Immunology and Serology Lecture Reviewer PDF

Preview

Summary

Download Immunology and Serology Lecture Reviewer PDF

Description

MODULE 1 Lesson 1. History and Definition of Terms NOBEL PRIZES AWARDED FOR IMMUNOLOGIC STUDIES

YEAR

NAME

DISCOVERY

1700

Edward Jenner

Vaccination of cowpox against smallpox

1885

Louis Pasteur

Reported live attenuated vaccine against rabies

1901

Emil Von Behring

Antiserum therapy esp. Against diphtheria

1905

Robert Koch

Tuberculosis

1908

Paul Ehrlich

Theories of Immunity (Cellular & Humoral)

Elie Metchnikoff

Phagocytosis

1912

Alexis Carell

Organ grafting

1913

Charles Richet

Anaphylaxis

1919

Jules Bordet

Theories of Immunity/Complement

1930

Karl Landsteiner

Human Blood Groups

1945

Sir Alexander Fleming

Penicillin

Sir Ernst Borischain Lord Howard Walter Floray 1949

Salk and Sabin

Development of polio

1951

Max Theiler

Yellow fever vaccine

1952

Selman Abraham

Streptomycin as first

Waksmann

antibiotic effective against TB

1957

Daniel Bovet

Antihistamine research

1959

Severo Ochoa

Mechanism of biological synthesis of DNA and RNA

Arthur Kornberg 1960

Sir Frank Macfarlane Burnet

Acquired Immunological Tolerance

Sir Peter Brian Medawar 1965

Francois Jacob

Genetic control of enzymes and viruses synthesis

Andrei Lwoff Jacques Monod 1966

Payton Rous

Tumor-inducing viruses

1968

Robert Holley

Genetic code and its function in protein synthesis

Har Gobind Khorana Marshall Nirenberg 1969

Max Delbruck

Replication mechanism and genetic structure of viruses

Alfred Hershey Salvador Luria

1972

Rodney Porter

Chemical structure of immunoglobulins

Gerald Edelman David Baltimore

Interaction between viruses

Renato Dulbecco

Genetic material of the cell

1975

Kohler

First monoclonal antibody

1977

Rosalyn Yallow

Radioimmunoassay of peptide hormones

1978

Werner Arber

Restriction enzymes/application to problems of molecular genetics

1975

Daniel Nathans Hamilton Smith 1980

Baruj Benacerraf

Immunogenetics and histocompatibility

Jean Dausset George Snell 1983

Barbara McClintok

Mobile genetic elements (transposons)

1984

Cesar Milstein

Hybridoma technology/Monoclonal antibodies

George Kohler Niels Jerne 1987

Susumo Tonegawa

Immunoglobulin genetics ab diversity

1989

J. Michael Bishop

Cellular origin of retroviral oncogenes

Harrold Varmus

1990

Organ and cell transplantation

Joseph Murray

E. Donnell Thomas 1996

Peter Doherty

Specificity of cell mediated immune defense

Rolf Zinkernagel 1997

Stanley Prusiner

Prions as a new biological principle of infection

1999

Gunter Blobel

Signal transduction

Durhan and Gruber

Agglutination

Graber and Williams

Immunoelectrophoresis

Isihazaka

IgE

Isaacs and Lindenmann

Interferons

Edward Jenner

Smallpox vaccine

Kraus

Precipitation

Frazer

Development of human

2005

Lesson 2. Immunity and the Immune System Immunology – an area of biology that is concerned with the process by which all living organisms defend themselves against infection. Immunity - ability of an organism to recognize and defend itself against specific pathogens or antigens. TWO General Types of Immunity: 1. NATURAL/INNATE IMMUNITY 2. ACQUIRED/ADAPTIVE IMMUNITY

1. NATURAL/INNATE IMMUNITY A. Anatomical Barriers – first line of defense 1. Mechanical Factors ● Skin ● Mucus ● Saliva ● Tears

2. Chemical Factors ● Fatty acids ● Lysozymes ● Defensins ● Surfactants 3. Biological Factors ● Normal flora of the skin and GIT B. Humoral barriers to infection Humoral factors play an important role in inflammation , characterized by edema and phagocytic cells. These factors are found in the serum or at the site of infection. ● B1. Non specific plasma proteins: 1. Complement system Once activated complement can lead to increased vascular permeability, recruitment of phagocytic cells, and lysis and opsonization of bacteria. 2. Coagulation system Some products of the coagulation system can contribute to the nonspecific defenses because of their ability to increase vascular permeability and act as chemotactic agents for phagocytic cells.

3. Lactoferrin and transferrin 4. Interferons - proteins that can limit virus replication in cells. 5. Betalysin - heat stable, found in serum only because it is released by platelets during coagulation. 6. Properdin - serum protein that exerts bactericidal and viricidal effects in the presence of C3 and magnesium. ○ B2. Interleukins INTERLEUKINS. C. Cellular barriers to infection These cells are the main line of defense in the nonspecific immune system. ● Neutrophils ● Macrophages ○ Tissue macrophages: ■ Liver: Kupffer cells ■ Kidney: Mesengial macrophage ■ Lung: Alveolar macrophage ■ Lymph nodes: dendritic cells ■ Spleen: Splenic macrophage ■ Skin: Langerhans cells ■ Brain and CNS: Microglial cells ■ Connective tissue: Histiocytes ■ Small intestines: Payer’s patches ○ Mast cells ○ Dendritic cells ○ Natural killer (NK) and lymphokine activated killer (LAK) cells ○ Eosinophils ○ Basophils ○ Monocytes 2. ADAPTIVE/ACQUIRED IMMUNITY Third line of defense ● Affords protection against re-exposure to the same pathogen

Lymphocytes - cells responsible for the specific immune response ● found in blood and lymph Types ○ B – cells – mature in marrow ○ T – cells – mature in thymus ○ Helper / Cytotoxic/Killer / Suppressor / Memory Types of Acquired/Adaptive Immunity Active Immunity – result of actual infection ● Naturally Acquired Active Immunity – exposure to antigen ○ immunity may be life long or temporary ○ body generates immune response to antigen

● Artificially Acquired Active Immunity – through vaccination ○ body generates immune response to antigen ○ immunity may be life long or temporary

Passive Immunity – result of transmission of antibodies ● Naturally Acquired Passive Immunity – natural antibodies ○ antibodies pass from mother to fetus via placenta

● Artificially Acquired Passive Immunity – injection of antibodies ○ immunity is short-lived

Types of Specific Immunologic Reactions ADAPTIVE can be Cellular (cell-mediated) and Humoral (antibody-mediated) HUMORAL Immunity ● involves B cell activation ● production of antibodies in blood plasma and lymph

● B cells that are stimulated are called plasma cells will actively secrete antibodies ● Antibodies are found in ECF(blood plasma, lymph, mucus, etc) and surface of B cells ● Defense against bacteria, bacterial toxins, and viruses that circulate freely in body fluids before they enter cells

CELLULAR Immunity ● action of T cells ● active against cancer cells and transplanted tissues ● kills cell through lysis ● important in viral and fungal infections and in infections caused by AFB

IMMUNIZATION ○ Process of inducing immunity naturally or artificially by vaccination or administration of antibody Vaccination ○ A type of active immunization wherein any vaccine or toxoid is administered for prevention of disease Herd Immunity ○ For every type of disease, there is a recommended percentage of immunized population to achieve herd immunity Vaccines ● Proteins, polysaccharides or nucleic acids delivered to the immune system to induce specific responses that inactivate, destroy or suppress the pathogen Cytokines ● chemical messengers that regulate the immune system, orchestrating both innate and adaptive response to infection

Lesson 3. Cells and Organs of the Immune System-2 Two major lineages: myeloid precursor and lymphoid precursor Myeloid Precursor ● mast cells ● monocytes ● PMN (polymorphonuclears) ● rbc ● platelets ● dendritic cells ● macrophages Lymphoid Precursor ● T cell ● B cell ● NK

Two Types of Immune System Organs ● PRIMARY – maturation sites ○ BONE MARROW ■ central organ where all immune cells are born ■ B cells maturation

○ THYMUS ■ T cell maturation

● SECONDARY – activation sites ○ LYMPH NODES ○ LYMPHATICS ○ SPLEEN ○ MALT (mucous associated lymphoid tissues) ■ Tonsils ■ Peyer’s patches ■ Appendix

The organs of the immune system are stationed throughout the body. They are generally referred to as lymphoid organs because they are concerned with the growth, development, and deployment of lymphocytes, the white cells that are the key operatives of the immune system. The blood and lymphatic vessels that carry lymphocytes to and from the other structures can also be considered lymphoid organs. Lymph nodes ●

are small, bean-shaped with clusters in the neck, armpit, abdomen, and groin. Each lymph node contains specialized compartments which contain platoons of B lymphocytes, T lymphocytes and other cells.

Spleen ●

fist-sized organ at the upper left of the abdomen, which contains two main types of tissue: the red pulp and the white pulp. Like the lymph nodes, the spleen is subdivided into compartments that specialize in different kinds of immune cells.

Phagocytes ●

are large white cells that can engulf and digest microorganisms and other antigenic particles. Important phagocytes are monocytes and macrophages.

Dendritic cells ● are irregularly shaped white blood cells found in the spleen and other lymphoid organs. Neutrophils ● are not only phagocytes but also granulocytes, they contain granules filled with potent chemicals which can destroy microorganisms. Mast cell ●

is a non circulating counterpart of the basophil. Located in the lungs, skin, tongue, and linings of the nose and intestinal tract, the mast cell is responsible for the symptoms of allergy.

MODULE 2

Lesson 1. Antigen ANTIGENS ○ Substances recognized as foreign by body ○ Proteins – strongest and most common antigens Antigens ● are foreign particles that may elicit an immune response Immunogens ●

any foreign particle that elicits an immune response

● All immunogens are antigens but not all antigens are immunogens Lipids and nucleic acids ● are only antigenic when combined with proteins or polysaccharides Parts of Antigen Carrier ● molecular weight over 10,000 dalton; high MW; almost always protein in nature Antigenic determinant or epitope or haptene ●

portion recognized as foreign; reacts specifically with an antibody receptor

Functions of Antigen Major ● stimulates production of antibodies or immune response Minor ●

shows capability of reacting with antibody

Classification Complete antigen ● with 2 parts carrier and haptene; perform two functions Incomplete antigen ● either carrier or haptene; one function is present Kinds of Antigen ● Agglutinogen, Precipitinogen, Virus, Rickettsiae, Toxin, Allergens

FACTORS AFFECTING IMMUNOGENICITY ● FOREIGNNESS ● MOLECULAR SIZE - at least 10,000 to be recognized by the immune system ● CHEMICAL COMPOSITION AND COMPLEXITY ○ Proteins are powerful immunogens ○ Carbohydrates are less immunogenic than protein ○ Lipids and nucleic acids are poor antigens ● ROUTE, DOSAGE AND TIMING OF PARENTERAL ADMINISTRATION Haptens ● partial antigens ● not antigenic ● must be coupled to a carrier molecule to be antigenic ● can react with specific antibody alone, but cannot produce a visible reaction such as precipitation or agglutination

RELATIONSHIP OF ANTIGENS TO THE HOST Autoantigens ● antigens that belong to the host ● do not evoke an immune response Alloantigens ● are from other species capable of eliciting an immune response ● important to consider in tissue transplantation and in blood transfusions. Heteroantigens ● are from other species, such as other animals, plants, or microorganisms. Heterophile antigens ● are heteroantigens that exist in unrelated plants or animals but are either identical or closely related in structure so that antibody to one will cross-react with antigen of the other. Activators of Lymphocytes There are three major categories of molecules that can trigger the activation of lymphocytes 1. Monoclonal activators – substances that stimulate cells expressing antigen receptors specific for an epitope. 2. Oligoclonal activators – molecules that are typically derived from bacteria. 3. Polyclonal activators – typically plant proteins that bind to molecules present on all T cells.

Lesson 2. Major Histocompatibility Complex MAJOR HISTOCOMPATIBILITY COMPLEX / HLA ○ cluster of genes found in mammals ○ Its products play a role in discriminating self/non-self ○ Participate in both humoral and cell-mediated immunity ○ MHC acts as an antigen presenting structure. The major histocompatibility complex is found on human chromosome 6, referred to as HLA complex. In mice, MHC is found on chromosome 17, referred to as H-2 complex. Terms HLA and MHC are used interchangeably. Clinically, they are relevant, because they may be involved in transfusion reactions, graft rejection, and autoimmune diseases. Genes controlling expression of these molecules are actually a system of genes known as the major histocompatibility complex (MHC). There were three kinds of molecules encoded by the MHC ● Class I ● Class II ● Class III Genetic Map In humans, there are three MHC Class I alpha chain genes: ● HLA-A ● HLA-B ● HLA-C

● HLA-DP ● HLA-DQ ● HLA-DR Class I MHC molecules ● Present on all nucleated cells in the body ● Recognition by CD8+ T cells ● highest on lymphocytes and low or undetected on liver hepatocytes, neural cells, muscle cells, and sperm.

● involved in the recognition and rejection of grafted kidneys and other forms of organ transplant. ● For protection against viruses and parasites ● These MHC class I-deficient diseased cells trigger and activate NK cells Chain structure – alpha 2, beta 2 macroglobulin Class II MHC molecules ● found primarily on antigen-presenting cells, which include B lymphocytes, monocytes, macrophages, and dendritic cells. ● Recognition by CD4+ T cells. ● important for antigen presentation and interactions between immunocompetent cells. ● For protection against bacteria, viruses and other exogenous antigens Chain structure – alpha, beta invariant chain Class III MHC genes ● minor MHC antigens ● activate complement factor 3 by either classical (C2, C4a, C4b) or alternative pathway (Factor B), TNF HLA TESTING There are two main approaches to histocompatibility testing: a. tissue matching b. tissue typing: Clinical Significance of HLA 1. Organ transplant and bone marrow transplant. 2. Platelet transfusion – matching between donor and recipient is useful to patients who are retractile to random donor platelets 3. HLA compatibility exerts the strongest influence on long-term kidney survival after a transplant. 4. HLA identical donors for bone marrow transplantation to reduce the frequency of graft vs host disease 5. Paternity testing 6. Disease association

MHC/HLA

RELATED DISEASES B27

Ankylosing

B8

Myasthenia gravis,

DR2

Multiple sclerosis

DR2/DR3

SLE

spondylitis

Celiac disease

DR3

Grave's / Myasthenia gravis

DR3/DR4

IDDM / Type I

DR4

RA or Pentigus

DR4/DR5

Hashimoto's disease

Diabetes

vulgaris

HLA Testing 1. Microlymphocytotoxicity test / Complement-dependent cytolysis Dye – trypan blue or eosin Classic method using purified T lymphocytes (class I typing) and B lymphocytes 2. Mixed lymphocyte culture – measurement of the degree of radioactivity by liquid scintillation counting 3. DNA-based typing methods – nucleic acid amplification (PCR) and sequencing

Lesson 3. Antibodies ANTIBODIES ● Made in response to exposure to the antigen. ● Each antibody has at least two identical sites that bind antigen ● Belong to a group of serum proteins called immunoglobulins ANTIBODY STRUCTURE Monomer: A flexible Y-shaped molecule with four protein chains: ○ 2 identical light chains ○ 2 identical heavy chains ○ Joined together by disulfide bonds Variable Regions ○ Two sections at the end of Y’s arms ○ Contain the antigen binding sites ○ Identical on the same antibody, but vary from one antibody to another. Constant Regions ○ Stem of monomer and lower parts of Y arms. Two Heavy Chains HEAVY CHAINS ● Molecular weight varies from 50,000-90,000 dalton ● Designated as u (IgM), delta (IgD), gamma (IgG), alpha (IgA), and epsilon (IgE) ● Each heavy chain is made of 3 constant domains: ○ CH1 ○ CH2 ○ CH3 ○ one variable (V) domain (VH) Two Light Chains LIGHT CHAINS - are designated as : ● Kappa (κ) or Lambda (λ)

● W. 23,000 d ● Kappa chain – consist of 214 amino acid residue ● Lambda chain – consist of 213 amino acid residue ● Each light chain is made of: ○ one constant domain, CL ○ one variable domain VL. Hinge region ● area that gives molecule flexibility allowing for multiple binding sites ● Located between the CH1 and CH2 domains

Properties of an Antibody: ● Protein in nature ● High MW more than 150,000 dalton ● Present in serum/plasma, CSF, saliva and seminal fluid

Classification of Antibody A. According to Temperature at which they react ● Cold antibodies – react at 4C to room temp ● Warm antibodies – react at 37C B. According to Occurrence ● Natural antibodies – appear without any apparent stimulus ● Immune antibodies - appear following the introduction of an antigen

C. According to Species ● Isoantibodies – produced after introduction of the antigen from the same species ● Heterophile antibodies – produced after introduction of the antigen from another species D. According to its Reaction with an antigen Agglutinins ● responsible for immobilization of motile organisms and for cell clumping Hemagglutinins ● agglutination of rbc Precipitins ● demonstrated only against soluble antigens Lysins ● cause dissolution of antigenic cells Opsonins ●

act upon bacterial invaders,

Neutralizing antibodies ●

render antigenic microorganism (usually viruses) harmless

Allergic antibodies ●

react with allergens

Antitoxins ●

which neutralize specific toxins

Complement fixing antibodies Blocking or inhibitory antibodies ●

combine with antigen but are not grossly detectable

Immunoglobulins Human Ig classes ● IgG - (γ) heavy chains ● IgM - (µ) heavy chains ● IgA - (α) heavy chains ● IgD - (δ) heavy chains ● IgE - (ε) heavy chains ● IgG Subclasses ○ IgG1 - Gamma 1 (γ1) heavy chains ○ IgG2 - Gamma 2 (γ2) heavy chains ○ IgG3 - Gamma 3 (γ3) heavy chains ○ IgG4 - Gamma 4 (γ4) heavy chains ● IgA subclasses ○ IgA1 - Alpha 1 (α1) heavy chains ○ IgA2 - Alpha 2 (α2) heavy chains Enzyme Hydrolysis 2 Enzymes – papain and pepsin useful in determining the function of speci...