1. Nonspecific Defenses of the Host
Chapter 16
Nonspecific Defenses of the Host

2. Immunity
Immunity - The ability to ward off disease through body defenses
1. Innate immunity or “nonspecific resistance”
Defenses against any pathogen.
Refers to defenses that are present at birth
2. Adaptive immunity or “specific resistance” :
Defenses to a specific pathogen.
Acquired during the lifetime.
Lack of immunity is called susceptibility.

3. Host Defenses
Figure 16.1

4. First line of defense 1. Mechanical Factors Skin Mucous membranes
Epidermis consists of tightly packed cells – keratinocytes.
Keratin is a protective protein.
Mucous membranes
Ciliary escalator:
Microbes trapped in mucus are transported away from the lungs.
Lacrimal apparatus:
Washes eye
Saliva: Washes microbes off.
Urine: Flows out.
Vaginal secretions: Flow out.

5. First line of defense 2. Chemical Factors
Fungistatic fatty acid in sebum
Low pH (3-5) of skin
Lysozyme in perspiration, tears, saliva, and tissue fluids
Low pH ( ) of gastric juice
Low pH (3–5) of vaginal secretions
Transferrins in blood find iron.

6. First line of defense 3. Normal Microbiota
We have about 1013 cells in our bodies and 1014 bacteria, most of which live in the large intestine.
There are 103–104 microbes per cm2 on the skin (Staphylococcus aureus, Staph. epidermidis, Corynebacteria (diphteroids), Streptococci, Candida, etc.).
Fill almost all of the available ecological niches in the body.
Produce factors all of which work to destroy other bacteria that compete for their niche in the body.
Microbial antagonism/competitive exclusion: Normal microbiota compete with pathogens.
The resident bacteria can become problematic when they invade spaces in which they were not meant to be.
Staphylococcus living on the skin can gain entry to the body through small cuts/nicks.
Clostridium difficile, - Some antibiotics, in particular clindamycin, kill some of the bacteria in our intestinal tract. This causes an overgrowth of
C. difficile, which results in pseudomembranous colitis, a rather painful
condition wherein the inner lining of the intestine cracks and bleeds.

7. Second line of defense 1. Defensive cells Phagocytic white blood cells
Natural killer (NK)cells
2. Inflammation
3. Fiver
4. Antimicrobial substances in blood
Complement system
Interferons
Transferins
Antimicrobial peptides

8. Fluid Systems of the Body
There are two main fluid systems in the body:
Blood
Lymph.
The blood and lymph systems are intertwined throughout the body
They are responsible for transporting the agents of the immune system.

9. Human blood cells Erythrocytes - red blood cells Platelets
Transport O2 and CO2
Platelets
Blood clotting
White Blood Cells - Leukocytes
Granulocytes
Neutrophils - phagocytic
Basophils ( Mast cells in tissues) – Histamine
Eosinophils – Kill parasites
Dendritic cells - antigen-presenting cells
Agranulocytes
Monocytes - Phagocytic as mature macrophages
Lymphocytes:
Natural killer cells
T cells
B cells (plasma cells)

10. White Blood Cells - Leukocytes
Granulocytes
Neutrophils - phagocytic
Nondividing, short-lived (half-life of 6–8 hours, 1–4 day lifespan), and have a segmented nucleus.
First on the scene to fight infection.
Chemotaxis (IL-8, INF-γ, C5a).
Basophils ( Mast cells in tissues) – Histamine
Circulating, store histamine granules.
Active against parasites, participate in allergic reaction
Eosinophils – Kill parasites
Granules containing chemical mediators, such as histamine and proteins such as eosinophil peroxidase, RNase, DNases, lipase, plasminogen, and Major Basic Protein
Some phagocytic
Dendritic cells
Their main function is to process antigen material and present it on the surface to other cells of the immune system, thus functioning as antigen-presenting cells
Initiation of adaptive immune response

11. White Blood Cells - Leukocytes
Agranulocytes
Monocytes - Phagocytic as mature macrophages
Promonocytes are made in the bone marrow, after which they are released into the blood and called circulating monocytes, which eventually mature into macrophages (meaning "big eaters", see below).
Long-lived, depend on mitochondria for energy, and are best at attacking dead cells and pathogens capable of living within cells.
Fixed macrophages in lungs, liver, and bronchi
The non-fixed macrophages roam the blood vessels and can even leave them to go to an infection site where they destroy dead tissue and pathogens.
Lymphocytes:
Natural killer cells move in the blood and lymph to lyses (cause to burst) cancer cells and virus-infected body cells.
They attach to the glycoproteins on the surfaces of infected cells and kill them
T cells - Cell- mediated immunity
B cells (plasma cells) - Produce antibodies

12. Differential White Cell Count
Percentage of each type of white cell in a sample of 100 white blood cells (Leukocytes)
Neutrophils
60-70%
Basophils
0.5-1%
Eosinophils
2-4%
Monocytes
3-8%
Lymphocytes
20-25%

13. The Concept of Immunity- Recognition
Host Toll-like receptors (TLRs) - a class of proteins that play a key role in the innate immune system
Membrane-spanning receptors that recognize structurally conserved molecules derived from microbes
Localized on cell surface
Monocytes/macrophages
B lymphocytes
Dendritic cells
Mast cells
Intestinal epithelium
These receptors are encoded in the germ line of each person.
Once microbes have breached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLRs which activates immune cell responses.
TLRs induce cytokines that regulate the intensity and duration of immune responses
This immunity is passed from generation to generation.
They are set to target both Gram-negative and Gram-positive bacteria.

14. Second line of defense 1. Phagocytosis
Phago: eat; Cyte: cell
Ingestion of microbes or particles by a cell, performed by phagocytes
Once a macrophage phagocytizes a cell, it places some of its proteins, called epitopes, on its surface—much like a fighter plane displaying its hits.
These surface markers serve as an alarm to other immune cells.
Adherence
Ingestion
Formation of a phagosome
Phagosome-Lysosome fusion
Digestion
Formation of a residual body
Discharge

15. Microbial Evasion of Phagocytosis
• Inhibit adherence: M protein, capsules
Streptococcus pyogenes,
S. pneumoniae
• Kill phagocytes: Leukocidins
Staphylococcus aureus
• Lyse phagocytes: Membrane attack complex
Listeria monocytogenes
• Escape phagosome
Shigella
• Prevent phagosome-lysosome fusion
HIV
• Survive in phagolysosome
Coxiella burnetti

16. Second line of defense 2. Inflammation
Inflammation is the process by which the body responds to injury or an infection
It is characterized by:
Redness
Pain
Heat
Swelling (edema)
Sometimes the loss of function.
Chemicals Released by Damaged Cells
• Histamine
Vasodilation, increased permeability of blood vessels
• Kinins
• Prostaglandins
Intensity histamine and kinins effect
• Leukotrienes
Increased permeability of blood vessels, phagocytic attachment

17. Inflammation
- Acute inflammation is a short, intense response to infection.
1. Tissue damage
2. Vasodilation
and increased
permeability
of blood vessel
3. Phagocytes
migration and
phagocytosis
4. Tissue repair
Chronic inflammation is a prolonged response (it is a disease)
It is associated with a broad spectrum of neurodegenerative diseases of aging - Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and also included are such peripheral conditions as osteoarthritis, rheumatoid arthritis, atherosclerosis, and myocardial infarction.

18. Second line of defense 3. Fever
Abnormally High Body Temperature
Hypothalamus normally set at 37°C
Gram-negative endotoxin cause phagocytes to release interleukin1
Hypothalamus releases prostaglandins that reset the hypothalamus to a high temperature
Body increases rate of metabolism and shivering to raise temperature
When IL-1 is eliminated, body temperature falls.
Disadvantages of fiver
Tachycardia
Acidosis
Dehydration

19. Second line of defense 4. Antimicrobial substances
The Complement system
Helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism
It is part of the innate immune system that is not adaptable and does not change over the course of an individual's lifetime.
However, it can be recruited and brought into action by the adaptive immune system.
It consist of over 25 proteins and protein fragments, produced by liver.
Account for about 5% of the globulin fraction of blood serum.
Complement protein are usually designated by letter C, C1- C9
The fragments are activated proteins and are indicated by the lower letters a and b – C3a and C3b.
Complement proteins act as a cascade
Once is activated, its destructive capabilities usually cease very quickly
Inherited deficiencies of complement component causing disease

20. The Complement System C serum proteins constantly present in the blood
Serum proteins activated in a cascade.
Membrane Attack Complex (MAC)
Figure 16.9

21. Three biochemical pathways activate the complement system:
Complement proteins – factors B, D, and P
Lectines - proteins that bind to carbohydrates. (When macrophages ingest bacteria, viruses, and other foreign matter by phagosytosis, they release chemicals that stimulate the liver to produce lectins).
1.Classical Pathway
2. Alternative Pathway
3. Lectin Pathway

22. Some bacteria evade complement
Capsules prevent C activation
Surface lipid-carbohydrates prevent membrane attack complex formation
Enzymatic digestion of C5a

23. Second line of defense 4. Antimicrobial substances
Interferons (IFNs) - proteins made and released by lymphocytes in response to the presence of pathogens
alpha-IFN,
beta-IFN
gamma-IFN
The mode of action of -IFN
and -IFN is to induce uninfected
cells to produce antiviral proteins
(AVPs) that prevent viral replication.
Interferons are host-cell–specific but not virus-specific.
Gamma-interferon activates neutrophils and macrophages to kill bacteria.

24. Second line of defense 4. Antimicrobial substances
Transferrins are iron-binding proteins found in blood, milk, saliva, and tears.
Inhibit bacterial growth by reducing the amounts of available iron.
Iron also suppress chemotaxis and phagocytosis
Antimicrobial peptides (also called host defense peptides) are an evolutionarily conserved component of the innate immune response and are found among all classes of life.
These peptides are potent, broad spectrum antibiotics which demonstrate potential as novel therapeutic agents.
Antimicrobial peptides may also have the ability to enhance immunity by functioning as immunomodulators.

25. Learning objectives
Differentiate between innate and adaptive immunity.
Describe the role of the skin and mucous membranes in innate immunity.
Differentiate physical from chemical factors, and list five examples of each.
Describe the role of normal microbiota in innate resistance.
Classify phagocytic cells, and describe the roles of granulocytes and monocytes.
Define differential white blood cell count.
Define phagocyte and phagocytosis.
Describe the process of phagocytosis, and include the stages of adherence and ingestion.
Identify methods of avoiding destruction by phagocytes.
List the stages of inflammation.
Describe the roles of vasodilation, kinins, prostaglandins, and leukotrienes in inflammation.
Describe phagocyte migration.
Describe the cause and effects of fever.
List the components of the complement system.
Describe three pathways of activating complement.
Describe three consequences of complement activation.
Define interferons.
Compare and contrast the actions of a-IFN and b-IFN with g-IFN.
Describe the role of transferrins in innate immunity.
Describe the role of antimicrobial peptides in innate immunity.