Innate Immune System

                                                               Abel Goa, Sunday, November 18, 2012
                                                               Power Point Presentation: Elective in Immunology
                                                               Topic: Innate Immune System

Innate Immune System

• Prevents entry of microorganism into tissues
• Once they gain entry, eliminates them prior to the occurrence of disease
• Nonspecific
• Fast! Occurs within minutes of pathogen recognition
• Does not generate immunologic memory

Function of Innate Immune System

• Acting as a physical and chemical barrier to infectious agents
• Recruiting immune cells to sites of infection, through the production of chemical factors, including specialized chemical mediators, called cytokines
• Activation of the complement cascade to identify bacteria, activate cells and to promote clearance of dead cells or antibody complexes
• The identification and removal of foreign substances present in organs, tissues, the blood and lymph, by specialized white blood cells
• Activation of the adaptive immune system through a process known as antigen presentation

Relationship of Innate Immune System to Adaptive Immune System

Defensive Barriers

Innate immunity can be seen to comprise of four types of defensive barriers

o Anatomic

o Physiologic

o Phagocytic/Endocytic

o Inflammatory

Anatomical Barrier

The skin consists of two distinct layers: a thinner outer layer—the epidermis—and a thicker inner layer—the dermis

• Epidermis: Epithelial surface impermeable to most infectious agents 
• The dermis: Sebaceous gland produce an oily secretion called sebum. Sebum consists of lactic acid and fatty acids, which maintain the pH of the skin between 3 and 5; this pH inhibits the growth of most microorganisms

Mucous membrane lines the conjunctivae and the alimentary, respiratory, and urogenital tracts.
Although many pathogens enter the body by binding to and penetrating mucous membranes, a number of nonspecific defense mechanisms tend to prevent this entry

• Saliva 
• Tears 
• Mucous secretion

Other properties of mucous membrane in dealing with pathogens

• Cilia: Synchronous movement of cilia propels mucus-entrapped microorganisms out of the lower respiratory tract 
• Peristalsis: Helps to remove infectious agent from the GIT 
• Normal flora: Generally out-compete pathogens for attachment sites and for necessary nutrients

Physiologic Barrier

Physiologic barriers that contribute to innate immunity

• Temperature, e.g. in many species of animals, their normal body temperature can inhibit growth of pathogens 
• pH, e.g. gastric acid-very few organism can survive the low pH of the stomach content 
• Various soluble and cell associate molecule

Various soluble and cell mediated molecule

• Lysozymes: a hydrolytic enzyme found in mucous secretions and in tears, is able to cleave the peptidoglycan layer of the bacterial cell wall 
• Alpha-defensins: anti-fungal peptides (intestinal tract) 
• Beta-defensins: anti-microbial peptides (respiratory, urogenital tract) 
• Surfactant-A and D proteins: opsonize pathogens for enhanced phagocytosis (lung)
• Interferon: a group of proteins produced by virus-infected cells. Inhibits viral replication and activates other cells which kill the pathogen 
• Complement: a group of about 25 serum proteins that circulate in an inactive state. Once activated, they either destroy pathogens directly or facilitating their clearance 
• Transferin and Lactoferin deprive microorganism of iron 
• Fibronectin coats (opsonizes) bacteria and promote their rapid phagocytosis 
• Toll like receptors- recognise microbial molecules, signals cells to secrete immunostimulatory cytokine

Phagocytic Barrier 

Another important innate defense mechanism is the ingestion of extracellular particulate material by phagocytosis

• Internalization of pathogen into phagosome 
• Fusion of phagosome with lysosomes that contain anti-microbial compounds (lysozyme) 
• This may be sufficient to kill the pathogen 
• If not, reactive oxygen and nitrogen species may need to be generated

Source: Image from Kuby Immunology Textbook

Leukocyte Player of the Innate Immune System

Source: Unknown

Inflamatory Response

• Inflammation is one of the first responses of the immune system to infection or irritation 
• Inflammation is stimulated by chemical factors released by injured cells and serves to establish a physical barrier against the spread of infection, and to promote healing of any damaged tissue following the clearance of pathogens 
• The end result of inflammation may be the marshalling of a specific immune response to the invasion or clearance of the invader by components of the innate immune system
• Initiated by cells already present in all tissues, mainly resident macrophages, dendritic cells, histiocytes, Kupffer cells and mastocytes. These cells present on their surfaces certain receptors named pattern recognition receptors(PRRs), which recognise molecules that are broadly shared by pathogens but distinguishable from host molecules, collectively referred to as pathogen-associated molecular patterns (PAMPs) 
• At the onset of an infection, burn, or other injuries, these cells undergo activation (one of their PRR recognize a PAMP) and release inflammatory mediators responsible for the clinical signs of inflammation
• 5 signs of Inflammation 
o rubor (redness),
o tumor (swelling),
o calor (heat), and
o dolor (pain).
o functio laesa (loss of function)

• The cardinal signs of inflammation reflect the three major events of an inflammatory response

1. Vasodilation—an increase in the diameter of blood vessels—of nearby capillaries occurs as the vessels that carry blood away from the affected area constrict, resulting in engorgement of the capillary network
2. An increase in capillary permeability facilitates an influx of fluid and cells from the engorged capillaries into the tissue. Accumulation of exudate contributes to tissue swelling
3. Influx of phagocytes from the capillaries into the tissues is facilitated by the increased permeability of the capillaries. Their migration through the tissue to the site of the invasion is called chemotaxis

• As phagocytic cells accumulate at the site and begin to phagocytose bacteria, they release lytic enzymes, which can damage nearby healthy cells. The accumulation of dead cells, digested material, and fluid forms pus
• The events in the inflammatory response are initiated by a complex series of events involving a variety of chemical mediators whose interactions are only partly understood

Source: Image from Kuby Immunology Textbook

Among the chemical mediators released in response to tissue damage are various serum proteins called acute-phase proteins

• C-reactive protein is a major acute-phase protein. C-reactive protein binds to the C-polysaccharide cell-wall component found on a variety of bacteria and fungi. This binding activates the complement system, resulting in increased clearance of the pathogen either by complement-mediated lysis or by a complement mediated increase in phagocytosis

Chemical factors produced during inflammation (histamine, bradykinin, serotonin, leukotrienes, and prostaglandins) sensitize pain receptors, cause vasodilatation of the blood vessels at the scene, and attract phagocytes, especially neutrophils. Neutrophils then trigger other parts of the immune system by releasing factors that summon other leukocytes and lymphocytes. Cytokines produced by macrophages and other cells of the innate immune system mediate the inflammatory response. These cytokines include TNF, HMGB1, and IL-1

Enzymes of blood clothing system

• These enzymes activate an enzyme cascade that results in the deposition of insoluble strands of fibrin, which is the main component of a blood clot. The fibrin strands wall off the injured area from the rest of the body and serve to prevent the spread of infection 
• Once the inflammatory response has subsided and most of the debris has been cleared away by phagocytic cells, tissue repair and regeneration of new tissue begins

Reference

Kuby Immunology Textbook

Note: Lost my references. Kuby Immunology Textbook is the only book I can remember (Not sure who the authors or any other details about the book)

Xanthoma and Xanthelasma

Abel Goa, Saturday, November 17, 2012

Xanthelasma

Xanthelasma (or xanthelasma palpebrum) is a sharply demarcated yellowish deposit of cholesterol underneath the skin, usually on or around the eyelids. Although not harmful or painful, this minor growth may be disfiguring and can be removed. They are common in people of Asian origin and those from Mediterranean origin.

Because of the hereditary component, they may or may not indicate high blood levels of cholesterol. Where there is no family history of xanthelasma, they usually indicate high cholesterol and may correlate with a risk of atheromatous disease.

A xanthelasma may instead be referred to as a xanthoma when becoming larger and nodular, assuming timorous proportions. Still, xanthelasma is often classified simply as a subtype of xanthoma.

ASSOCIATION     

• Familial hypercholesterolem
• Primary biliary cirrhosis 
• Menopaus
• Diabetes

TREATMENT

Xanthelasma can be removed with a trichloroacetic acid peal, surgery, laser vaporization, electrodesiccation or cryotherapy (application of extreme cold to destroy abnormal or diseased tissue). Removal can cause scaring and pigment changes, but it is usually after treatment with trichloroacetic acid.

Xanthoma

Xanthomas are skin lesions caused by the accumulation of fats in macrophage immune cells in the skin and more rarely in the layer of fat under the skin.

Some types of xanthoma are indicative of lipid metabolism disorders (e.g. hyperlipidaemia or high blood fats), where they may be associated with increased risk of coronary artery heart disease and occasionally with pancreatitis.

TYPES

• Xanthomas are classified in the following types based on where they are found on the body and how they develop.
• Xanthelasma palpebrum – characterized by deposition of cholesterol underneath the skin, usually on or around the eyelids
• Xanthoma tendinosum – characterized by papules and nodules found in the tendons of hand, feet, and Achilles
• Eruptive xanthoma – characterized by small yellowish-orange to reddish-brown papules that appear all over the body
• Palmar xanthoma – characterized by yellowish plaques that involve the palms and the flexural surface of the fingers
• Tuberoeruptive xanthoma – characterized by red papules and nodules that appear inflamed and tend to coalesce
• Plane xanthomas – lesions are flat papules or patches that can occur anywhere on the body
• Diffuse plane xanthomatosis – associated with an abnormal antibody in the blood called a paraprotein. Presents with large flat reddish-yellow plaques over the face, neck, chest, buttocks and in skin folds (such as the armpits and groin)
• Xanthoma disseminatum – xanthoma like lesion due to a rare form of hystiocytosis. The skin lesions usually consist of hundreds of yellowish-brown bumps, which are usually spread on both side of the trunk. They may particularly affect the armpit and groin

ASSOCIATION

•      Certain cancers
•        Diabetes
•        Hyperlipidaemia
•        Familial hypercholesterolaemia
• ·     Primary biliary cirrhosis

TREATMENT

The main aim of treatment for xanthomas that are associated with an underlining lipid disorder is to identify and treat the lipid disorder. In many cases, treating the underlining disorder will reduce or resolve the xanthomas. In addition, treating the hyperlipidaemia will reduce the risk of heart disease, and treating hypertriglyceridaemia will prevent pancreatitis. Dietary and lifestyle modification with or without medication are used to treat lipid disorder.

Dietary measure should include:

•         Prepare most food from vegetables, salads, cereals and fish
•         Minimize saturated fats (found in meat, butter, other dairy product, coconut oil, palm oil)
•         Minimize intake of simple refine sugars found in fizzy drinks, sweets, biscuits and cakes
•         If obese or overweight, aim to slowly reduce weight by reducing caloric intake and increasing exercise

Effective medication may also be prescribed. This may include: statins (HMG CoA reductase inhibitors, such as simvastatin and atoravastin, reduce cholesterol production by the liver), fibrates (such as bezafibrate, may be added to reduce triglyceride production by the liver), Ezetimibe (reduces cholesterol absorption from gut) may be added in high risk patient or if higher doses of statin are poorly tolerated, nicotinic acid (lowers cholesterol and triglyceride).

Surgery or locally destructive modalities can be used to remove xanthomas that do not resolve spontaneously or with treatment of the underlining cause.

                                                              Images

                                                                                                                                                 

Reference

Dermnetnz.org by Mobify. [Online]. Available: Http://www.dermnetnz.mobify.me [2012, August 6]

Xanthelasma – Wikipedia, the free encyclopedia. [Online]. Available: http://en.m.wikipedia.org [2012, August 6]

Xanthoma – Wikipedia, the free encyclopedia. [Online]. Available: http://en.m.wikipedia.org [2012, August 6]

The Normal Blood Pressure

Abel Goa, Saturday, November 17, 2012

Classification of Blood Pressure for Adults, 18 years of age and older

The optimal blood pressure is < 120 mm Hg systolic and <80 mm Hg diastolic The normal blood pressure is <130 mm Hg systolic and <85 mm Hg diastolic Hypertension: Mild is 140 – 159 mm Hg systolic and 90 – 99 mm Hg  diastolic Moderate 160 – 179 mm Hg systolic and 100 – 109 mm Hg diastolic Severe ≥ 180 mm Hg systolic and ≥ 110 mm Hg Diastolic

                                                                                    From: SAM-CD connected; Scientific America, 2002.

Blood pressure is the tension of the blood within the systemic arteries, maintained by the contraction of the left ventricle, the resistance of the arterioles and capillaries’, the elasticity of the arterial walls, as well as the viscosity and volume of the blood; expressed as relative to the ambient atmospheric pressure. Blood pressure normally rises as you age and grow.

Experts consider the normal blood pressure to be less than 120/80 mm Hg. At one point, blood pressure at or above 120/80 and less than 140/90 was considered normal to high; these numbers are now considered pre – hypertensive.

Normal blood pressure readings for children are lower than for adults, while blood pressure for adult and teenagers are similar.

In children height has a significant effect; taller kids have higher blood pressure. So a normal blood pressure range for children accounts for age, height and gender.

Children’s Normal Blood Pressure Range:

•          3 – 5 years; upper limit systolic 104 – 116, upper limit diastolic 63 – 74
•          6 – 9 years; upper limit systolic 108 – 121, upper limit diastolic 71 – 81
•         10 – 12 years; upper limit systolic 114 – 127, upper limit diastolic 77 – 83

How is Blood Pressure measured?

Blood pressure is measured using a stethoscope and a sphygmomanometer, which contains a rubber cuff to wrap around the upper arm and a pump to inflate it with air. When inflated, pressure stops the blood flow for a moment. Then as air is release from the cuff, the blood flow starts up again. A stethoscope is placed over the arm to listen for the sound of blood pulsing through the arteries. The first sound of rushing blood refers to systolic pressure; once the sound fades, the second number indicates the diastolic pressure.

Convenient wrist model sphygmomanometers are available. The wrist one is probably the simplest. A firm cuff slips around the wrist; a small visual display unit is opened, and the button pressed. Within about one minute, the systolic and diastolic readings show up in large clear figures on the screen followed by the pulse rate.

Blood pressure is measured in mm Hg and recorded with the systolic number first, followed by the diastolic number.  Systolic blood pressure refers to the pressure inside the arteries when the heart is pumping; diastolic pressure is the pressure inside the arteries when the heart is resting between beats.

Blood pressure reading can be affected by factors like:

• Smoking
• Coffee or other caffeine drink
• A full bladder
• Recent physical activity

Blood pressure is also affected by emotional state and the time of the day. Since so many factors can affect blood pressure readings, blood pressure should be taken several times to get an accurate measurement.

Since high blood pressure can exist without any symptoms, it is important to know your numbers.  Getting your blood pressure checked is quick, painless, and one of the most important things you can do to better your health.

Reference

Goss, V.H., 2011. Normal Blood Pressure Range for Children. [Online]

Available: http://www.everydayhealth.com [2012, June 27]

Illiades, C. How is Blood Pressure Measured and What do the Numbers Mean? [Online].

 Available: http://www.livestrong.com [2012, June 27]

Wright, J. 2005. Family Medical Care, Vol. 3, Signs Publishing Company, Victoria, Australia, 7^th Ed., pp. 57.