“Immunology deals with understanding how the body distinguishes between what is self andwhat is nonself; all the rest is technical detail.”(Benjamini et al.)

The word immunity is derived from a Latin wordmeaning exempt from taxation

Historical perspectives on immunology

Ancient Greece: if people recovered from theplague they didn’t catch it again1718- Lady Montagu- variolation

1798- Edward Jenner

Louis Pasteur (1800s)- vaccine designcholera (in chickens)anthrax (in sheep)

Von Behring and Kitasato, 1890serum from immunized animals could betransferred to other animals and protectthem (Kabat: immunoglobulin, 1930s)

Metchnikoff, 1883- phagocytes could ingestmicrobesmore phagocytes in immunized animals

Chase, Glick, 1950s importance of lymphocytes

Lymphocytes are antigen-specific

Why?

Clonal selection theory (Jerne, Talmadge, Burnet,1950s) is the prevailing paradigm

Clonal selection theory

p. 15

Clonal selection theory

T and B cells with different antigen specificitiesexist before they encounter antigen

Lymphocytes have antigen-specific receptorson their surfaces

Once receptor combines with antigen, the cellsproliferate and differentiate into clones

Somehow, cells that recognize self-antigensare prevented from developing

The immune reaction consists of two related activities:

Recognition (of a specific foreign substancepathogen or antigen)

Response that eliminates or neutralizes thatsubstancememory- subsequent exposure to thatsubstance leads to a faster, more intenseresponse

What are the components of the immune response?

There are many!

Innate (non-specific; immediate)

Acquired (adaptive)- specific, has memory

Components of innate immunity

Prevent entry of pathogen

Prevent growth of pathogen

Kill the pathogen

Eliminate pathogen and repair damage

p. 5

Ingestion by phagocytes

p. 40

Introduction to inflammation

p. 8

Vasodilationerythema (redness) and heatcapillaries are more permeable

Influx of fluid (edema)

Influx of phagocytes, which release enzymes thatkill cells. Pus is produced

Various chemicals are produced in the inflammatory response- by the microbes, the damaged cells, plasma proteins,and immune cells

Acute-phase proteins (activate complement)

Histamine (promotes vasodilation)

Kinins- become activated and promote vaso-dilationBradykinin- stimulates pain receptors

Increase in capillary permeability allowsblood-clotting proteins to enter tissue

What cells act in innate immunity?

HematopoiesisIn bone marrow

p. 25

Neutrophils

Basophils

Eosinophils

Macrophages

Natural killer cells

If “innate immune cells” are not antigen-specific,how do they become activated?

Janeway, et al. proposes three mechanisms(summarized Science 296, 2002)

1. Microbial nonself- cells detect conserved sequences that are present on microbes but

not self (LPS, peptidoglycan)costimulatory signal by antigen-presenting

cells (APCs)

2. Missing self- ligands that are normally presentinhibit immune response. Example: MHCclass I

p. 333

Other structures signal different functions

On senescent or apoptotic cell- targeted forphagocytosis

Cell damage; necrosis- repair? Or does it inducean immune response (danger model)

Acquired immunity

Unlike innate mechanisms, these have:

SpecificityDiversityMemorySelf-nonself recognition

Principal types of cells are lymphocytesand “antigen-presenting cells”

p. 11

Immunological molecules

1. Antigen receptors2. Antibodies3. Class I MHC molecules4. Class II MHC molecules5. Cytokines6. Membrane-bound receptors7. Plasma proteins8. Adhesion molecules9. Enzymes

MHC and antigen recognition

p. 13

p. 14

Requirement for antigen-presenting cells

Examples of antigen-presenting cells

Macrophages

Dendritic cells

B cells

Acquired immunity:

Clonal selection

Proliferation

Enhanced secondary response

p. 17

Components of immune activation:

Antigen recognition

Requirement of T cell help for B cell activation (Bretscher and Cohn)

Requirement of costimulatory signals for T cellsFrom antigen-presenting cells (APCs)

APCs themselves may not be constitutivelyactive

Danger model (first proposed in early 1990s;Matzinger and Fuchs)

Activation signal may be damaged tissue or cells

How does immune system continue to recognize“self” throughout development?

Why do different types of immune responses occur in different tissues?

Why are fetuses tolerated by the pregnant woman?

p. 12

p. 16, humoral response

p. 16, cell-mediated

Immunological molecules

1. Antigen receptors2. Antibodies3. Class I MHC molecules4. Class II MHC molecules5. Cytokines6. Membrane-bound receptors7. Plasma proteins8. Adhesion molecules9. Enzymes

p. 19

What happens when the immune system malfunctions?

Allergy and asthma

Graft rejection and graft-vs-host disease

Autoimmune disease

Immune deficiency