Immunoserology Notes Comprehensive PDF

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HISTORY OF IMMUNOLOGYIMMUNE SYSTEM Composed of special cells, protein, tissues and organs that protect against germs and microorganisms Defends our body against invaders, such as viruses, bacteria and foreign bodies IMMUNITY The condition of being resistant to infection IMMUNE RESPONSE The reaction ...

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HISTORY OF IMMUNOLOGY IMMUNE SYSTEM -

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Composed of special cells, protein, tissues and organs that protect against germs and microorganisms Defends our body against invaders, such as viruses, bacteria and foreign bodies

1000 A.D 1500’s -

IMMUNITY -

The condition of being resistant to infection

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IMMUNE RESPONSE -

The reaction of the cells and fluids of the body to the presence of a substance which is not recognized as a constituent of the body itself

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IMMUNOLOGY -

Study of a host’s reactions when foreign substances are introduced into the body

The narrowness of the range of substances with which an antibody or other agent acts or is effective

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MEMORY -

Ability to remember; powers of recall

PHAGOCYTOSIS -

The ingestion of bacteria or other material by phagocytes and amoeboid protozoans

HISTORY 430 B.C. -

Thucydides “immune” status Plague

Chinese develop a practice to produce protection against this dreaded disease by using powdered smallpox crusts inserted with a pin into the skin This exposes an individual to material from smallpox lesions Discouraged because some die Variolation o Method use to immunize an individual against smallpox (variola) with material taken from a patient or a recently varioated/infected individual

1700’s

SPECIFICITY -

Smallpox virus Chinese practiced immunization Inhalation of the powder scabs of smallpox (Variolation) Inoculation

An English scientist observed that milkmaids who were exposed to cowpox had apparent immunity to smallpox Edward Jenner (1798) o Relationship between exposure to cowpox and immunity to smallpox o Cross Immunity- phenomenon in which exposure to one agent produces protection against another agent o Vaccination – procedure of injecting cellular material; “vacca”- Latin word for cow

VARIOLATION -

Method of immunization where administration of LIVE VIRUSES takes place against viral infectious agent

VACCINATION -

Method of immunization where administration of an ATTENUATED VIRUS takes place against a viral infectious agent

1862 -

HAECKEL- discovered phagocytosis- the ingestion of bacteria or other material by phagocytes and a amoeboid protozoans

Louis Pasteur

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Von Behring & Kitasata -

Humoral theory of immunity proposed

1891 Koch

18080-1881

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1890

Key figure in both development of Microbiology and Immunology Live, attenuated chick cholera and anthrax vaccines Development of the Germ theory of furthered the advancement of the fledging science of immunology FATHER OF IMMUNOLOGY Invented attenuated vaccines Attenuation – a pathogenic organism or vaccine reduced in virulence Germ Theory – most diseases are caused by microorganisms, transmitted from an infected individual to a noninfected one Immunization protects people against disease by exposing them to a version of a microbe that is harmless but is just enough like the disease-causing organism or pathogen, that the immune system learns to fight it

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Development of cutaneous (delayedtype) hypersensitivity

1900 Ehrlich -

Antibody formation theory

1902 Portier & Richet -

Immediate-hypersensitivity anaphylaxis

1903 Arthus -

Arthus reaction of intermediate hypersensitivity

1938 Marrack -

Hypothesis of antigen-antibody binding

1944 -

Hypothesis of allograft rejection

1949 Salk & Sabin -

Development of polio vaccine

1883-1900’s Metchnikoff

1951 Reed

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Discovers cellular immunity through phagocytosis

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Vaccine against yellow fever

1953 -

CELLS AND FUNCTION OF IMMUNE SYSTEM Graft-versus-host-reaction

1957

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Burnet -

Neutrophil

Clonal selection theory

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1957- Interferon 1958-1962 -

Human leukocyte antigens (HLAs) Clonal selection theory

Eosinophil -

1964-1968 -

T-cell and B-cell cooperation in immune response

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Kohler -

First monoclonal antibodies

1986

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Th1 versus Th2 model of T helper cell function

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1996-1998 -

Identification of Toll-like receptors

2001- FOXP3, the gene directing regulatory T cell development 2005

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Development of human papilloma virus vaccine

Resembles basophils but they are connective tissue cells of mesenchymal origin Widely distributed throughout the body and are larger than basophils, with a small round nucleus and more granules

Dendritic Cell

Frazer -

Large phagocytic cell found in stationary form in the tissues or as a mobile white blood cells, especially at sites of infection

Mast Cell Monoclonal hepatitis B vaccine

Mosmann -

Similar in appearance and function with mast cell Alkali loving granules Responsible for inflammatory reactions

Macrophage

1985-1987- Identification of genes for T-cell receptor

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Having acidophilic granules attracting eosin and has affinity for acid dyes Responsible for fighting multicellular parasites

Basophil

1972- Identification of antibody molecule 1975

Most abundant type of granulocytes Help fight infection by ingesting microorganisms Plays a key role in the front-line defense against invading pathogens

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Covered with long membrane extensions that make them resemble nerve cell dendrites Phagocytose antigen and present it to help T lymphocytes Most potent antigen presenting cell

Natural Killer Cell -

A lymphocyte able to bind to certain tumor cells and virus-infected cells without the stimulation of antigens, and kill them by the insertion of granules containing perforin

T Regulatory Cell -

Known as suppressor T cells Type of immune cell that suppresses potentially harmful actions of autoreactive T helper cells

Helper T Cell -

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Influences or controls the differentiation or activity of other cells of the immune system Referred to as CD4+ T cells and expresses an antigen on MHC Class II

Cytotoxic T Cell -

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Referred to as CD8+ T cells Cytotoxic against tumor cells and host cells infected with intracellular pathogens Destroy any cell that expresses MHC Class I complex

PRINCIPAL FUNCTION OF CELLS • • •

Specific recognition of antigens Capture of antigens for display to lymphocytes Elimination of antigens

FUNCTION OF IMMUNOLOGY Recognize self from nonself -

Nonself substances o Ranging from life-threatening infectious microorganisms to a lifesaving organ transplantation

Defense against infections -

Deficient immunity results in increased susceptibility to infections Vaccinations boosts immune defences and protects against infections

Defense against tumors -

Potential for immunotherapy of cancer

Can injure cells and induce phatologic inflammation -

Immune responses are the cause of allergic, autoimmune and other inflammatory diseases

B Cell -

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A lymphocyte not processed by the thymus gland, and responsible for producing antibodies Fight bacteria and viruses by making Yshaped proteins called antibodies

Plasma Cell -

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A fully differentiated B-lymphocyte (white blood cell) which produces a single type of antibody Short-lived antibody-producing cell derived from B cell

Recognizes and responds to tissue grafts and newly introduced proteins -

Immune responses are barriers to transplantation and gene therapy

FUNCTION OF IMMUNOLOGY • • •

Defending the body against infections Recognizing and responding to foreign antigens Defending the body against the development of tumors

CONSEQUENCES OF IMMUNITY

o o o o o

DESIRABLE • • •

Natural resistance Recovery Acquired resistance

UNDESIRABLE • • •

Allergy Rejection Autoimmune Disorder (the body’s own tissues are attacked as if they were foreign)

Complement Properdin Interferon Tumor necrosis factor Betalysin

Adaptive Immunity -

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Third line of defense o B cells o Immunoglobulins o T cells o Antibodies Cell mediates and Humoral

INNATE AND ADAPTIVE IMMUNE RESPONSE BODY LINE OF DEFENSES IMMUNITY -

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External Defense System o Structural barriers o Unbroken Skin o Secretions o Cilia Internal Defense System o cells o soluble factors

Competitive exclusion -

normal flora that often keeps pathogens from establishing themselves in these areas

INNATE IMMUNITY -

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First line of Defense o Unbroken skin o Normal flora o Mucosal membranes o Secretions Second line of defense o Phagocytes o Fever o Inflammation o Antimicrobial resistance

IMMUNITY -

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The condition of being resistant to infection Innate Immunity o Native or natural o Resist infection by means of normally present body functions Adaptive imunity o Acquired or specific o Remember prior exposure, increase response upon repeated exposure

NATURAL Present at birth For structures shared by groups of microbes Limited diversity No memory Lysozyme, complement, defensins, APRs, interferon Neutrophils, eosinophils,basophils, mast cells, NK cells, monocytes macrophages

ADAPTIVE Not present at birth For specific antigens of Microbial and nonmicrobial agents High diversity Has memory Immunoglobulis

Lymphocytes (except NK cells)

Toll-like receptors (TLR): pattern recognition receptors that recognize PAMPS

Memory cells: activated B and T cells; subsequent exposure to a previously encountered antigen results to a stronger, quicker immune response

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PATHOGEN ASSOCIATED MOLECULAR PATTERN -

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Molecules associated with groups of pathogens that are recognized by cells of the innate immune system Repeating molecular patterns Absent in humans B-glucan, polysaccharide, peptidoglycan, nucleic acid segment

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PATTERN RECOGNITION RECEPTORS -

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Receptors that recognize PAMPs Secreted PRRs o Complement cascade o Opsonisation o Phagocytosis Cell Surface Receptors o Release of cytokines o Phagocytosis receptors Toll-like receptors o Expression of cytokine genes o TLR-1 (gram +) o TLR-2 (gram -) o TNF-alpha o IL-1 o Chemokines

HUMORAL-MEDIATED IMMUNITY -

CELL-MEDIATED IMMUNITY AND HUMORALMEDIATED IMMUNITY HISTORY -

Late 1800s, ELLIE METCHNIKOFFphagocytosis(scavenger cells)

1903, ALMONTH WRIGHT- opsonins (antibodies) HUMORAL IMMUNITY is mediated by proteins called antibodies, which are produced by cells called B LYMPHOCYTES; nonspecific factors called acute-phase reactants Defense against such intracellular microbes is called cell-mediated immunity; it is mediated by T LYMPHOCYTES HUMORAL IMMUNITY o B lymphocytes secrete antibodies that eliminate extracellular microbes CELL-MEDIATED IMMUNITY o Different types of T lymphocytes recruit and activate phagocytes to destroy ingested microbes and kill infected cells

These serum factor include specific proteins known as antibodies and nonspecific factors called acut-phase reactants that increase nonspecifically in any infection o C-reactive protein o Serum amyloid A o Complement components o Mannose-binding protein o Alpha1-antitrypsin o Haptoglobin o Fibrinogen o Ceruloplasmin ACUTE-PHASE REACTANTS o Cytokines o Hepatocytes (liver parenchymal cells) o Acute-phase reactants C-Reactive Protein o Most widely used indicator of acute inflammation

Capable of opsonisation (coating of foreign particles), agglutination, precipitation and activated complement by the classical pathway o Elevated levels= bacterial infections, rheumatic fever, viral infections, malignant diseases, tuberculosis and after a heart attack o Noninvasive means of following the course of malignancy and organ transplant, rise in the level mean a return of the malignancy or organ rejection o Response time= 6-10 HR o Normal cxn. = 0.5 o Increase= 1000x Serum Amyloid A o Associated with HDL cholesterol and it is thought to play a role in metabolism of cholesterol o Removing cholesterol from cholesterol-filled macrophages at the site of tissue injury = cleaning up the area o Recycling of cell membrane cholesterol and phospholipids for reuse in building membranes of new cells required during acute inflammation o Increase levels= bacterial infections o Response Time= 24 HR o Normal cxn.= 3.0 o Increase= 1000x Complement o Series of serum proteins that are normally present and whose overall function is mediation of inflammation o Opsonisation, chemotaxis and lysis of cells

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Classical cascade – nine proteins that are activated by bound antibodies o Classical pathway, alternate pathway and Lectin Pathway o Response Time= 48-72 HR o Normal cxn. = 60-140 o Increase= 2x Mannose-Binding Protein o Mannose binding lectin o Activates the complement cascade and helps to promote phagocytosis o Opsonin recognize foreign carbohydrates such as mannose and several other sugars found primarily on bacteria, some yeasts, viruses and several parasites o Calcium-dependent o Widely distributed on mucosal surfaces throughout the body o Lack of MBP= recurrent yeast infections o Response Time = ? o Normal cxn. = 0.15-1.0 o Increase= ? Alpha1-Antirypsin o General plasma inhibitor of proteases release from leukocytes, especially elastase o Elastase- endogenous enzyme that can degrade elastin and collagen o “mop up”= regulates expression of proinflammatory cytokines o Counteract the effects of neutrophil invasion during inflammatory response o Major component of the alpha band when serum is electrophoresed o Deficiency= premature emphysema and liver disease o

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Can also react with any serine protease, such as those generated by triggering of the complement cascade of fibrinolysis o Response Time= 24 HR o Normal cxn = 200-400 o Increase= 2-5x Haptoglobin o Alpha2-globulin o Preventing loss of free haemoglobin o Preventing the loss of iron by urinary excretion o Provide protection against oxidative damage mediated by free haemoglobin o Increase= inflammation, stress or tissue necrosis o Rise in plasma haptoglobin is due to de novo synthesis by the liver and does not represent release of previously formed haptolgobin from other sites o Plays an important role in protecting the kidney o Free haemoglobin- powerful oxidizing agent that can generate peroxides and hydroxyl radicals o Response Time= 24HR o Normal cxn = 40-200 o Increase = 2-10x Fibrinogen o Forms the fibrin in clot o Most abundant coagulation factors in plasma o Cleaved by thrombin to form fibrils that make up a fibrin clot o Barrier that helps prevent the spread of microorganisms further into the body o Also serves to promote aggregation of RBCs

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Increased= risk for developing coronary artery disease, especially in women o Response Time= 24 HR o Normal cxn. = 110-400 o Increase = 2-5x Ceruloplasmin o Principal copper-transporting protein in human plasma o Acts as ferroxidase, oxidizing iron from Fe2+ to Fe3 + o Accumulates in the liver and subsequently in other tissues such as the bran, cornea, kidneys and bones o Decrease= Wilson’s diseaseautosomal recessive genetic disorder; increase of copper in the tissues o Response Time= 48-72 HR o Normal cxn. = 2-40 HR o Increase= 2x o

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TWO TYPES OF ACQUIRED IMMUNITY ACTIVE -

Can be induced in an individual by infection (natural) or vaccination (artificial)

PASSIVE -

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Conferred on an individual by transfer of antibodies or lymphocytes from an actively immunized individual Transfer in vivo or colostrum (Natural); Infusion of serum plasma (artificial)

Cellular Response -

T lymphocyte responds to antigens presented by other cells in the context of major histocompatibility complex (MHC) proteins

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T lymphocytes recognizes when antigen is present on the surface of an antigenpresenting cell (APC)

CELL-MEDIATED IMMUNITY Myeloid Line -

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Types of leukocytes that participate in the process of phagocytosis and arise from a common pre-cursor in the marrow o Neutrophils o Eosinophils o Basophils o Monocytes o Lymphocytes o Mast Cells (tissue) o Macrophages (tissue) o Dendritic Cell (tissue) Neutrophil o Polymophonuclear neutrophilic (PMN) leukocyte o 50-70 % o Contain large number of neutral staining granules o Azrurophilic granule – Primary granules o Secondary Granulescollagenase, lactoferrin, lysozyme, reduced nicotinamid adenine phosphate (NADPH) oxidase o Tertiary granules contain gelatinase and plasminogen activator o Diapedesis – movement through blood vessel walls o Selectin- receptor; help make PMN sticky and enhance adherence to endothelial cells that make up the vessel wall o Chemotaxins- chemical messengers that cause cells to migrate in a particular direction

Chemotactic factorcomplement components, proteins from the coagulation cascade, products from bacteria and viruses, platelet activating factor, and secretions form mast cells o Life span of 5 Days in the tissue o Increase= acute infection Eosinophils o 1-3% o Increase= allergic reaction or parasitic infections o Primary granules contain acid phosphatase and arylsulfatase o Neutralizing basophil and mast cell products and killing certain parasites Basophils o 1% o Granules are histamines, a small amount of heparin and eosinophil chemotactic factor A= immediate hypersensitivity reactions o Exist only a few hours in the bloodstream Mast Cells o Widely distributed throughout the body o Contain acid phosphatase, alkaline phosphatase and protease o Plays a role in hypersensitivity reaction by binging IgE Monocytes o Largest cell in the peripheral blood o Two types of granules § Peroxidase, acid phosphatase and arylsulfatase; indicates that these granules are o

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similar to the lysosomes of neutrophils § Beta-glucuronidase, lysozyme and lipase, but no alkaline phosphatase o 70 hours in peripheral blood o Migrate to tissues and become macrophages Tissue Marcophages o Contain no peroxidase o Immobile and amoeboid action o Mircrobial killing, tumoricidal activity, intracellular parasite eradication, phagocytosis, secretion of cell mediators and antigen presentation=T cell= cytokines Dendritic Cell o Phagocytose antigen and present it to helper T lymphocytes o Classified according to their tissue location o They are the most potent phagocytic cell in the tissue Lymphocyte o T lymphocytes and B lymphocytes o Recognize foreign antigens, directly destroy some cells or produce antibodies as plasma cells

PHAGOCYTOSIS -

Process which certain cells of the innate immune system, including macrophages and neutrophils, engulf l...