What is immunity?

Immunity is the ability of the body to protect against all types of foreign bodies like bacteria, virus, toxic substances, etc. which enter the body. Immunity is also called disease resistance. The lack of immunity is known as susceptibility.

The science dealing with the various phenomena of immunity, induced sensitivity and allergy is called immunology.

There are two major types of immunity: innate or natural or nonspecific and acquired or adaptive.

(A) Innate or Natural or Nonspecific Immunity (L. innatus = inborn):
Innate immunity is inherited by the organism from the parents and protects it from birth throughout life. For example humans have innate immunity against distemper, a fatal disease of dogs.

As its name nonspecific suggests that it lacks specific responses to specific invaders. Innate immunity or nonspecific immunity is well done by providing different barriers to the entry of the foreign agents into our body. Innate immunity consists of four types of barriers— physical, physiological, cellular and cytokine barriers

They are mechanical barriers to many microbial pathogens. These are of two types. Skin and mucous membrane.

(a) Skin:
The skin is physical barrier of body. Its outer tough layer, the stratum corneum prevents the entry of bacteria and viruses.

(b) Mucous Membranes:
Mucus secreted by mucous membrane traps the microor¬ganisms and immobilises them. Microorganisms and dust particles can enter the respiratory tract with air during breathing which are trapped in the mucus. The cilia sweep the mucus loaded with microorganisms and dust particles into the pharynx (throat). From the pharynx it is thrown out or swallowed for elimination with the faeces.

The skin and mucous membranes secrete certain chemicals which dispose off the pathogens from the body. Body temperature, pH of the body fluids and various body secretions prevent growth of many disease causing microorganisms. Some of the important examples of physiological barriers are as follows:

(a) Acid of the stomach kills most ingested microorganisms,
b) Bile does not allow growth of microorganisms,
(c) Cerumen (ear wax) traps dust particles, kills bacteria and repels insects,
(d) Lysozyme is present in tissue fluids and in almost all secretions except in cerebrospinal fluid, sweat and urine. Lysozyme is in good quantity in tears from eyes. Lysozyme attacks bacteria and dissolves their cell walls. Lysoenzyme is also found in saliva,
(e) Nasal Hair. They filter out microbes and dust in nose,
(f) Urine. It washes microbes from urethra,
(g) Vaginal Secretions. It is slightly acidic which discourages bacterial growth and flush microbes out of vagina,
(h) Sebum (sweat). It forms a protective acid film over the skin surface that inhibits growth of many microbes.

These are certain white blood corpuscles (leucocytes), macroph¬ages, natural killer cells, complement system, inflammation, fever, antimicrobial substances, etc.

(i) Certain Leucocytes:

Neutrophils and monocytes are major phagocytic leucocytes.

As they have multilobed nucleus they are normally called polymorphonuclear leucocytes (PMNL-neu- trophils). Neutrophils are short lived and are highly motile phagocytic killers. Neutrophils are formed from stem cells in the bone marrow. Neutrophils are the most numerous of all leucocytes. They die after a few days and must therefore, be constantly replaced. Neutro¬phils constitute about 40% to 75% of the blood leucocytes in humans.

They are the largest of all types of leucocytes and somewhat amoeboid in shape. They have clear cytoplasm (without cytoplasmic granules). The nucleus is bean-shaped. Monocytes constitute about 2-10% of the blood leucocytes. They are motile and phagocytic in nature and engulf bacteria and cellular debris. Their life span is about 10 to 20 hours. Generally they change into macrophages after entering tissue spaces.

i. Pulmonary alveolar macrophages in the lung

ii. Histiocytes in connective tissues,

iii. Kupffer cells in the liver

iv. Glomerular Mesangial cells in the kidney

v. Microglial cells in the brain

vi. Osteoclasts in bone

Natural Killer Cells (NK Cells):

Besides the phagocytes, there are natural killer cells in the body which are a type of lymphocytes and are present in the spleen, lymph nodes and red bone marrow. NK cells do not have antigen receptors like T cells and В cells. NK cells cause cellular destruction in at least two ways:

(a) NK cells produce perforins which are chemicals that when inserted into the plasma membrane of a microbe make so weak that cytolysis (breakdown of cells particu¬larly their outer membrane) occurs and creates pores in the plasma membrane of the target cells. These pores allow entry of water into the target cells, which then swell and burst. Cellular remains are eaten by phagocytes.

(b) Another function of NK cells is apoptosis which means natural cell death. It occurs naturally as part of the normal development, maintenance and renewal of cells, tissues and organs.

Thus functions of NK cells are to destroy target cells by cytolysis and apoptosis. NK cells constitute 5%-10% of the peripheral blood lymphocytes in humans.

(iv) Complement (Fig. 8.7): Complement is a group of 20 proteins, many of which are enzyme precursors and are produced by the liver. These proteins are present in the serum of the blood (the fluid portion of the blood excluding cells and clotting factors) and on plasma mem¬branes. They are found circulating in the blood plasma and within tissues throughout the body. They were named complement by Ehrlich be¬cause they complement the actions of other components of the immune system (e.g., action of antibody on antigen) in the fight against infec¬tion. Jules Bordet is the discoverer of complement.

Complement proteins create pores in the plasma membrane of the microbes. Water enters the microbes. The latter burst and die. The pro¬teins of complement system destroy microbes by (i) cytolysis (ii) inflammation and (iii) phago¬cytosis. These proteins also prevent excessive damage of the host tissues.

(v) Inflammation:

Inflammation is a defensive response of the body to tissue damage. The conditions that may produce inflammation are pathogens, abrasions (scraping off) chemical irritations, distortion or disturbances of cells, and extreme temperatures. The signs and symptoms of inflammation are redness, pain, heat and swelling.

Inflammation can also cause the loss of function in the injured area, depending on the site and extent of the injury. Inflammation is an attempt to dispose of microbes, toxins, or foreign material at the site of injury to prevent their spread to other tissues, and to prepare the site for tissue repair. Thus, it helps restore tissue homeostasis.

Broken mast cells release histamine. Histamine causes dilation of capillaries and small blood vessels. As a result more blood flows to that area making it red and warm and fluid (plasma) takes out into the tissue spaces causing its swelling. This reaction of the body is called inflammatory response.

(vi) Fever:

Fever may be brought about by toxins produced by pathogens and a protein called endogenous pyrogen (fever producing substance), released by macrophages. When enough pyrogens reach the brain, the body’s thermostat is reset to a higher temperature, allowing the temperature of the entire body to rise.

Mild fever strengthens the defence mechanism by activating the phagocytes and by inhibiting the growth of microbes. A very high temperature may prove dangerous. It must be quickly brought down by giving antipyretics.

4. Cytokine Barriers:

Cytokines (Chemical messengers of immune cells) are low molecular weight proteins that stimulate or inhibit the differentiation, proliferation or function of immune cells. They are involved in the cell to cell communication. Kinds of cytokines include interleukins produced by leucocytes, lymphocytes produced by lymphocytes, tumour necrosis factor and interferon’s (IFNs). Interferon’s protect against viral infection of cells.

(B) Acquired Immunity (= Adaptive or Specific Immunity):

The immunity that an individual acquires after the birth is called acquired or adaptive or specific immunity. It is specific and mediated by antibodies or lymphocytes or both which make the antigen harmless.

It not only relieves the victim of the infectious disease but also prevents its further attack in future. The memory cells formed by В cells and T cells are the basis of acquired immunity. Thus acquired immunity consists of specialized В and T lymphocytes and Antibodies.

(i) Specificity:

It is the ability to differentiate between various foreign molecules (for-eign antigens).

(ii) Diversity:

It can recognise a vast variety of foreign molecules (foreign antigens).

(iii) Discrimination between Self and Non-self:

It can recognise and respond to foreign molecules (non-self) and can avoid response to those molecules that are present within the body (self) of the animal.

(iv) Memory:

When the immune system encounters a specific foreign agent, (e.g., a microbe) for the first time, it generates immune response and eliminates the invader. This is called first encounter. The immune system retains the memory of the first encounter. As a result, a second encounter occurs more quickly and abundantly than the first encounter.

The cells of the immune system are derived from the pluripotent stem cells in the bone marrow. Pluripotent means a cell that can differentiate into many different types of tissue cells. The pluripotent stem cells can form either myeloid stem cells or lymphoid stem cells.

Myeloid stem cells give rise to monocytes, macrophages and granulocytes (neutrophils eosinophil’s, and basophils). RBCs and blood platelets (lymphoid stem cells) form В lym¬phocytes (B cells), T lymphocytes (T-cells) and natural killer (NK) cells.

Components of Acquired Immunity:

Acquired immunity has two components: humeral immunity or Antibody mediated immune system (AMIS) and cellular immunity or cell mediated immune system (CMIS).

I. Antibody Mediated Immune System (AMIS) or Humoral Immunity:

It consists of antibodies (specialised proteins produced in the body in response to antigen) that circulate in the body fluids like blood plasma and lymph. The word ‘humor’ pertains to fluid. В lymphocytes (B cells) produce antibodies that regulate humoral immunity. The T-lymphocytes themselves do not secrete anti-bodies but help В lymphocytes produce them.

Certain cells of the bone marrow produce В lymphocytes and mature there. Since В lymphocytes produce antibodies, therefore, this immunity is called antibody mediated or humoral immunity. Humoral immunity or antibody-mediated immune system (AMIS) provides defence against most extracellular bacterial pathogens and viruses that infect through the respiratory and intestinal tract.

Formation of Plasma В cells and Memory В cells:

When antibodies on В cell’s surface bind antigens (any substances that cause antibodies formation) the В cell is activated and divides, producing a clone (descendants of a single cell) of daughter В cells. These clones give rise to plasma В cells and memory В cells. This phenomenon is called clonal selec¬tion.

(a) Plasma В Cells (Effector В cells):

Some of the activated В cells enlarge, divide and differentiate into a clone of plasma cells. Although plasma cells live for only a few days, they secrete enormous amounts of antibody during this period.

(b) Memory В Cells:

Some activated В cells do not differentiate into plasma cells but rather remain as memory cells (Primed cells). They have a longer life span. The memory cells remain dormant until activated once again by a new quantity of the same antigen.

Role of AMIS:

The AMIS protects the body from (i) viruses (ii) some bacteria and (iii) toxins that enter the body fluids like blood and lymph.

II. Cell-Mediated Immune System (CMIS) or Т-Cell Immunity:

A healthy person has about a trillion lymphocytes. Lymphocytes are of two types: T lymphocytes or T cells and В lymphocytes or В cells. As we know both types of lymphocytes and other cells of the immune system are produced in the bone marrow. The process of production of cells of immune system in the bone marrow is called haematopoiesis.

Because T lymphocytes (T cells) mature in the thymus, this immunity is also called T- cell immunity.

The T-cells play two important functions—effector and regulatory.

The effector function includes cytolysis (destruction of cells by immune processes) of cells infected with microbes and tumour cells and lymphokine production. The regulatory functions are either to increase or to suppress other lymphocytes and accessory cells.

1. Helper T cells (TH):

TH cells are most numerous of the T cells. They help in the functions of immune system. They produce a growth factor that stimulates В-cell proliferation and differentiation and also stimulates antibody production by plasma cells; enhance activity of cytotoxic T cells.

2. Cytotoxic T cells (Tc) or Killer cells:

These cells are capable of killing microorganisms and even some of the body’s own cells directly hence they are called killer cells. The antigen receptors on the surfaces of the cytotoxic cells cause specific binding with antigens present on the surface of foreign cell.

Cell after binding, the cytotoxic T cell secretes hole-forming proteins, called perforins, that punch large round holes in the membrane of the foreign cell. Then fluid flows quickly into the cell from the interstinal space. In addition, the cytotoxic T cell releases cytotoxic substances directly into the foreign cell. Almost immediately, the foreign cell becomes greatly swollen and it usually dissolves shortly thereafter.

Thus they destroy body cells infected by viruses and attack and kill bacteria, fungi, parasites and cancer cells.

3. Memory T Cells (Primed Cells):

These cells are also formed by T-lymphocytes as a result of exposure to antigen and remain in the lymphatic tissue (e.g., spleen, lymph nodes). They recognize original invading antigens even years after the first encounter.

These cells keep ready to attack as soon as the same pathogens infect the body again. They proliferate and differentiate into cytotoxic T cells, helper T cells, suppressor T cells, and additional memory cells.

4. Suppressor Cells (Regulatory T cells (TR)):

These cells are capable of suppressing the functions of cytotoxic and helper T cells. They also inhibit the immune system from attacking the body’s own cells. It is believed that suppressor cells regulate the activities of the other cells. For this reason, the suppressor cells are classified as regulatory T cells.

Natural Killer (NK) Cells:

NK cells attack and destroy target cells, participate in antibody dependent cell mediated cytotoxicity. They can also attack parasites which are much larger than bacteria.

Acquired (= Adaptive) Immunity is of two types: active immunity and passive immunity.

1. Active Immunity:

In this immunity person’s own cells produce antibodies in response to infection or vaccination. It is slow and takes time in the formation of antibodies. It is long lasting and is harmless. Active immunity may be natural or artificial.

(a) A person who has recovered from an attack of small pox or measles or mumps develops natural active immunity.

(b) Artificial active immunity is the resistance induced by vaccines. Examples of vaccines are as follows: Bacterial vaccines, (a) Live- BCG vaccine for tuberculosis, (b) Killed vaccines- TAB vaccine for enteric fever. Viral vaccines, (a) Live – sabin vaccine for poliomyelitis, MMR vaccine for measles, mumps, rubella, (b) Killed vaccines- salk vaccine for poliomyelitis, neural and non-neural vaccines for rabies. Bacterial products. Toxoids for Diphtheria and Tetanus.

2. Passive Immunity:

When ready-made antibodies are directly injected into a person to protect the body against foreign agents, it is called passive immunity. It provides immediate relief. It is not long lasting. It may create problems. Passive immunity may be natural or artificial.

(a) Natural passive immunity is the resistance passively transferred from the mother to the foetus through placenta. IgG antibodies can cross placental barrier to reach the foetus. After birth, immunoglobulin’s are passed to the new-born through the breast milk. Human colostrum (mother’s first milk) is rich in IgA antibodies. Mother’s milk contains antibodies which protect the infant properly by the age of three months.

(b) Artificial passive immunity is the resistance passively transferred to a recipient by administration of antibodies. This is done by administration of hyper-immune sera of man or animals. Serum (pi. sera) contains antibodies. For example, anti-tetanus serum (ATS) is prepared in horses by active immunisation of horses with tetanus toxoid, bleeding them and separating the serum. ATS is used for passive immunisation against tetanus. Similarly anti-diphtheric serum (ADS) and anti-gas gangrene serum (AGS) are also prepared.

Immune Response:

The immune response involves primary immune response and secondary immune response.

(a) The primary immune response:

After an initial contact with an antigen, no anti¬bodies are present for a period of several days. Then, a slow rise in the antibody titer o(arbitrary units) occurs, first IgM and then IgG followed by a gradual decline in antibody titer. This is called the primary immune response.

(b) The secondary immune response:

Memory cells may remain in the body for decades. Every new encounter with the same antigen results in a rapid proliferation of memory cells. This is also called “booster response”. The antibody titer after subsequent encounters is far greater than during a primary response and consists mainly of IgG anti¬bodies. This accelerated, more intense response is called the secondary immune response. Antibodies produced during a secondary response have an even higher affinity for the antigen.

A person who had been suffering from diseases like measles, small pox or chicken pox becomes immune to subsequent attacks of these diseases. It includes spleen, lymph nodes, tonsils, Peyer’s patches of small intestine and appendix.

The increased power and duration of the secondary immune response explain why immunization (method of providing immunity artificially, it is called vaccination) is usually accomplished by injecting antigen in multiple doses.

1.Cold Hands

If your blood vessels are inflamed, it can be harder for your fingers, toes, ears, and nose to keep warm. The skin in these areas may turn white, then blue, when you’re exposed to the cold. Once blood flow returns, the skin may then turn red.

2. Bathroom Problems

Diarrhea that lasts more than 2 to 4 weeks can be a warning sign that your immune system is harming the lining of your small intestine or digestive tract.

Constipation is a concern, too. If your bowel movements are hard to pass, very firm, or look like they’re made up of small rabbit pellets, your immune system may be forcing your intestine to slow down. Other possible causes include bacteria, viruses, and other health conditions.

3. Dry Eyes

If you have an autoimmune disorder, that means your immune system attacks your body instead of defending it. Rheumatoid arthritis and lupus are two examples.

Many people who have an autoimmune disorder find that they have dry eyes. You might feel a sandy, gritty feeling like something is in your eye. Or you may notice pain, redness, a stringy discharge, or blurred vision. Some people find they can’t cry even when they’re upset.

4. Fatigue

Feeling extremely tired, like you do when you have the flu, could mean something’s going on with your body’s defenses. Sleep is unlikely to help. Your joints or muscles can ache, too. Again, there could be many other reasons why you feel this way.

5. Mild Fever

If you’re running a higher temperature than normal, it could be that your immune system is starting to overwork. That can happen due to an oncoming infection or because you're starting to have a flare of an autoimmune condition.

6. Headaches

In some cases, headaches can be related to the immune system. For example, it could be vasculitis which is inflammation of a blood vessel caused by an infection or autoimmune disease.

7. Rash

Your skin is your body’s first barrier against germs. How it looks and feels can reflect how well your immune system is doing its job.

Itchy, dry, red skin is a common symptom of inflammation. So is a rash that is painful or doesn’t clear up. People with lupus often get a butterfly-shaped rash across their nose and cheeks.

8. Joints Ache

When the lining inside your joints becomes inflamed, the area around them is tender to the touch. It might also be stiff or swollen, and it can happen with more than one joint. You may notice that it’s worst in the morning.

9. Patchy Hair Loss

Sometimes the immune system attacks hair follicles. If you lose hair on your scalp, face, or other parts of your body, you could have a condition called alopecia areata. Strands or clumps of hair coming out can also be a symptom of lupus.

10. Repeated Infections

If you need to take antibiotics more than twice a year (four times for children), your body may not be able to attack germs well on its own.

Other red flags: Chronic sinus infections, being sick with more than four ear infections in a year (for anyone over the age of 4), or having pneumonia more than once.

11. Sensitive to Sun

People with an autoimmune disorder sometimes have an allergic reactionto ultraviolet (UV) rays called photodermatitis. You may get blisters, a rash, or scaly patches after being in the sun. Oyou may get chills, a headache, or nausea.

12. Tingling or Numbness in Your Hands and Feet

It can be completely innocent. But in some cases it can mean that your body is attacking nerves that send signals to your muscles. People who have Guillain-Barre syndrome, for instance, may have numbness that starts in their legs then moves up to their arms and chest.

Chronic inflammatory demyelinating polyneuropathy has symptoms similar to the demyelinating form of GBS, (called acute inflammatory demyelinating polyneuropathy, or AIDP), but while GBS lasts two weeks to 30 days. CIPD lasts much longer.

13. Trouble Swallowing

If you have a tough time getting food down, your esophagus (the tube that carries food from your mouth to your stomach) could be swollen or too weak to work well. Some people feel like food is stuck in their throat or chest. Others gag or choke when they swallow. One of the possible causes can be a problem with your immune system.

14. Unexplained Weight Change

You find yourself gaining extra pounds even though your eating habits and workouts haven’t changed. Or the number on your scale may drop for no clear reason. It's possible this is because of damage to your thyroid gland from an autoimmune disease.

15. White Patches

Sometimes your immune system decides to fight the skin’s pigment-making cells, called melanocytes. If so, you’ll start to see white patches of skin on your body.

16. Yellowing of Your Skin or Eyes

Called jaundice, it may mean that your immune system is attacking and destroying healthy liver cells. That can lead to a condition called autoimmune hepatitis.