Chapter 35 - Immunity And Allergy

Question 1

What aspects are included in the innate immunity?

Answer 1

1. Phagocytosis of bacteria
2. Destruction of swallowed organisms by the acid secretions of the stomach and the digestive enzymes
3. Resistance of the skin to invasion by organisms
4. Presence in the blood of certain chemicals and cells that attach to foreign organism or toxins and destroy them. Some of these are 1. lysosomes (mucolytic polysaccharide that attacks bacteria and causes them to dissolute), 2. basic polypeptides which react with and inactivate certain types of gram-positive bacteria, 3. The complement complex, 4. Natural killer lymphocytes that can recognise and destroy foreign cells, Tumor cells and even some infected cells.

Question 2

Where are antibodies and activated lymphocytes formed?

Answer 2

In the lymphoid tissue

Question 3

What does it take for a substance to be antigenic?

Answer 3

A molecular weight of 8000 or more. Furthermore the process of antigenicity usually depends on regularly recurring molecular groups called epitopes on the surface of the large molecule.

Question 4

Where are lymphocytes located?

Answer 4

Most extensively in the lymph nodes but are also found in special lymphoid tissues such as the spleen, submucosal areas of the GI tract, thymus and bone marrow.

Question 5

What are T lymphocytes responsible for?

Answer 5

Forming the activated lymphocytes that provide cell mediated immunity.

Question 6

What are B lymphocytes responsible for?

Answer 6

Forming antibodies that provide humoral immunity.

Question 7

What are both types of lymphocytes derived from?

Answer 7

From multipotent hematopoietic stem cells that form common lymphoid progenitor cells as one of their most important offspring as they differentiate.

Question 8

Where are the lymphoid progenitor cells that are eventually destined to form activates T lymphocytes first migrate to?

Answer 8

They migrate to and are processed in the Thymus. They are responsible for cell mediated immunity.

Question 9

Where are the B lymphocytes (that are destined to form antibodies) processed?

Answer 9

In the liver during mid fetal life and after birth and in the bone marrow in late fetal life and after birth.

Question 10

In which 2 ways are B lymphocytes different from T lymphocytes?

Answer 10

1. Instead of the whole cell developing reactivity against the antigen as occurs for the T lymphocytes, the B lymphocytes actively secrete antibodies that are reactive agents. These agents are large proteins that are capable of combining with and destroying the antigenic substance.
2. The B lymphocytes have even greater diversity than the T lymphocytes thus forming many millions of types of B lymphocyte antibodies.

After preprocessing, the B lymphocytes, like the T lymphocytes migrate to lymphoid tissue throughout the body where the lodge near but slightly removed from the T lymphocyte areas.

Question 11

Millions of different types of preformed B lymphocytes and preformed T lymphocytes capable of forming highly specific types of antibodies or T cells are stored in the lymph tissue. Each of these preformed lymphocytes is capable of forming only one type of antibody or one type of T cell with a single type of specificity. What happens to the lymphocyte when it’s activated by its antigen?

Answer 11

It reproduces wildly, forming tremendous numbers of duplicate lymphocytes. All the different lymphocytes that are capable of forming one specific antibody or T cell are called a clone of lymphocytes.

Question 12

How many antigen specificities does the B or T lymphocyte code for?

Answer 12

It codes only for a single antigen specificity.

Question 13

Mechanism for activating lymphocyte clones.

What are the role of macrophages in the activation process?

Answer 13

Most invading organisms are first phagocytosised and partially digested by the macrophages and the antigenic products are liberated into the macrophage cytosol. The macrophages then pass these antigens by cell to cell contact directly to the lymphocytes thus leading to activation of the specified lymphocytic clones.

The macrophages in addition secrete a special activating substance, IL 1, that promotes still further growth and reproduction of the specific lymphocytes.

Question 14

What is the role of T cells in activation of B-lymphocytes?

Answer 14

Most antigens activate both T lymphocyte and B lymphocytes at the same time. Some of the T cells that are formed called T helper cells, secrete lymphokines that activate the specific B lymphocytes.

Question 15

Where are the clones of B lymphocytes before exposure to a specific antigen?

Answer 15

The remain dormant in the lymphoid tissue.

Question 16

What does the B lymphocytes specific for the antigen do when machrophages present an antigen for the B lymphocytes?

Answer 16

The B lymphocytes specific for the antigen immediately enlarge and take on the appearance of lymphoblasts.

Question 17

What are plasmablasts?

Answer 17

Precursors of plasma cells

Question 18

What happens in the plasmablasts?

Answer 18

The cytoplasm expands and the rough endoplasmic reticulum proliferates vastly. The plasmablasts then begin to divide at a rate of about once every 10 hours for about 9 divisions giving a total population of about 500 cells for each original plasmablast in 4 days. The mature plasma cell then produces gamma globulin antibodies at an extremely rapid rate (2000 molecules per second for each plasma cell). In turn, the antibodies are secreted into the lymph and carried to the circulating blood. This process continues for several days or weeks until finally exhaustion and death of the plasma cells occur.

Question 19

What are memory cells?

Answer 19

A few of the lymphoblasts formed by activation of a clone of B lymphocytes do not go on to form plasma cells but instead form moderate numbers of new B lymphocytes similar to those of the original clone. The B cell population of the specifically activated clone becomes greatly enhanced and the new B lymphocytes are added to the original lymphocytes of the same clone. They also circulate throughout the body to populate all the lymphoid tissue. Immunologically they remain dormant until activated once again by a new quantity of the same antigen.

Question 20

What happens when naive B lymphocytes encounter their associated antigens, become activated and undergo clonal expansion?

Answer 20

They differentiate into short lived or long lived plasma cells that produce large amounts of antibodies. The short lived plasma cells provide rapid protection but undergo apoptosis after a few days of intense antibody secretion. However the long lived plasma cells reside in tissues such as the bone marrow and gut associated lymphoid tissue and can continue producing antibodies for many years.

Question 21

What are antibodies constituted of?

Answer 21

They are gamma globulins called immunoglobulins that have a molecular weights between 160.000 and 970.000 and constitute about 20% of all the plasma proteins. All the immunoglobulins are composed of combinations of light and heavy polypeptide chains. Most are a combination of two light and two heavy chains. Each heavy chain is paralleled by a light chain at one of its ends thus forming a heavy-light pair. There are always at least two and as many as 10 such pairs in each immunoglobulin molecule.

Question 22

What portions do the antibodies consist of and what do they do?

Answer 22

Variable portion: it’s different for each antibody and it’s this portion that attaches specifically to a particular type of antigen.

Constant portion: determines other properties of the antibody establishing such factors as antibody diffusivity in the tissues, adherence to specific structures in the tissues, attachment to the complement complex, ease with which the antibodies pass through membrane and other biological properties of the antibody.

Question 23

What hold the light and heavy chains together in the antibody?

Answer 23

A combination of noncovalent and covalent bonds (disulfide).

Question 24

How can each antibody be specific for a particular antigen?

Answer 24

This characteristic is a result of the unique structural organisation of amino acids in the variable portions of the light and heave chains. The amino acid organisation has a different steric shape for each antigen specificity.

Question 25

When the antibody is highly specific for the antigen, there are so many boding sites that the antibody-antigen coupling is exceedingly strong held together by different factors. Which are these?

Answer 25

1. Hydrophobic bonding
2. Hydrogen bonding
3. Ionic attractions
4. Van der Waals forces

Question 26

What is the formula for calculating the affinity constant measuring how tightly the antibody binds with the antigen?

Answer 26

Ka = (concentration of bound antibody-antigen) / (concentration of antibody x concentration of antigen)

Question 27

What are the five general classes of antibodies and which are most important?

Answer 27

IgM, IgG, IgA, IgD and IgE

IgG is very important, it’s a bivalent antibody and constitutes about 75% of the antibodies.

IgE constitutes only a small percentage of the antibodies but is especially involved in allergies.

Question 28

In what 2 ways do antibodies act to protect the body against invading agents?

Answer 28

1. By direct attack on the invader
2. By activation of the complement system that then has multiple means of its own for destroying the invader.

Question 29

Which are the ways that antibodies can inactivate the invading agent?

Answer 29

1. Agglutination
2. Precipitation (in which the molecular complex of soluble antigen and antibody becomes so large that it’s rendered insoluble and precipitates.
3. Neutralisation - in which the antibodies cover the toxic sites of the antigenic agent
4. Lysis - in which some potent antibodies are occasionally capable of directly attacking membranes of cellular agent and thereby cause rupture of the agent.

Question 30

What is the main function of the complement system?

Answer 30

To enhance the actions of antibodies and phagocytic cells in neutralising and destroying pathogens, removing damaged cells from the body and promoting inflammation.

Question 31

What are the principal protein “actors” in the complement system and where are they located?

Answer 31

11 proteins designated C1 through C9, B and D. All these are present normally among the plasma proteins in the blood as well as among the proteins that leak out of the capillaries into the tissue spaces. The enzyme precursors are normally inactive but can be activated by the so called classical pathway.

Question 32

How is the classical pathway initiated and what happens when it’s initiated?

Answer 32

It’s initiated by an antigen-antibody reaction. When an antibody binds with an antigen, a specific reactive site on the constant portion of the antibody becomes uncovered or activated and this in turn binds directly with the C1 molecule of the complement system. This starts a cascade of sequentia reaction beginning with activation of proenzyme C1. The C1 enzymes that are formed then activate successively increasing quantities of enzymes in the later stages of the system so that from a small beginning, an extremely large amplified reaction occurs. Multiple end products are formed and several of these have important effects that help prevent damage to the body’s tissues caused by the invading organism or toxin.

Question 33

What are among the most important effects of the classical pathway?

Answer 33

1. Opzononisation and phagocytosis. One of the products of the complement cascade (C3) strongly activates phagocytosis by neutrophils and macrophages, causing these cells to engulf the bacteria to which the antigen-antibody complexes are attached. This process is called opsonisation.
2. Lysis
3. Agglutination
4. Neutralisation of virus Les
5. Chemotaxis
6. Activation of mast cells and basophils

7, inflammatory effects

Question 34

In the classical pathway, what happens with opsonisation and phagocytosis?

Answer 34

One of the products of the complement cascade, C3B strongly activates phagocytosis by neutrophils and macrophages causing these cells to engulf the bacteria to which the antigen-antibody complexes are attached. The process often enhances the number of bacteria that can be destroyed by many hundredfold.

Question 35

Name 7 important effects of the classical pathway.

Answer 35

1. Opsonisation and phagocytosis
2. Lysis
3. Agglutination
4. Neutralisation of viruses
5. Chemotaxis
6. Activation of mast cells and basophils
7. Inflammatory effects

Question 36

Describe the effect lysis in the classical pathway.

Answer 36

Membrane attach complex (cytokin complex) are a combination of multiple complement factors designated ata C5b6789. This membrane attach complex inserts itself into the lipid bilayer of the cell membrane creating pores that are permeable to ions and causing osmotic ruptured of the cell membranes of bacteria or other invading organisms.

Question 37

Describe the product agglutination in the classical pathway.

Answer 37

The complement products also change the surfaces of the invading organisms causing them to adhere to one another thus promoting agglutination.

Question 38

Describe the product neutralisation of viruses in the classical pathway.

Answer 38

The complement enzymes and other complement products can attach the structures of some viruses and thereby render them nonvirulent.

Question 39

Describe the product Chemotaxis in the classical pathway.

Answer 39

Fragment C5a initiates Chemotaxis of neutrophils and macrophages thus causing large numbers of these phagocytes to migrate into the tissue area adjacent to the antigenic agent.

Question 40

Describe the product activation of mast cells and basophils in the classical pathway.

Answer 40

Fragments C3a, C4a and C5a activate mast cells and basophils causing them to release histamine, heparin, and several other substances into the local fluids. These substances in turn cause increased local blood flows increased leakage of fluid and plasma protein into the tissue and other local tissue reactions that help inactivate or immobilise the antigenic agents.

Question 41

Describe the inflammatory effects of the classical pathway.

Answer 41

In addition to inflammatory effects caused by activation of the mast cells and basophils, several other complement products contribute to local inflammation. These products cause
1. The already increased blood flow to increase further
2. The capillary leakage of proteins to be increased
3. The interstitial fluid proteins to coagulate in the tissue spaces thus preventing movement of the invading organism through the tissues.

Question 42

What do T cells do on exposure to proper antigen?

Answer 42

On exposure to proper antigen, as presented by adjacent macrophages, the T lymphocytes of a specific lymphocyte clone proliferate and release large numbers of activated specially reacting T cells in ways that parallel antibody release by activated B cells. Whole activated T cells are formed and released into the lymph and then pass into the circulation, are distributed throughout the body, pass through the capillaries walls into tissue spaces, back into the lymph and blood again. They circulate over and over again, sometimes lasting for months or even years.

Also T lymphocyte memory cells are formed meaning that when a clone of T lymphocytes is activated by an antigen many of the newly formed lymphocytes are preserved in the lymphoid tissue to become additional T lymphocytes of that specific clone and spread throughout the lymphoid tissue of the entire body. Therefore on subsequent exposure to the antigen anywhere in the body, release of activated T cells occurs far more rapidly and much more powerfully than during first exposure.

Question 43

What does it take for T lymphocytes to recognise and respond to antigens?

Answer 43

They respond only when antigens are bound to specific molecules called MHC proteins on the surface of antigen presenting cells in the lymphoid tissues.

Question 44

What are the 3 major types of antigen presenting cells?

Answer 44

Macrophages
B lymplymphocytes
Dendritic cells

Question 45

Where are dendritic cells located and what are their function?

Answer 45

They’re located throughout the body and the main function is to present antigens to T cells.

Question 46

What is the large group of genes that MHC proteins are encoded by?

Answer 46

Major histocompatibility complex

Question 47

What does MHC proteins do?

Answer 47

They bind peptide fragments of antigen proteins that are degraded inside antigen presenting cells and then transport them to the cell surface.

Question 48

What are the two types of MHC proteins?

Answer 48

1. MHC 1 proteins which present antigen to cytotoxic T cells
2. MHC II proteins which present antigens to T helper cells.

Question 49

What are the 3 multiple types of T cells?

Answer 49

1. T helper cells
2. Cytotoxic T cells
3. Regulatory T cells ( suppressor T cells)

Question 50

How much of the T cells are T helper cells?

Answer 50

Usually more than 75%

Question 51

What do the T helper cells do?

Answer 51

Serve as major regulator to virtually all immune functions. They so this by forming a series of protein mediators called lymphokines that act on other cells of the immune system as well as on bone marrow cells. When stimulated, naive CD4+ T helper cells can differentiate into subsets that produce different lymphokines and perform different functions.

Question 52

What will happen in absence of T helper cells?

Answer 52

The clones for producing cytotoxic T cells and regulatory T cells are activated only slightly by most antigens.

The lymphokine interleukin 2 has an especially strong stimulatory effect in causing growth and proliferation of cytotoxic and regulatory T cells.

Several of the other lymphokines have less potent effects.

The directs actions of antigens to cause B cell growth are also slight without the help of the T helper cells.

Question 53

Which three interleukins are especially important in the B cell response and what are they called?

Answer 53

Interleukin 4, 5, 6
They are called B cell stimulating factors or B cell growth factors

Question 54

How do the lymphokines affect the macrophages?

Answer 54

They slow or stop the migration of the macrophages after they have been chemotactically attracted into inflamed tissue area thus causing much accumulation of macrophages. Second they activate the macrophages to cause more efficient phagocytosis allowing them to attach and destroy increasing numbers of invading bacteria or other tissue destroying agents.

Question 55

Some of the lymphokines have a directs positive feedback effect in stimulating activation of T helper cells - especially one, which one of them?

Answer 55

Interleukin- 2
This acts as an amplifier by further enhancing the helper cell response as well as the entire immune response to an invading agent.

Question 56

What are cytotoxic T cells?

Answer 56

Directs attack cell (CD8+ cytotoxic cells) that is capable of killing microorganisms and at the times, also own body cells.

Question 57

Describe how the cytotoxic T cells kill the attacked cell?

Answer 57

The receptor proteins on the surfaces of the CD8+ cytotoxic cells cause them to bind tightly to the organisms or cells that contain the appropriate binding specific antigen. After binding, the cytotoxic T cell secretes hole forming proteins called perforins that literally punch round holes in the membrane of the attacked cells.
Fluid the flows rapidly into the cell from the interstitial space. In addition, the cytotoxic T cells release cytotoxic substances directly into the attacked cell. Almost immediately, the attacked cell becomes greatly swollen and dissolves shortly thereafter.

The cytotoxic killer cell can pull away from the victim cells and move on to kill more cells. They can persist for months in the tissue.

Question 58

What are the regulatory T cells capable of?

Answer 58

Suppressing the functions of both cytotoxic and T helper cells.