Monday, January 24, 2011


Cholesterol The cholesterol is a lipidic molecule, indispensable to the body because:
it is one of the main components of the cellular membranes, brain and nerve cells, and bile, which helps the body absorb fats and fat-soluble vitamins.
it is a precursor of steroid hormones (oestrogens, androgens…).
The body uses cholesterol to make vitamin D.
Cholesterol is synthetized by the liver, but some also comes from the animal fats of the diet.
Synthesis and metabolism
Transport of cholesterol in the bloodThere is always a flow of cholesterol in the blood, to satisfy the requirements of the different organs. Because of its lipidic structure that makes it insoluble, it is carried along inside large molecules, the lipoproteins, that are soluble in the blood. There are 4 main types of lipoproteins, synthetized by the intestinal cells and/or by the liver. They are classified according their respective density. (The higher the density is, the less lipids they contain).
VLDL (Very Low Density Lipoproteins)
LDL (Low Density Lipoproteins)
HDL (High Density Lipoproteins : compared to LDL, they have an opposite role. They collect cholesterol in excess throughout the body, and bring it back to the liver that will store, redispatch or eliminate it through the bile. Here we speak about " good cholesterol ".
these are VLDL, once they have " delivered " their triglycerides. Then they supply the hepatic cholesterol to the organs and tissues. It is commonly called the " bad cholesterol " .
they are mainly in charge to dispatch the triglycerides synthetized in the liver to the different organs of the body.
: exclusively produced by the small intestine cells after a meal. They go through the lymphatic vessels before reaching the general circulation. Their major role is to transport dietary triglycerides up to the liver.
Cholesterol is then mostly carried along by LDL and HDL. In man, the most important lipoproteins are LDL. These are the ones that can cause fat deposits inside the arteria (atheroma), and be at the origin of so common diseases in man: coronary diseases, myocardial infarction… On the contrary, in dogs and cats, there are twice as much HDL than LDL, and 80 % of the total cholesterol is binded to HDL. Here, the " good cholesterol " is the most important. This physiological difference could explain why atheromatosis is so rare in these species.
Disorders of the lipidic metabolismThe fact that cholesterol does not deposit in the vascular system does not mean that there is no possible disorder in the lipidic metabolism of cats and dogs.
When there is a global excess of lipids in the blood, one speaks about hyperlipemia. In that case, the serum is cloudy, with a " strawberry milk " colour. After sedimentation during one night, a white " creamy " appears on the surface. A clear serum does not mean however that everything is normal. When there is only an excess of cholesterol in the blood, there is no modification of the serum visible. Only the dosage of cholesterol and triglycerides (after 12 hours fasting), can confirm hyperlipemia.
Those troubles of the lipidic metabolism are scarcely observed alone. Only a few cases are known: in miniature Schnauzer and in cats. In general, it is rather the consequence of another disbalance, mostly from hormonal origin.
Htpothyroidism70 % of hypothyroidism cases induce an abnormal rise in blood cholesterol- Dogs with hypothyroidism aren't producing enough T3 hormone. T3 stimulates the liver's LDL cholesterol receptors, which scrub LDL from the blood and thyroid harmone increases HMG-CoA reductase activity. A lack of T3 hormone means a higher LDL level. Dysfunctionment of surrenal glands (hypercorticism) . The adrenal glands of dogs with hypradrenocorticism produce excessive amounts of corticosteroids. These hormones increase the dog's lipase production to levels that raise cholesterol by releasing stored fat into the bloodstream.Glucocorticoids decrease HMG-CoA reductase activity.Diabetes- A dog's pancreas normally produces the enzyme lipase, which helps metabolize dietary fats. With diabetes mellitus, a dog doesn't release enough insulin to stimulate normal lipase production, causing elevated levels of cholesterol.Also, insulin increases HMG-CoA reductase activity. Acute pancreatitis-
Nephrotic Syndrome-Nephrotic syndrome is a kidney disorder that raises both HDL and LDL cholesterol
Drug intoxication
Hepatic deficiency
In obese animals, such as obese cats that suddenly stop eating, one can notice an elevation of blood cholesterol and triglycerides, but it is not a constant phenomenon
(fat storage in excess in cats): hypercholesterolemia can be one the first signs of an hepatic disorder If the liver itself is diseased, it may not be able to excrete cholesterol at all- Obstruction of the bile ducts (cholestasis). It should not be neglected.
: steroid anti-inflammatory drugs, contraceptive hormones…
Necrotic pancreas is thought to release inhibitors of lipoprotein lipase and both cholesterol and triglyceride concentration increases.
An increase level of cholesterol affects dogs more than cats. Dogs and cats with high cholesterol are however not predisposed to
Hyperlipidemia is diagnosed if your pet has a fasted triglyceride level greater than 500mg/dl and/or a fasted cholesterol level greater than 300mg/dl
Conclusion On a dietetic aspect, the dietary fats have to be drastically restricted. However, the supply of essential fatty acids must not be forgotten. Increasing the fiber content of the diet is also advised. Fibers adsorb biliary salts and prevent from the recycling of cholesterol contained in these salts.
1.The principle regulatory enzyme in the pathway of cholesterol synthesis is HMG-CoA reductase2.Cholesterol is transported in plasma in lipoproteins.
3.Cholesterol is excreated from body in bile.
5.Good cholesterol is HDL6.
7.Glucagon or glucocorticoids decrease HMG-CoA reductase activity
8.Cheif synthetic and catabolic organ for cholesterol is liver.9.Primary or inherited disorders in cholesterol metabolism are seen in Miniature Schnauzer dogs    
Dogs, cholesterol is binded to HDL which contributes to their general resistance to atherosclerosis. Plasma cholesterol values greater than 750 mg/dl predispose dogs to atherosclerosis despite their natural resistance.
heart disease as in people. Warning symptoms and signs such as abdominal pain, seizures, patches on the skin, yellow bumps filled with a greasy, fatty fluid(cutaneous xanthomata) and nervous system abnormalities may be an indication that your pet has high cholesterol. Plasma cholesterol values greater than 750 mg/dl predispose dogs to atherosclerosis despite their natural resistance

Sunday, January 23, 2011


What Is Stress?
Stress is a feeling that's created when we react to particular events. It's the body's way of rising to a challenge and preparing to meet a tough situation with focus, strength, stamina, and heightened alertness.
The events that provoke stress are called stressors, and they cover a whole range of situations — everything from outright physical danger to making a class presentation or taking a semester's worth of your toughest subject.
The human body responds to stressors by activating the nervous system and specific hormones. The hypothalamus signals the adrenal glands to produce more of the hormones adrenaline and cortisol and release them into the bloodstream. These hormones speed up heart rate, breathing rate, blood pressure, and metabolism. Blood vessels open wider to let more blood flow to large muscle groups, putting our muscles on alert. Pupils dilate to improve vision. The liver releases some of its stored glucose to increase the body's energy. And sweat is produced to cool the body. All of these physical changes prepare a person to react quickly and effectively to handle the pressure of the moment.
This natural reaction is known as the stress response. Working properly, the body's stress response enhances a person's ability to perform well under pressure. But the stress response can also cause problems when it overreacts or fails to turn off and reset itself properly.
Good Stress and Bad Stress
The stress response (also called the fight or flight response) is critical during emergency situations, such as when a driver has to slam on the brakes to avoid an accident. It can also be activated in a milder form at a time when the pressure's on but there's no actual danger — like stepping up to take the foul shot that could win the game, getting ready to go to a big dance, or sitting down for a final exam. A little of this stress can help keep you on your toes, ready to rise to a challenge. And the nervous system quickly returns to its normal state, standing by to respond again when needed.
But stress doesn't always happen in response to things that are immediate or that are over quickly. Ongoing or long-term events, like coping with a divorce or moving to a new neighborhood or school, can cause stress, too.
Long-term stressful situations can produce a lasting, low-level stress that's hard on people. The nervous system senses continued pressure and may remain slightly activated and continue to pump out extra stress hormones over an extended period. This can wear out the body's reserves, leave a person feeling depleted or overwhelmed, weaken the body's immune system, and cause other problems.
What is the healthy response to stress?
A key aspect of a healthy adaptational response to stress is the time course. Responses must be initiated rapidly, maintained for a proper amount of time, and then turned off to ensure an optimal result. An over-response to stress or the failure to shut off a stress response can have negative biological consequences for an individual. Healthy human responses to stress involve three components:
The brain handles (mediates) the immediate response. This response signals the adrenal medulla to release epinephrine and norepinephrine.

The hypothalamus (a central area in the brain) and the pituitary gland initiate (trigger) the slower maintenance response by signaling the adrenal cortex to release cortisol and other hormones.

Many neural (nerve) circuits are involved in the behavioral response. This response increases arousal (alertness, heightened awareness), focuses attention, inhibits feeding and reproductive behavior, reduces pain perception, and redirects behavior.
The combined results of these three components of the stress response maintain the internal balance (homeostasis) and optimize energy production and utilization. They also gear up the organism for a quick reaction through the sympathetic nervous system (SNS). The SNS operates by increasing the heart rate, increasing blood pressure, redirecting blood flow to the heart, muscles, and brain and away from the gastrointestinal tract, and releasing fuel (glucose and fatty acids) to help fight or flee the danger.
What is the role of the hypothalamus-pituitary-adrenal (HPA) axis (grouping) in stress?
The HPA axis is a grouping of responses to stress by the brain and the pituitary and adrenal glands. First, the hypothalamus (a central part of the brain) releases a compound called corticotrophin releasing factor (CRF), which was discovered in 1981. The CRF then travels to the pituitary gland, where it triggers the release of a hormone, adrenocorticotrophic hormone (ACTH). ACTH is released into the bloodstream and causes the cortex of the adrenal gland to release the stress hormones, particularly cortisol, which is a corticosteroid hormone. Cortisol increases the availability of the body's fuel supply (carbohydrate, fat, and glucose), which is needed to respond to stress. However, if cortisol levels remain elevated for too long, then muscle breaks down, there is a decreased inflammatory response, and suppression of the immune (defense) system occurs.
Because they suppress the immune system, corticosteroids in measured doses are used to treat many illnesses that are characterized by inflammation or an overactive immune system, such as asthma and inflammatory bowel disease. For the same reason, they are used to help reduce the chances that our body will immunologically reject a transplanted organ. Corticosteroids also can cause fluid retention and high blood pressure. Therefore, it is critical that the response to corticosteroids be carefully controlled (modulated). This control usually is accomplished by a feedback mechanism in which increased cortisol levels feeding back to the hypothalamus and pituitary turn off production of ACTH. In addition, extremely high levels of cortisol can cause mental changes, including depression and psychosis, which disappear when the levels return to normal.


Sunday, November 28, 2010

biochemistry of digestive disorder,19,20


INTRODUCTION-: The entire digestive process consist of
Swallowing in the mouth followed by passing to stomach
through pharynx and oesophagus.In stomach initiation of
digestion of protein takes place in addition stomach may reject
irritating substances and destroy micro organism.
                                      The biochemical aspect of digestive disorder
Mainly concerned with Nature of secreation like gastric secreation,
Intestinal secreation, pancreas secreation and way in which this
Secreation is disturbed in various digestive disorder.
                                       Various disease of stomach may depend
Upon infectness of gastric mucosa the rate of secreation of HCL by 
Uninjured parietal cell,rate and volume of other secreation in stomach
HCL in the stomach convert pepsinogen to active pepsin and provide
 Optimum ph for peptic digestion in the stomach.
                                        Achlorhydria-is the absence of Hcl due to
 histamine induced gastric this condition gastric juice
 containmore than normal amount of base in combination of cl` and
                                         Hypochlorhydria-is the possibility of
occurance of chronic Gastritis.
PEPTIC ULCER-:Term refers to the loss of tissue confind to the
stomach and upper portion of duodenum bcz of action of acid containing
 gastric juice more than 1004 ml/day but normal value is 580 ml/day
                                              Treatment of peptic ulcer is use of alkaline
Materials such as Caco3,Na2co3,Mgo2
                                                Glucose tolerance is altered in patient with
Peptic ulcer and decrease plasma level of Vit ^A^
DISEASE OF INTESTINE-:Are observed such as inflammation,
Neoplasm,ulcerative disease and functional disorders
                                                  The volm of pancreatic juice secreated daily
Is about 1500 ml/day and ph is 7.8-8.4
                                                   The loss of intestinal juice result in
dehyderation and acidosis.that laeds to hyporetinimia hyporcholoridia is
characterize by the presence of excessive amount of Fat in stool this is
caused by cystic fibrosis of pancreas.the failure of fat absorption is known
as celiac disease.
 ULCERATIVE COLITIS-:Ulceration of mucosa of colon cause
Ulcerative colitis a negative Nitrogen balance has been observed hence
Electrolyte patern of serum plasma is altered.The concentration of ca+,na+
cl- are definitely decreased below the normal levels
                                                    The fatty liver develops due to the lack of
Lipotrophic agentssuch as methionine and this prothrombin level
 go down and if give 1mg of vit k administered parentaly level will be
 normal. sometimes in Hepatocellulor disease even huge amounts of vit K
will not affect the decreased level of prothrombin.
ACUTE RUMEN TYMPANY/BLOAT-:Seen when cattle consume
 Large Quantity of legumes or fed with high concentrate diet bcz of change
 in the ruminal content to a foamy or froathy bcz  of altered surface tention
and gas become traped in small bubbles and can not eliminated
                                                     Treatment-is give only balance diet and
 purgatives like  oil.
 BOVINE KETOSIS-:Seen in bovines due to increase in milk
 Production particularly soon after parturition if animal not getted
suffiecient diet of CHO and Ketone bodies formed.
 diet in sheep particularly when it gives birth twins
GALL BLADER STONES- Interfere release of bile and effect fat digesition
Mouth                   salivary           CHO(starch and              Maltose                                                                                salivary gland      amylase             glycogen)

Stomach              pepsin               protein                        protease(more A.A) and    
Gland                                                                               peptones(less A.A)

Pancreas             Trypsin               protein,protease       polypeptides and dipeptides       

                       Chymotrypsin         same                        same

                 Corboxypeptidase       polypeptides at the    lower peptides and free A.A
                                                     Free carboxyl end
                                                     Of  the chain
              Pancreatic amylase         starch and glycogen      maltose

               Lipase                             fat                             fatty acid mono and diacyl

Liver and   bile salts and              fats                         emulsifications of fats
and Gall        alkali

Small          aminopeptidase       polypeptides         lower peptides and free A.A

                 Dipeptidase          dipeptides                     A.A                                              
                 Sucrase              sucrose                        glucose

                 Maltase             maltose                        glucose

                Lactase              lactose                            same
         COMPILED  BY-:
                                           RV/O7-I6 IMRAN KHAN
                                           RV/O7-19 KALYANI
                                           RV/O7-20 KARTHIKA

functions of kidney,32,33

Urinary system
Functions of the Kidneys:
1.        Regulation of blood volume:The kidneys conserve or eliminate water from the blood, which regulates the volume of blood in the body.
2.        Regulation of blood pressure:The kidneys regulate blood pressure in 3 ways, by:-
o    Adjusting the volume of blood in the body (by regulating the quantity of water in the blood - see above),
o    Adjusting the flow of blood both into, and out of, the kidneys, and
o    Via the action of the enzyme renin. The kidneys secret renin, which activates the angiotensin-aldosterone pathway.
3.        Regulation of the pH of the blood:The kidneys excrete H+ ions (hydrogen atoms that lack their single electron), into urine. At the same time, the kidneys also conserve bicarbonate ions (HCO3-), which are an important buffer of H+.
4.        Regulation of the ionic composition of blood:The kidneys also regulate the quantties in the blood of the ions (charged particles) of several important substances. Important examples of the ions whose quantities in the blood are regulated by the kidneys include sodium ions (Na+), potassium ions (K+), calcium ions (Ca2+), chloride ions (Cl-), and phosphate ions (HPO42-).
5.        Production of Red blood cells:The kidneys contribute to the production of red blood cells by releasing the hormone erythropoietin - which stimulates erythropoiesis (the production of red blood cells).
6.        Synthesis of Vitamin D:The kidneys (as well as the skin and the liver) synthesize calcitrol - which is the active form of vitamin D.
7.        Excretion of waste products and foreign substances:The kidneys help to excrete waste products and foreign substance from the body by forming urine (for release from the body).
Examples of waste products from metabolic reactions within the body include ammonia (from the breakdown of amino acids), bilirubin (from the breakdown of haemoglobin), and creatinine (from the breakdown of creatine phosphate in muscle fibres). Examples of foreign substances that may also be exceted in urine include pharmaceutical drugs and environmental toxins.
Structure of nephron



Cystitis causes irritation of the lining and the wall of the urinary bladder. It occurs due to bacterial infection or due to mechanical abrasion. Cystitis is characterized by bloody or cloudy urine and pain in the lower abdomen. The urine also emits an unpleasant odor. According to Medline Plus, a website of the National Institutes of Health, this condition affects more women than men. This is primarily due to the fact that the urethra of women is much shorter than that of men. Escherichia coli, also known as E. coli, bacterium primarily is responsible for this condition.


Inflammation of the kidney is medically termed "nephritis." Prolonged use of acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin can sometimes result in nephritis. It can also be a side effect of other medications such as antibiotics. Symptoms of nephritis include protein in the urine, urine suppression and convulsion. In cases of chronic nephritis, there is a danger of the kidney being damaged permanently. According to the U.S. Centers for Disease Control and Prevention (CDC), nephritis accounted for approximately 45,000 deaths in the U.S. in 2008.


Enuresis is a condition in which a person has little control over urination. Loss of control over bladder muscles is the primary cause. Neurologic disease, weakening of the bladder due to childbirth, injury or bladder obstruction can cause enuresis. Other causes of enuresis include stress, hormonal and genetic factors, and urinary tract infections. Malfunctions in the spinal cord and small bladder can also lead to this condition. A urologist can treat and sometimes cure this disorder with medication or surgery.

Kidney Stones

Calcium oxalate salts and uric acid results in formation of deposits or stones in the kidneys. These stones have a nucleus which can harbor bacteria, foreign bodies or blood clumps. Intake of excess calcium leads to formation of kidney stones. These stones develop inside or near the kidney, the ureter or the bladder. Passing these stones through the ureter results in severe pain. In few cases, kidney stones need to be removed surgically.


Bacterial infection can lead to urethritis. This disease is more predominant in males than females. Urethritis is characterized by symptoms such as burning sensation while passing urine or semen during ejaculation. A discharge from the tip of the penis is also observed in some cases. Urethritis can be treated with antibiotics. It is a sexually transmitted disease, thus abstaining from unprotected sex will lower the risk of contracting
Blood in the urine is a symptom and not a disease. This could mean that there is the presence of a serious disease of the ureter, bladder, kidney, prostate gland, urethra, or any part of the genito-urinary system. Sometimes blood exists in the urine as a first indication of cancer
of the kidney or bladder. Even kidney stones may cause bleeding. Certain respiratory infections, such as tuberculosis, also may contribute to blood in the urine
 Pyelonephritis is generally called "pelvis nephritis" and refers to inflammation of the renal pelvis and connective tissues of the kidney. As with cystitis, pyelonephritis is usually caused by bacterial infection but can also result from viral infection, mycosis, calculi, tumors, pregnancy, and other conditions. Acute pyelonephritis develops rapidly and is characterized by chills, fever, pain in the sides (flank), nausea, and an urge to urinate frequently. This often is the result of the spread of infection from the lower urinary tract or through the blood from other organs. Chronic pyelonephritis is thought to be caused by an autoimmune disease but is often preceded by a bacterial infection or urinary blockage.
respiratory infections, such as tuberculosis, also may contribute to blood in the urine
Azoturia /az·o·tu·ria/  excess of urea or other nitrogenous compounds in the urine. Polyuria: The excessive passage of urine (at least 2.5 liters per day for an adult) resulting in profuse urination and urinary frequency (the need to urinate frequently).
Polyuria is a classic sign of diabetes mellitus that is under poor control or is not yet under treatment. Polyuria occurs in some other conditions such as:
·         Nephrogenic diabetes insipidus -- a genetic disease
·         Polycystic kidney disease -- another genetic disease
·         Sickle cell disease
·         Pyelonephritis -- infection of kidneys
·         Amyloidosis -- deposits of a substance called amyloid in the kidney
·         Sjogren syndrome, and
·         Myeloma.
·         Uremia or uraemia is a term used to loosely describe the illness accompanying kidney failure (also called renal failure), in particular the nitrogenous waste products associated with the failure of this organ.[1]
·         In kidney failure, urea and other waste products, which are normally excreted into the urine, are retained in the blood. Early symptoms include anorexia and lethargy, and late symptoms can include decreased mental acuity and coma. Other symptoms include fatigue, nausea, vomiting, cold, bone pain, itch, shortness of breath, and seizures. It is usually diagnosed in kidney dialysis patients when the glomerular filtration rate, a measure of kidney function, is below 50% of normal.[2]
·         Azotemia is another word that refers to high levels of urea, but is used primarily when the abnormality can be measured chemically but is not yet so severe as to produce symptoms. Uremia can also result in fibrinous pericarditis. There are many dysfunctions caused by uremia affecting many systems of the body, such as blood (lower levels of erythropoietin), sex (lower levels of testosterone/estrogen) and bones (osteoporosis and metastatic calcifications

Tuesday, November 23, 2010



What is creatinine?
Creatinine is a chemical waste molecule that is generated from muscle metabolism. Creatinine is produced from creatine, a molecule of major importance for energy production in muscles. Approximately 2% of the body's creatine is converted to creatinine every day. Creatinine is transported through the bloodstream to the kidneys. The kidneys filter out most of the creatinine and dispose of it in the urine.
Because the muscle mass in the body is relatively constant from day to day, the creatinine level in the blood normally remains essentially unchanged on a daily basis.

Estimation by jaffe’s method
Principle:- creatinine present in serum or plasma directly reacts with alkaline picrate resulting in the formation of a red colour, the intensity of which is measured at 505nm/green filter. Protein interference is eliminated using sodium lauryl sulphate. A second absorbance reading after acidifying with 30% acetic acid corrects for non-specific chromogens in the samples

Why is it important to check blood creatinine levels?
The kidneys maintain the blood creatinine in a normal range. Creatinine has been found to be a fairly reliable indicator of kidney function.
As the kidneys become impaired for any reason, the creatinine level in the blood will rise due to poor clearance by the kidneys. Abnormally high levels of creatinine thus warn of possible malfunction or failure of the kidneys. It is for this reason that standard blood tests routinely check the amount of creatinine in the blood. A more precise measure of the kidney function can be estimated by calculating how much creatinine is cleared from the body by the kidneys and it is referred to creatinine clearance.

What are "normal" blood creatinine levels?
Normal levels of creatinine in the blood are approximately 0.6 to 1.2 milligrams (mg) per deciliter (dl) in adult males and 0.5 to 1.1 milligrams per deciliter in adult females. (In the metric system, a milligram is a unit of weight equal to one-thousandth of a gram, and a deciliter is a unit of volume equal to one-tenth of a liter.)
Muscular young or middle-aged adults may have more creatinine in their blood than the norm for the general population. Elderly persons, on the other hand, may have less creatinine in their blood than the norm. Infants have normal levels of about 0.2 or more, depending on their muscle development. In people with malnutrition, severe weight loss, and long standing illnesses the muscle mass tends to diminish over time and, therefore, their creatinine level may be lower than expected for their age.
A person with only one kidney may have a normal level of about 1.8 or 1.9. Creatinine levels that reach 2.0 or more in babies and 10.0 or more in adults may indicate severe kidney impairment and the need for a dialysis machine to remove wastes from the blood.

What are the reasons for elevated blood creatinine?
Any condition that impairs the function of the kidneys will probably raise the creatinine level in the blood. It is important to recognize whether the process leading to kidney dysfunction (kidney failure, azotemia) is longstanding or recent.
The most common causes of longstanding kidney disease in adults are high blood pressure and diabetes mellitus. Certain drugs can sometimes cause abnormally elevated creatinine levels. Serum creatinine can also transiently rise after ingestion of large amount of dietary meat.

Are there any symptoms associated with elevated blood creatinine levels?
The symptoms of kidney dysfunction (renal insufficiency) vary widely. Some people may have a incidental finding of severe kidney disease and elevated creatinine on routine blood work without having any symptoms at all. In others, depending on the cause of problem, many different symptoms may be present including:
feeling dehydrated,
shortness of breath,
confusion, or
many other nonspecific symptoms.

Friday, November 19, 2010


The human immune system is a truly amazing constellation of responses to attacks from outside the body. It has many facets, a number of which can change to optimize the response to these unwanted intrusions. The system is remarkably effective, most of the time. This note will give you a brief outline of some of the processes involved.
An antigen is any substance that elicits an immune response, from a virus to a sliver.
The immune system has a series of dual natures, the most important of which is self/non-self recognition. The others are: general/specific, natural/adaptive = innate/acquired, cell-mediated/humoral, active/passive, primary/secondary. Parts of the immune system are antigen-specific (they recognize and act against particular antigens), systemic (not confined to the initial infection site, but work throughout the body), and have memory (recognize and mount an even stronger attack to the same antigen the next time).
Self/non-self recognition is achieved by having every cell display a marker based on the major histocompatibility complex (MHC). Any cell not displaying this marker is treated as non-self and attacked. The process is so effective that undigested proteins are treated as antigens.
Sometimes the process breaks down and the immune system attacks self-cells. This is the case of autoimmune diseases like multiple sclerosis, systemic lupus erythematosus, and some forms of arthritis and diabetes. There are cases where the immune response to innocuous substances is inappropriate. This is the case of allergies and the simple substance that elicits the response is called an allergen.

Fluid Systems of the Body
There are two main fluid systems in the body: blood and lymph. The blood and lymph systems are intertwined throughout the body and they are responsible for transporting the agents of the immune system.
The Blood System
The 5 liters of blood of a 70 kg (154 lb) person constitute about 7% of the body's total weight. The blood flows from the heart into arteries, then to capillaries, and returns to the heart through veins.
Blood is composed of 52–62% liquid plasma and 38–48% cells. The plasma is mostly water (91.5%) and acts as a solvent for transporting other materials (7% protein [consisting of albumins (54%), globulins (38%), fibrinogen (7%), and assorted other stuff (1%)] and 1.5% other stuff). Blood is slightly alkaline (pH = 7.40 ± .05) and a tad heavier than water (density = 1.057 ± .009).
All blood cells are manufactured by stem cells, which live mainly in the bone marrow, via a process called hematopoiesis. The stem cells produce hemocytoblasts that differentiate into the precursors for all the different types of blood cells. Hemocytoblasts mature into three types of blood cells: erythrocytes (red blood cells or RBCs),
leukocytes (white blood cells or WBCs), and thrombocytes (platelets).
The leukocytes are further subdivided into granulocytes (containing large granules in the cytoplasm) and agranulocytes (without granules). The granulocytes consist of neutrophils (55–70%), eosinophils (1–3%), and basophils (0.5–1.0%). The agranulocytes are lymphocytes (consisting of B cells and T cells) and monocytes. Lymphocytes circulate in the blood and lymph systems, and make their home in the lymphoid organs.
All of the major cells in the blood system are illustrated below.
There are 5000–10,000 WBCs per mm3 and they live 5-9 days. About 2,400,000 RBCs are produced each second and each lives for about 120 days (They migrate to the spleen to die. Once there, that organ scavenges usable proteins from their carcasses). A healthy male has about 5 million RBCs per mm3, whereas females have a bit fewer than 5 million.
Normal Adult Blood Cell Counts
Red Blood Cells













The goo on RBCs is responsible for the usual ABO blood grouping, among other things. The grouping is characterized by the presence or absence of A and/or B antigens on the surface of the RBCs. Blood type AB means both antigens are present and type O means both antigens are absent. Type A blood has A antigens and type B blood has B antigens.
Some of the blood, but not red blood cells (RBCs), is pushed through the capillaries into the interstitial fluid.

The Lymph System
Lymph is an alkaline (pH > 7.0) fluid that is usually clear, transparent, and colorless. It flows in the lymphatic vessels and bathes tissues and organs in its protective covering. There are no RBCs in lymph and it has a lower protein content than blood. Like blood, it is slightly heavier than water (density = 1.019 ± .003).
The lymph flows from the interstitial fluid through lymphatic vessels up to either the thoracic duct or right lymph duct, which terminate in the subclavian veins, where lymph is mixed into the blood. (The right lymph duct drains the right sides of the thorax, neck, and head, whereas the thoracic duct drains the rest of the body.) Lymph carries lipids and lipid-soluble vitamins absorbed from the gastrointestinal (GI) tract. Since there is no active pump in the lymph system, there is no back-pressure produced. The lymphatic vessels, like veins, have one-way valves that prevent backflow. Additionally, along these vessels there are small bean-shaped lymph nodes that serve as filters of the lymphatic fluid. It is in the lymph nodes where antigen is usually presented to the immune system.
The human lymphoid system has the following:
  • ·        primary organs: bone marrow (in the hollow center of bones) and the thymus gland (located behind the breastbone above the heart), and
  • ·        secondary organs at or near possible portals of entry for pathogens: adenoids, tonsils, spleen (located at the upper left of the abdomen), lymph nodes (along the lymphatic vessels with concentrations in the neck, armpits, abdomen, and groin), Peyer's patches (within the intestines), and the appendix.

Innate Immunity
The innate immunity system is what we are born with and it is nonspecific; all antigens are attacked pretty much equally. It is genetically based and we pass it on to our offspring.
Surface Barriers or Mucosal Immunity
  1. The first and, arguably, most important barrier is the skin. The skin cannot be penetrated by most organisms unless it already has an opening, such as a nick, scratch, or cut.
  2. Mechanically, pathogens are expelled from the lungs by ciliary action as the tiny hairs move in an upward motion; coughing and sneezing abruptly eject both living and nonliving things from the respiratory system; the flushing action of tears, saliva, and urine also force out pathogens, as does the sloughing off of skin.
  3. Sticky mucus in respiratory and gastrointestinal tracts traps many microorganisms.
  4. Acid pH (< 7.0) of skin secretions inhibits bacterial growth. Hair follicles secrete sebum that contains lactic acid and fatty acids both of which inhibit the growth of some pathogenic bacteria and fungi. Areas of the skin not covered with hair, such as the palms and soles of the feet, are most susceptible to fungal infections. Think athlete's foot.
  5. Saliva, tears, nasal secretions, and perspiration contain lysozyme, an enzyme that destroys Gram positive bacterial cell walls causing cell lysis. Vaginal secretions are also slightly acidic (after the onset of menses). Spermine and zinc in semen destroy some pathogens. Lactoperoxidase is a powerful enzyme found in mother's milk.
  6. The stomach is a formidable obstacle insofar as its mucosa secrete hydrochloric acid (0.9 < pH < 3.0, very acidic) and protein-digesting enzymes that kill many pathogens. The stomach can even destroy drugs and other chemicals.

Normal flora are the microbes, mostly bacteria, that live in and on the body with, usually, no harmful effects to us. We have about 1013 cells in our bodies and 1014 bacteria, most of which live in the large intestine. There are 103–104 microbes per cm2 on the skin (Staphylococcus aureus, Staph. epidermidis, diphtheroids, streptococci, Candida, etc.). Various bacteria live in the nose and mouth. Lactobacilli live in the stomach and small intestine. The upper intestine has about 104 bacteria per gram; the large bowel has 1011 per gram, of which 95–99% are anaerobes (An anaerobe is a microorganism that can live without oxygen, while an aerobe requires oxygen.) or bacteroides. The urogenitary tract is lightly colonized by various bacteria and diphtheroids. After puberty, the vagina is colonized by Lactobacillus aerophilus that ferment glycogen to maintain an acid pH.
Normal flora fill almost all of the available ecological niches in the body and produce bacteriocidins, defensins, cationic proteins, and lactoferrin all of which work to destroy other bacteria that compete for their niche in the body.
The resident bacteria can become problematic when they invade spaces in which they were not meant to be. As examples: (a) staphylococcus living on the skin can gain entry to the body through small cuts/nicks. (b) Some antibiotics, in particular clindamycin, kill some of the bacteria in our intestinal tract. This causes an overgrowth of Clostridium difficile, which results in pseudomembranous colitis, a rather painful condition wherein the inner lining of the intestine cracks and bleeds.
A phagocyte is a cell that attracts (by chemotaxis), adheres to, engulfs, and ingests foreign bodies. Promonocytes are made in the bone marrow, after which they are released into the blood and called circulating monocytes, which eventually mature into macrophages (meaning "big eaters", see below).

Some macrophages are concentrated in the lungs, liver (Kupffer cells), lining of the lymph nodes and spleen, brain microglia, kidney mesoangial cells, synovial A cells, and osteoclasts. They are long-lived, depend on mitochondria for energy, and are best at attacking dead cells and pathogens capable of living within cells. Once a macrophage phagocytizes a cell, it places some of its proteins, called epitopes, on its surface—much like a fighter plane displaying its hits. These surface markers serve as an alarm to other immune cells that then infer the form of the invader. All cells that do this are called antigen presenting cells (APCs).
The non-fixed or wandering macrophages roam the blood vessels and can even leave them to go to an infection site where they destroy dead tissue and pathogens. Emigration by squeezing through the capillary walls to the tissue is called diapedesis or extravasation. The presence of histamines at the infection site attract the cells to their source.
Natural killer cells move in the blood and lymph to lyse (cause to burst) cancer cells and virus-infected body cells. They are large granular lymphocytes that attach to the glycoproteins on the surfaces of infected cells and kill them.
Polymorphonuclear neutrophils, also called polys for short, are phagocytes that have no mitochondria and get their energy from stored glycogen. They are nondividing, short-lived (half-life of 6–8 hours, 1–4 day lifespan), and have a segmented nucleus. [The picture below shows the neutrophil phagocytizing bacteria, in yellow.] They constitute 50–75% of all leukocytes. The neutrophils provide the major defense against pyogenic (pus-forming) bacteria and are the first on the scene to fight infection. They are followed by the wandering macrophages about three to four hours later.

The complement system is a major triggered enzyme plasma system. It coats microbes with molecules that make them more susceptible to engulfment by phagocytes. Vascular permeability mediators increase the permeability of the capillaries to allow more plasma and complement fluid to flow to the site of infection. They also encourage polys to adhere to the walls of capillaries (margination) from which they can squeeze through in a matter of minutes to arrive at a damaged area. Once phagocytes do their job, they die and their "corpses," pockets of damaged tissue, and fluid form pus.
Eosinophils are attracted to cells coated with complement C3B, where they release major basic protein (MBP), cationic protein, perforins, and oxygen metabolites, all of which work together to burn holes in cells and helminths (worms). About 13% of the WBCs are eosinophils. Their lifespan is about 8–12 days. Neutrophils, eosinophils, and macrophages are all phagocytes.
Dendritic cells are covered with a maze of membranous processes that look like nerve cell dendrites. Most of them are highly efficient antigen presenting cells. There are four basic types: Langerhans cells, interstitial dendritic cells, interdigitating dendritic cells, and circulating dendritic cells. Our major concern will be Langerhans cells, which are found in the epidermis and mucous membranes, especially in the anal, vaginal, and oral cavities. These cells make a point of attracting antigen and efficiently presenting it to T helper cells for their activation. [This accounts, in part, for the transmission of HIV via sexual contact.]
Each of the cells in the innate immune system bind to antigen using pattern-recognition receptors. These receptors are encoded in the germ line of each person. This immunity is passed from generation to generation. Over the course of human development these receptors for pathogen-associated molecular patterns have evolved via natural selection to be specific to certain characteristics of broad classes of infectious organisms. There are several hundred of these receptors and they recognize patterns of bacterial lipopolysaccharide, peptidoglycan, bacterial DNA, dsRNA, and other substances. Clearly, they are set to target both Gram-negative and Gram-positive bacteria.

Adaptive or Acquired Immunity
Lymphocytes come in two major types: B cells and T cells. The peripheral blood contains 20–50% of circulating lymphocytes; the rest move in the lymph system. Roughly 80% of them are T cells, 15% B cells and remainder are null or undifferentiated cells. Lymphocytes constitute 20–40% of the body's WBCs. Their total mass is about the same as that of the brain or liver. (Heavy stuff!)
B cells are produced in the stem cells of the bone marrow; they produce antibody and oversee humoral immunity. T cells are nonantibody-producing lymphocytes which are also produced in the bone marrow but sensitized in the thymus and constitute the basis of cell-mediated immunity. The production of these cells is diagrammed below.
Parts of the immune system are changeable and can adapt to better attack the invading antigen. There are two fundamental adaptive mechanisms: cell-mediated immunity and humoral immunity.
 Cell-mediated immunity
Macrophages engulf antigens, process them internally, then display parts of them on their surface together with some of their own proteins. This sensitizes the T cells to recognize these antigens. All cells are coated with various substances. CD stands for cluster of differentiation and there are more than one hundred and sixty clusters, each of which is a different chemical molecule that coats the surface. CD8+ is read "CD8 positive." Every T and B cell has about 105 = 100,000 molecules on its surface. B cells are coated with CD21, CD35, CD40, and CD45 in addition to other non-CD molecules. T cells have CD2, CD3, CD4, CD28, CD45R, and other non-CD molecules on their surfaces.
The large number of molecules on the surfaces of lymphocytes allows huge variability in the forms of the receptors. They are produced with random configurations on their surfaces. There are some 1018 different structurally different receptors. Essentially, an antigen may find a near-perfect fit with a very small number of lymphocytes, perhaps as few as one.
T cells are primed in the thymus, where they undergo two selection processes. The first positive selection process weeds out only those T cells with the correct set of receptors that can recognize the MHC molecules responsible for self-recognition. Then a negative selection process begins whereby T cells that can recognize MHC molecules complexed with foreign peptides are allowed to pass out of the thymus.
Cytotoxic or killer T cells (CD8+) do their work by releasing lymphotoxins, which cause cell lysis. Helper T cells (CD4+) serve as managers, directing the immune response. They secrete chemicals called lymphokines that stimulate cytotoxic T cells and B cells to grow and divide, attract neutrophils, and enhance the ability of macrophages to engulf and destroy microbes. Suppressor T cells inhibit the production of cytotoxic T cells once they are unneeded, lest they cause more damage than necessary. Memory T cells are programmed to recognize and respond to a pathogen once it has invaded and been repelled.

Humoral immunity
An immunocompetent but as yet immature B-lymphocyte is stimulated to maturity when an antigen binds to its surface receptors and there is a T helper cell nearby (to release a cytokine). This sensitizes or primes the B cell and it undergoes clonal selection, which means it reproduces asexually by mitosis. Most of the family of clones become plasma cells. These cells, after an initial lag, produce highly specific antibodies at a rate of as many as 2000 molecules per second for four to five days. The other B cells become long-lived memory cells.
Antibodies, also called immunoglobulins or Igs [with molecular weights of 150–900 Md], constitute the gamma globulin part of the blood proteins. They are soluble proteins secreted by the plasma offspring (clones) of primed B cells. The antibodies inactivate antigens by, (a) complement fixation (proteins attach to antigen surface and cause holes to form, i.e., cell lysis), (b) neutralization (binding to specific sites to prevent attachment—this is the same as taking their parking space), (c) agglutination (clumping), (d) precipitation (forcing insolubility and settling out of solution), and other more arcane methods.
Constituents of gamma globulin are: IgG-76%, IgA-15%, IgM-8%, IgD-1%, and IgE-0.002% (responsible for autoimmune responses, such as allergies and diseases like arthritis, multiple sclerosis, and systemic lupus erythematosus). IgG is the only antibody that can cross the placental barrier to the fetus and it is responsible for the 3 to 6 month immune protection of newborns that is conferred by the mother.
IgM is the dominant antibody produced in primary immune responses, while IgG dominates in secondary immune responses. IgM is physically much larger than the other immunoglobulins.
Notice the many degrees of flexibility of the antibody molecule. This freedom of movement allows it to more easily conform to the nooks and crannies on an antigen. The upper part or Fab (antigen binding) portion of the antibody molecule (physically and not necessarily chemically) attaches to specific proteins [called epitopes] on the antigen. Thus antibody recognizes the epitope and not the entire antigen. The Fc region is crystallizable and is responsible for effector functions, i.e., the end to which immune cells can attach.
Lest you think that these are the only forms of antibody produced, you should realize that the B cells can produce as many as 1014 conformationally different forms.
The process by which T cells and B cells interact with antigens is summarized in the diagram below.

In the ABO blood typing system, when an A antigen is present (in a person of blood type A), the body produces an anti-B antibody, and similarly for a B antigen. The blood of someone of type AB, has both antigens, hence has neither antibody. Thus that person can be transfused with any type of blood, since there is no antibody to attack foreign blood antigens. A person of blood type O has neither antigen but both antibodies and cannot receive AB, A, or B type blood, but they can donate blood for use by anybody. If someone with blood type A received blood of type B, the body's anti-B antibodies would attack the new blood cells and death would be imminent.
All of these of these mechanisms hinge on the attachment of antigen and cell receptors. Since there are many, many receptor shapes available, WBCs seek to optimize the degree of confluence between the two receptors. The number of these "best fit" receptors may be quite small, even as few as a single cell. This attests to the specificity of the interaction. Nevertheless, cells can bind to receptors whose fit is less than optimal when required. This is referred to as cross-reactivity. Cross-reactivity has its limits. There are many receptors to which virions cannot possibly bind. Very few viruses can bind to skin cells.
The design of immunizing vaccines hinges on the specificity and cross-reactivity of these bonds. The more specific the bond, the more effective and long-lived the vaccine. The smallpox vaccine, which is made from the vaccinia virus that causes cowpox, is a very good match for the smallpox receptors. Hence, that vaccine is 100% effective and provides immunity for about 20 years. Vaccines for cholera have a relatively poor fit so they do not protect against all forms of the disease and protect for less than a year.
The goal of all vaccines is promote a primary immune reaction so that when the organism is again exposed to the antigen, a much stronger secondary immune response will be elicited. Any subsequent immune response to an antigen is called a secondary response and it has
    1. a shorter lag time,
    2. more rapid buildup,
    3. a higher overall level of response,
    4. a more specific or better "fit" to the invading antigen,
    5. utilizes IgG instead of the large multipurpose antibody IgM.

Immunity can be either natural or artificial, innate or acquired=adaptive, and either active or passive.
  • Active natural (contact with infection): develops slowly, is long term, and antigen specific.
  • Active artificial (immunization): develops slowly, lasts for several years, and is specific to the antigen for which the immunization was given.
  • Passive natural (transplacental = mother to child): develops immediately, is temporary, and affects all antigens to which the mother has immunity.
  • Passive artificial (injection of gamma globulin): develops immediately, is temporary, and affects all antigens to which the donor has immunity.

Know: antigen, overall properties of the immune system, allergen; major fluid systems of the body; hematopoiesis occurs in stem cells of the bone; erythrocytes, leukocytes, and thrombocytes; types of white blood cells; lymphoid system and lymph nodes; mucosal immunity and types of surface barriers to infection; normal flora; phagocytes, macrophages, antigen presenting cells, neutrophils, B cells and T cells are produced in the bone marrow and T cells are primed in the thymus, CD4+ and CD8+ cells, helper cells, memory cells, cytotoxic cells, suppressor cells; priming and clonal selection; antibody and Igs; differences between identifying self and non-self, innate and acquired immunity, primary and secondary immunity, active and passive immunity; specificity and cross-reactivity

SUBMITTED TO                                                                              SUBMITTED BY
DR.VASILI ASHOK                                                                          RV/2007-21
ASST.PROFESSOR                                                                          RV/2007-22
DEPT.OF VBC                                                                                 RV/2007-24