Transcript Range of Targets

Objective 6
Immunity
There are two intrinsic defense systems involved in protecting human
organisms from disease:
Response Time
Non-Specific (innate) systems
Specific (adaptive) systems
immediate; are preformed
some delay
Range of Targets each system is effective against
a wide variety of targets
selective; adaptive responses
selective responses to each
target
Body Structures
B lymphocytes, T lymphocytes
antigen presenting cells
barriers to invasion (skin, mucous
membranes), chemicals and
cells (phagocytes, NK cells)
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.
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
2. 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
macrophages (derived from monocytes),
include
neutrophils, eosinophils (weakly phagocytic) and
mast cells

mechanism of phagocytosis
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)
2. Natural Killer Cells
large, granular lymphocytes

are a group of

they lyse and kill cancer cells and virus infected cells by releasing
perforins and granzyme B;
perforins
create defects in the plasma membranes and
nuclear membranes of pathogens; (perforins poke holes)
granzyme B stimulates apoptosis (programmed cell death)
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:
1.
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
2. Activate macrophages
3. 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
1.
Activated C3 is cleaved into two fragments (C3a and C3b)
2.
C3b enhances phagocytosis by acting as an opsonin
3.
C3a enhances inflammation
4.
C3b plus activated C5, C6, C7, C8 and C9 combine to form membrane attack
complex (MAC) (the MAC attack!)
5.
MAC inserted into target cell plasma membrane and causes lyses
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
D. 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
1.
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:
leukocytosis
: increased WBC production in bone marrow
margination
:
WBCs adhere to the capillary wall in areas of
inflammation
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
Think LMDC
Leukocytosis
Margination
Diapedesis
Chemotaxis
Chemotaxis
Cardinal Signs of Inflammation – Swelling,
Redness (Erythema), Heat and Pain