Lecture 21 Flashcards
Antibody-Mediated (humoral) Immunity
a function of the B-lymphocytes; immunological competence probably develops in the bone marrow;
Immunologically competent B-lymphocytes move to lymphoid tissues - mainly the lymph nodes and spleen;
the B-lymphocytes tend to be found in separate areas of lymphoid tissue from the T-lymphocytes.
Mature B-cells, once activated, produce antibodies
Antibodies
highly specific proteins also called immunoglobulins;
Y-shaped protein
The basic antibody structure has 4 polypeptide chains - 2 identical heavy (400+ amino acids) and 2 identical light chains (214 amino acids);
One light chain is covalently bound to each heavy chain; and the two heavy chains are covalently bound to each other
each chain has a constant C-region and variable V-region;
Five classes of immunoglobulin are recognised based on the amino acid sequence of the heavy chain at the C-region;
the V-region has a three dimensional shape which binds to the appropriate antigen;
Antigen
Antigen : any molecule which generates an immune response
Antigens have a number of antigenic regions or determinants which may be recognised by different antibodies.
Antigenic determinants are also known as epitopes
Immunoglobulin classes
IgG
Found: 75% of plasma Ig; binds to macrophages, neutrophils; secondary response
Activate: complement system
Effective: bacteria, viruses; cross placenta
IgM
Found: blood type - primary response
(pentamer: 5 Ab units)
Activate: complement system, Agglutination, precipitation
Effective: Bacteria
IgA
Found: body secretions - mucus, saliva, tears, milk
(dimer: 2 Ab units)
Activate: N/A
Effective: viral/bacterial attachment
IgD
Found: on B-lymphocyte surface
Activate: rarely secreted
Effective: B-cell receptor
IgE
Found: bound to mast cells and basophils
Activate: allergic response, anaphylactic resp.
Effective: parasitic worms
Antibody action
1: Direct action: Agglutination, precipitation, neutralisation
2: Activation of the complement system #Mostly
3: Activate of the anaphylactic system
Antibodies do not directly destroy the antigen;
Antibody Action – Direct action
- Agglutination
clumps antigenic agents on cells together - Precipitation
a soluble antigen becomes insoluble and precipitates out; - Neutralization
The antibodies bind to specific sites on bacterial exotoxins - inhibiting their action
or on viral surface antigens - inhibiting their attachment to and entry into cells
Formation of Ab-Ag complex resulting in precipitation
IgM is a potent agent of precipitation
5 Ab subunits joined together, giving 10 antigen binding sites in one molecule
Antibody action 2: Activation of Complement System
-The complement system consists of >20 soluble proteins circulating in the blood stream
-Once early components are activated, there is a cascade of proteolytic cleavage reactions activating downstream components
-IgM and IgG antibodies form antigen-antibody complexes, which activate the first component (C1) of the complement system;
-resulting in a number active proteins; the results not antigen specific:
Antibody action: actions of Complement System
- Lysis - direct lysis of pathogen cell membrane;
- Opsonization - coats the pathogen which allows phagocytosis by macrophages and neutrophils;
- Chemotaxis - attracts neutrophils and macrophages to the area;
- Inflammation - increase local reaction by stimulating the release of histamine.
“Membrane attack complex” generates hole in pathogen cell membrane (MAC attack)
A neutrophil chases a bacterium through a blood sample, attracted by chemotaxis
“Opsonin is what you butter the disease germs with to make your white blood corpuscles eat them” – GB Shaw, “The Doctor’s Dilema” ,1906
Antibody action 3: Activation of Anaphylactic System
Activation of this system is through the IgE immunoglobulins;
these attach themselves to mast cells in the tissues and basophils in the blood;
when the antigen reacts with exposed IgE on the mast cell this causes the cell to enlarge, rupture and release histamine and other substances;
these cause local vasodilation and inflammation; attracting other elements of the immune system to the area
Mast cell releases contents: degranulation
Antibody action 3: Activation of Anaphylactic System
however some individuals show an extreme systemic response as well from the basophils in the blood system: allergy
the allergens are usually drugs, venoms or foods such as peanuts;
histamine and other chemicals are released in vast quantities causing extreme vasodilation and capillary permeability;
severe constriction of the bronchioles may follow, with the rapid loss of blood pressure resulting in anaphylactic shock and death. ¶
Activation of B-cells
There are thousands of competent B-lymphocytes each capable of responding to a particular antigen;
A complex system is involved in recognizing a particular antigen and activating the appropriate the B-cell
The activated B-cell grows and undergoes cell division, multiplication and differentiation
B-Lymphocyte ActivationB-lymphocytes are activated by T-cells
- A phogocytic cell such as a macrophage or neutrophil engulfs a pathogen, degrades it, and presents some of its peptides on the surface of the APC in complex with MHC.
- An inactive T-helper cell, specific for that antigen, interacts with the MHC-peptide complex on the surface of the APC and becomes activated.
- Meanwhile, an inactive B-cell specific for that antigen is waiting….It interacts with the antigen via its B-cell receptor and the antigen is engulfed. Portions of the antigen are displayed on the surface of the B-cell in complex with MHC
- The activated T-helper cell interacts with the MHC-antigen complex on the surface of the B-cell
- This interaction stimulates the T-cell to activate the B-cell via the release of various cytokines
B-Cell Activation:activation of T-helper cell
- A phogocytic cell such as a macrophage or neutrophil engulfs a pathogen, degrades it, and presents some of its peptides on the surface of the APC in complex with MHC.
- An inactive T-helper cell, specific for that antigen, interacts with the MHC-peptide complex on the surface of the APC and becomes activated.
B-Cell Activation:Th activates specific B-cell
- Meanwhile, an inactive B-cell specific for that antigen is waiting….It interacts with the antigen via its B-cell receptor and the antigen is engulfed. Portions of the antigen are displayed on the surface of the B-cell in complex with MHC
- The activated T-helper cell interacts with the MHC-antigen complex on the surface of the B-cell
- This interaction stimulates the T-cell to activate the B-cell via the release of various cytokines
B-Lymphocyte Activation
once activated the B-cells increase in size, divide and differentiate to become plasma cells and memory cells;
the plasma cells remain in lymph nodes and produce and release antibodies;
a given B-cell produces only one specific idiotype of antibody;
B-memory cells continue to produce small amounts of antibody for many years;
they also show the same secondary response as the T-memory cells.
B-Cell Activation
B-Cell Differentiation
Allergy
Allergy: “an exaggerated or inappropriate immune response initiated by exposures to antigen”
persons with an allergic tendency produce antibodies against mild antigens called allergens;
these do not elicit a response in non-allergic individuals;
there seems to be a genetic disposition in the inheritance of allergies.
About 20% of the population show an allergic disorder such as asthma, hay fever or some type of food allergy;
- this is due to a malfunction of normal immune response
Allergic Rhinitis step 1
The first step is sensitization where the degraded allergen (often pollen, in the case of rhinitis) is presented by an APC to a T-cell which is activated and differentiates into T-cell subsets
In allergic individuals T-helper 2 cells are produced which release Interleukin-4 which in turn stimulates B-cells to produce IgE;
these antibodies attach themselves to receptors on mast cells;
Generally, an allergic reaction does not occur on the first exposure to the antigen – but memory cells are produced which produce a much stronger response on a second exposure
