innate immune response
Post on 13-Jan-2016
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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› Provide physical separation› Membranes bathed in
antimicrobial secretions Antimicrobial substances
and Normal Flora pH changes
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
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
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
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
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
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
Granulocytes› Contain
cytoplasmic graduals
› Divided into three types Neutrophils Basophils Eosinophils
Granulocytes› Contain cytoplasmic graduals
Neutrophils› Most abundant and important in innate
response› Granules contain chemicals which kill
microbes› Sometimes called polymorphonuclear
neutrophilic leukocytes (PMNs)
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
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
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
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
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
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
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
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
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
Figure 15.7
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
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
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
Figure 15.8
Long Double-Stranded RNA (dsRNA)
Induction of alpha and beta interferons› Cells express
iAVPs› Leads to
apoptosis
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
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
Inflammation occurs in response to tissue damage
Four cardinal signs› Heat› Pain› Redness› Swelling› Loss of function
Fifth sign that can also be present
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
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
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
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
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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