How to Understand and Use the Nutrition Facts Label

• The Nutrition Facts Panel - An Overview
• The Serving Size
• Calories (and Calories from Fat)
• The Nutrients: How Much?
• Understanding the Footnote
• How the Daily Values (DV) Relate to the %DVs
• The Percent Daily Value (%DV)
• Quick Guide to %DV
• Nutrients With a %DV but No Weight Listed - Spotlight on Calcium
• Nutrients Without a %DV: Trans Fats, Protein, and Sugars

People look at food labels for different reasons. But whatever the reason, many consumers would like to know how to use this information more effectively and easily. The following label-building skills are intended to make it easier for you to use nutrition labels to make quick, informed food choices that contribute to a healthy diet.

The Nutrition Facts Label - An Overview:

The information in the main or top section (see #1-4 and #6 on the sample nutrition label below), can vary with each food product; it contains product-specific information (serving size, calories, and nutrient information). The bottom part (see #5 on the sample label below) contains a footnote with Daily Values (DVs) for 2,000 and 2,500 calorie diets. This footnote provides recommended dietary information for important nutrients, including fats, sodium and fiber. The footnote is found only on larger packages and does not change from product to product.

In the following Nutrition Facts label we have colored certain sections to help you focus on those areas that will be explained in detail. You will not see these colors on the food labels on products you purchase.

The Serving Size

(#1 on sample label):

The first place to start when you look at the Nutrition Facts label is the serving size and the number of servings in the package. Serving sizes are standardized to make it easier to compare similar foods; they are provided in familiar units, such as cups or pieces, followed by the metric amount, e.g., the number of grams.

The size of the serving on the food package influences the number of calories and all the nutrient amounts listed on the top part of the label. Pay attention to the serving size, especially how many servings there are in the food package. Then ask yourself, "How many servings am I consuming"? (e.g., 1/2 serving, 1 serving, or more) In the sample label, one serving of macaroni and cheese equals one cup. If you ate the whole package, you would eat two cups. That doubles the calories and other nutrient numbers, including the %Daily Values as shown in the sample label.

Example
	Single Serving	%DV		Double Serving	%DV
Serving Size	1 cup (228g)			2 cups (456g)
Calories	250			500
Calories from Fat	110			220
Total Fat	12g	18%		24g	36%
Trans Fat	1.5g			3g
Saturated Fat	3g	15%		6g	30%
Cholesterol	30mg	10%		60mg	20%
Sodium	470mg	20%		940mg	40%
Total Carbohydrate	31g	10%		62g	20%
Dietary Fiber	0g	0%		0g	0%
Sugars	5g			10g
Protein	5g			10g
Vitamin A		4%			8%
Vitamin C		2%			4%
Calcium		20%			40%
Iron		4%			8%

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Calories (and Calories from Fat)

Calories provide a measure of how much energy you get from a serving of this food. Many Americans consume more calories than they need without meeting recommended intakes for a number of nutrients. The calorie section of the label can help you manage your weight (i.e., gain, lose, or maintain.) Remember: the number of servings you consume determines the number of calories you actually eat (your portion amount).

(#2 on sample label):

In the example, there are 250 calories in one serving of this macaroni and cheese. How many calories from fat are there in ONE serving? Answer: 110 calories, which means almost half the calories in a single serving come from fat. What if you ate the whole package content? Then, you would consume two servings, or 500 calories, and 220 would come from fat.

General Guide to Calories

• 40 Calories is low
• 100 Calories is moderate
• 400 Calories or more is high
  

The General Guide to Calories provides a general reference for calories when you look at a Nutrition Facts label. This guide is based on a 2,000 calorie diet.

Eating too many calories per day is linked to overweight and obesity.

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The Nutrients: How Much?

(#3 and 4 on sample label):
Look at the top of the nutrient section in the sample label. It shows you some key nutrients that impact on your health and separates them into two main groups:

Limit These Nutrients

(#3 on sample label):

The nutrients listed first are the ones Americans generally eat in adequate amounts, or even too much. They are identified in yellow as Limit these Nutrients. Eating too much fat, saturated fat, trans fat, cholesterol, or sodium may increase your risk of certain chronic diseases, like heart disease, some cancers, or high blood pressure.

Important: Health experts recommend that you keep your intake of saturated fat, trans fat and cholesterol as low as possible as part of a nutritionally balanced diet.

Get Enough of These

(#4 on sample label):

Most Americans don't get enough dietary fiber, vitamin A, vitamin C, calcium, and iron in their diets. They are identified in blue as Get Enough of these Nutrients. Eating enough of these nutrients can improve your health and help reduce the risk of some diseases and conditions. For example, getting enough calcium may reduce the risk of osteoporosis, a condition that results in brittle bones as one ages (see calcium section below). Eating a diet high in dietary fiber promotes healthy bowel function. Additionally, a diet rich in fruits, vegetables, and grain products that contain dietary fiber, particularly soluble fiber, and low in saturated fat and cholesterol may reduce the risk of heart disease.

Remember: You can use the Nutrition Facts label not only to help limit those nutrients you want to cut back on but also to increase those nutrients you need to consume in greater amounts.

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Understanding the Footnote on the Bottom of the Nutrition Facts Label

(#5 on sample label)

Note the * used after the heading "%Daily Value" on the Nutrition Facts label. It refers to the Footnote in the lower part of the nutrition label, which tells you "%DVs are based on a 2,000 calorie diet". This statement must be on all food labels. But the remaining information in the full footnote may not be on the package if the size of the label is too small. When the full footnote does appear, it will always be the same. It doesn't change from product to product, because it shows recommended dietary advice for all Americans--it is not about a specific food product.

Look at the amounts circled in red in the footnote--these are the Daily Values (DV) for each nutrient listed and are based on public health experts' advice. DVs are recommended levels of intakes. DVs in the footnote are based on a 2,000 or 2,500 calorie diet. Note how the DVs for some nutrients change, while others (for cholesterol and sodium) remain the same for both calorie amounts.

How the Daily Values Relate to the %DVs

Look at the example below for another way to see how the Daily Values (DVs) relate to the %DVs and dietary guidance. For each nutrient listed there is a DV, a %DV, and dietary advice or a goal. If you follow this dietary advice, you will stay within public health experts' recommended upper or lower limits for the nutrients listed, based on a 2,000 calorie daily diet.

Examples of DVs versus %DVs
Based on a 2,000 Calorie Diet

Nutrient	DV	%DV	Goal
Total Fat	65g	= 100%DV	Less than
Sat Fat	20g	= 100%DV	Less than
Cholesterol	300mg	= 100%DV	Less than
Sodium	2400mg	= 100%DV	Less than
Total Carbohydrate	300g	= 100%DV	At least
Dietary Fiber	25g	= 100%DV	At least

Upper Limit - Eat "Less than"...

The nutrients that have "upper daily limits" are listed first on the footnote of larger labels and on the example above. Upper limits means it is recommended that you stay below - eat "less than" - the Daily Value nutrient amounts listed per day. For example, the DV for Saturated fat (in the yellow section) is 20g. This amount is 100% DV for this nutrient. What is the goal or dietary advice? To eat "less than" 20 g or 100%DV for the day.<

Lower Limit - Eat "At least"...

Now look at the section in blue where dietary fiber is listed. The DV for dietary fiber is 25g, which is 100% DV. This means it is recommended that you eat "at least" this amount of dietary fiber per day.

The DV for Total Carbohydrate (section in white) is 300g or 100%DV. This amount is recommended for a balanced daily diet that is based on 2,000 calories, but can vary, depending on your daily intake of fat and protein.

Now let's look at the %DVs.

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The Percent Daily Value (%DV):

The % Daily Values (%DVs) are based on the Daily Value recommendations for key nutrients but only for a 2,000 calorie daily diet--not 2,500 calories. You, like most people, may not know how many calories you consume in a day. But you can still use the %DV as a frame of reference whether or not you consume more or less than 2,000 calories.

The %DV helps you determine if a serving of food is high or low in a nutrient. Note: a few nutrients, like trans fat, do not have a %DV--they will be discussed later.

Do you need to know how to calculate percentages to use the %DV? No, the label (the %DV) does the math for you. It helps you interpret the numbers (grams and milligrams) by putting them all on the same scale for the day (0-100%DV). The %DV column doesn't add up vertically to 100%. Instead each nutrient is based on 100% of the daily requirements for that nutrient (for a 2,000 calorie diet). This way you can tell high from low and know which nutrients contribute a lot, or a little, to your daily recommended allowance (upper or lower).

Quick Guide to %DV:

5%DV or less is low and 20%DV or more is high
(#6 on sample label):
This guide tells you that 5%DV or less is low for all nutrients, those you want to limit (e.g., fat, saturated fat, cholesterol, and sodium), or for those that you want to consume in greater amounts (fiber, calcium, etc). As the Quick Guide shows, 20%DV or more is high for all nutrients.

Example: Look at the amount of Total Fat in one serving listed on the sample nutrition label. Is 18%DV contributing a lot or a little to your fat limit of 100% DV? Check the Quick Guide to %DV. 18%DV, which is below 20%DV, is not yet high, but what if you ate the whole package (two servings)? You would double that amount, eating 36% of your daily allowance for Total Fat. Coming from just one food, that amount leaves you with 64% of your fat allowance (100%-36%=64%) for all of the other foods you eat that day, snacks and drinks included.

1 serving
2 servings

Using the %DV for:

Comparisons: The %DV also makes it easy for you to make comparisons. You can compare one product or brand to a similar product. Just make sure the serving sizes are similar, especially the weight (e.g. gram, milligram, ounces) of each product. It's easy to see which foods are higher or lower in nutrients because the serving sizes are generally consistent for similar types of foods, (see the comparison example at the end) except in a few cases like cereals.

Nutrient Content Claims: Use the %DV to help you quickly distinguish one claim from another, such as "reduced fat" vs. "light" or "nonfat." Just compare the %DVs for Total Fat in each food product to see which one is higher or lower in that nutrient--there is no need to memorize definitions. This works when comparing all nutrient content claims, e.g., less, light, low, free, more, high, etc.

Dietary Trade-Offs: You can use the %DV to help you make dietary trade-offs with other foods throughout the day. You don't have to give up a favorite food to eat a healthy diet. When a food you like is high in fat, balance it with foods that are low in fat at other times of the day. Also, pay attention to how much you eat so that the total amount of fat for the day stays below 100%DV.

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Nutrients With a %DV but No Weight Listed - Spotlight on Calcium:

Calcium: Look at the %DV for calcium on food packages so you know how much one serving contributes to the total amount you need per day. Remember, a food with 20%DV or more contributes a lot of calcium to your daily total, while one with 5%DV or less contributes a little.

Experts advise adult consumers to consume adequate amounts of calcium, that is, 1,000mg or 100%DV in a daily 2,000 calorie diet. This advice is often given in milligrams (mg), but the Nutrition Facts label only lists a %DV for calcium.

For certain populations, they advise that adolescents, especially girls, consume 1,300mg (130%DV) and post-menopausal women consume 1,200mg (120%DV) of calcium daily. The DV for calcium on food labels is 1,000mg.

Don't be fooled -- always check the label for calcium because you can't make assumptions about the amount of calcium in specific food categories. Example: the amount of calcium in milk, whether skim or whole, is generally the same per serving, whereas the amount of calcium in the same size yogurt container (8oz) can vary from 20-45 %DV.

Equivalencies

30% DV = 300mg calcium = one cup of milk

100% DV = 1,000mg calcium

130% DV = 1,300mg calcium

Nutrients Without a %DV: Trans Fats, Protein, and Sugars:

Note that Trans fat, Sugars and, Protein do not list a %DV on the Nutrition Facts label.

Plain Yogurt

Fruit Yogurt

Trans Fat: Experts could not provide a reference value for trans fat nor any other information that FDA believes is sufficient to establish a Daily Value or %DV. Scientific reports link trans fat (and saturated fat) with raising blood LDL ("bad") cholesterol levels, both of which increase your risk of coronary heart disease, a leading cause of death in the US.

Important: Health experts recommend that you keep your intake of saturated fat, trans fat and cholesterol as low as possible as part of a nutritionally balanced diet.

Protein: A %DV is required to be listed if a claim is made for protein, such as "high in protein". Otherwise, unless the food is meant for use by infants and children under 4 years old, none is needed. Current scientific evidence indicates that protein intake is not a public health concern for adults and children over 4 years of age.

Sugars: No daily reference value has been established for sugars because no recommendations have been made for the total amount to eat in a day. Keep in mind, the sugars listed on the Nutrition Facts label include naturally occurring sugars (like those in fruit and milk) as well as those added to a food or drink. Check the ingredient list for specifics on added sugars.

Take a look at the Nutrition Facts label for the two yogurt examples. The plain yogurt on the left has 10g of sugars, while the fruit yogurt on the right has 44g of sugars in one serving.

Now look below at the ingredient lists for the two yogurts. Ingredients are listed in descending order of weight (from most to least). Note that no added sugars or sweeteners are in the list of ingredients for the plain yogurt, yet 10g of sugars were listed on the Nutrition Facts label. This is because there are no added sugars in plain yogurt, only naturally occurring sugars (lactose in the milk).

Plain Yogurt - contains no added sugars

Fruit Yogurt - contains added sugars

If you are concerned about your intake of sugars, make sure that added sugars are not listed as one of the first few ingredients. Other names for added sugars include: corn syrup, high-fructose corn syrup, fruit juice concentrate, maltose, dextrose, sucrose, honey, and maple syrup.

To limit nutrients that have no %DV, like trans fat and sugars, compare the labels of similar products and choose the food with the lowest amount.

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Comparison Example

Below are two kinds of milk- one is "Reduced Fat," the other is "Nonfat" milk. Each serving size is one cup. Which has more calories and more saturated fat? Which one has more calcium?
REDUCED FAT MILK 2% Milkfat	NONFAT MILK

Immune System

Introduction

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		5.0*106/mm3
Platelets		2.5*105/mm3
Leukocytes		7.3*103/mm3
	Neutrophil		50-70%
	Lymphocyte		20-40%
	Monocyte		1-6%
	Eosinophil		1-3%
	Basophil		<1%

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 (<>
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 <>

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.

Summary

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.

Objectives 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.

Source: uhaweb.hartford.edu