GENERAL PATHOLOGY OF INFECTIOUS DISEASES
In unsanitary living conditions and malnutrition lead to a massive burden of infectious diseases especially respiratory and diarrheal infections caused by bacteria and viruses . despite vaccination and antibiotics ,infectious diseases continue to have a heavy role in patient with immunosuppressive drugs or with (IDIS).There are a relationships between microorganisms and humans. without our normal gut flora, we would be at risk for vitamin K deficiency and the normal vaginal flora prevent recurrent Candida ("yeast") infections.
The majority of these relationships are :-
1- Symbiotic (of benefit to both partners) or,2-Commensals (the microorganisms that live and shares the host's food without causing harm).
* Pathogens :- are microorganisms that injure the host .they include bacteria , viruses , fungi , protozoa , and parasites (or worms).
* pathogenicity:- the capacity of the organism to cause disease.
* Virulence :- is the degree of pathogenicity.
* Apportunistic infections:- the commensal microorganisms become pathogenic in immuncompromised patients.
e.g.
1- E. coli is a normal flora (inhabitant) in GIT but when enter the urinary tract it becomes pathogenic and lead to sever urinary infection.
2- during tooth extraction , diseased heart valves may become infected by Streptococcus viridance which are normal commensals of the mouth . such an infection leads to serious disease (bacterial endocarditis ) .
• *infection :- is the presence of microorganism in a part of the body where its normally absent and where if allowed to multiply ,it stimulate a host immune response and cause infectious disease . the outcome depends on balance between the microorganisms aggressive mechanisms and the host defenses.
• * Invasion :- is the first step of causing an infection ,it depends on the penetration of the hosts tissues by micro-organisms .
When microbes cause disease, the nature and extent of the pathology depend on (1) the virulence (or pathogenicity) of the microorganism and (2) the response of the host.
Host Defenses are divided in to :-
A- non specific defense mechanisms , these are operative irrespective of the nature of the pathogens.1- mechanical barriers e.g. clean dry skin , mucous layer of the conjunctiva , respiratory and GIT mucosa. If any one of these barriers is broken , infection may occur e.g. infection are a recognized complication of burns , because the latter damage the skin barrier.
2- Glandular secretions
- Acidity of sweat is bactericidal for some pathogens.
- Acidity of gastric juice is effective in killing most types of micro-organisms that contaminate food and water.
- Lysozyme enzymes secreted by mucous membranes can digest mucopeptide of bacterial cell wall. Its found in lacrimal , salivary , and nasal glands .
3- Secretion currents
- Continuous secretion of tears prevents conjunctival infection.
- Ciliated respiratory epithelial cells prevent infection . failure of this mechanism permits influenza virus to combine with epithelial cells.
- Smoking damage to respiratory epithelium predisposing to bacterial infection .
- Increase peristalsis movement of the intestine and diarrhea during intestinal pathogen e.g. salmonella this is a defending mechanism to get ride of the offending bacteria.
- Obstruction of urinary flow lead to stasis of the urine lead to subsequent urinary tract infection this seen in prostatic enlargement and urinary calculi.
4-phaocytosis
- Neutrophils migrate to tonsillar crypts and microphage migrate in to the alveoli.
- Both engulf particles and micro organisms and prevent invasion.
B- Specific defenses which are by immune system directed against infectious agents.
categories of infectious agents
Agents that cause infectious diseases range in size from 20-nm poliovirus to the 10-m tapeworm.
Viruses
Viruses are obligate intracellular organisms that commandeer the host cell's biosythetic and replicative apparatus for their own proliferation. They consist of a nucleic acid genome surrounded by a protein coat (called a capsid) and, occasionally, a host-derived lipid membrane. Viruses may be classified by some combination of their nucleic acid genome (DNA or ribonucleic acid [RNA], but not both), the shape of the capsid (icosahedral or helical), the presence or absence of a lipid envelope, the mode of replication, the preferred host cell type (called tropism), or the type of pathology they cause .Because viruses are individually smaller than the limits of light microscopic resolution (20-300 nm in size), they are best visualized by electron microscopy. However, certain viruses have the propensity to aggregate within the cells they infect and form characteristic inclusion bodies.
Bacteria
Bacterial infections are common causes of disease . Bacterial cells are prokaryotes: they have a cell membrane but lack membrane-bound nuclei and other membrane-enclosed organelles. Bacterial cell walls generally occur in one of two varieties: a thick wall surrounding the cell membrane that retains crystal violet stain (Gram-positive) or a thin cell wall sandwiched between two phospholipid bilayer membranes (these do not retain crystal violet stain and are thus Gram-negative) .Bacteria are classified by Gram staining (positive or negative), shape (e.g., spherical ones are cocci ; rod-shaped ones are bacilli), and form of respiration (aerobic or anaerobic) Many bacteria have flagella that permit movement; others possess pili that allow attachment to host cells.Chlamydiae, Rickettsias, and Mycoplasmas
Like bacteria, these organisms divide by binary fission and are sensitive to antibiotics. However, they are considered separately here because they lack certain structures (e.g., Mycoplasma lack a cell wall) or metabolic capabilities (e.g., Chlamydia cannot synthesize adenosine triphosphate [ATP]) that distinguish them from bacteria. These organisms species are obligate intracellular organisms that replicate in membrane-bound vacuoles in epithelial cells and the cytoplasm of endothelial cells.Fungi
Fungi may cause superficial or deep infections. Superficial infections typically involve the skin, hair, or nails. Dermatophytes ("skin lovers") are fungal species confined to superficial skin layers; these infections are commonly referred to by the term "tinea. fungal infections usually heal or remain latent in normal hosts; in immunocompromised hosts, however, they can spread systemically and invade tissues, destroying vital organs such as (opportunistic fungi such as Candida, Aspergillus , Mucor , and Cryptococcus).
Protozoa
Protozoa, single-celled eukaryotes . The protozoa can replicate intracellularly in many cell types (e.g., malaria in erythrocytes, Leishmania in macrophages) or extracellularly in the urogenital system, intestine, or blood. Trichomonas vaginalis is a sexually transmitted protozoan that can colonize in vagina and male urethra. The most prevalent intestinal protozoans is Entamoeba histolytica and Giardia lambliamajor causes of morbidity and mortality . Blood-borne protozoa (e.g., Plasmodium, Trypanosoma, and Leishmania) replicate within insect vectors before transmission to new human hosts.Helminths
Parasitic worms are highly differentiated multicellular organisms with complex life cycles; most alternate between sexual reproduction in the definitive host and asexual multiplication in an intermediary host or vector. depending on the species, humans may harbor adult worms (e.g., Ascaris lumbricoides), immature forms (e.g., Toxocara canis), or asexual larval forms (e.g., Echinococcus species).Helminths comprise three classes:
- Roundworms (nematodes)
-Flatworms (cestodes)
-Flukes (trematodes)
Ectoparasites
Ectoparasites are insects (lice, bedbugs, fleas , mites, ticks, spiders) that attach to and live on or in the skin. These parasites may produce disease by direct tissue damage or indirectly by serving as the vectors for transmission of infectious agents.
Routes of Infection and Dissemination of Microbes within the Body
Microbes can enter the host body by inhalation, ingestion, sexual transmission, insect or animal bites, or injection.
Microbes spread rapidly along the wet epithelial surfaces of intestine ,lung .and genitourinary tract and slow on the dry surface of the skin .
Release of microbes From the Body
For transmission of disease to occur, exit of microorganisms from the host is as important as the original entry. Release may occur through skin shedding , coughing, sneezing, urination, or defecation, or via insect vectors . Some pathogens may be spread even though the host is asymptomatic.Microorganisms can be transmitted from animals to humans by invertebrate vectors such as insects (i.e., mosquitoes), ticks, or mites that either spread infection or occasionally serve as necessary hosts for microbial replication and development. Transmission can also occur directly from animals to humans (called zoonotic infections), either by direct contact or by eating the infected animal .
How infectious agent cause disease
After breaking host barriers, infectious agent injure the cells and cause tissue damage by three general mechanisms:-1- infectious agent can come into contact with or enter host cells and directly cause cell death.
2-pathogen can
- Release endotoxin or exotoxin that kill the cells.
- release enzymes that degrade tissue components.
- damage blood vessels and cause ischemic injury.
3-Pathogens can induce host immune and inflammatory responses that may cause additional tissue damage.
Mechanisms of Viral Injury
Viruses can directly damage host cells by entering them and replicating in it .Viral tropism is tendency of a virus to infect certain cells and not others e.g influenza virus infect respiratory epithelial cells . similarly hepatitis A , B, and C virus infect liver .
Viral tropism is determined by several factors:-
1-Host-cell receptors for a particular virus. Viruses possess specific cell surface proteins ( ligand ) that bind to selected host cell surface proteins (receptor) . Many viruses use normal cellular receptors of the host to enter cells. Thus, HIV gp120 binds to CD4 ( T helper lymphocytes) .
2- Physical barriers. For example , enteroviruses replicate in the intestine because they can resist inactivation by acids, bile, and digestive enzymes.
Viruses can kill host cells in several ways:-
1-Lysis of host cells. Viral replication interferes with normal cellular functions and may lead to cell death. For example, viral replication and release is the mechanism by which influenza virus kills respiratory epithelial cells.2-Immune cell-mediated killing. Viral proteins expressed on host cell surfaces are recognized as foreign by the immune system and induce attack by cytotoxic T lymphocytes.
3-Alteration of apoptosis pathways. some viruses encode genes that inhibit apoptosis .
4- Induction of cell proliferation and transformation, resulting in cancer e.g. hepatitis B may lead to liver cancer .
5-Inhibition of host cell DNA, RNA, or protein synthesis. These effects may eventually cause cell death, or they may lead to more subtle cellular dysfunction.
6- Damage to plasma membranes. Viral proteins can insert into host plasma membranes and thereby alter their integrity or promote cell fusion.
7-Damage to cells involved in antimicrobial defense, leading to secondary infections. For example, viral damage to respiratory epithelium predisposes to subsequent bacterial pneumonia, and HIV depletion of CD4+ helper T lymphocytes leads to opportunistic infections.
Mechanisms of Bacterial Injury
The ability of bacteria to cause disease (virulence) depends on(1)their ability to adhere to host cells,
(2) their ability to invade cells and tissues,
(3) their ability to deliver toxins that damage cells and tissues.
Bacteria adher to the host cells by adhesion ,which are molecules that bind bacteria to host ,next they will inhibit protein synthesis of target cell. This followed by multiplication of bacteria with lysis of host cells.
Bacterial toxins are two types:-
1- Endotoxin is a lipopolysaccharide that is a major component of the outer cell wall of gram-negative bacteria.
The biological activity of endotoxins include :-
1- induction of fever.
2- septic shock.
3-acute respiratory distress syndrome
4- disseminated intravascular coagulation
2-Exotoxins are secreted proteins that directly cause cellular injury and frequently underlie disease manifestations are include :-
A- dephtheria toxin secreted by Corynebacterium diphtheria .this toxin cause neural and
myocardial dysfunction.
B- Tetanospasm secreted by clostridium tetani that contaminate wound this toxin cause tetanus.
Immune evasion by microbes
The micro organism escapes humeral and cellular immune responses of the host by :-1-remaining inaccessible (e.g. residing within the host cells) .
2- cleaving antibodies , resisting complement mediated lysis or surviving in phagocytic cells.
3-varying or shedding antigens
4- causing immunosuppression
Inflammatory Responses to Infection
1- Suppurative Inflammation
there is acute tissue damage , characterized by increased vascular permeability and leukocytic infiltration , predominantly neutrophils .In many cases, this is a response to extracellular bacteria. The neutrophils are recruited to the site of infection by chemoattractants released from organisms and from host cells.
2-Mononuclear and Granulomatous Inflammation
Diffuse mononuclear infiltrates in response to viruses, intracellular bacteria, or intracellular parasites. In addition, and helminths provoke chronic inflammatory responses.
3-Cytopathic-Cytoproliferative Response
These reactions are usually produced by viruses and are characterized by sparse inflammation and either cell death (cytopathic response) or proliferation (cytoproliferative response).
4-Necrotizing Response
Some organisms produce potent toxins that cause such rapid and severe necrosis that tissue damage is the dominant feature (e.g., C. perfringens). Similarly, E. histolytica can cause colonic ulcers and liver abscesses with extensive tissue destruction and liquefactive necrosis without a prominent inflammatory infiltrate.
5-chronic inflammation and scarring