micr 304 s2010 lecture 1.ppt

MICR 304 Immunology &

Serology

MICR 304 Immunology &

Serology

Lecture 1OverviewChapter 1

Lecture 1OverviewChapter 1

Immunology

• Recognition of self and non-self– Antigens

• Elimination of non-self– Exogenous targets

Microbes Allergens Foreign material

– Endogenous targets Tumors

Microbial Targets of the Immune System

(Pictures from Tortora et al, 2004)

Allergens

Foreign Bodies

http://www.mdchoice.com/photo/pto0023.asp

Tumors as Targets

Breast cancer

Tumor CellNK-Cell

Before

After

No responseResponse

Desired response

Response associated with disease

The Birth of the Science “Immunology”

• Edward Jenner (England, 1796)

• Cowpox (vaccinia) protects against small pox

• First reported vaccination

Milestones in Immunology

• Metchnikoff 1884– Phagocytosis

• Pasteur 1885– Systematic development

of a vaccine (rabies)

• von Behring and Kitasato 1890– Discovered antibodies

• Landsteiner 1902 – Blood groups

• Wassermann 1906– Complement fixation test

• Fleming 1921– Lysozyme

• Jacob & Wollmann 1953– Clonal selection theory

• Porter 1962– Antibody structure

• Koehler & Milstein 1975– Monoclonal antibodies

A Major Principle in Immunology: Antibody:Antigen Binding

• Antibody: a host protein that binds specifically to a molecule (soluble or particular)

• Antigen: any molecule that can be recognized by and bound to an antibody; typically induces production of antibodies in the host (“antibody generating”)

Evolution of Immunity

AdaptiveImmunity

InnateImmunityJawed fish

Two Arms of Host Defense

• Innate immunity– Natural immunity– Defense system

functional at birth– Preformed or

available within hours after infection

– Pattern recognition– Widely present in

nature

• Adaptive immunity– Acquired– Available within

days– Specificity– Memory– In higher

vertebrates

Innate Adaptive

Key Players in Immunology

Innate Adaptive

Cells PhagocytesEpithelial Cells NK

Cells

Lymphocytes(B-Ly, T-Ly)

Effector Molecules

ComplementAntimicrobial (Poly)PeptidesAntimicrobial

lipids?

Antibodies

Defense Cells Have Specific Tasks

• Epithelial cells– Barrier

• Phagocytes– Ingest– Kill– Digest

• NK-cells– Lyse infected cells or

tumor cells

• B-lymphocytes– Produce antibodies

• T-helper lymphocytes– Strengthen defense

cells to improve their function

– Regulate immune responses

• T-killer lymphocytes– Lyse with specificty

infected cells or tumor cells

Infection Triggers an Innate Inflammatory Response

Dendritic Cells Initiate Adaptive Immune Responses

Adaptive Immune Responses Augment Innate Immune

Responses

Immune Cells Interact via Cytokines and Surface

MoleculesInnate Adaptive

Cells PhagocytesEpithelial Cells

NK Cells

Lymphocytes(B-Ly, T-Ly)

Effector molecules

ComplementAntimicrobial (Poly)PeptidesAntimicrobial

lipids?

Antibodies

Immune Cells are also Activated by Defense

MoleculesInnate Adaptive

Cells PhagocytesEpithelial Cells

NK Cells

Lymphocytes(B-Ly, T-Ly)

Effector molecules

ComplementAntimicrobial (Poly)PeptidesAntimicrobial

lipids?

Antibodies

Time Course of the Immune Response

Most Immune Cells are Found in Blood

Granulocytes

Monocytes

Lymphocytes

Natural Killer Cells

Normal Blood Distribution of Leukocytes

• Neutrophils: 40-75%• Lymphocytes: 20-50%• Monocytes: 2-10%• Eosinophils: 1-6%• Basophils: <1%

Most Immune Cells Originate in the Bone

Marrow• Hematopoiesis

– Development of blood cells and constituent

• All blood cells originate from the pluripotent hematopoietic stem cell

Bone marrow, low power Bone marrow, higher power

Hematopoiesis

Hematopoiesis by Other Organs

• Sites– Spleen, liver

• Condition– Normal fetal sites of hematopoiesis– Malignancies– Myelofibrosis (bone marrow replaced

by fibrotic tissue)• Precursor cells are found in blood

Immature Blood Cells in Peripheral Blood

•More acidophil cytoplasma•Large cells with nuclei•Prominent nucleoli

Lymphatic Tissue

• Central– Bone marrow – Thymus

• Secondary– Spleen– Lymph nodes– GALT (gut associated

lymphatic tissue)• Tonsils• Peyer’s patches• Appendix

Production

Interactionwith Ag

Maturation

Thymus

Immature T-Cells

Mature naive T-Cells

Hassall’s corpuscule

(Cell destruction?)

Bone marrow precursor

Blood stream

Lymph Node

The Spleen

Organization of the Spleen

• White pulpa– Leukocytes

arranged around the blood vessels and sinuses

• Red pulpa:– Blood vessels and

sinuses

• Marginal Zone– Border between

white and red pulpa

Peyer’s Patches

Appendix

References

• Janeway’s Immunobiology, 7th edition, 2008• Textbook of Hematology, McKenzie, 2nd

edition, 1996• Microbiology: An Introduction; Tortora et al, 8th

edition, 2004• http://www-medlib.med.utah.edu/WebPath/HE

MEHTML/HEMEIDX.html• http://www.siumed.edu/%7Edking2/erg/smallin

t.htm• Primary literature: available per request