Immunology & Serology Review Notes

IMMUNOLOGY & SEROLOGY Source: Immunology and Serology Review 2016-2017 by Jude Anthony Trinidad, RMT, MSMT, MLS(ASCPi) Immunology  Study of our immune system; Study of host’s reaction when foreign antigens are introduced to the body HISTORY 1978 Edward Jenner Vaccination (smallpox) cowpox 1868 Louise Pateur “Founder of Immunology” 1880-1800 Elli Methnikof Cellular Theory of Immunity 1901 Bordet and Gengou Complement Fixation 1952-1953 Grabar and Williams Immunoelectrophoresis Analysis in Gels 1896 Erhlich Side Chain Theory 1930 Friedrich Brent/Felix Haurowitz Template Theory of Antibody Production 1955-1957 Niels K. Jerne/Frank Burnet Clonal Selection theory 1958 Dausset/Rapaport Histocompatibility complex 1973 Milstein/Kohler Hybridoma for the production of Monoclonal Antibodies Categories/Components of the Immune system NATURAL IMMUNITY Innate; non-specific-ADAPTIVE IMMUNITY Acquired; specific (e.g. targets all

antibodies)

 Ability of an individual to resist infection by means of normally present body functions  No prior exposure required  Response does not change with subsequent exposures (lacks memory)  Cells under natural: Phagocytes – eating organisms w/ digestive enzymes e.g. N, Mono, Macro Natural Immunity EXTERNAL DEFENSE SYSTEM

 Specificity foe each individual pathogen  Ability to remember a prior exposure  Results in an increased response upon repeated exposure (has memory)  Cells under adaptice: Lymphocytes

Physical  Skin, mucous membrane  Cilia lining in respiratory tract Biochemical  Lactic acid in sweat  Lysozymes  Acidity of GIT and vagina Normal Flora

Cellular  Phagocyte  Natural Killer cells (Kiss or death) Humoral (Soluble factors)  Acute phase reactants  Interferons (A&B)  Defensins  Complement proteins

e.g. B-cell (bone marrow) T-cell (thymus)

INTERNAL DEFENSE SYSTEM

PREVENTS ENTRY OF INVADING PATHOGENS

*Hansel’s stain – stain for Eosinophils

RECOGNIZES THE INVADING PATHOGEN

PART I. INNATE IMMUNITY A. Acute Phase Reactants  Plasma proteins that increases rapidly by at least 25% due to infection, trauma or injury (produced primarily by hepatocytes)

Protein C-reactive protein Seum amyloid A Alpha 1 antitrypsin Fibrinogen Haptoglobin Ceruloplasmin

Response time

Complement C3

6-10 24 24 24 24 48-72

Increase 1000x 1000x 2-5x 2-5x 2-10x 2x

48-72

2x

Functions Opsonization, complement activation Removal of cholesterol Protease inhibitor Clot formation Binds hemoglobin Binds copper and oxidizes iron (e.g. wilsons dse)

Opsonization, lysis

Source: Stevens, 2010

B. Cellular Defense Mechanisms  Myeloid line  Neutrophils  Basophils

 

Monocytes Dendritic cells (best; presenting cells)

 Eosinophils C. Toll-like Receptors  Highest concentration on:  Monocytes  Macrophages  Neutrophils

Phagocytes - TLR binds phagocytosis will occur

Examples  TLR2 – gram+bacteria  TLR4 – gram- bacteria

D. Phagocytosis  Kills extracellular organisms; First described by Metchmikof  Steps:  Initiation Stage - ↑ surface receptors that allows for adherence  Chemotaxis - Migration of neutrophils and monocytes to the site of injury 

Engulfment

- Chemotoxin E3 C3a C5a – acts as signal - 2 types of Chemotaxin: Positive and Negative - enclosing the pathogen into a phagocytic vacuole phagolysosome - opson-make organism more susceptible to organism

 Digestion and Excretion Summary: 1. Chemotaxis and adherence of microbe to phagocyte 2. Ingestion of microbe by phagocyte 3. Formation of a phagosome 4. phagosome + lysosome = Phagolysosome 5. Digestion of ingested microbe by enzymes 6. Formation of residual body containing indigestible material 7. Discharge of waste materials.  HOW MICROORGANISMS ARE DESTROYED  Activation of NADPH oxidase  Nitric Oxide  Disease associated to Phagocytosis  Chronic Granulomatous dse  Afects neutrophil microbicidal action  Impaired NADPH production  Test: Nitro Blue Tetrazolium test (+) Colorless (N) Blue precipitate  Lazy Leukocyte Syndrome  Job’s Syndrome – normal random movement E. Inflammation  Rxn to tse injury  Cardinal signs:  Rubor - Redness (↑ bloodflow)  Calor - Heat (Interleukin 1 production) e.g. Dracula Medenisis  Dolor - Pain (WBC) lactic acid formation; Pyrugenia sensation;  Tumor - Swelling (release of plasma fluid in surrounding tse.)  Function laesa - Loss of fxn  Stages:  Vascular response - most cells release histamine- vasoconstriction; basophils  Cellular response  Resolution & Repair 

PART II. ACQUIRED/ADAPTIVE/SPECIFIC IMMUNITY A. TYPES 1. Naturally Acquired (Antigen) Long-term (response time is slow) a. Active – includes the type of immunity that develops during convalescence from an infection b. Passive – develops after the placental passage of antibody from mother to fetus 2. Artificially Acquired (Anti-body) Immediate (short term 3-6 mos.) a. Active – immunity from vaccination

b.

Passive – immunity obtained after injection f gamma globulin for the induction of immune state

Cells involve: lymphocytes  Marker: Terminal Deoxynucleotidul Transferase (TDT)  20-40% of circulation WBC  With large rounded nucleus, Nuclear Chromatin is dense  No granules SURFACE IG –- ANTIBODY FOUND IN THE SUFACE

T CELLS B CELLS  Cell Mediated immunity  Humoral immunity (soluble)  Thymus  Bone marrow  Lymphokines – soluble factor produce Tcells  Antibodies  60-80%  20-35%  Longer lifespan (4-10 yrs)  Shorter lifespan (3-5 days)  Identified by erythrocyte-Rosette assay  Surface immunoglobulin B. LYMPHOID ORGANS site of diferentiation and maturation; growth of lymphocyte A. Primary Lymphoid Organs: Bone marrow & Thymus B. Secondary Lymphoid Organs – drops the pathogens a. Spleen - filtering antigens found in the blood (largest); main site of antibody production b. Lymph nodes - filtering antigens found in tse fluid c. Tonsils d. Appendix e. Peyer’s patches f. Adenoid Fxns of secondary lymphoid:  Trapping site of pathogens  Stand-by areas of T-cells, B- cells and Phagocytes  Place of encounter for pathogens and the cells  Production of antibodies, lymphokines; phagocytosis occurs  Antigenic dependent lymphopoesis LOCATION T CELLS B CELLS  Medullary, Perifolliculare and Paracortical  Follicular and medullary (germinal center) of regionof Lymph nodes lymph nodes  Periarteriolar Regions of spleen  Primary follicles and red pulp of spleen  Thoracic duct of the circulatory system  Follicular region of GALT T LYMPHOCYTES - 80% of the circulating lymphocytes in the peripheral blood Subsets: T CELL RECEPTORS  T-helper cells (70% CD4+) Receptor of the HW  CD2 – sheep RBC receptor  CD3 – part of T cell antigen-receptor complex  T- suppressor cells → (30% CD 8+)  CD4 – receptor of MHC class II molecule (Th)  T- cytotoxic cells ↗ C specific  CD8 – receptor of MHC class I molecule (Ts & Tc);  T- delayed hypersensitivity major histocomplatibility Development  Double Negative Thymocytes (CD4- & CD8-)  Double positive thymocytes (CD4 & CD8+)  Mature T cell Single positive  Activated T cell Interleukin II (CD25) sensitized T-cell produce lymphokines Memory T cell – act as reserved/back-up  Sensitixed T cell NATURAL KILLER CELL (NK) A.k.a. large granular lymphocyte (LGL); non-specific Virgin lymphocyte – not yet exposed by the foreign antigen

-

Kill infected and malignant cells Identified by presence of CD56& CD16, absence of CD3 Activated by IL2 & IFN-gamma to become LAK cells o LAK – Lymphokine Activated Killer cells (specific) Laboratory Identification of lymphocytes  Flow cytometry – Cooled standard in identifying lymphocyte  Fluoresence Microscopy  Rosette assay  Density Gradient Centrifugation o Ficoll-Hypaque - separate other lymphocyte fr other blood cells o Roswell part Memorial Institute (RPMI) – culture media of the lymphocyte (4-10 yrs) *1.077 gravity