1. Objective Immunity
There are two intrinsic defense systems involved in protecting human organisms from disease:
Non-Specific (innate) systems Specific (adaptive) systems
Response Time immediate; are preformed some delay
Range of Targets each system is effective against selective; adaptive responses a wide variety of targets selective responses to each target
Body Structures barriers to invasion (skin, mucous B lymphocytes, T lymphocytes membranes), chemicals and antigen presenting cells cells (phagocytes, NK cells)

2. Figure 1-3 The principal mechanisms of innate and adaptive immunity
Figure 1-3 The principal mechanisms of innate and adaptive immunity. The mechanisms of innate immunity provide the initial defense against infections. Some of the mechanisms prevent infections (e.g., epithelial barriers) and others eliminate microbes (e.g., phagocytes, natural killer [NK] cells, the complement system). Adaptive immune responses develop later and are mediated by lymphocytes and their products.

3. Barriers to Infection: Skin and Mucous Membranes
Objective 7 Non-specific Resistance: Barriers, Chemicals, Phagocytes and Inflammation
There are several mechanisms that are effective against a wide range of targets:
Barriers to Infection: Skin and Mucous Membranes
1. Intact Skin
Characteristics that make intact skin a good barrier include:
 it is made of rows of stratified, keratinized epithelium
 it has a slightly acidic pH (3-5)
 it is salty due to NaCl in sweat (discourages most bacterial growth)
 it is relatively dry
 skin secretions contain antibacterial chemicals (lysozyme, fatty acids)
 normal flora compete with pathogens

5.  non-keratinized, stratified squamous epithelium
Mucous Membranes
Characteristics of mucous membranes that make it a good barrier include:
 non-keratinized, stratified squamous epithelium
 acidic pH (stomach, vagina during childbearing years)
 hair, cilia, mucous which helps to trap foreign particles
 saliva contains lysozyme
 normal flora compete with pathogens

6. B. Cells 1. Phagocytes  include
 mechanism of phagocytosis
macrophages (derived from monocytes), neutrophils, eosinophils (weakly phagocytic) and mast cells

7. For phagocytosis to occur……
Adherence – phagocytes must first adhere to the microbe
How? Carbohydrates on the cell surface of the pathogen
Opsonization – coating of the pathogen with antibodies or complement proteins (plasma proteins)

9. Note:
In addition to phagocytosis, other mechanisms exist to kill pathogens
 respiratory burst
Free radicals
H2O2
 defensins (antibiotic like compounds)

10. large, granular lymphocytes
Natural Killer Cells
 are a group of
 they lyse and kill cancer cells and virus infected cells by releasing perforins and granzyme B;
create defects in the plasma membranes and nuclear membranes of pathogens; (perforins poke holes)
stimulates apoptosis (programmed cell death)
large, granular lymphocytes
perforins
granzyme B

11. C9 – Natural Killer Cells

12. A. Antimicrobial Proteins
1. Interferon:
 produced by a variety of cell types:
 (alpha) IFN is produced by all leukocytes except lymphocytes
 (beta) IFN is produced by fibroblasts (beta, blasts)
 (gamma) IFN is produced by lymphocytes

13. Interferon functions:
Antiviral effects - blocks viral replication
body cells infected with virus secrete interferon (IFN)
interferon diffuses to nearby healthy cells and induces them to synthesize PKR
PKR blocks the production of proteins the virus needs to replicate
Activate macrophages
Activate natural killer cells

14. Complement a group of plasma proteins that circulate in an inactive form
 Functions :
1. amplification of the inflammatory response
2. pathogen lysis
 Activation of complement:
1. classical pathway - requires antibody antigen complexes
2. alternative pathway - requires lack of inhibitors on microbial cell)
3. lectin pathway – lectins produced by cells of innate immunity bind to microorganisms

15. Activated C3 is cleaved into two fragments (C3a and C3b)
C3b enhances phagocytosis by acting as an opsonin
C3a enhances inflammation
C3b plus activated C5, C6, C7, C8 and C9 combine to form membrane attack complex (MAC) (the MAC attack!)
MAC inserted into target cell plasma membrane and causes lyses

16. Opsonization:. coating of a target with a substance
Opsonization: coating of a target with a substance that enhances its attachment to a phagocyte; it improves adherence

17. What does the complement system do?
Think Oil !
Opsonization
Inflammation
Lysis

18. C Reactive Protein acute phase protein made by the liver; it binds to surfaces of pathogens and damaged body cells and then binds to C1, activating complement in the classical pathway

19. Inflammation a nonspecific response of vascular tissue to injury
 Goals of inflammation: 
1. destroy injurious agents and remove them from the inflammatory site
2. wall off the area to confine these agents to protect healthy tissues
3. stimulate and enhance the immune response
4. promote healing

20. The mechanism of inflammation: vasodilation and increased vascular permeability
Vascular Changes :  
 mast cells, macrophages, injured tissue cells, lymphocytes and other cells release molecules that act as chemical mediators of inflammation
 mediators include histamine, kinins, prostaglandins, complement and cytokines
 these mediators induce the following effects:
vasodilation: causes local hyperemia; increased blood flow brings more O2 , nutrients and WBC’s to the area; causes the area to become red and warm

21. Increased capillary permeability:
Fluid with clotting proteins and antibodies (exudate) moves into tissue from the blood; this causes edema
Normal Inflammed
Pain occurs because sensory nerve endings are activated by pressure (edema) and perhaps because of bacterial toxins, a local decrease in pH and the effects of prostaglandins and kinins

23. Phagocyte Mobilization
 phagocytes migrate to the injured area (neutrophils first, monocytes/macrophages later)
 migration involves the following steps:
: increased WBC production in bone marrow
: WBCs adhere to the capillary wall in areas of inflammation
leukocytosis
margination

24. Margination and Diapedesis of Neutrophils in a Dilated Blood Vessel

25. diapedesis chemotaxis leukocytes squeeze through the capillary wall
chemical mediators of inflammation attract the WBCs to the site of inflammation
diapedesis
chemotaxis

26. Think LMDC
Leukocytosis
Margination
Diapedesis
Chemotaxis

27. Chemotaxis

29. Cardinal Signs of Inflammation – Swelling, Redness (Erythema), Heat and Pain