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
• Phagocytes (eg. macrophages)
• Complement
• Fever
• Inflammation
• NK cells
• Lysozyme
• Interferons
Innate defense
Lysozyme
L
ysozyme 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
INF-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 T-
lymphocytes 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
– 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
• 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
Antigenic determinants
RCB
Antigen A
Binding sites
Variable portion Hinge
region Light
chain
Constant portion Disulfide
bonds
Heavy chain Carbohydrate
FcBinding site Antibody A Antigen-antibody complex
(agglutinated RBC)
Antibodies are made by B cells;
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 IgG
1, IgG
3bind 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
G randmother ")
IgA
• 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
Function
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)