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 First line of defense are barriers that shield interior of body from external surroundings  Anatomical barriers include skin and mucous membranes.

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Presentation on theme: " First line of defense are barriers that shield interior of body from external surroundings  Anatomical barriers include skin and mucous membranes."— Presentation transcript:

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3  First line of defense are barriers that shield interior of body from external surroundings  Anatomical barriers include skin and mucous membranes › Provide physical separation › Membranes bathed in antimicrobial secretions  Antimicrobial substances and Normal Flora  pH changes

4  Skin › Provides the most difficult barrier to penetrate › Composed of two main layers  Dermis  Contains tightly woven fibrous connective tissues  Makes extremely tough  Epidermis  Composed of many layers of epithelial cells  As cells reach surface, they become increasingly flat  Outermost sheets of cells embedded with keratin  Makes skin water-repellent  Outer layers slough off, taking microbes with it

5  Mucous membranes › Constantly bathed with mucus  Help wash surfaces › Some mucous membranes have mechanisms (cilia)to propel microorganisms and viruses to areas where they can be eliminated

6  Antimicrobial substances › Both skin and mucous membranes are protected by variety of antimicrobial substances including  Lysozyme  Enzymes that degrade peptioglycan  Found in tears, saliva, blood and phagocytes  Peroxidase  Found in saliva, body tissues and phagocytes  Breaks down hydrogen peroxide to produce reactive oxygen  Lactoferrin  Sequesters iron from microorganisms  Iron essential for microbial growth  Found in saliva, some phagocytes, blood and tissue fluids  Defensins  Antimicrobial peptides inserted into microbial membrane  Found on mucous membranes and in phagocytes

7  Normal Microbiota (Flora) › Defined as microorganisms found growing on body surfaces of healthy individuals › Not technically part of immune system  However, provides significant protection › Protects through competitive exclusion  Covers binding sites  Pathogens can’t bind  Competes for nutrients  Nutrients unavailable for pathogens

8  Always found in normal blood › Numbers increase during infection  Some cells play dual roles in both innate and adaptive immunity  Blood cell formation called hematopoiesis › Blood cells including immune cells originate from hematopoietic stem cells in bone marrow › Blood cells stimulated to differentiate by colony-stimulating factor

9  General categories of blood cells › Red blood cells (RBC)  a.k.a erythrocytes  Carry oxygen in blood › Platelets  Fragments of megakaryocytes  Important component in blood clotting › White blood cells (WBC)  a.k.a leukocytes  Important in host defenses  Divided into four categories  Granulocytes - Mononuclear phagocytes  Dendritic cells- Lymphocytes

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11  Granulocytes › Contain cytoplasmic graduals › Divided into three types  Neutrophils  Basophils  Eosinophils

12  Granulocytes › Contain cytoplasmic graduals  Neutrophils › Most abundant and important in innate response › Granules contain chemicals which kill microbes › Sometimes called polymorphonuclear neutrophilic leukocytes (PMNs)

13  Basophils › Granules contain histamine and other chemicals which increase capillary permeability. › Similar to mast cells › Involved in allergic reaction  Eosinophils › Important in expelling parasitic worms › Active in allergic reactions › Granules contain histamase and antimicrobial chemicals

14  Mononulcear phagocytes › Constitute collection of phagocytic cells called mononuclear phagocyte system › Include monocytes  Circulate in blood  Macrophages differentiate from monocytes  Present in most tissues  Abundant in liver, spleen, lymph nodes, lungs and peritoneal cavity  Dendritic cells › Branched cells involved in adaptive immunity › Function as scout in tissues  Engulf material in tissue and bring it to cells of adaptive immunity

15  Lymphocytes › Involved in adaptive immunity › Two major groups  B lymphocytes  B cells-mature in bone marrow  T lymphocytes  T cells-mature in the thymus › Another type  Natural killer  Lacks specificity of B and T cells

16  Surface receptors › Membrane proteins to which signal molecules bind › Receptors specific to molecule to which it bonds  Binding molecules called ligands › When ligand binds, receptor becomes modified and sends signal to cell  Cell responds by initiating some action

17  Cytokines › Cytokines bind to surface receptors and regulate cell function › Numerous cytokine classes  Chemokines – important in chemotaxis  Colony stimulating factors – Important in multiplication and differentiation of leukocytes  Interferons – important in control of viral infections  Interleukins – produced by leukocytes  Tumor necrosis factor – kill tumor cells

18  Adhesion molecules › Allow cells to adhere to each other › Responsible for the recruitment of phagocytes to area of injury  Epithelia cells lining blood vessels produce adhesion molecules that catch phagocytes as they pass by  Cause phagocytes to slow and leak out of vessels to area of injury

19  Systems within blood detect signs of tissue damage or microbial invasion  Respond to patterns associated with danger by › Directly destroying invading microbe › Recruiting other host defenses

20  Toll-like receptors (TLR) and NOD proteins › Pattern recognition receptors › TLR allow cells to “see” molecules signifying presence of microbes outside the cell › TLR found in variety of cell types  Recognize distinct “danger” compounds  Signal is transmitted  Results in change of gene expression of cell › NOD proteins do same for inside cell

21  Complement system › Series of proteins circulating in blood and fluids  Circulate in inactive form › Augment activities of adaptive immune response › Stimulation of inactive proteins initiates cascade of reactions  Results in rapid activation of components › Three pathways of activation  Alternative pathway  Lectin pathway  Classical pathway

22 Figure 15.7

23  Classical pathway › Activation requires antibodies  Antibodies interact complement C1  Activates protein  Leads to activation of all complex proteins  Alternative pathway › Quickly and easily initiated › Relies on binding of complement protein C3b to cell surface  Initiates activation of other compliment proteins  Allows formation of complement complex › C3b always circulating in blood

24  Lectin pathway › Activation requires mannan-binding lectins (MBL) › Pattern recognition molecules  Detect mannan  Polymer of mannose  Found in microbial cells › MBL attaches to surface  Activates complement proteins

25  Lysis of foreign cells › Complexes of C5b, C6, C7, C8 and multiple C9 spontaneously assemble  Forms donut-shaped structure called membrane attack complex (MAC)  Creates pores in membrane  Most effective on Gram-negative cells  Little effect on Gram-positive cells

26 Figure 15.8

27  Long Double- Stranded RNA (dsRNA)  Induction of alpha and beta interferons › Cells express iAVPs › Leads to apoptosis

28  Process of phagocytosis › Chemotaxis  Cells recruited to infection › Recognition/attachment  Use receptors to bind invading microbes › Engulfment  Phagocyte engulfs invader-forming phagosome › Phagosome lysosome fusion  Phagosome binds lysosome, forming phagolysosome › Destruction and digestion  Organism killed due to lack of oxygen and decreased pH › Exocytosis  Phagocyte expels material to external environment

29  Role of Neutrophiles › First responders › Granules contain antimicrobial chemicals › NETs-neutrophile extracellular traps  Contain DNA and anti microbial chemicals  Trap bacteria and destroy them with chemicals › Short lived but lots in reserve

30  Inflammation occurs in response to tissue damage  Four cardinal signs › Heat › Pain › Redness › Swelling › Loss of function  Fifth sign that can also be present

31  Factors that initiate inflammatory response › Microbial products trigger toll-like receptors of macrophages  Causes release of pro-inflammatory cytokines › Microbial cell surface can trigger complement › Tissue damage results in enzymatic cascade  Cascades initiate inflammation

32  The inflammatory process › Initiation leads to a cascade of events  Results in dilation of blood vessels, leakage of fluid from vessels and migration of leukocytes and phagocytes  Leakage of phagocytes from blood vessels called diapedesis › Certain pro-inflammatory mediators cause the diameter of blood vessels to increase  Results in increased blood flow  Increased blood flow responsible for cardinal signs of inflammation

33  Outcomes of inflammation › Intent is to limit damage and restore function  Inflammation itself can cause considerable damage  Release of toxic products and enzymes from phagocytic cells is responsible for tissue damage › If inflammation is limited to area of injury, damage is usually nominal › If inflammation results in delicate systems, consequences are more severe  Inflammation around brain and spinal cord can lead to meningitis

34  Apoptosis › Programmed cell death  Destroys cell without eliciting inflammatory response › During apoptosis, cells undergo changes to signal macrophages  Cells are engulfed without triggering inflammatory cascade

35  One of the strongest indicators of infection › Especially of bacterial infection  Important host defense mechanism  Temperature regulation center of body responds to fever-inducing substances called pyrogens › Fever-inducing cytokines termed endogenous pyrogens › Microbial products termed exogenous pyrogens  Resulting fever inhibits growth of pathogens by › Elevating temperature above maximum growth temperature › Activating and speeding up other body defenses


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