Download Innate defense

Basics of Immunity
Assoc. Prof. Edyta Mądry MD.PhD
Department of Physiology
Poznań University of Medical Sciences
Innate defense
The innate immune response is the first line of defense
against invading microorganisms.
This system is not specific for a given pathogen, but can aid
in the induction of cell-mediated immunity (antibody and
specific killer cells).
Nonspecific Body Defenses
1. Physical Barriers
-Mechanical (skin, mucus, cilia in respiratory
tract, sebum, cerumen ( earwax) )
2. Chemical Barriers (low pH – stomach,
vagina, genito-urinary tract, sweat/ high pH
–small intestinal juice
3. Others: vomiting, diarrhea, sneezing,
coughing
Nonspecific Defenses
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Phagocytes (eg. macrophages)
Complement
Fever
Inflammation
NK cells
Lysozyme
Interferons
Innate defense
Lysozyme
Lysozyme protects us from the ever-present danger of bacterial infection.
It is a small enzyme that attacks the cell walls of bacteria.
Lysozyme breaks the carbohydrate chains of bacterial walls, destroying
their structural integrity. The bacteria burst under their own internal
pressure.
•tears
•mucus
•blood
•salive
•urine
Interferons
IFN-alpha-is made by almost all type of cell
infected with virus( fibroblsts are the principal
source of INFα)
INFα recently is used in treatment:AIDS,hair cell
leucemia, hepatitis B and hepatitis C
IFN-beta treats autoimmune disease: multiple
sclerosis.
INF-gamma-produced by activated Tlymphocytes and NK cells.Currently is used to
treat chronic granulomatous disease and rare
hereditary disease of blood
Interferon alpha
Interferons
Complement
Complement- Membrane Attack Complex
After cleavage by the C5 convertase, C5b is loosely membrane associated. Additional interaction
with C6 and C7 leads to the formation of a complex that can insert itself into a cell's lipid bylayer.
When C8 associates, the complex is capable of initiating lysis, but further assoication with C9 is
required for full MAC (membrane attack complex) generation. Four molecules of C9 confer
full lytic activity, but as many as 15 can associate to make larger pores. The animation below
demonstrates how this pore formation works.
Complement- Activation by a Pathogen
An invading bacteria initiates the complement response.
The C3bBb3b complex is the C5a convertase; an enzyme that is able to cleave C5
to C5a and C5b.
Complement
A critical byproduct of complement fixation is the C5a peptide. This small
protein has a large number of functions and its receptor is expressed in many different
cell types. Since it is an enzyme, the C5 convertase complex continually cleaves C5 to
C5a, increasing a concentration gradient. The concentration of C5a is highest near the
area of production, decreasing farther from this region. This gradient can lead to the
chemotactic migration of immune effector cells including macrophages, which can then
kill bacteria and initiate an immune response.
Complement-macrophage migration to C5a
After the C5 convertase cleaves C5 to C5a and C5b, the C5a protein diffuses away
from the production area to set up a concentration gradient. Different cell types
including macrophages, neutrophils and mast cells can recognize this gradient and
"crawl" toward the area of activation. .
Complement -Tissue specific cell migration
After migrating to the area of C5a production, the macrophages can then phagocytize the
offending microorganism. At that point, the cell must make a choice.
"Do I stay and find some more goodies to eat?" OR "Do I move out of this area,
become a professional antigen presenting cell (dendritic cell), and go to a local lymph
node?”
Complement
Inflammation
• Bodies response to tissue injury
• Classic signs
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Heat
Redness
Swelling
Pain
Impairment of function
Skin
Blood
Tissue Damaged
Histamine Released
Capillary More Permeable
Plasma Leaks Out
Capillary More Permeable
Antibodies Leaks Out
Capillary More Permeable
WBCs Leave by
Diapedesis
Wall of Fibrin Forms
Pus Forms
Lymphatic System Capillaries
Functions of Lymphatic System
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Drain fluid from around cells
Absorb fat from intestines
Circulate lymph
Filter lymph
Immunity
Lymphatic System
Right
Lymphatic Duct
Thoracic
Duct
Lymphatic organs -Lymph Nodes
• Filter lymph
– Microorganisms
– Cancer cells
• Lymphocytes
• Monocytes
Lymphatic organs - Thymus
• Programs some
lymphocytes to
develop into T-cells
Lymphatic organs -Spleen
• Filters blood
– Worn out RBC
– Bacteria
• Lymphocytes
• Monocytes
Lymphatic organs - Bone Marrow
T Cells
B Cells
Lymphatic organs – GALT
70% of human lymphocytes is localized in GALT
Binding sites
Antigenic
determinants
Light
chain
Hinge
region
Disulfide
bonds
RCB
Antigen A Carbohydrate
Heavy chain
FcBinding site
Antibody A
Antigen-antibody complex
(agglutinated RBC)
Antibodies are made by B cells;
Variable
portion
Constant
portion
basic unit : 2 identical light
chains; 2 identical heavy chains;
stabilized and linked by disulfide
bonds-form a Y-shaped molecule
Each chain has constant and
variable region; Ag binds to
variable region on each arm.
Light chains exist in 2 forms:
kappa and lambda
Heavy chains exist in 5 forms:
alpha, gamma, delta, epsilon and
mu.
Fc of the haevy chains can bind
complement and receptors on
macrophages,monocytes,
neutrophils and natural killer
cells
IgG
• The major immunoglobulin in normal
blood (9-14 g/L),
• 4 types, monomers
• Can cross the epithelium and placenta,
are secreted with mother’s milk
• It contributes immunity against many
kinds of pathogens, including bacteria,
viruses, and fungi.
• Distributed evenly between the blood
and extravascular fluids.
•After IgG1, IgG3 bind the bacteria
they initiate the classical pathway of
complement reaction
• include anti-Rh antibodies
IgM
• primary importance in
bacterial defense
• initiate the classical
pathway of complement
activation
• pentamer –consist of 5
monomers
• can NOT cross the
epithelium
• always produce as 1st
• antibodies of ABO
system are IgM
immunoglobulins.
Ig M – ALWAYS 1st,
IgG indicates old infection (" G for
Grandmother ")
IgA
Function
• Provides „mucosal immunity”
• found in various secretions, such as
mucus (respiratory and digestive
tract), blood, saliva, milk (
COLOSTRUM !). tears, and fluids
secreted into the genitourinary and
digestive tracts.
• IgA antibodies provide defense
against pathogens that contact the
body surface or are ingested or
inhaled.
• Monomer or dimer or trimar ( we
discuss DIMERIC Ig A)
• IgA does NOT activate the
complement-has NOT properties to
kill bacteria
•They prevent bacteria to adhere to mucosa,
they neutralize viruses and toxines
IgE
• 0.3x10-3 g/L (1000x more in people with
allergy)
• rarely are found as free circulating
antibodies but commonly are found on
the surface of basophils and mast cellls
of connective tissue (bind by Fc)
•When engaged by an antigen, IgE
stimulate basophils and mast cells to
release histamine that mediate the
allergic response .
• important role in defense against
parasites (worms)
• are produced in tonsills, lymph nodes,
mucosa of GI tract.
• are involved directly in diseases
characterized by hypersensitivity
( eg.asthma, hay fever)
IgD
• monomer
• present on the plasma
membranes of many
circulating B-lymphocytes
• Involved in
differentiation and
development of plasma
cells and memory cells
from B-lymphocytes.
AQUIRED vs. INNATE IMMUNITY
3 main characteristics that differ aquired and innate
immunity :
1.MEMORY 2. SPECIFISITY 3. TIME DEPENANCE