Lecture 21

Question 1

Antibody-Mediated (humoral) Immunity

Answer 1

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

Question 2

Antibodies

Answer 2

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;

Question 3

Antigen

Answer 3

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

Question 4

Immunoglobulin classes

IgG

Answer 4

Found: 75% of plasma Ig; binds to macrophages, neutrophils; secondary response

Activate: complement system

Effective: bacteria, viruses; cross placenta

Question 5

IgM

Answer 5

Found: blood type - primary response
(pentamer: 5 Ab units)

Activate: complement system, Agglutination, precipitation

Effective: Bacteria

Question 6

IgA

Answer 6

Found: body secretions - mucus, saliva, tears, milk
(dimer: 2 Ab units)

Activate: N/A

Effective: viral/bacterial attachment

Question 7

IgD

Answer 7

Found: on B-lymphocyte surface

Activate: rarely secreted

Effective: B-cell receptor

Question 8

IgE

Answer 8

Found: bound to mast cells and basophils

Activate: allergic response, anaphylactic resp.

Effective: parasitic worms

Question 9

Antibody action

Answer 9

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;

Question 10

Antibody Action – Direct action

Answer 10

1. Agglutination
   clumps antigenic agents on cells together
2. Precipitation
   a soluble antigen becomes insoluble and precipitates out;
3. 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

Question 11

IgM is a potent agent of precipitation

Answer 11

5 Ab subunits joined together, giving 10 antigen binding sites in one molecule

Question 12

Antibody action 2: Activation of Complement System

Answer 12

-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:

Question 13

Antibody action: actions of Complement System

Answer 13

1. Lysis - direct lysis of pathogen cell membrane;
2. Opsonization - coats the pathogen which allows phagocytosis by macrophages and neutrophils;
3. Chemotaxis - attracts neutrophils and macrophages to the area;
4. 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

Question 14

Antibody action 3: Activation of Anaphylactic System

Answer 14

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

Question 15

Antibody action 3: Activation of Anaphylactic System

Answer 15

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. ¶

Question 16

Activation of B-cells

Answer 16

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

Question 17

B-Lymphocyte ActivationB-lymphocytes are activated by T-cells

Answer 17

1. 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.
2. An inactive T-helper cell, specific for that antigen, interacts with the MHC-peptide complex on the surface of the APC and becomes activated.
3. 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
4. The activated T-helper cell interacts with the MHC-antigen complex on the surface of the B-cell
5. This interaction stimulates the T-cell to activate the B-cell via the release of various cytokines

Question 18

B-Cell Activation:activation of T-helper cell

Answer 18

1. 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.
2. An inactive T-helper cell, specific for that antigen, interacts with the MHC-peptide complex on the surface of the APC and becomes activated.

Question 19

B-Cell Activation:Th activates specific B-cell

Answer 19

3. 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
4. The activated T-helper cell interacts with the MHC-antigen complex on the surface of the B-cell
5. This interaction stimulates the T-cell to activate the B-cell via the release of various cytokines

Question 20

B-Lymphocyte Activation

Answer 20

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.

Question 21

B-Cell Activation

Answer 21

Question 22

B-Cell Differentiation

Answer 22

Question 23

Allergy

Answer 23

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

Question 24

Allergic Rhinitis step 1

Answer 24

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

Question 25

Allergic Rhinitis step 2

Answer 25

The second step is the activation of the mast cell;

further exposure to aerial pollen grains (from grasses, trees, etc.) stimulates more IgE antibody release from the sensitised plasma cells in the nasal mucosa;

the IgE attaches to the mast cells by the C-region;

pollen combines with V-region causing the release of histamine, seratonin and other substances from the mast cell;

these dilate the capillaries causing oedema and inflammation resulting in sneezing, running nose, etc.

Question 26

allergic rhinitis

Answer 26

Question 27

Vaccination

Answer 27

The secondary response is much more powerful that the primary response

May even prevent the development of symptoms

Vaccination involves the deliberate exposure of the immune system to antigen in order to generate memory cells and antibody.

The antigen used for vaccination will not be the active pathogen itself, but may be :
killed pathogen
attenuated pathogen
non-pathogenic strain
coat protein derived from pathogen
altered (non-toxic) bacterial toxin
etc.