The Immune Response

• Inside your body there is an amazing protection mechanism called the immune system. It is designed to defend you against millions of bacteria, microbes, viruses, toxins and parasites that would love to invade your body

Functions of the immune system• Primary function: defense; resist pathogens, foreign bodies

and abnormal cells• Immunity acquired by:

– natural infection– vaccination

• When it fails: – congenital immunodeficiency diseases– immunocompromise – DEATH

Pathogen: a disease causing organism

1) Bacteria

2) Viruses

3) Protozoans

4) Fungi

5) Parasitic worms

Pathogens

E coli bacteria

Bacillus anthracis

Bacteria vs. Viruses

• First organisms on earth

• Most species on earth• Living cells• Prokaryotic (simpler:

no nucleus, circular DNA)

• A virus is a different breed altogether.

• A virus is not really alive.

• A virus particle is nothing but a fragment of DNA in a protective coat.

• The virus comes in contact with a cell, attaches itself to the cell wall and injects its DNA (and perhaps a few enzymes) into the cell.

• The DNA uses the machinery inside the living cell to reproduce new virus particles. Eventually the hijacked cell dies and bursts, freeing the new virus particles; or the viral particles may bud off of the cell so it remains alive. In either case, the cell is a factory for the virus.

The Lytic Cycle

Bacterial antibiotic resistance

How does it happen?

1. Spontaneous mutation

Bacterial antibiotic resistance

How does it happen?

1. Spontaneous mutation2 Plasmid transfer

Bacterial antibiotic resistance

How does it happen?

1. Spontaneous mutation2. Plasmid transfer3. Sex

Types of WBCs

• Can be classified based on the appearance of granules when viewed under the light microscope.

1. Granulocytes– Contain visible granules.

Includes:• Basophils• Eosinophils• Neutrophils

2. Agranulocytes– Do not contain visible

granules. Includes:• Lymphocytes• Monocytes

1

2

WBC Circulation and Movement

• Use the bloodstream mainly to travel from organ to organ or to quickly go to areas of invasion/injury.

• Characteristics of circulating WBCs:

– Capable of amoeboid movement• What role might this play in WBC function?

– They can migrate out of the bloodstream by squeezing thru endothelial cells (this process is called diapedesis)

– They are attracted to specific chemical stimuli. This is known as positive chemotaxis and allows WBCs to converge on pathogens and damaged tissues

Agranulocytes - Lymphocytes

• 20-30% of circulating leukocytes• Slightly larger than RBCs. In blood

smears, you typically only see a thin halo of cytoplasm around a relatively large nucleus.

• Continuously migrate from the bloodstream thru peripheral tissues and back into the bloodstream.

• Circulating lymphocytes are only a minute fraction of the total # in the body. Most are in other connective tissues and in lymphatic organs.

• Circulating blood contains 3 classes:– T cells: defend against foreign cells and tissues and coordinate the immune

response– B cells: produce and distribute antibodies that attack foreign materials

Agranulocytes - Monocytes

• 2-8% of circulating WBCs• Almost twice as big as an RBC• Nucleus is large and tends to be

oval or kidney-shaped• Individual monocytes use the

bloodstream as a highway, staying in circulation for only about 24hrs before entering peripheral tissues to become a tissue macrophage, an aggressive phagocyte.

Granulocytes -Basophils

• >1% of circulating leukocytes• Smaller than neutrophils and

eosinophils, only about 8-10µm in diameter.

• Contain granules that appear deep purple or blue

• Basophils migrate to injury sites and discharge the contents of their granules – histamine (a vasodilator and increaser of capillary permeability) and heparin (an anticoagulant). This enhances the local inflammation initiated by mast cells and attracts other WBCs

Granulocytes -Eosinophils

• 2-4% of circulating WBCs• Similar in size to neutrophils but have reddish-

orange staining granules (Eos is the Greek goddess of dawn) and a bilobed nucleus.

• Move into tissues after several hours and survive from minutes to days.

• They will phagocytize antibody-coated bacteria, protozoa, and cellular debris, but their main method of attack is the exocytosis of toxic compounds onto the surface of their target.

• Important defenders against large, multi-cellular parasites such as flukes or parasitic worms. They in # dramatically during a parasitic infection.

• Also sensitive to allergens and in # during allergic reactions as well.

Granulocytes -Neutrophils

• 50-70% of circulating WBCs• Cytoplasm is packed with pale

(“neutral colored”) granules that contain bactericidal compounds

• Mature neutrophils have a segmented nucleus. They are a.k.a polymorphonuclear leukocytes.

• About 12µm in diameter.• Highly mobile and generally the

first WBCs to arrive at an injury site.

• Specialize in attacking and digesting bacteria that have been “marked” for destruction.

• Survive in the bloodstream for only about 10hrs

Types of acquired immunityTypes of acquired immunity

• Active immunity • stimulated by immunizations (infection or

vaccination)

• immune response plays an active role in the generation of response

• takes time for it to be generated

• memory; next time, response will be faster

Types of acquired immunityTypes of acquired immunity

• Passive immunity• passive transfer of antibodies or cells

• no active effort in the part of the immune response

• example: antibodies against venoms

• works fast

• no memory

Types of acquired immunityTypes of acquired immunity

• Humoral immunity• mediated by antibodies produced by plasma cells

(B cells)

• can be transferred • http://www.msjensen.gen.umn.edu/webanatomy/wa_lymphatic_immunology/wa_lymph_antibody_mov.html

• Cellular immunity• mediated by T cells

• T cells produce cytokines which activate other cells such as macrophages to effectively deal with antigen

• http://www.msjensen.gen.umn.edu/webanatomy/wa_lymphatic_immunology/wa_lymph_cytotox_mov.html

Primary and secondary Primary and secondary immune responseimmune response

• Primary• after antigen recognition, there is lag phase of 3-

5 days -activation phase

• first antibody to be produced is IgM

• IgG is produced next

• levels of antibody peak between days 20-30

• antibody levels decrease, antigen is cleared

Primary and secondary Primary and secondary immune responseimmune response

• Secondary• immune response is quicker

• antibodies peak 2-5 days (activation phase is short)

• higher magnitude response

• longer duration

• predominantly IgG

Features of the specific immune Features of the specific immune systemsystem

• Self-regulation• decreases with time because of antigen disappearance

• Discrimination of self-non-self• response to FOREIGN antigens

• remains unresponsive to self antigens via TOLERANCE; breakdown of tolerance leads to autoimmune diseases

Major Histocompatability Complex

Protein markers that occur on surface of all body cells

Interact with cytotoxic T cells Different for individual--only the same in identical

twins Used to distinguish self from nonself This ability to distinguish self happens early in life

by T-cell in the Thymus This is the reason organ donors have to closely

match recipients

MHC Complex

How do diseases act as agents that promote natural selection?

• Influenza of 1918--can be compared to the plague in terms of its devastation

• Changed WWI and killed more than the war

Natural immunity to the 1918 flu

No natural immunity to the 1918 flu

1890’s

Population of NY city with respect to immunity to the 1918 flu

1890’s

1918 Flu

Population of NY city with respect to immunity to the 1918 flu

Survivors of 1918 flu

Their children

1890’s

1990’s

Population of NY city with respect to immunity to the 1918 flu(assuming no immigration)