Objective 6 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)

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.

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 30-50 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

 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

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

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)

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

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

C9 – Natural Killer Cells

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

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

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

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

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

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

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

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

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  

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

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

Margination and Diapedesis of Neutrophils in a Dilated Blood Vessel

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

Think LMDC Leukocytosis Margination Diapedesis Chemotaxis

Chemotaxis

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