IMMUNOSERO

• Inhalation of dried powder from smallpox lesions

• 1000 AD

Chinese

Injection of material from small pox crusts/blisters

Lady Montagu

Cross immunity

Edward Jenner

• Father of Immunology

• Attenuation

Louis Pasteur

Precipitins

Rudolf Kraus

Serum antitoxins

Emil Von Behring

Cellular immunity of TB

Robert Koch

Phagocytosis

Elie Metchnikoff

Opsonization

Wright & Douglas

Anaphylaxis

Charles Richet

Complement System

Jules Bordet

ABO blood group

Karl Landsteiner

Immunologic tolerance

Burnet & Medawar

Antibody structure

Edelman & Porter

Major Histocompatibility Complex (MHC)

Snell, Dausset, Benacerraf

Radioimmunoassay

Rosalyn Yallow

Immunoregulation

Niels Jerne

Monoclonal Antibody

Kohler & Milstein

Antibody diversity

Susumo Tonegawa

Transplantation

Thomas & Murray

Penicillin

Alexander Flemming

HPV vaccine

Frazer & Zhou

Serum sickness

Von Pirquet & Schick

Polio vaccine

Salk & Sabin

Yellow Fever

Reed

HIV

Montagnier & Gallo

Discovery of T-cell receptor gene

1984

Liver

Kupffer Cell

CNS

Microglial Cell

Bone

Osteoclasts

Lung

Alveolar/Dust cells

Connective Tissue

Histiocytes

Placenta

Hofbauer Cell

Spleen

Littoral Cell

Kidney

Mesangial Cell

Synovium

Type A Lining Cell

• Leuokocyte IFN

• inhibits viral replication

IFN-a

• Epithelial cell and fibroblast IFN

• Inhibits viral replication

IFN-b

• Immune IFN

• Secreted by Th1 and NK cells

• Activates macrophages

IFN-y

• aka cachetin

• Produced by macrophages and NK cells

TNF-a

• aka lymphotoxin

• Produced by CD4 and CD8 T-cells

TNF-b

IL-1

Fever

IL-2

Stimulates T-cells

IL-3

Stimulates bone marrow

IL-4

Stimulates IgE production

IL-5

Stimulates IgA production

IL-6

Stimulates acute phase reactants

Potential marker for stone disease

IL-1b

inflammation, fever, initiation of the acute phase response

TNF-a

inflammation, initiation of acute phase response, death of tumor cells

IL-6

Initiation of the acute-phase response, activation of B & T cells

TGF-b

Inhibition of both T and B cells proliferation, induction of IgA, inhibition of macrophages

IFN-a, IFN-b

Protects cells against viruses, increases class I MHC expression, activates NK cells

Interleukin-2 (IL-2)

Growth and proliferation of T and B cells, NK activation and proliferation

Interleukin-4 (IL-4)

Promotion of Th2 differentiation, stimulation of B cells to switch to IgE production

Interleukin-5 (IL-5)

Eosinophil generation and activation, B-cell differentiation

Interleukin-10 (IL-10)

Suppression of Th2 cells, inhibition of antigen presentation, inhibition of IFN-y

Interferom-gamma (IFN-y)

Activation of macrophages, increased expression of class I and II MHC molecules, increased antigen presentation.

• Lipopeptides

• MTB

TLR-1

• Peptidoglycan, lipoproteins, zymosan

• Gram positive bacteria, MTB, yeast

TLR-2

• LPS, fusion proteins, mannan

• Gram negative bacteria, RSV fungi

TLR-4

• flagellin

• bacteria w/ flagellae

TLR-5

• Lipopeptides, lipoteichoic acid, zymosan

• Gram positive bacteria, MTB, yeasts

TLR-6

• dsRNA

• RNA viruses

TLR-3

• ssRNA

• RNA viruses

TLR-7

TLR-8

• dsDNA

• DNA viruses

TLR-9

Acute Phase Reactant:

• NV: 0.5 mg/dL

• 1000x increase in acute inflammation

• Opsonization and complement activation

• Risk marker for cardiovascular disease

  • LR: <1 mg/dL

  • AR: 1-3 mg/dL

  • HR: >3 mg/dL

CRP

Acute Phase Reactant:

• Increase 1000x in acute inflammation

• Removes cholesterol

• Associated with atherosclerosis

• Increase significantly more in bacterial infection

Serum Amyloid A

Acute Phase Reactant:

• Protease inhibitor

• Decrease in premature emphysema and juvenile cirrhosis

a-1 Antitrypsin

Acute Phase Reactant:

• Clot formation

• Increase risk of coronary artery disease

Fibrinogen

Acute Phase Reactant:

• Binds hemoglobin

• Decrease in intravascular hemolysis

Haptoglobin

Acute Phase Reactant:

• Binds copper

• Decrease in Wilson’s disease

Ceruloplasmin

Acute Phase Reactant:

• Opsonization and lysis

• Decrease in glomerulonephritis

Complement C3

Acute Phase Reactant:

• Complement activation

• Deficiency leads to increase infection

Mannose-binding Protein

Procalcitonin

Biomarker for sepsis

Immunoglobulins:

• Most abundant in serum

• Longest half-life (23-25 days)

• Most efficient in precipitation

• Secondary anamnestic response

• Most efficient in crossing the placenta

  • IgG1>3>4>2

• Most efficient in complement fixation

  • IgG3>1>2>4

IgG

Immunoglobins:

• Monomer in circulation, dimer in secretions

• Antibody in mucosal surfaces and secretions

IgA

Immunoglobulins:

• Largest antibody and mainly intravascular

• Most efficient in agglutination and complement fixation

• Monomer on B-cells, pentamer in circulation

IgM

Immunoglobulins:

• Has a role in immunoregulation

• Susceptible to proteolysis due to long hinge region

IgD

Immunoglobulins:

• Least abundant and the most heat labile

• Mediates antihelminthic and allergic response

IgE

Located between CH1 and CH2; joins heavy chains and is rich in proline for flexibility

Hinge Region

Consists of 1 light chain and ½ heavy chain

FAB fragment

Unit for sedimentation rate of immunoglobulins

Svedberg

19S - IgM

8S- IgE

7S- IgG, IgA, IgD

Sedimentation Coefficient

Variation in the heavy chain which is unique to each immunoglobulins class

Isotype

Variation in the variable region of heavy and light

Idiotype

Variation in the constant region of heavy and light chain

Allotype

Activated by IgM and IgG requires calcium

CLASSICAL

Activated by microbe surface molecule Properdin stabilizes C3 convertase requires magnesium

ALTERNATIVE

Activated by mannose or other sugars

LECTIN

C4b2a

C3 convertase of the classical and lectin pathway

C4b2a3b

C5 convertase of the classical and lectin pathway

C3bBb

C3 convertase of the alternative pathway

C3bBb3b

C3 convertase of the alternative pathway

C1qrs

Recognition unit

C4, C2, C3

C3a, C4a, C5a

Anaphylaxis

C3b

Opsonization

C5a

Neutrophil chemotaxis

C5b-9

Cytolysis by membrane attack complex

Lupus like syndrome, recurrent infection

C1