1. Non-specific Host Defense Mechanisms
Lecture 8
Non-specific Host Defense Mechanisms
NORBEL A. TABO, RM, SM

2. Learning Objectives Briefly describe the three lines of defenses
Differentiate non-specific from specific host defense mechanism
Identify three ways by which the digestive system is protected from pathogens
Name three cellular and chemical responses to microbial invasion
Describe the benefits of complement activation
List the cardinal signs and symptoms associated with inflammation
Outline the four steps in phagocytosis.
Cite ways in which pathogens escape destruction by phagocytes
Categorize the disorders and conditions that affect the body’s non-specific host mechanisms

3. Overview of the Immune System

4. Anatomical Barriers - Mechanical Factors
System or Organ
Cell type
Mechanism
Skin
Squamous epithelium
Physical barrier
Desquamation
Mucous Membranes
Non-ciliated epithelium (e.g. GI tract)
Peristalsis
Ciliated epithelium (e.g. respiratory tract)
Mucociliary elevator
Epithelium (e.g. nasopharynx)
Flushing action of tears, saliva, mucus, urine

5. Anatomical Barriers - Chemical Factors
System or Organ
Component
Mechanism
Skin
Sweat
Anti-microbial fatty acids
Mucous Membranes
HCl (parietal cells)
Tears and saliva
Low pH
Lysozyme and phospholipase A
Defensins (respiratory & GI tract)
Antimicrobial
Sufactants (lung)
Opsonin

6. Anatomical Barriers - Biological Factors
System or Organ
Component
Mechanism
Skin and mucous membranes
Normal flora
Antimicrobial substances
Competition for nutrients and colonization

10. Microbial antagonism Inhibitory capability of normal flora
Competition for colonization sites
Competition for nutrients
Production of substance that kill other bacteria
The effectiveness of this antagonism is frequently decreased after prolonged administration of broad spectrum antibiotics

11. Superinfection of Candida albicans

12. Pseudo-membraneous colitis

13. Humoral Components Complement system Coagulation system
Lactoferrin and transferrin
Interferons
Lysozymes
Cytokines

14. Complement System The major humoral non-specific defense mechanism.
Once activated, complement can lead to increased vascular permeability, recruitment of phagocytic cells, and lysis of bacteria

16. Coagulation system
Some products of coagulation system are directly antimicrobial
Example:
Beta lysin
Protein produced by platelets can lyse G+ bacteria by acting as a cationic detergent

18. Lactoferrin and Transferrin
Proteins that can limit bacterial growth.

19. Interferons protect cells from viral attack (among other functions).
alpha, beta, and gamma interferon
produced by virus-infected cells and also by macrophages and some lymphocytes, which are stimulated to produce interferon via activation by antigens.
the effect of interferon on healthy cells is to stimulate them to produce antiviral proteins (AVP) which protects them from viral infection.

21. Lysozymes
Breaks down the cell wall of bacteria

22. Interleukin I
Induces fever and production of acute phase proteins (C-reactive proteins which is a laboratory marker for inflammation)

23. Cytokines
Chemical mediators that are released from different types of cells.
They enable cells to communicate with each other.

24. Cellular Components Cell Functions Neutrophils
Phagocytosis and intracellular killing
Inflammation and tissue damage
Macrophages
Extracellular killing of infected or altered self targets
Tissue repair
Antigen presentation for specific immune response
NK and LAK cells
Killing of virus-infected and altered self targets
Eosinophils
Killing of certain parasites

27. Leukocytes
There are typically 5,000 to 10,000 of these per cubic millimeter of human blood ( 5-10 billion per liter ).
The white cell count typically increases in response to infection.
Leucocytes play a role in both specific (antibody-based) and non-specific host defense mechanisms.

28. Types of Leukocytes about 55-70% of circulating wbc's are PMNs.
Polymorphonuclear neutrophils (PMNs)
about 55-70% of circulating wbc's are PMNs.
These are phagocytic cells that play an important role in the defense against bacterial pathogens.
Eosinophils
represent about 5 % of circulating wbc's.
These are capable of phagocytosis under some conditions, but are more directly concerned with the extracellular destruction of invading organisms, particularly parasites such as helminths.
High eosinophil numbers are typically associated with helminth infections.

29. Types of Leukocytes….. Basophils
constitute 1% or less of circulating wbc's.
Basophils produce a variety of biologically active chemicals including histamine (involved in allergic response) and heparin (an anticoagulant).
Monocytes
Constitute about 5-8 % of circulating wbc's.
Like, PMNs, these cells are capable of phagocytosis.
In the tissues, these cells can be transformed into macrophages which phagocytize invading cells and process and "present" antigens to B-lymphocytes, stimulating them to produce antibodies.

30. Types of Leukocytes….. Lymphocytes
about 20% of circulating wbc's are lymphocytes.
These cells are largely responsible for both humoral and cellular immunity.
There are two general types of lymphocytes,
B cells (plasma cells) that produce soluble (humoral) antibodies, and
T cells which are responsible for cellular immunity. There are 5 different types of T-cells, each with its own set of functions (discussed later):
Helper cells (Th)
Suppressor cells (Ts)
Delayed hypersensitivity cells (Td)
Cytoxic [killer] cells (Tc)

31. Lymphocytes
Natural killer cells (Nk) - destroy tumor cells, transplanted tissue, and cells infected with intracellular bacteria such as the Rickettsia and Chlamydias.
Both Tc and Nk cells produce a protein called perforin which bores a hole in the membrane of the attacked cell, much like the membrane attack complex( MAC) of complement.
While lymphocytes are generally considered to be part of the "specific" immunity system (involving antigens and antibodies), the Nk cells do not require an antigen to activate them, and so are perhaps best considered to be part of the body's non-specific defense system.

32. Phagocytosis and Inflammatory Response

33. Phagocytosis
able to engulf and destroy bacteria and some other invading organisms
polymorphonuclear neutrophils and monocytes and other cells called macrophages (tissue cells derived from monocytes)

34. Phagocytosis
Chemotaxis
Attachment
Ingestion
Digestion

36. Inflammation
a complex interwoven series of processes that increase the blood supply to an infected site.
The symptoms of inflammation: swelling, warming, reddening, and pain are all the result of the increased blood supply brought about by capillary dilation.
A series of chemical mediators including histamine and the prostaglandins are also involved in inflammatory processes.

37. Inflammatory Response
Large number of phagocytes are attracted to the wound area
Blood vessels dilate
Phagocytes move out from the blood
Phagocytes engulf the pathogen

38. Classical signs and symptoms
Calor - heat
Dolor - pain
Rubor - redness
Tumor – swelling
Fluor - secretions

40. Importance of Inflammation
To localize infection
To prevent spread of pathogens
To destroy and detoxify pathogens
To aid in repair and healing

41. fever
Creates an unfavorable thermal environment for bacteria whose thermal optimum is 37o C.
Speeds-up chemical reactions that are part of the chemical defense mechanism

42. Mechanisms by which pathogens escape destruction by phagocytes
Production of capsules
Secretion of leukocidins
Presence of waxes in the cell wall (M. tuberculosis)
Growth within the phagocytes (Rickettsia, Legionella, Brucella, Coxiella, Listeria)
Growth within the leukocytes (Ehrlichia, Anaplasma)

43. Disorders and conditions that adversely affect phagocytic and inflammatory processes
Leukopenia
Low number of circulating leukocytes
Chediak-Higashi Syndrome
Inability of leukocytes to migrate in response to chemotactic agents
Chronic Granulomatous Disease
Incapability of phagocytes to kill the pathogens

44. Factors that can impair host defense mechanisms
Nutritional status
Increased iron levels
Stress
Age
Cancer and Cancer chemotherapy
AIDS
Drugs
B-cell and T-cell deficiency