1. Dr Sahar Saad Zalam Innate(non-specific)immunity

2. Lecture Objectives By the end of this lecture the student will be able to: 1) Define innate immunity 2) Know the importance of the innate immunity 3) Know the different components of the innate immunity 4) Understand how each one work and communicate with other components

3. Innate(non-specific)immunity It is the natural inborn barrier against invasion by microorganisms. It is non-specific, acting against any foreign invader. It is not acquired through previous exposure to the infectious agents. It functions through: I. First line of natural defense: which include: 1. Mechanical ( physical) barriers at the portal of entry. 2. Chemical barriers at the portal of eatery. 3. Normal bacterial flora.

4. First line of natural defense 1) Mechanical barriers at the portal of entry. These include: The intact skin and mucous membranes. The hair at the nares, coughing and sneezing help to expel foreign particales. Mucous secretions trap many organisms which are pushed outside the body by the continuous movement of cilia in the respiratory tract. The blinking reflex and tears expel forign particles or bacteria entering the conjunciva.

5. First line 2) Chemical & biochemical inhibitors and barriers - Sweet and sebaceous secretion - Hydrolytic enzymes in saliva - HCl of the stomach - Proteolytic enzyme in small intestine - Lysozyme in tears - Acidic pH in the adult vagina

6. First line of natural defense 3-Normal bacteria flora: Present at the portal of entry suppress the growth of many pathogenic bacteria and fungi by competition for essential nutrients or the production of inhibitory substances as acids or colicins. For example, in the adult vagina an acidic pH is maintained by normal flora namely lactobacilli, that interfere with the establishment of pathogenic organisms. Suppression of normal flora by antibiotics leads to superinfection with potential pathogens

7. Second line of natural defense If the invading microorganism gets through the first line of defense and enters the tissue, other non-specific host defenses operate. These include:

8. Innate(non-specific)immunity I. Second line of natural defense: which include: 1. Circulating effector proteins. 2. Cells of innate immunity. 3. Inflammatory barriers. 4. Cytokines of innate immunity.

9. Second line 1- Soluble factors 1- Acute phase protein (Plasma protein, CRP=C reactive protein, Fibrin.) 2- Complement (proteins in serum, body fluids) 2- Interferons (Proteins against viral infections) 3- Properdin (Complement activation) 4- Beta lysine (Antibacterial protein from Platelets) 5- Lactoferrrin,Transferrin (Iron binding protein) 6- Lactoperoxidase (Saliva & Milk) 7- Lysozyme (Hydrolyze cell wall)

10. Cambridge University Immunology Lectures (www)www Complement Activation

11. Second line of natural defense  Acute phase proteins: These are substances that increase in response to inflammation and include; C-reactive protein(CRP), fibrinogen, serum amyloid A protein, mannose binding lectins. They are synthesized in the liver in response to certain cytokines namely IL-1, IL-6 and TNF- α, these are produced by macrophages when stimulated by microbial products. For example CRP can bind to microbes resulting in activation of the complement and deposition of C3b on the surface of microbes and enhancing phagocytosis. Measuring CRP is a useful laboratory test to assess activity of inflammatory diseases.

12. Second line of natural defense  Interferons (IFNs): These are a family of proteins which are important in the non-specific defense mechanisms against viral infections. There is type Ι IFN which consists of IFN- α produced by mononuclear phagocytes (MQ) and leukocytes and INF- β produced by fibroblasts and type ΙΙ INF or INF- γ produced by T cells and NK 2) Cells of innate immunity are the phagocytes and natural killer (NK) cells. Natural killer cells (NK): They are a group of nonphagocytic granular lymphocytes present in small numbers. NK have Fc receptors on their surface that are capable of binding IgG, which have been shown to trigger antibody – mediated cytotoxicity. NK are responsible for recognizing and destroying virally infected cells, bacteria, fungi, helminths and tumors.

13. Second line of natural defense Phagoctes are body cells specilized for capture, ingestion, and destruction of invading microorganisms i.e phagocytosis. There are 2 main types of phagocytic cells: 1. Polymorphonuclear leucocytes ( especially neutrophils). 2. Mononuclear phagocytes ( monocytes in the blood and macrophages in the tissues).

14. Second line of natural defense The process of phagocytosis includes the following steps: 1. Chemotaxis (delivary) of the phagocytic cells to the site of infection. 2. Attachment of the foreign particle to the phagocyte. 3. Engulfment or ingestion of the foreign particle. 4. Fusion with a lysosome and formation of the phagolysosome 5. Intracellular killing and digestion. 6. Release of the contents and antigen presentation. All phagocytes contain membrane vesicles filled with destructive and degradative compounds (Lysosomes) that are available for the destruction of engulfed microbes.

15. Second line of natural defense How do phagocytes distinguish between self and non-self?  The phagocytes have many receptors on their surface e.g. Toll-like receptors, scavenger receptors, Fc receptors and C3b receptors; these are called pathogen recognition receptors ( PRR) through which they attach to molecular structures widely expressed on viruses and bacteria. These are called pathogen associated molecular patterns (PAMPs). These may be sugars, proteins, lipids, nucleic acids or a combination of these molecules.

16. 4) Inflammatory Barriers * Tissue damage by a wound or by invading pathogen induce * Inflammatory response: Tissue damage Release of chemical mediators from Leukocytes (Histamine, fibrin, kinins, cytokines) Invading microbe Redness of tissue Tissue temperature Vasodilatation of capillaries Capillary permeability Influx of fluids Influx of phagocytes into tissues

17. Second line of natural defense Definition of cytokines: they are a large and heterogeneous group of secreted proteins produced by many different cell types, mediate and regulate all aspects of innate and adaptive immunity. 5)Cytokines of innate immunity: A)Several pro-inflammatory cytokines play a key role in inflammation, they are secreted by monocytes and macrophages(MQ) as IL-1, IL-6, IL-8, IL-12,TNF- α and IFN- γ B) Interferons (IFNs) : IFN- γ produced by NK cells activates MQ. IFN- α produced by viral infected cells inhibits viral replication and prevents spread of infection to uninfected cells