Body defense or Immune system

 

Immunology has its origins in the study of how the body protects itself against infectious diseases caused by microorganisms, such as bacteria, viruses, protozoa, and fungi, and also parasitic organisms, such as helminth worms.

 

The immune system is made up of special organs, cells and chemicals that fight infection (microbes). 

 Two major mechanisms that protect the body:

1. Innate, nonspecific system of

2. Adaptive system that fights specific pathogens

 

1.     Innate, Nonspecific Resistance

Physical Barriers

1st major level of protection from invasion and infection

nonspecific –To prevent entry of athogens into body

1. Intact Skin

tightly packed cells filled with waxy keratin thick, multiple layers of dead keratinized cells shed regularly rarely, if ever, penetrated while intact only a few parasitic worms (cercariae) can do this.

If skin is broken:

·        staphs and streps are most likely to get in sebaceous glands provides protective film over skin.

·        acidity of skin secretions ('acid mantle') inhibit bacterial & fungal growth; also contains bacteriocidal chemicals but

·        if skin is moist, not cleaned frequently enough may permit yeasts and fungi already present to become a problem.

2. Mucous Membranes

·        line all systems that open to outside of body nasal hairs trap pathogens mucous thick, sticky, traps pathogens.

Cilia; in respiratory system move mucous out of system coughing and sneezing speed up process

3. Gastric juices; secreted by lining of stomach contains HCl and enzymes; highly acidic (pH~1.3-3.5) kill and dissolve most bacteria and toxins except S. aureus and C. botulinum

 

4. Lacrimal Apparatus:

continual blinking flushes and wipes away pathogens lysozyme kills and dissolves some bacteria. (lysozyme also found in sweat, saliva, and nasal secretions)

5. Saliva:

continual flushing of bacteria to stomach lysozyme kills and dissolves some bacteria.

6. Urine:

continual flushing of bacteria entering urethra low flow  bladder infection acidity also inhibits bacterial growth

7. Vaginal Secretions:

flushing and trapping pathogens in mucous acidity inhibits bacterial growth but: some pathogens thrive in moisture and if they occur in large enough numbers they are able to penetrate eg. Treponema

 

 

Parts of the immune system

The main parts of the immune system are:

 

a)     White blood cells

b)    Complement system

c)     Lymphatic system

d)    Spleen

e)     Bone marrow

f)      Thymus.

g)     Tonsil

h)    Antibodies

 

White blood cells

White blood cells are the key players in your immune system. They are made in your bone marrow and are part of the lymphatic system.

White blood cells move through blood and tissue throughout your body, looking for foreign invaders (microbes) such as bacteria, viruses, parasites and fungi. When they find them, they launch an immune attack.

White blood cells include lymphocytes (such as B-cells, T-cells and natural killer cells), and many other types of immune cells.

 

Lymphatic system

The lymphatic system is a network of delicate tubes throughout the body. The main roles of the lymphatic system are to manage the fluid levels in the body

react to bacteria deal with cancer cells deal with cell products that otherwise would result in disease or disorders

absorb some of the fats in our diet from the intestine.

The lymphatic system is made up of:

 

Lymph nodes (also called lymph glands) -- which trap microbes

lymph vessels -- tubes that carry lymph, the colourless fluid that bathes your body's tissues and contains infection-fighting white blood cells.

 

Spleen

The spleen is a blood-filtering organ that removes microbes and destroys old or damaged red blood cells. It also makes disease-fighting components of the immune system (including antibodies and lymphocytes).

 Bone marrow

Bone marrow is the spongy tissue found inside your bones. It produces the red blood cells our bodies need to carry oxygen, the white blood cells we use to fight infection, and the platelets we need to help our blood clot.

 

Thymus

The thymus filters and monitors your blood content. It produces the white blood cells called T-lymphocytes.

 

Bone marrow:

 is the primary lymphoid organ .It is a soft tissue within the cavity of bones .Bone marrow .

Majority of lymphid progenitors develop into B- lyphocytes in the bone marrow. Some of lymphoid progenitors migrate into the thymus , where they develop into the T-lypmhocytes. During secondary immune response large number of plasma cells are produced in the bone marrow.

 

They secrete large amount of abs. So bone marrow is a source of ab synthesis. The bone marrow is the site of generation of all circulating blood cells in the adult including lympocytes and is the site of B- cell maturation

•         The white blood cells of the immune system are known as Lymphocytes.  These WBC   are also found in the spleen and blood.

•         Lymphocytes are wbcs that activate the immune response. 

 

 

Tonsil:

•         clusters of lymphatic cells and extracellular matrix not completely surrounded by a connective tissue capsule.

•         Consist of multiple germinal centers and crypts

•         Several groups of tonsils form a protective ring around the pharynx.

–       pharyngeal tonsils (or adenoids) in nasopharynx

–       palatine tonsils in oral cavity

–       lingual tonsils along posterior one-third of the tongue

 

Antibodies

Antibodies help the body to fight microbes or the toxins (poisons) they produce. They do this by recognising substances called antigens on the surface of the microbe, or in the chemicals they produce, which mark the microbe or toxin as being foreign. The antibodies then mark these antigens for destruction. There are many cells, proteins and chemicals involved in this attack.

.

ANTIBODY STRUCTURE

 

 An antibody (Ab), also known as an immunoglobulin (Ig)

 It’s a large Y-shape protein produced by B cells that is used by the immune system to identify and neutralize foreign objects such as bacteria and viruses.

The antibody recognizes a unique part of the foreign target, called an antigen.

 Antibody composed of four polypeptide chains – two identical heavy chains and two identical light chains.

 

1.     two heavy chain

2.     two light chain

3.     constant region

4.     variable region

5.     hinge region

6.     Fab fragment(antigen-binding fragment)

7.     Fc fragment(crystallizable fragment ) and

8.     disulfide bond present

Composed of 4 polypeptide chains.

 • 2 identical light and 2 identical heavy chains

 • Linked by disulphide bonds

 • Light chains similar in all immunoglobulins

• Light chains occur in 2 varieties kappa and lambda

• Light and Heavy chains are subdivided into variable and constant region.

 • Each heavy and light chain contains amino terminal in variable region, carboxyl terminal in constant region

• Each immunoglobulin peptide chain has intra chain disulphide bonds- form loops

 • Antibody or immunoglobulin basically glycoprotein, made by activated B cell called a plasma cell. antibody protects ageist foreign material (antigen)and  foreign bacteria.

 

Each heavy chain and light chain connected by disulfide bonds. Two identical light chain consists of about 220 amino acid and mass of approximately 25,000 Da and each heavy chain consists of about 440 amino acid and 50,000 to 70,000 Da mass.

 Both light (L) and heavy (H) chains contain two different regions.

 · Constant (C) regions

· Variable (V) regions

 

The constant region in both chains has an amino acid sequence that does not vary significantly between antibodies of the same class. When variable regions both chain vary significantly from antibodies and they contain different amino acids of different antibodies.

 

Both variable regions folded together, and from the antigen-binding site. That region antigen bite with antibodies.

 

An antibody can tag a microbe or an infected cell for attack by other parts of the immune system, or can neutralize its target directly. • The production of antibodies is the main function of the humoral immune system.

• Antibodies are secreted by a type of white blood cell called a plasma cell.

 

 

Classification • Based on structure and antigenic nature of H chain the immunoglobulins are classified into 5 classes.

1.     Ig G- (gamma)

2.     Ig A- (alpha)

3.     Ig M- (mu)

4.     Ig D- (delta)

5.     Ig E - (epsilon)

Immunity:

 

• The response is directed at specific targets and is not restricted to initial site of infection

• delay in  time occurs between exposure and maximal response

• The adaptive immune system allows for a stronger immune response as well as immunological memory, where each pathogen is "remembered" by its signature antigen

• Antigens are proteins or carbohydrate chain of a glycoprotein within a plasma membrane

• The specific immune response is antigen-specific and requires the recognition of specific “non-self” antigens during a process called antigen presentation

• Antigen specificity allows for the generation of responses that are tailored to specific pathogens or pathogen-infected cells.

• The ability to mount these tailored responses is maintained in the body by "memory cells“

• Should a pathogen infect the body more than once, these specific memory cells are used to quickly eliminate.

 

There are two types of immunity:

 

2.     Humoral Immunity: or Antibody Mediated Immunity (AMI; )defends against extracellular pathogens by binding to antigens and making them easier targets for phagocytes and complement proteins •

3.     Celluralr immunity  – defends against intracellular pathogens and cancer.

 

 

1.     Humoral or antibody-mediated response –

It is also termed  anti-body mediated because B cells produce antibodies. because antibodies are released into the blood stream.

 B cells - are produced and mature in the bone marrow – they possess a protein on the outer surface known as the B-cell receptor (BCR) which allows them to bind to a specific  antigen

Plasma B cells also known as plasma cells,  produce antibodies 

Memory B cells – ready for the next invasion

4.     B cell comes into contact with antigen on microbe.

5.     it attaches to the antigen and becomes an antigen-presenting B-cell with antigen-MHC complex.

• Helper T cell that binds to the complex

• Helper T secretes interleukin that stimulates mitosis in B cells so they multiply

• Some B cells mature into plasma cells and other become memory cells

• The plasma cells produce antibodies also called immunoglobins – proteins which attach to the antigens.

• Antibodies can clump microbes for destruction, mark microbes for destruction by phagocytes, activate complement proteins that rupture/lyse microbe cell membranes or infected host cells.

 

 

 

Cellular Immunity: Cell Mediated Immunity = CMI or T cell Immunity

Mediated by T lymphocytes (T-cells)

involves a more diverse group of cells than for B cell activation usually, slower to respond antigens are usually larger than in AMI .

 

T-Cell Development & Activation

 

1. Probably also first develop in fetal liver from stem cells

2. Then move to thymus where they develop and proliferate

3. Move into lymph nodes and spleen as t- cells

4. T-cells cannot recognize free antigens in the blood generally need cell to cell contact to work

A. Specific T cells activated by exposure to a specific antigen eg. Viral infected cell, cancer cell, bacterial cell

B. Initiate clonal selection and multiplication

C. Differentiation into several cell types

D. Various t-cells secrete immunoactive chemicals =lymphokines;=cytokines, not antibodies which direct the activities of both b and t cells and phagocytes

 

T cells mature into helper t cells which regulate immunity by increasing the response of other immune cells

• memory T cells persist sometimes for life and protect in case of re-infection

 

Significance of immune system

·         The immune system is a complex network of cells and proteins that defends the body against infection. 

·         The immune system keeps a record of every germ (microbe) it has ever defeated so it can recognise and destroy the microbe quickly if it enters the body again.

·         Abnormalities of the immune system can lead to allergic diseases, immunodeficiencies and autoimmune disorders.