1. Infection 2006 Dr. Nasser Rizk

2. Infection Invasion and multiplication of microorganisms inside body producing S&S and immune response. Severity of infection depends on : 1- Pathogenicity 2- number 3- host defenses Transmission of infection needs: 1- Causative agent 2- reservoir 3-port of transmission 4- susceptible host

3. Risk Factors 1-Weak defense mechanisms 2- Enviromemental factors 3- Developmental factors ----------------------- Weak Defense mechanisms: 1.Immunodeficiency or Immunocompromise 2.Impaired WBCs and low level of T and B cells (immunodeficiency) 3.May be congenital (before or at birth) or acquired (after birth) 4.body’s ability to recognize and fight pathogens is impaired

4. Risk Factors (continued) Conditions which suppress immune Response: 1-Diabetes mellitus 2 –Renal failure 3- Liver cirrhosis 4- Steroids 5-Immunosuppresive drugs (transplantation) 6- Chemotherapy. Acquired immune suppression in: stress malnutrition infections pregnancy

5. 2- Enviromemental factors Conditions weaken a person immune defense are: 1- Poor hygiene 2- Malnutrition 3- Inadequate barriers 4- Stressors 5- Chronic diseases 6- Inadequate treatment 7-Inadeqaute immunization Dust facilities transport of pathogens, e.g., Aspergillus, (lung) conditions Poor hygiene Chronic diseases Inadequate immunization Treatment stressors Inadequate barrier

6. 3- Developmental factors Children and old age at high risk. Children : immune system is not fully developed (6 months) most common: respiratory infections Exposure to communicable diseases is high in care- centers and schools. Old age: decline in immune system DM and atherosclerosis: weak delivery of nutrients by impaired blood flow to organs

7. Components of the chain of infection Agents: Bacteria, Viruses, Fungi, Parasites, Mycoplasma, Ricketessia, Chlamydia Reservoir: Microbes can survive E.g., humans, animals, etc 6 components Causative agents Reservoir Portal of Exit Mode of Transmission Portal of Entry Susceptible host

8. Components (continued) Portal of exit (entry): infectious agent leave (enter) the organism Respiratory, genitourinary, GIT, skin, Mucus membranes, and placenta. Secretions as : blood, sputum, emesis, stools, urine, wound drainage and genital secretions act as portal. Mode of transmission Means from portal of exit to host 4 modes: chart 3 Vector- born: flea, mosquito (tropical) Mode of transmission ContactDropletAirborneEnteric Chart 3

9. Stages of infection 1- Incubation: replication, transmission. 2-Prodromal stage: vague complaint, transmission. 3- Acute illness: microbes destroy host cells, affecting systems. 4- Convalescent stage: body defense take over the microbe, healing.

10. Pathophysiologic changes Characteristic changes: Prodromal stage 1- Fever 2- Muscle aches 3- Headache 4- Lethargy Acute stages: Moe specific symptoms

11. Inflammation A major reactive defense mechanism against infective agents. It may result from: 1- tissue injury 2- infection 3- allergy Stages: 1- Vascular 2- Cellular Vascular: arterioles constrict then dilate--------edema Cellular: inflamm. Cells release histamine---edema Which dilute microbes

12. Signs and Symptoms of Inflammation Redness Heat Pain Edema Loss of function

13. Five classic local signs of acute inflammation These were known –Heat –Redness –Swelling –Pain –Loss of function by the Romans –Calor –Rubor –Tumor –Dolor –Functio laesa Added Later

14. Five classic local signs of acute inflammation The major components responsible for these local signs are –Heat - vasodilatation –Redness - vasodilatation –Swelling - vascular permeability –Pain - mediator release/pmn’s –Loss of function - mediator release/pmn’s

15. Alerts !! 1- Localized infections: produce rapid inflammatory response Obvious symptoms and signs 2- Disseminated infections: Slow inflammatory response Long time for treatment

16. Acute - minutes to days –Characterized by fluid and protein –PMN’s Chronic - weeks to years –Lymphocytes and macrophages ACUTE Inf - PMN’s (Polymorphonuclear Cells) CHRONIC Inf - Mononuclear Cells Inflammation EXUDATE

17. Fever After introduction of infectious agent Elevated temperature helps to fight infection Many organisms can’t survive Diaphoresis is the method of cooling down Improve immune system rspone.

18. Leukocytosis Body’s response to introduction of pathogens; WBCs increases Neutrophils count increases, with increase immature cells “bands”, but not function Neutrophils, monocytes, and macrophages begin phagocytosis of dead tissues and bacteria They identify the foreign antigen and kill the microbe Elevated count of WBCs is common; N in acute stages and Monocytes during resolution or chronic stages

19. Chronic inflammation Infection longer than 2 weeks May occur after acute Inflammation Permanganate scarring and loss of function may occur E.g., Mycobacterium tuberculosis

20. Diagnosis Medical history Examination Investigations-tests WBCs and CBC (first test) ESR: increased, inflammatory response Gram stain, silver stains Culture- sensitivity tests MRI to locate infection sites Chest X-ray (lung) Gallium scan for abscess detection

21. Treatment Vary widely Use vaccines----1ry immune response Drugs when appropriate Supportive therapy Antibiotics, antiviral, antifungal----- Overuse of medication----resistance Proper prevention of epidemic and pandemic transmission.

22. Acute inflammation The immediate and early response to injury The point? Get the pmn’s to the site as fast as possible Vasodilatation Endothelial permeability Extravasation of pmn’s

23. Acute inflammation major components Vasodilatation Endothelial permeability Extravasation of pmn’s

24. Vascular changes you need to know this Vasodilation (forget the few seconds of vasoconstriction) Exudation of protein rich fluid Blood stasis Margination Emigration/Transmigration

25. Vascular changes you need to know this Vasodilation (forget the few seconds of vasoconstriction) Exudation of protein rich fluid Blood stasis Margination Emigration/Transmigration

26. Fig 2.1 Graphic of Acute Inflammation

27. Vascular permeability Vasodilation, increased blood flow Increased intravascular hydrostatic pressure Transudate - ultrafiltrate blood plasma (contains little protein) –Again, this is very transient and just gets the process started. Think Acute Inflammation, think EXUDATE Increased vascular permeability

28. Vascular permeability Exudate - (protein-rich with pmn’s) –Exudate is the characteristic fluid of acute inflammation Intravascular osmotic pressure decreases Osmotic pressure of interstitial fluid increases Outflow of water and ions - edema

29. Fig 2.2 Graphic of Vascular Changes

30. How do endothelial cells become leaky? Endothelial cell contraction Junctional retraction Direct endothelial injury (immediate sustained response) Leukocyte-dependent endothelial injury Increased transcytosis of fluid

31. Direct endothelial injury (immediate sustained response) Endothelial cell necrosis and detachment Result of severe injury or burn Occurs immediately and lasts until vessel repaired

32. Occurs at sites of leukocyte accumulation Due to leukocyte activation which releases proteolytic enzymes and toxic oxygen Leukocyte-dependent endothelial injury

33. Leukocyte Cellular Events Margination and Rolling Adhesion and Transmigration Migration into interstitial tissue

34. Fig 2.4

35. Margination Normal flow - RBC’s and WBC’s flow in the center of the vessel A cell poor plasma is flowing adjacent to endothelium As blood flow slows, WBC’s collect along the endothelium This is “Margination”

36. Endothelial Activation The underlying stimulus causes release of mediators which activate the endothelium causing selectins and other mediators to be moved quickly to the surface

37. Selectins Selectins bind selected sugars –Selected + Lectins (sugars) = Selectins Some selectins are present on endothelial cells (E-Selectin) Some selectins are present on leukocytes (L- Selectin) Some selectins are present on platelets (P- Selectin)

38. Chemotaxis Movement toward the site of injury along a chemical gradient –Chemotactic Factors include Complement components Arachadonic Acid (AA) metabolites Soluble bacterial products Chemokines

39. Leukocyte Activation Chemokines also “activate” PMN’s –AA metabolite production –Degranulation and Secretion of lysosomal enzymes –Oxidative burst –Modulation of adhesion molecules

40. Phagocytosis & Degranulation Phagocytosis (to eat and destroy) –Attach –Engulf –Kill Degranulation and the oxidative burst destroy the engulfed particle

41. Leukocyte-induced tissue injury Lysosomal enzymes are released into the extracellular space during phagocytosis causing cell injury and matrix degradation Activated leukocytes release reactive oxygen species and products of arachidonic acid metabolism which can injure tissue and endothelial cells These events underlie many human diseases (e.g. Rheumatoid arthritis)

42. Normal Lung

43. Pneumonia

44. Another picture of the same thing… At a higher power!