rabies virus) ( ( َ ل بداء الكَ .

ii- Insect Bite: E.g. Dengue (caused by Dengue virus), West Nile

virus.

iii- Animal Excreta (waste): E.g. Hantavirus, Arenavirus.

This diagram shows the

sites of viral entry.

Incubation Period

It is the time between exposure to the virus (or other pathogens) and

appearance of symptoms (not sure if the following list is to be memorized, but

the doctor discussed each virus separately… seems important…).

Minor note on the table: The rubella (also known as the 3 day

measles) virus is less severe than the measles (also known as the 5

day measles) (Rubella= األلمانيةالحصبة , Measles= حصبة).

More Terms

Communicability: Ability of the virus to shed into secretions (and so it can be

transmitted to others).

Localised Infection: The infection is limited to the site of entry.

Disseminated Infection: The infection gets spread throughout the body.

Primary Viremia: The virus moves from the site of entry to the regional lymph

node and then to the blood.

Secondary Viremia: The virus moves from the site of entry to the regional

lymph node then to the blood then to the organs and then back to the blood.

Primary Infection

Each virus has specific receptors to which it can bind and then initiate entry to

the host cell, usually this would be only one cell type in a certain region of the

body, but sometimes the virus can infect several cells at entirely different sites.

This specificity of the virus often determines whether the infection is localised

or spread (disseminated).

Secondary Infection

This infection type is specific to systemic infections in which the virus

goes on, after infecting a certain site, to infect several areas of th e

body. E.g. The poliovirus first enters via the GI into the intestines and

initiates an infection in the lymphoid follicles (called Peyer’s patches)

in the small intestines. From there, the poliovirus goes to the nervous

system by a viremia (going to blood then to organs, see “More

Terms”), usually the affected nervous tissues are the peripheral ones.

Infecting the nervous system causes paralysis to the patient (usually it

is children who get infected by this virus).

[I think the following information is additional, but not really sure…:

There are two types of paralysis, spastic (تشنج في العضالت) and flaccid

The poliovirus causes flaccid paralysis. Tetanus .(ضمور في العضالت)

is a viral disease that causes spastic paralysis; the virus first (الكزاز)

enters into the body via a cut in the skin (so it enters into the blood)

and it gets inoculated in this way. The virus replicates in its initial

infection site and then it enters the nervous system either via a viremia

or by directly entering into nerves that are in contact with the infected

region of the skin. The first paralytic symptom of tetanus is the

paralysis of the muscles of the jaw (locked jaw) and then the paralysis

of the muscles of the back ( س الظهرتقو ). Any stimulus, even light, can

cause this paralytic action in the patient’s body, so the patients

infected with this disease are kept in a dark room (if the paralysis

reaches the respiratory muscles the patient would die, so they are put

on ventilators). There is a vaccine against tetanus called DPT

(Diptheria, pertussis (whooping cough) and tetanus). The poliovirus

also has a vaccine that can be either given as an injection (inactivated

viruses) (becoming more common nowadays) or by mouth (given as

drops, living attenuated viruses). The poliovirus vaccine prevents the

secondary infection from occurring; when the weakened (or

inactivated) virus is given to the patient, the body produces antibodies

against the virus (IgM, then IgE and finally IgA are produced and

remain in the body for a veeeeeeeery long time giving immunity

against polio), so when the virus, later in life, enters into the patient’s

body, it will be controlled at the Peyer’s patches and prevented from

reaching the nervous system by these antibodies and no symptoms of

the disease are seen (in viruses that cause systemic infections you can

stop the effect of the virus by stopping its spreading rather than its

entry)].

As you can see, the criteria

for enteroviruses are very

similar to what we saw with

the poliovirus, in fact, the

poliovirus is one of the

enteroviruses.

The upper respiratory tract

infections caused by

rhinovirus (common cold) are

often referred to as “Rhinitis”

or “Coryza”.

Mechanisms of Spreading

- Cell-cell contact.

- Via the bloodstream.

- Via the nervous system.

Via the Bloodstream: The virus first enters into the body via direct inoculation

(read “Routes of Viral Entry”) (good examples: Malaria (an arthropod carrying

the pathogen sucks blood from the patient and, in the process, the pathogen is

inserted into the blood). Blood transfusion (in many cases, the donor’s blood is

not screened and it may contain a pathogen which will then be transmitted to the

patient). Drug abusers who use injections).

When the virus enters into the blood it may be transferred free in the plasma

(Togaviruses, Enteroviruses), associated with the red blood cells (Orbiviruses),

associated with platelets (HSV), associated with lymphocytes (EBV, CMV) or

associated with monocytes (Lentiviruses). [Examples are not to be memorized].

(Primary viremia is common in this route; secondary viremia may be seen in

more severe cases).

Via the Nervous System:

The infection may spread by the direct contact of the neuron with the infected

area (e.g. in the skin) or after the virus enters into the bloodstream (primary

viremia) it may reach the peripheral nerves from which the infection can spread

towards the central nervous system via axonal transport. Moving from one

neuron to the next is easy for the viruses as the synaptic junctions often contain

viral receptors. [The HSV hides in the dorsal root ganglia (latent) and when the

immune system gets suppressed, for any reason, it enters into the neurons and

travels to the hips or mucous membranes causing diseases there (treated with

Zovirax (scientific name: acyclovir)). The shingles disease (الحزام الناري) is

caused by VZV which is also latent and hides in the dorsal root ganglia; when

VZV gets reactivated, it enters a specific nerve that innervates a certain region

of the skin and blisters are seen there; the disease is usually unilateral

(symptoms seen only on one side of the body)].

Virulence and Cytopathogenicity

Virulence: The ability of the virus to cause a disease in the infected cell.

Virulent viruses kill the target cell and cause the disease (productive response).

The persistent (دائمة) infections caused by viruses can be divided to two main

types:

1- Latent infections (like the HSV and VZV mentioned in the previous section)

(the viruses enter the lysogenic cycle).

2- Chronic infections

The viruses can infect either permissive or non-permissive cells; while the

permissive ones allow the virus to replicate (produce virions) and may or may

not transform the cell (change it to a cancerous cell) the non-permissive cells do

not allow the virus to reproduce, but there is a chance for them to get

transformed.

Some viral infections are “Abortive”; when the virus uncoats releasing its

genome and proteins, its proteins directly kill the cell not allowing the virus to

reproduce (leading to the death of both, the virus and the cell).

Cytopathic Effects: this describes the changes (damage) the virus induces to

the cell. There are 8 main cytopathic effects:

I- Changes in size and shape (of the cell) (all the viruses do this).

II- Cytoplasmic inclusion bodies are seen (inclusions are large cluster

formed due to the viral proteins; this is not seen in all viral infections).

III- Nuclear inclusion bodies (only some viruses can cause this effect).

IV- Cells fuse forming a multinucleated cell (called syncytia).

V- Cell lysis

VI- DNA alteration

VII- Transforming the cell into a cancerous one (RNA viruses usually).

VIII- Virokines and viroreceptors (these are proteins produced by some genes

of the host cell, induced by the virus, which prevent the immune system

from attacking the infected gene allowing the virus to evade the immune

system. They are ONLY produced by some DNA viruses).

The doctor said that we are not to

memorize this table, but then he

said that we must “know” some

of those mentioned and then he

specifically mentioned the

smallpox virus, the herpes

simplex virus, the poliovirus,

rabies and HIV. [Note: the

production of inclusion bodies

depends on the replicative cycle

(mechanism of replication) of the

virus.

Patterns of Viral Infections

- Inapparent infection (no symptoms, or very mild ones, seen).

- Apparent infection (two types):

➢ Acute Infection

➢ Persistent Infection (three types):

▪ Chronic (مزمنة) Infection (the infection remains for months or years with

mild or no symptoms, but after that it ends).

▪ Latent Infection (like the HSV and VSV mentioned previously, they

usually remain in the patient for the rest of his life).

▪ Slow Chronic Virus Infection (This takes a veeeery long time to develop

its symptoms) (I don’t know why this type was not mentioned by the

doctor (even in his slides) when we discussed persistent infections

previously).

The following diagram summarizes the patterns of apparent infections (the x-

axis shows “Time”, the y-axis shows the “Virus production”).

As you can see, in an acute infection, the virus reproduces a lot and then the

infection is controlled and everything returns back to normal.

In chronic infections, the virus reproduces and stays for a veeery long time

inside the body with very high numbers.

In the latent infection, the virus reproduces each time the immune system gets

compromised and gets cleared again once the immune system returns to normal.

In the slow chronic infection, the number of viruses continuously increases, but

over a veeeery long time.

Note: the chronically infected patient is considered a carrier of the virus and so

is not allowed to donate blood to others (may spread the infection).

Overall Fate of the Cell

- In cytocidal infections, the cell dies whether the infection is acute (brief and

self-limiting infection) or chronic (drawn out infection).

- Persistent infections may be productive (virions produced) or non-productive

or may alternate between the two (latency and reactivation; like HSV and

VSV).

- Transformation may occur to the cell (the cell becomes cancerous):

➢ RNA viruses (the types that cause cancer) usually transform the host cell to a

malignant phenotype by integrating their own genome into the cell’s genome

and they may produce infectious progeny. [Retroviruses include HTLV I

(Human T-lymphocyte virus) and HIV which are very similar to each other

such that HIV used to be called HTLV III, but later own it was figured out

that it is a totally different virus (the doctor said that the details of

retroviruses mentioned in the slides are not important].

➢ DNA viruses (the ones that cause cancer) are often cytocidal.

➢ The p53 protein can inhibit cancer by initiating apoptosis(again, the details

are not required).

This table summarizes

the types of viral

infections.

Mechanisms of Cytopathogenesis

Note that these mechanisms are very similar to what antibiotics do to bacterial

cells. (examples are not required)

Slide #28 is not included in the exam and it was not explained by the doctor