PATHOGENESIS: Understanding the Immune System

Pathogenesis

Steps or mechanisms involved in the devo of the diseases

Infection

Penetration, multiplication, invasion of the tissues, toxin production by the infectious agent leading to production of clinical signs and symptoms

• Sporadic

• Endemic

• Epidemic

• Pandemic

Manifestation of the Infections in communities

Sporadic infections

Appear occasionally, at irregular intervals of time, in a low number, disseminated iin the territory and without connection between cases

Endemic Infections

A constant presence of an infection in a community, with a frequency that varies very little from year to year

Epidemic

• A sudden rise of the frequency of an infection in a community, over the estimated one, with demonstrated connections among them

• Epidemic in a small community is called an outbreak

Pandemic

Epidemic at an international scale

EP - IP - PP- PI - C/D/D

Course of Infectious disease

Incubation period

the time that elapses between the entry of the pathogen and the onset of symptoms

Prodromal period

time during which the patient starts to feel something wrong but does not yet experience the actual symptoms

Period of illness

Time when the person experiences typical symptoms

Convalescence

• Time of recuperation and recovery from ilness

• Permanent damge or complete recovery

Virulence Factors

• The pathogen-produced extracellular proteins that aid in the establishment and maintenance of disease

• Most are enzymes that help the pathogens colonize, grow or spreaad within the tissues o

Virulence factors

express the pathogenicity degree of a microorganism

• MLD

• LD50

1. Entry

2. Attachment

3. Multiplication

4. Invasion/Spread

5. Evasion of host defences

6. Damage to Host

Steps in the pathogenesis of infectioous disease

• Horizontal type

• vertical type

• Animal-Human

• Environmental contact

Types of Transmission (Entry)

• Direct physical contact

• Indirect contact

• Airborne transmission

• Droplet contact

• Fecal-oral transmission

Environmental contact

Adherence (Attachment)

• Avoids peristalsis, ciliary action, urine flow

• Prevents early clearance

  Adhesin-receptor interaction

• E.coli: Type 1 fimbriae bind to mannose-containing receptors

• Penetration and spread in the host

Colonization

Multiplication of a pathogen after it has gained access to the host’s tissues

1. Protection against phagocytes and complement, by

   • capsule, antigen O, agressins, resistance to microbicidal mechanism

2. Neutralization of the acid gastric barrier by production of urease

3. Avoidance of host’s immune response

4. Similarity between bacterial structures and host’s structures

5. Masking of the parasite with host’s antigens

6. Multitude of serovars defined by virulence antigens

7. Antigenic variation

8. Survival Strategies within Phagocytes

Survival in the Host

• Localization of the microorganism in “priveleged” sites

• Immune response suppression

Avoidance of host’s immune response

• A niche without competitors

• Phagosomal escape

• Blocking lysosomal fusion

  Mycobacterium (tuberculosis)

  Salmonella (food poisoning or typhoid fever)

  Legionella (Legionnaire’s disease)

Survival Strategies within Phagocytes

1. Act on the extra-cellular matrix of CT

2. A-B type toxins

3. Toxins that inhibit protein biosynthesis

4. Neurotoxins

5. Membrane damaging toxins

Classes of Exotoxins

Exotoxins acting on the extra-cellular matrix

May cause food poisoning even in absence of organism

• A part: Active, enzymatic part

• B part: cell binding part

A-B type toxins

Diptheria toxin

• B binds to the cells in the respiratory tract

• A is endocytosed and is the effectro part

Shiga toxin

• A part binds to RNA – inibition of protein synthesis death of GIT cells – poor water absorption – diarrhea

Toxins that inhibit protein biosynthesis

• Tetanus toxin (Clostridium tetani) - rigid paralysis

• Botulinum toxin (Clostridium botulinum) - flaccid paralysis

Neurotoxins

• Hemolysins

  - cause cell-lysis: Stretolysin

• Phospholipases

  Membrane damaging toxins- cleave lipids in membranes: Clostridium perfringens (Gas gangrene)

Endotoxins

• Lipopolysaccharide in the cell envelope

• Cause septic shock, Gram negative sepsis

• Inflammation: bacterial meningitis

• Antigen-body complexes: settle in kidney or joints

• Cross-reactive antibodies: antibodies against payhogen may crossreact wih host tissues

Damage due to the immune system