Transcript Chapter 15: Nonspecific Immunity

Chapter 16: Nonspecific Immunity
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Specific vs. Nonspecific responses
Innate nonspecific immunity
Cells and tissues involved in immune responses
Molecular immunity
 Complement
 Cytokines
 Inflammation
 Physiological changes
 Fever
 Metabolism
Nonspecific vs. Specific Immune
Response
 Vertebrates (humans too) have two lines of defense
against invaders, nonspecific and specific immune
response
 The first line of defense is the nonspecific response
 These are physical barriers and physiological defense
mechanisms
 It is called nonspecific because they are directed at any
invading organism
 Specific immunity takes time to develop and is only
effective following the nonspecific response
Innate nonspecific immunity
 Tissue barriers and nonspecific factors are important in nonspecific
immunity
 Physical barriers
 Skin - Sweat
 Mucous membranes - Saliva, tears, mucus
 Urine flow
 Nonspecific antimicrobial factors
 Lysozyme - Destroys cell walls
 Beta-lysin - kills G+
 Defensins - small, antimicrobial peptides
 Peroxidase - found in saliva and neutrophils
 Complement - Punch holes in bacteria
 Interferons - interfere with viral replication
 Lactoferrin - Competes with bacteria for iron
Structure of the skin
Complement cascade system
 Complement is a series of proteins that are activated
by infection, and form an antimicrobial complex
 Complement can be activated by three different
pathways, the classical pathway (antibody based), the
alternative pathway (endotoxin or cell wall activated),
or the lectin pathway
 Both result in the formation of a membrane attack
complex that punches holes in the cell membranes of
bacteria and other invaders (not viruses, why?)
The
Classical
Pathway
 An antibody-antigen complex interacts with C1, which
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produces an active enzyme that cleaves C2 and C4
The cleaved products of C2 and C4 (C4bC2a) produce
an enzyme called the C3 convertase
The C3 convertase cleaves C3, producing C3b
C3b is the C5 convertase, which cleaves C5 into C5a
and C5b
C5b organizes C6, C7, C8, and C9 into the membrane
attack complex (MAC), which results in lysis of the
bacterial cell
The alternative pathway
 The alternative pathway skips a few steps of the
classical pathway
 C3b is produced in very low levels spontaneously from
C3
 C3b interacts with endotoxin and other bacterial cell
wall components and Factors B, D, and P to form
C3bBb, which is an alternative C3 convertase, which
produces more C3b, the C5 convertase
 This produces C5b, which results in formation of the
MAC
Lectin Pathway
 The lectin pathway is very similar to the classical
pathway, except for activation
 Activation occurs when mannose binding lectin (MBL)
binds to mannose found on the surface of some
bacterial cells (often part of LPS)
 This then activates two proteins called MASP-1 and
MASP-2, and all three stick together
 This complex then cuts C4 and C2, and off we go!
http://www.medicine.uiowa.edu/martinlab/complement.html
Chemical defense mechanisms
 Cytokines are molecular messages between cells that
are important in the immune response as well as other
communications between cells
 There are many different kinds of cytokines, which act
in specific ways to stimulate different aspects of the
immune response
 Some important cytokines
 Interferons (INF)
 Interleukins (IL)
 Tumor necrosis factors (TNF)
Cytokines
 Interferons (IFN’s) - Antiviral proteins. Three types are
known
 IFN-alpha - produced by white blood cells (leukocytes); antiviral
 IFN-beta - produced by tissue cells (fibroblasts); antiviral
 IFN-gamma - produced by immune cells (T-cells); antiviral, also
involved in other immune responses
 Interleukins (IL) - Function in many aspects of the
immune response. Will be discussed in subsequent
chapters
 Colony-stimulating factors - Cause a proliferation of
certain cell types
 Tumor necrosis factors (TNF’s) - Kill some tumor cells, also
involved in other immune responses
Inflammation
 The first host response to invading organisms (injury) is
inflammation
 There are four cardinal signs associated with inflammation
 Redness
 Heat
 Swelling
 Pain
 The same sequence of events occurs in response to any
injury, whether caused by invading bacteria, burns or
trauma
The inflammatory response
 During inflammation, C3a and C5a (complement)
cause the release of chemicals from tissue mast cell
granules (histamine, leukotrienes, and kinins, in
particular)
 These chemicals increase permeability of the small
capillaries, leading to increased blood flow
 Circulating leukocytes (white blood cells) adhere to
receptors on the inner walls of blood vessels and
migrate out in response to chemical attractants
(chemotaxis)
 Neutrophils show up first, then moncytes
(macrophages) and lymphocytes (pus)
http://www.biologymad.com/Immunology/i
nflammation.jpg
Phagocytosis
 Phagocytosis involves the process of phagocytic cells engulfing and
killing microorganisms
 Step one - Find the invader
 Chemical products of microorganisms, components of complement (C5a)
and phospholipids released by the mammalian cell are all chemoattractants
for phagocytes
 Step two - Attach and engulf
 C3b helps with this part (opsonization)
 Step three - Kill, kill, kill
 Neutrophils contain granules, monocytes have lysosomes that contain
digestive enzymes that kill the invader
 http://www.exploratorium.edu/imaging_station/gallery.php?Asset
=Human%20macrophage%20%20phagocytosis&Group=&Category=Blood%20Cells&Section=Intr
oduction
Physiological changes affect the immune
response - Fever
 Fever - Normal body temperature is closely regulated, but
in the case of infection, a higher setting is used to:
 Elevate the temperature above that preferred for optimal growth of
pathogens
 Activate and speed up a number of body defenses
 Fever can be activated by the cytokine IL-1, which is
released by phagocytic cells that have come in contact with
microorganisms. It can also be activated by TNF-alpha
 By slowing the growth rate of the bacteria, and increasing
enzymatic activity of the immune response, fever helps
speed clearing of an infection
Changes in iron metabolism
 The ability to limit iron availability to invading
organisms is a major nonspecific defense mechanism
 There are two important iron-binding proteins in
blood
 Transferrin
 Lactoferrin
 High iron levels in blood can increase the chances for
infection
Cells involved in the immune
response
 All blood cells (white blood cells = leukocytes; red
blood cells = erythrocytes and platelets) arise from a
single precursor, the hematopoietic stem cell
 Leukocytes are the cells primarily responsible for the
defense of the body against microorganisms
 Granulocytes - Neutrophils, Basophils and Eosinophils
 Agranulocytes –
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Mononuclear phagocytes - Monocytes and macrophages
Lymphocytes – B, T, and NK cells
Natural Killer cells
 NK cells are so named because they don’t seem to
require recognition of MHC (which we’ll learn about
in the next chapter) and don’t have a TCR (ditto)
 NK cells recognize (how, we’re not sure) our cells that
are infected or have mutated, and kill them without
being specific