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Page 1: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Main problems of Main problems of clinical immunology clinical immunology and allergologyand allergology. . Principes of the Principes of the function of the immune function of the immune systemsystem.. Evaluation of Evaluation of the immune statethe immune state. .

Page 2: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

ASSESMENT OF THE ASSESMENT OF THE IMMUNE SYSTEMIMMUNE SYSTEM

Page 3: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

What is the immune What is the immune system?system? The body’s defense against The body’s defense against

disease causing organisms, disease causing organisms, malfunctioning cells, and foreign malfunctioning cells, and foreign particlesparticles

Page 4: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

ImmunityDefinition ;

It is a homeostatic condition in which the body maintains protection against infection and tumor growth.

Function – major defense against infectious organisms & abnormal or damaged cells

Defends against bacteria, viruses, fungi & parasitesRemoves & destroys damaged/dead cellsIdentifies & destroys malignant cells

Page 5: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Three Characteristics Three Characteristics Unique to the Immune Unique to the Immune SystemSystem

Self-regulationSelf-regulation SpecificitySpecificity MemoryMemory

Page 6: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Three Biological Three Biological Defense Mechanisms Defense Mechanisms That Protect the BodyThat Protect the Body First line of defense (anatomic/biochemical barrier)First line of defense (anatomic/biochemical barrier)

– Skin and mucous membranesSkin and mucous membranes Second line of defense (mechanical clearance)Second line of defense (mechanical clearance)

– Skin sloughing, respiratory cilia, and urinationSkin sloughing, respiratory cilia, and urination Third line of defense (immune response)Third line of defense (immune response)

– Long-lasting and sometimes permanent protectionLong-lasting and sometimes permanent protection– StructuresStructures

ThymusThymus Red bone marrowRed bone marrow SpleenSpleen Lymph nodes, vessels, and tissuesLymph nodes, vessels, and tissues SkinSkin

Page 7: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

The First Line of The First Line of DefenseDefense~Skin~~Skin~

- The dead, outer layer The dead, outer layer of skin, known as the of skin, known as the epidermisepidermis, forms a , forms a shield against shield against invaders and secretes invaders and secretes chemicals that kill chemicals that kill potential invaders potential invaders

- You shed between 40 You shed between 40 – 50 thousand skin – 50 thousand skin cells every day!cells every day!

Page 8: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Defensins (epithelium)

Figure 8.6

Page 9: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Progression of ImmunityProgression of Immunity

At least three cell types reside within or beneath the epithelium and induce inflammation in response to trauma or microbial products: Macrophages, Mast Cells, and Langerhan’s cells (a skin dendritic cell)

Page 10: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

- As you breathe in, As you breathe in, foreign particles and foreign particles and bacteria bump into bacteria bump into mucusmucus throughout throughout your respiratory your respiratory system and become system and become stuckstuck

- Hair-like structures Hair-like structures called called ciliacilia sweep sweep this mucus into the this mucus into the throat for coughing throat for coughing or swallowingor swallowing

The First Line of Defense~Mucus and Cilia~

Page 11: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

The First Line of Defense~Saliva~

What’s the first thing you do when What’s the first thing you do when you cut your finger?you cut your finger?

- Saliva contains many chemicals that break down bacteria

- Thousands of different types of bacteria can survive these chemicals, however

Page 12: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

- Swallowed bacteria are Swallowed bacteria are broken down by broken down by incredibly strong acids incredibly strong acids in the stomach that in the stomach that break down your foodbreak down your food

- The stomach must The stomach must produce a coating of produce a coating of special mucus or this special mucus or this acid would eat through acid would eat through the stomach!the stomach!

The First Line of Defense~Stomach Acid~

Page 13: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Escherichia coliEscherichia coliis common and plentiful in is common and plentiful in all of our digestive tracts. all of our digestive tracts.

- These bacteria are technically outside the body and aid in digesting material we cannot

- Only if E.Coli are introduced in an unnatural manner they can break through the first line of defense and harm us

Page 14: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

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DefensesDefenses Phagocytic immune Phagocytic immune

responseresponse

Humoral/antibody responseHumoral/antibody response

Cellular immune responseCellular immune response

Chemical ResponseChemical Response

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Chemical Immune Chemical Immune ResponseResponse

Histamine- source: Histamine- source: basophils, mast cells, basophils, mast cells, platelets platelets – causes vasodilation and causes vasodilation and vascular vascular

permeabilitypermeability

Kinins- source: Kinins- source: precursor factor from precursor factor from clotting systemclotting system– causes vasodilation and causes vasodilation and vascular vascular

permeability as well as pain receptors permeability as well as pain receptors stimulatedstimulated

Fibrinopeptides- source: Fibrinopeptides- source: activation of activation of clotting systemclotting system– vascular permeability and stimulates vascular permeability and stimulates

ChemotaxisChemotaxis

Prostaglandins/leukotrienes- source: Prostaglandins/leukotrienes- source: substances synthesized from the substances synthesized from the phospholipids of cell membranes of most phospholipids of cell membranes of most body tissuesbody tissues vascular permeability and stimulates vascular permeability and stimulates

ChemotaxisChemotaxis

Page 16: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

ComplementComplement

Consists of approx 25 enzymes that work with antibodies to help with Consists of approx 25 enzymes that work with antibodies to help with puncturing bacterial cell walls to destroy (during humoral response)puncturing bacterial cell walls to destroy (during humoral response)

Circulating plasma proteins, know as complement, are made in the liver Circulating plasma proteins, know as complement, are made in the liver and are activated when an antibody connects with and antigen.and are activated when an antibody connects with and antigen.

Complement SystemComplement System Three major physiologic functionsThree major physiologic functions

– Defending the body against bacterial infectionDefending the body against bacterial infection– Bridging natural and acquired immunityBridging natural and acquired immunity– Disposing of immune complexes and the byproducts associated with Disposing of immune complexes and the byproducts associated with

inflammationinflammation

The proteins that comprise the complement system interact sequentiallyThe proteins that comprise the complement system interact sequentially

Three ways to active:Three ways to active:– Classic pathwayClassic pathway– Alternative pathwayAlternative pathway– Lectin pathwayLectin pathway

Page 17: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Fig 7.27 Parham

Complement pathways

Page 18: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

- Virus-infected Virus-infected body cells body cells release release interferoninterferon when when an invasion an invasion occursoccurs

~Interferon~~Interferon~

Page 19: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Effects on viralgrowth

Improved recognitionby adaptive immunity

Increased innate immune activity

Effects of interferon

Fig 8.7

Page 20: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Blood CellsBlood Cells

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Development of Cells of the Development of Cells of the Immune SystemImmune System

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Phagocytic Immune Phagocytic Immune ResponseResponse

WBC’s (leukocytes) participate in both, natural WBC’s (leukocytes) participate in both, natural and acquired immunityand acquired immunity

Granulocytes (granular leukocytes) release Granulocytes (granular leukocytes) release mediators (such as histamine, bradykinin mediators (such as histamine, bradykinin and prostaglandins) and engulf antigen and prostaglandins) and engulf antigen

(include neutrophils, eosinophils and (include neutrophils, eosinophils and basophils)basophils)

Neutrophils- first cells to arrive on sceneNeutrophils- first cells to arrive on scene

– Nongranular leukocytes Nongranular leukocytes Monocytes or macrophages (called Monocytes or macrophages (called

Histiocytes when they enter the tissue Histiocytes when they enter the tissue spaces)- ingest and destroy greater number spaces)- ingest and destroy greater number of foreign bodies/toxins that granulocytes of foreign bodies/toxins that granulocytes do.do.

Page 23: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

PhagocytesPhagocytes

Produced throughout life by the Produced throughout life by the bone marrow.bone marrow.

Scavengers – remove dead cells Scavengers – remove dead cells and microorganisms.and microorganisms.

Page 24: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Circulating and Tissue Effector Cells

Neutrophils - Early phagocytosis and killing of microbes

Mast Cells - Release of inflammatory granules

Macrophages - Efficient phagocytosis and killing of microbes: cytokines

Eosinophils - Nasty toxic cells designed to kill helminths (worms)

Natural killer (NK) cells - Lysis of infected cells, activation of macrophages

Page 25: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state
Page 26: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

~White Blood Cells~ Neutrophil~White Blood Cells~ Neutrophil

- If invaders actually get If invaders actually get withinwithin the body, then the body, then your white blood cells your white blood cells (WBCs) begin their (WBCs) begin their attackattack

- WBCs normally WBCs normally circulate throughout circulate throughout the blood, but will enter the blood, but will enter the body’s tissues if the body’s tissues if invaders are detectedinvaders are detected

Page 27: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

NeutrophilsNeutrophils

60% of WBCs60% of WBCs ‘‘Patrol tissues’ as they squeeze out of Patrol tissues’ as they squeeze out of

the capillaries.the capillaries. Large numbers are released during Large numbers are released during

infectionsinfections Short lived – die after digesting bacteriaShort lived – die after digesting bacteria Dead neutrophils make up a large Dead neutrophils make up a large

proportion of puss.proportion of puss.

Page 28: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

LPS receptor:

CD14

toll-like receptor-4

CR3,4:

Complement (C’) receptors (C3b)

Scavenger receptor:

sialic acid-bearing protein

Mannose receptor:

Binds mannose on bacteria, activates C’

Glycan receptor:

Polysaccharides

Figure 8.8

Page 29: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Effective against worm infections. Granules contain mediators-smooth muscle contraction and worm toxicity

Express some of the same receptors found on macrophages. These cells are specialized in killing and swallowing microbes

Figure 1.6ef

Page 30: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Mast cells are also found in the tissues

Mast cells can release histamines which induce inflammation

Redness, swelling(erythema, edema)

Neutrophils and monocytes are recruited

Figure 1.14

TNF

Page 31: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

- Injured body cells Injured body cells release chemicals called release chemicals called histamineshistamines, which , which begin begin inflammatory inflammatory responseresponse

- Capillaries dilateCapillaries dilate- Pyrogens released, reach Pyrogens released, reach

hypothalamus, and hypothalamus, and temperature risestemperature rises

- Pain receptors activatePain receptors activate- WBCs flock to infected WBCs flock to infected

area like sharks to bloodarea like sharks to blood

BasophilBasophil~The Inflammatory Response~~The Inflammatory Response~

Page 32: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Function in disease, not entirely understood

Contains high affinity receptors for IgE, and preformed granules that contain inflammatory mediators including: histamine; heparin; TNF; chondroitin sulfate; neutral proteases; and other.

Mast cells can also secrete: cytokines to induce inflammation; chemokines to induce infiltration by monocytes, and neutrophils, leukotriences to induce muscle contraction and increase vascular permeability

Mast cells are capable of inducing an inflammatory cascade

Figure 1.6gh

Page 33: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

MacrophagesMacrophages

Larger than neutrophils.Larger than neutrophils. Found in the organs, not the blood.Found in the organs, not the blood. Made in bone marrow as Made in bone marrow as monocytesmonocytes, ,

called macrophages once they reach called macrophages once they reach organs.organs.

Long livedLong lived InitiateInitiate immune responses as they immune responses as they

display antigens from the pathogens display antigens from the pathogens to the lymphocytes.to the lymphocytes.

Page 34: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Alveolar macrophages (lung) Histiocytes (connective tissue) Kupffer cells (liver) Mesangial cells (kidney) Microglial cells (brain)Tissue macrophage

Figure 1.6ij

Macrophages are important first responders to infection and tissue damage.

Page 35: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Receptors on Macrophages:

LPS receptor-CD14

Toll-like receptors

Fc receptors

Mannose receptor

Complement receptors

IFN receptor

Chemokine receptors

Figure 1.13Macrophages phagocytose and degrade foreign particles,bacteria and dead (and dying) host cells.

Page 36: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

PhagocytosisPhagocytosis

Page 37: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

MacrophagesMacrophages

Page 38: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

PhagocytosisPhagocytosis

If cells are under attack they release If cells are under attack they release histamine.histamine. Histamine plus chemicals from pathogens mean Histamine plus chemicals from pathogens mean

neutrophilsneutrophils are attracted to the site of attack. are attracted to the site of attack. Pathogens are attached to antibodies and Pathogens are attached to antibodies and

neutrophils have neutrophils have antibody receptorsantibody receptors.. Enodcytosis of neutrophil membrane Enodcytosis of neutrophil membrane

phagocytic vacuole.phagocytic vacuole. Lysosomes attach to phagocytic vacuole Lysosomes attach to phagocytic vacuole

pathogen digested by proteasespathogen digested by proteases

Page 39: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

White Blood CellsWhite Blood Cells~T-Cells~~T-Cells~

T-Cells, often called T-Cells, often called “natural killer” cells, “natural killer” cells, recognize infected recognize infected human cells and human cells and cancer cellscancer cells

T-cells will attack these T-cells will attack these infected cells, quickly infected cells, quickly kill them, and then kill them, and then continue to search for continue to search for more cells to kill more cells to kill

Page 40: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Figure 1.6cd

Natural Killer Cells play several interesting roles in the immune system. One is to monitor cells for identification. If a cell doesn’t reveal its identity papers, it is killed.

Dendritic cells are the most important antigen presenting cells (APCs) in the immune system

Page 41: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Two Divisions of the Two Divisions of the Immune SystemImmune System- The efforts of the WBCs known as The efforts of the WBCs known as

phagocytes and T-cells is called phagocytes and T-cells is called the the cell-mediated immune cell-mediated immune system.system.

- Protective factor = living cellsProtective factor = living cells- Phagocytes – eat invadersPhagocytes – eat invaders- T-cells – kill invadersT-cells – kill invaders

Page 42: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

The other half of the immune The other half of the immune system is called antibody-system is called antibody-mediated immunity, meaning that mediated immunity, meaning that is controlled by antibodiesis controlled by antibodies

This represents the third line of This represents the third line of defense in the immune systemdefense in the immune system

Two Divisions of the Two Divisions of the Immune SystemImmune System

Page 43: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Cellular Components of Cellular Components of Immune ResponseImmune Response

LymphocytesLymphocytes– Primary cells concerned with the Primary cells concerned with the

development of immunitydevelopment of immunity– Have the ability of self-recognition, Have the ability of self-recognition,

specificity, and memoryspecificity, and memory– Two types Two types

B lymphocytes (B cells) (humoral immune B lymphocytes (B cells) (humoral immune response)response)

T lymphocytes (T cells) (cell-mediated T lymphocytes (T cells) (cell-mediated immune response)immune response)

Page 44: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Cell-Mediated Immune Cell-Mediated Immune ResponseResponse When presented with an antigen, When presented with an antigen,

helper T cells produce signaling helper T cells produce signaling substances such as interferon, substances such as interferon, interleukin, and tumor necrosis interleukin, and tumor necrosis factorfactor

Inflammation and other body Inflammation and other body activities are promotedactivities are promoted

Page 45: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

LymphocytesLymphocytes

Produce antibodiesProduce antibodies B-cellsB-cells mature in mature in bone marrowbone marrow then then

concentrate in lymph nodes and spleenconcentrate in lymph nodes and spleen T-cellsT-cells mature in mature in thymusthymus B and T cells mature then circulate in B and T cells mature then circulate in

the blood and lymphthe blood and lymph Circulation ensures they come into Circulation ensures they come into

contact with pathogens and each othercontact with pathogens and each other

Page 46: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

T-LymphocytesT-Lymphocytes

Mature T-cells have T cell receptors Mature T-cells have T cell receptors which have a very similar structure which have a very similar structure to antibodies and are specific to 1 to antibodies and are specific to 1 antigen.antigen.

They are activated when the They are activated when the receptor comes into contact with the receptor comes into contact with the Ag with another host cell (e.g. on a Ag with another host cell (e.g. on a macrophage membrane or an macrophage membrane or an invaded body cell)invaded body cell)

Page 47: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Cell-Mediated Immune Cell-Mediated Immune ResponseResponse

Comprised of a variety of T cellsComprised of a variety of T cells Th (helper T)Th (helper T)

– Exhibits TCR receptorsExhibits TCR receptors– CD (clusters of differentiation) markersCD (clusters of differentiation) markers– Interacts with macrophage antigen-presenting Interacts with macrophage antigen-presenting

cell (APC)cell (APC)– Causes binding of entire Th to antigenCauses binding of entire Th to antigen– Produces signaling substancesProduces signaling substances

Interleukins, interferon, and tumor necrosis factorInterleukins, interferon, and tumor necrosis factor

– Tc and B cells (and others) stimulatedTc and B cells (and others) stimulated

Page 48: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Lymphocytes are entirely involved with acquired immunity. These come in two types: T lymphocytes (T cells) that differentiate in the thymus and B lymphocytes or B cells that differentiate in the bone marrow.

B cells can further differentiate after antigen-activation to plasma cells that produce antibodies

Page 49: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Humoral Immune Humoral Immune ResponseResponse Initiated when an antigen binds Initiated when an antigen binds

with the antibody receptors on with the antibody receptors on the surface of the mature B cell the surface of the mature B cell

Triggers a sequence of events Triggers a sequence of events that results in production of that results in production of plasma cells that secrete plasma cells that secrete antibodies (immunoglobulin antibodies (immunoglobulin molecules)molecules)

Page 50: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

T-LymphocytesT-Lymphocytes

After activation the cell divides to form:After activation the cell divides to form: T-helper cellsT-helper cells – secrete CYTOKINES – secrete CYTOKINES help B cells dividehelp B cells divide stimulate macrophagesstimulate macrophages Cytotoxic T cellsCytotoxic T cells (killer T cells) (killer T cells) Kill body cells displaying antigenKill body cells displaying antigen Memory T cellsMemory T cells remain in bodyremain in body

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Page 52: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Humoral Immune Humoral Immune ResponseResponse PrimaryPrimary

– First exposure to antigenFirst exposure to antigen– Latent periodLatent period

SecondarySecondary– Rapid production of large amounts Rapid production of large amounts

of antibodiesof antibodies– Immediate response; may last for Immediate response; may last for

several yearsseveral years

Page 53: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Humoral Immune Humoral Immune ResponseResponse Comprised of B cellsComprised of B cells

– Assisted in the beginning by Th cellsAssisted in the beginning by Th cells Plasma cells are produced and Plasma cells are produced and

secrete antigen-specific secrete antigen-specific antibodiesantibodies

Memory cellsMemory cells– Long livesLong lives– React swiftly to specific antibodiesReact swiftly to specific antibodies

Page 54: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

B -LymphocytesB -Lymphocytes

There are near 10 million different There are near 10 million different B-lymphocytes, each of them B-lymphocytes, each of them produces a different antibody.produces a different antibody.

The huge variety is caused by The huge variety is caused by genes coding for abs changing genes coding for abs changing slightly during development.slightly during development.

There are a small group of clones There are a small group of clones of each type of B-lymphocyteof each type of B-lymphocyte

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LymphocytesLymphocytes B lymphocytes mature in the bone marrow; T B lymphocytes mature in the bone marrow; T

lymphocytes mature in the thymus where they also lymphocytes mature in the thymus where they also differentiate into cells with various functionsdifferentiate into cells with various functions

Page 56: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

B -LymphocytesB -Lymphocytes

At the clone stage antibodies do not At the clone stage antibodies do not leave the B-cells.leave the B-cells.

The abs are embedded in the plasma The abs are embedded in the plasma membrane of the cell and are membrane of the cell and are

called antibody receptors.called antibody receptors. When the receptors in the membrane When the receptors in the membrane

recognise and antigen on the surface of recognise and antigen on the surface of the pathogen the B-cell divides rapidly.the pathogen the B-cell divides rapidly.

The antigens are presented to the B-The antigens are presented to the B-cells by cells by macrophagesmacrophages

Page 57: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

B -LymphocytesB -Lymphocytes

Some activated B cells Some activated B cells PLASMA PLASMA CELLSCELLS these produce lots of these produce lots of antibodies, antibodies,

The antibodies travel to the blood, The antibodies travel to the blood, lymph, lining of gut and lungs.lymph, lining of gut and lungs.

The number of plasma cells goes down The number of plasma cells goes down after a few weeksafter a few weeks

Antibodies stay in the blood longer but Antibodies stay in the blood longer but eventually their numbers go down too.eventually their numbers go down too.

Page 58: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

B -LymphocytesB -Lymphocytes

Page 59: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

- Most infections never Most infections never make it past the first and make it past the first and second levels of defensesecond levels of defense

- Those that do trigger the Those that do trigger the production and release of production and release of antibodiesantibodies

- Proteins that latch onto, Proteins that latch onto, damage, clump, and slow damage, clump, and slow foreign particlesforeign particles

- Each antibody binds only to Each antibody binds only to one specific binding site, one specific binding site, known as an known as an antigenantigen

The Third Line of The Third Line of DefenseDefense~Antibodies~~Antibodies~

Page 60: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Antibody ProductionAntibody Production

- WBCs gobble up invading WBCs gobble up invading particles and break them particles and break them upup

- They show the particle They show the particle pieces to T-cells, who pieces to T-cells, who identify the pieces and identify the pieces and find specific B-cells to help find specific B-cells to help

- B-cells produce antibodies B-cells produce antibodies that are equipped to find that are equipped to find that specific piece on a that specific piece on a new particle and attachnew particle and attach

Page 61: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

AntibodiesAntibodies Also known as Also known as immunoglobulinsimmunoglobulins Globular glycoproteinsGlobular glycoproteins The heavy and light chains are polypeptidesThe heavy and light chains are polypeptides The chains are held together by disulphide The chains are held together by disulphide

bridgesbridges Each ab has 2 identical ag binding sites – Each ab has 2 identical ag binding sites –

variable regions.variable regions. The order of amino acids in the variable The order of amino acids in the variable

region determines the shape of the binding region determines the shape of the binding sitesite

Page 62: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

How Abs workHow Abs work

Some act as Some act as labelslabels to identify to identify

antigens for phagocytesantigens for phagocytes Some work as Some work as antitoxinsantitoxins i.e. they block toxins for i.e. they block toxins for

e.g. those causing diphtheria and tetanuse.g. those causing diphtheria and tetanus Some attach to bacterial flagella making them Some attach to bacterial flagella making them

less active and easier for phagocytes to engulfless active and easier for phagocytes to engulf Some cause Some cause agglutination (clumping together)agglutination (clumping together) of of

bacteria making them less likely to spreadbacteria making them less likely to spread

Page 63: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Humoral Immune Humoral Immune ResponseResponse Five classes of immunoglobins Five classes of immunoglobins

(MADGE is acronym to aid (MADGE is acronym to aid memory)memory)– IgMIgM– IgAIgA– IgDIgD– IgGIgG– IgEIgE

Page 64: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Different Different ImmunoglobulinsImmunoglobulins

Page 65: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

Five types of IgFive types of Ig

IgA, IgG and IgM respond to IgA, IgG and IgM respond to viral and bacterial invasion.viral and bacterial invasion.

IgD may assist in B cell IgD may assist in B cell binding with antigenbinding with antigen

IgE is present during IgE is present during inflammatory responses and inflammatory responses and causes allergic response causes allergic response

Page 66: Main problems of clinical immunology and allergology. Principes of the function of the immune system. Evaluation of the immune state

TypeType Number Number of ag of ag binding binding sitessites

Site of actionSite of action FunctionsFunctions

IgGIgG 22 BloodBloodTissue fluidTissue fluidCAN CROSS CAN CROSS PLACENTAPLACENTA

Increase Increase macrophage macrophage activityactivityAntitoxinsAntitoxinsAgglutinationAgglutination

IgMIgM 1010 BloodBloodTissue fluidTissue fluid

AgglutinationAgglutination

IgAIgA 2 or 42 or 4 Secretions (saliva, Secretions (saliva, tears, small tears, small intestine, vaginal, intestine, vaginal, prostate, nasal, prostate, nasal, breast milk)breast milk)

Stop bacteria Stop bacteria adhering to host adhering to host cellscellsPrevents Prevents bacteria forming bacteria forming colonies on colonies on mucous mucous membranesmembranes

IgEIgE 22 TissuesTissues Activate mast Activate mast cellscells

HISTAMINEHISTAMINEWorm responseWorm response

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Role of AntibodiesRole of Antibodies Agglutination- (clumping of antigens)Agglutination- (clumping of antigens)

– Helps clear the body of the invading organism by Helps clear the body of the invading organism by facilitating phagocytosisfacilitating phagocytosis

Opsonization- the antigen-antibody molecule is Opsonization- the antigen-antibody molecule is coated with a sticky substance to facilitate coated with a sticky substance to facilitate phagocytosisphagocytosis

Promote release of vasoactive substances; activation Promote release of vasoactive substances; activation of complement system and phagocytosisof complement system and phagocytosis

Act in concert with other components of the immune Act in concert with other components of the immune systemsystem

Types of immunoglobulins: IgA, IgD, IgE,IgG, and IgMTypes of immunoglobulins: IgA, IgD, IgE,IgG, and IgM

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Immune FunctionImmune Function

Natural immunity:Natural immunity: nonspecific response to any nonspecific response to any foreign invader foreign invader – White blood cell action: release cell mediators White blood cell action: release cell mediators

such as histamine, bradykinin, and prostaglandins, such as histamine, bradykinin, and prostaglandins, and engulf (phagocytize) foreign substancesand engulf (phagocytize) foreign substances

– Inflammatory responseInflammatory response– Physical barriers, such as intact skin, chemical Physical barriers, such as intact skin, chemical

barriers, and acidic gastric secretions or enzymes barriers, and acidic gastric secretions or enzymes in tears and salivain tears and saliva

Acquired immunityAcquired immunity: specific against a foreign : specific against a foreign antigenantigen– Result of prior exposure to an antigen Result of prior exposure to an antigen – Active or passiveActive or passive

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Types of Immune Types of Immune ResponseResponse Cell-Mediated – occurs when antigen Cell-Mediated – occurs when antigen

lives within the body cell (bacteria, lives within the body cell (bacteria, virus, fungus, cancer) virus, fungus, cancer)

Macrophages identify antigen & T cells Macrophages identify antigen & T cells (killer T’s, cytoxic cells) & defend (killer T’s, cytoxic cells) & defend against it. against it.

Delayed response- graft rejection, Delayed response- graft rejection, hypersensitivity reactions, tumor hypersensitivity reactions, tumor immunity, immunity against bacteria, immunity, immunity against bacteria, virus & fungusvirus & fungus

Antigen specific – Antigen must be Antigen specific – Antigen must be present on cell surfacepresent on cell surface

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What is immunity?What is immunity?

- Resistance to a disease causing Resistance to a disease causing organism or harmful substanceorganism or harmful substance

- Two typesTwo types- Active ImmunityActive Immunity- Passive ImmunityPassive Immunity

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Passive ImmunityPassive Immunity

You You don’tdon’t produce produce the antibodiesthe antibodies– A mother will pass A mother will pass

immunities on to her immunities on to her baby during pregnancy baby during pregnancy

– These antibodies will These antibodies will protect the baby for a protect the baby for a short period of time short period of time following birth while its following birth while its immune system immune system develops. develops.

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Variables That Affect Variables That Affect Immune System Function Immune System Function

Age and genderAge and gender NutritionNutrition

Presence of conditions and disorders: cancer/neoplasm, chronic Presence of conditions and disorders: cancer/neoplasm, chronic illness, autoimmune disorders, surgery/traumaillness, autoimmune disorders, surgery/trauma

AllergiesAllergies History of infection and immunizationHistory of infection and immunization Genetic factorsGenetic factors LifestyleLifestyle Medications and transfusions: see Table 50-6Medications and transfusions: see Table 50-6 Pyschoneuroimmunologic factorsPyschoneuroimmunologic factors

ALTERED IMMUNE RESPONSESALTERED IMMUNE RESPONSES ImmunoincompetanceImmunoincompetance

– Severe infection, immunodeficiency diseases, malignancySevere infection, immunodeficiency diseases, malignancy Overactive SystemOveractive System

– hypersensitivitieshypersensitivities

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Health History and Physical Health History and Physical Examination: Key AssessmentsExamination: Key Assessments

Disorders and diseasesDisorders and diseases– Autoimmune diseaseAutoimmune disease– Neoplastic diseaseNeoplastic disease– Chronic illnessChronic illness– SurgerySurgery

PainPain MedicationMedication Blood transfusionsBlood transfusions Lifestyle, stress, and other factorsLifestyle, stress, and other factors AgeAge NutritionNutrition Recent infectionsRecent infections Immunization statusImmunization status AllergiesAllergies Weight changes, skin lesion, rashes, or impaired healing.Weight changes, skin lesion, rashes, or impaired healing. Activity intolerance, frequent sore throats, URI, swollen glands, easy Activity intolerance, frequent sore throats, URI, swollen glands, easy

brusing, joint pain, swelling, enlarged lymph nodes.brusing, joint pain, swelling, enlarged lymph nodes. Acute: erythema, local heat, pain Acute: erythema, local heat, pain

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Assessment – chronic Assessment – chronic allergyallergy Skin – rashes, itchingSkin – rashes, itching – – conjunctivitis, dark circles under conjunctivitis, dark circles under

eyes, excessive rubbing/ blinking, eyes, excessive rubbing/ blinking, recurrent ear infection, recurrent ear infection, diminished hearing, nasal voice diminished hearing, nasal voice rhinitis, pale, swollen mucous rhinitis, pale, swollen mucous membranes, throat clearing, membranes, throat clearing, swollen lips/ tongue, enlarged swollen lips/ tongue, enlarged lymph nodeslymph nodes

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Tests to Evaluate Immune Tests to Evaluate Immune FunctionFunction WBC count and differentialWBC count and differential

– Bone marrow release more neutrophils, Bone marrow release more neutrophils, may release “bands” which are may release “bands” which are immature cells to keep up. “shift to the immature cells to keep up. “shift to the left” means acute bacteria infection. left” means acute bacteria infection. (mature neutrophils=segmented (mature neutrophils=segmented neutrophils)neutrophils)

Bone marrow biopsyBone marrow biopsy Phagocytic cell function testPhagocytic cell function test Complement component testsComplement component tests Hypersensitivity testsHypersensitivity tests Specific antigen–antibody testsSpecific antigen–antibody tests HIV infection testsHIV infection tests