1. Introduction to Immunology Innate Immunity
Chapter 1

2. Introduction to Immunology:
The Term Immunity is derived from the Latin word Immunitas (exemption from various legal prosecution offered to Roman senators)
Immunity means all the mechanisms used by the body as protection/ reaction to a foreign substance (microorganisms and their product, foods, chemicals, drugs, pollen or animal hair)
The cells and molecules responsible for the immunity called Immune- system
The immune system distinguishes self from non-self and eliminates potentially harmful non-self molecules and cells from the body. The immune system also has the capacity to recognize and destroy abnormal cells that derive from host tissues. Any molecule capable of being recognized by the immune system is considered an antigen (Ag).

3. The Body’s Defenses (from Google Images)

4. Property
Innate
adaptive/acquired
characteristics
-Non-specific
-Specific
-Rapid response
-Slow response
-No memory
-Memory
Immune components
-Natural barriers
-Cells phagocytic cells NK cells
-Chemical barrier soluble molecules such as lysozymes
Pattern recognition molecules
-Lymphocytes
-Antigen-recognition Molecules such T/B cells Receptors

5. Innate Immunity
The innate immune response is the body’s 1st line of defense and includes:
1) physical barriers between inside & outside
•the skin and the mucous membranes of the digestive, respiratory and genito- urinary tracts
•all substances secreted at these barriers and all of the normal microbiota that live on these surfaces
2) non-specific cellular & physiological responses
•i.e., inborn (innate) general responses to the presence of pathogens that breach the body’s physical barriers
•independent of prior exposure, response is immediate
•eliminates the vast majority of pathogens that gain entry

6. Physical Defenses Key features of the Skin:
dry, acidic surface (resists microbial growth)
multiple layers of tough yet dead keratinized cells
continual loss of outer dead skin layers removes potential pathogens
sebum from hair follicles (lowers pH)
Keratinocytes in the skin secrete antimicrobial peptides (defensins), and sebaceous and sweat glands secrete microbe-acid pH substances, (eg, lactic acid, fatty acids, lysozyme).

7. Key features of the Eyes:
-tears continually released by lacrimal ducts -contain antimicrobial substances (e.g. lysozyme), wash away any microbes, debris on the eye surface

8. Key features of the Mucous Membranes:
•vulnerable due to very thin epithelial layer, moist surface •continually produce mucus, a viscous glycoprotein that traps microbes and debris •includes the linings of the respiratory, digestive & genitourinary tracts •acidic environment of stomach kills most microbes •Mucosa of the respiratory, GI, and GU tracts: The mucus contains antimicrobial substances, such as lysozyme, and lactoferrin.

9. Summary of Physical Defenses

10. Antimicrobial Substances
Soluble proteins including Interferon and complements found in the blood contribute to non-specific immunity.
Interferons are a group of proteins made by cells in response to viral infections and has antiviral properties.
Complements are also a group of serum protein made mainly by the liver, involve in the control of inflammation, the activation of phagocytic cells and lytic attack on microbial cells membrane.

11. Antimicrobial Substances
In addition to the chemicals barriers mentioned in the previous slides, there are many different kinds of antimicrobial substances, however we will focus our attention on 2 of them:
Complements are also a group of serum protein made mainly by the liver, involve in the control of inflammation, the activation of phagocytic cells and lytic attack on microbial cells membrane.
Interferons : Interferons are a group of proteins made by cells in response to viral infections and has antiviral properties.
Transferrins (bind & keep iron away from pathogens)

12. Roles of the Normal Microbiota
The “normal microbiota” are the microorganisms that live on the body surfaces of a healthy individual and inhibit the growth of pathogens in the following ways:
•acidifying body surfaces
•e.g., in the female reproductive tract, inhibits yeast inf.
•the production of bacteriocins and other toxins
•i.e., toxins that are specific for other microorganisms
•e.g., in the large intestine (E. coli)
•out-competing pathogens for nutrients
•on the skin and basically all mucous membranes

14. Cell of Innate immunity
Macrophages mature from monocytes that leave the circulation to migrate into tissues throughout the body. In the liver known as Kupffer cells, large cells with many cytoplasmic cells projections, Alveolar macrophages in the lung, and Splenic macrophages.
The second major family of phagocytes—the neutrophils, or polymorph nuclear leukocytes—are short-lived cells that are found in in the circulation but not present in normal, healthy tissues.
Eosinophils: The level of eosinophils in the blood is normally quite low (approx. 5%) most eosinophils are found in tissues, can kill microorganisms and parasites, also cause significant tissue damage in allergic reactions.

15. Natural killer (NK) cells: can kill in virally infected or abnormal (tumor) cells by a number of pathways.
Dendritic cells are present in the skin (as Langerhans cells), lymph nodes, and tissues throughout the body. Dendritic cells in the skin act as antigen presenting cells (APCs), taking up Antigen, then traveling to local lymph nodes where they can activate T cells.

16. Basophils constitute < 5% of WBCs and share several characteristics with mast cells.
Mast cells occur in different tissues of the body. Mucosal mast cell granules contain; mast cells play a key role in generating protective acute inflammatory responses; basophils and mast cells are the source of type I hypersensitivity reactions associated with atopic allergy.

17. Cell of Innate immune systems

18. Organs of the Immune System

19. The Lymphoid Organs Bone Marrow Thymus
•blood cell formation
•“where all blood cells (red & white) are made”
Thymus
•where T cells are “educated”
•Eliminate out T cells that would react to “self”molecules
Spleen
•immune response to pathogens

20. the Lymphatic System Lymph Node
•immune response to pathogens, foreign material in lymph
Lymph (& Blood)
•fluids through which immune cells patrol the body

21. What is Inflammation?
Inflammation is a localized response initiated by damaged or infected tissues to aid tissue repair and the elimination of pathogens.
Vasodilation & increased capillary permeability
•increases blood flow to area, blood fluid in tissue
The basic stages of inflammation are as follows:
Migration of phagocytes, phagocytosis
•phagocytes exit the blood, enter affected tissue via chemotaxis & consume pathogens
Tissue repair
•removal of dead cells, regeneration of the tissue

22. Inflammation
Any type of physical damage to and/or microbial penetration of a tissue will trigger a local inflammatory response:
•can be short-lived (acute) or extended (chronic)
•initiated by the release of inflammatory mediators from cells in the tissue that is damaged
e.g. histamine prostaglandins leukotrienes

23. Vasodilation & Increased Permeability
Increased blood flow due to vasodilation and the increased permeability of capillaries results in fluid from blood seeping into affected tissue:
•causes swelling of the region (edema)
facilitates clotting
facilitates entry of antimicrobial proteins, leukocyte

25. Tissue Repair
Tissue Healing. During wound repair, collagen fibers are laid down randomly by fibroblasts that move into repair the area.

26. What is Phagocytosis?
Engulfment of a foreign particles such as bacteria by a phagocytic cells.
Microorganisms are killed when phagocytosis generates lytic enzymes and reactive O2 compounds (eg, superoxide, hypochlorous acid) and triggers release of granule contents (eg, defensins, proteases, bactericidal permeability- increasing protein, lactoferrin, lysozymes).
Phagocytosis is enhanced by a variety of molecules, called Opsonins, such as complement and antibodies. These molecules binds to the microbes and make it an easier target for ingestion (Opsonisation)

27. Types of Phagocytes
All of the phagocytes in the human body are types of white blood cells (leukocytes).Phagocytic cells (neutrophils and monocytes in blood, macrophages and dendritic cells in tissues) ingest and destroy invading microbes.
Both these phagocytic cells have a key role in innate immunity because they can recognize, ingest, and destroy many pathogens without involvement of adaptive immune system. Macrophages are the first to encounter pathogens in the tissues but later they are strengthened by the recruitment of large numbers of neutrophils to sites of infection.
Macrophages and neutrophils recognizes such pathogens by means of receptors; these receptors bind to a special molecules on the surface of the pathogen called pattern- recognition receptors (PRR):
-mannose receptor, which is found on macrophages but not on monocytes or neutrophils
-Scavenger receptors, Found in neutrophils
-CD14, a receptor for bacterial lipopolysaccharide (LPS) found on monocytes and macro-phages.
-Pathogens can also interact with macrophages and neutrophils through receptors for complement system.

28. Main Steps of phagocytosis: