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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
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Lecture 8
Non-specific Host Defense Mechanisms
NORBEL A. TABO, RM, SM
Learning Objectives
1. Briefly describe the three lines of defenses2. Differentiate non-specific from specific host defense
mechanism3. Identify three ways by which the digestive system is
protected from pathogens4. Name three cellular and chemical responses to microbial
invasion5. Describe the benefits of complement activation6. List the cardinal signs and symptoms associated with
inflammation7. Outline the four steps in phagocytosis.8. Cite ways in which pathogens escape destruction by
phagocytes9. Categorize the disorders and conditions that affect the
body’s non-specific host mechanisms
Overview of the Immune SystemImmune System
Innate(Nonspecific)
Adaptive(Specific)
Anatomical Barriers
Humoral Components
Cellular Components
Mechanical
Chemical
Biological
Complement
Coagulation
Cytokines
Neutrophils
Eosinophils
Monocytes and Macrophages
Anatomical Barriers - Mechanical Factors
System or Organ Cell type Mechanism
Skin Squamous epithelium Physical barrierDesquamation
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
Anatomical Barriers - Chemical Factors
System or Organ Component Mechanism
Skin Sweat Anti-microbial fatty acids
Mucous Membranes
HCl (parietal cells)Tears and saliva
Low pHLysozyme and phospholipase A
Defensins (respiratory & GI tract)
Antimicrobial
Sufactants (lung) Opsonin
Anatomical Barriers - Biological Factors
System or Organ Component Mechanism
Skin and mucous membranes
Normal flora Antimicrobial substancesCompetition for nutrients and colonization
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
Superinfection of Candida albicans
Pseudo-membraneous colitis
Humoral Components
1. Complement system2. Coagulation system3. Lactoferrin and transferrin4. Interferons5. Lysozymes6. Cytokines
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
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
Lactoferrin and Transferrin
Proteins that can limit bacterial growth.
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.
Lysozymes
Breaks down the cell wall of bacteria
Interleukin I
Induces fever and production of acute phase proteins (C-reactive proteins which is a laboratory marker for inflammation)
Cytokines
Chemical mediators that are released from different types of cells.
They enable cells to communicate with each other.
Cellular Components
Cell Functions
Neutrophils Phagocytosis and intracellular killingInflammation and tissue damage
Macrophages Phagocytosis and intracellular killingExtracellular killing of infected or altered self targetsTissue repairAntigen presentation for specific immune response
NK and LAK cells Killing of virus-infected and altered self targets
Eosinophils Killing of certain parasites
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.
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.
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.
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)
Types of Leukocytes…..
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.
Lymphocytes
Phagocytosis and Inflammatory Response
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)
Phagocytosis
1. Chemotaxis2. Attachment3. Ingestion4. Digestion
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.
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
Classical signs and symptoms
1. Calor - heat2. Dolor - pain3. Rubor - redness4. Tumor – swelling5. Fluor - secretions
Importance of Inflammation
1. To localize infection2. To prevent spread of pathogens3. To destroy and detoxify pathogens4. To aid in repair and healing
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
Mechanisms by which pathogens escape destruction by phagocytes1. Production of capsules2. Secretion of leukocidins3. Presence of waxes in the cell wall (M.
tuberculosis)4. Growth within the phagocytes (Rickettsia,
Legionella, Brucella, Coxiella, Listeria)5. Growth within the leukocytes (Ehrlichia,
Anaplasma)
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
Factors that can impair host defense mechanisms1. Nutritional status2. Increased iron levels3. Stress4. Age5. Cancer and Cancer chemotherapy6. AIDS7. Drugs8. B-cell and T-cell deficiency
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