Chapter 57

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies

The Immune System

Chapter 57

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Skin: First Line of Defense

• Three Lines Of Defense Skin – barrier to penetration

- Mucous membranes also important Cellular Counterattack – cells engulf

and/or produce chemicals to kill microbes Immune Response – immunoglobulins, B

cells and T cells attack foreign antigens



• Skin is largest vertebrate organ, provides first line of defense against microbe invasion Also barrier to dehydration

• Skin has three layers 1) Epidermis

- 10-30 cells thick Stratum corneum - Outer layer

Continuously shed Basal Layer - Innermost layer

Rapid division, replace lost cells of stratum corneum



2) Dermis- 15-40 times thicker than epidermis- Provides structural support for epidermis- Contains sensory receptors, blood

vessels, etc. 3) Subcutaneous layer

- Composed of fat-rich cells acting as shock absorbers and insulators


Other External Body Surfaces

Digestive Tract- Saliva/lysozyme- Acidic environment of stomach

Respiratory Tract- Thick mucus layer traps microbes- Cilia “flush” microbes out to be

swallowed into digestive tract Vomiting, diarrhea, coughing and sneezing

also expel microbes, etc.


Cellular Counterttack: Second Line of Defense

• Lymphatic System - Central location for the collection and distribution of immune system cells Consists of a network of lymphatic

capillaries, ducts, nodes, and lymphatic organs.



White Blood Cells That Kill Invading Microbes• Macrophages

Ingest bacteria Fuse with lysosome

• Neutrophils Ingest microbes like macrophage Also release chemicals

- Create “kill zone”, includes releasing cell• Natural Killer Cells –

Attack body cells infected by invading microbes Also kill cancer cells, before detectable tumor Puncture plasma membrane with perforins




Proteins That Kill Invading Microbes

• Complement System Approximately 20 different proteins

circulating freely in blood plasma- Some aggregate to form membrane

attack complex Insert into cell’s plasma membrane

and form pore, allowing water to rush in and burst cell

Others attract phagocytes to infection area or make cells easier to phagocytose



Interferons

• Alpha, beta and gamma varieties• Produced by viral-infected cells• Act on neighboring cells to prevent

replication of new viruses which might infect them

• Gamma interferon may be involved in defense against cancer


The Inflammatory Response

• Localized, nonspecific response to infection• Injured cells release chemical alarm signals

(histamine and prostaglandins) that cause blood vessels to dilate Increased blood flow to site of injury

- Stretches capillary walls increasing permeability

Redness and swelling of affected area due to increased blood flow

- Phagocyte migration into tissue


Local Inflammation



The Inflammatory Response

• Temperature Response When macrophages initiate counterattack,

they send a message to brain to raise body temperature

- Fever inhibits microbial growth- But body temperature over 103 F

dangerous and over 105 often fatal


The Immune Response: Third Line of Defense

• Key Concepts Antigen - molecule that provokes a specific

immune response- Antigenic Determinant Sites - Different

portions/shapes of a large antigen, each stimulating a different immune response

Lymphocytes called B cells respond to antigens by producing antibodies

- Antibody proteins are secreted into the blood and other body fluids and thus provide humoral immunity


The Immune Response: Third Line of Defense

• T cells directly attack cells carrying specific antigens Cell-mediated immunity

• Active or Acquired Immunity– use antibodies readily produced as a result of this or a previous exposure

• Passive Immunity - immunity gained by transference of antibodies via placenta, breast feeding or injection


Immune System

• Involve actions of leukocytes T and B Cells are lymphocytes

- T Cells originate in bone marrow and migrate to thymus

Develop ability to identify foreign particles by antigens exposed on their surfaces


Cells of the Immune System

• T Cell types Inducer - Oversee T cell development Helper - Initiate immune response Cytotoxic - Lyse infected cells Supressor - Terminate immune response


Cells of the Immune System

• B Cells Are produced and complete maturation in

bone marrow- Circulate in blood and lymph

When bind antigen can convert to plasma cells and produce large quantities of antibodies


Initiating the Immune Response

• Macrophages inspect surfaces of cells encountered for MHC (major histocompatability complex) proteins Self versus nonself recognition MHC genes highly polymorphic (170+ alleles) T cells only bind to antigens presented to them

on surface of cells- Foreign particles are taken in and partially

digested Antigens are processed and moved to the

surface of plasma membrane Antigen Presenting Cells






Initiating the Immune Response

• Macrophages that encounter pathogens lacking proper MHC proteins, or a virus-infected cell with viral proteins stuck to surface, secrete alarm signal Interleukin-1

- Stimulates helper T cells to initiate: Cellular response of T cells Humoral response of B cells


T Cells: Cell-Mediated Immune Response

• Helper T cells become activated when they bind to complex of MHC proteins and antigens presented by macrophages. Helper T cells secrete interleukin-2.

- Stimulates production of cytotoxic T cells Any cytotoxic T cell whose receptor

fits the particular antigen-MHC protein complex begins to multiply rapidly

Any cells bearing traces of viral infection are destroyed




B Cells: Humoral Immune Response

• B cells recognize invading microbes and use proteins (antibodies) to mark pathogen for destruction Can bind to free, unprocessed antigens Antigen particles enter B cells by

endocytosis and get processed- Helper T cells that recognize the specific

antigen bind to the complex and stimulate B cells to divide


B Cells: Humoral Immune Response

• Antibodies are proteins in class immunoglobulins (Ig), which is subdivided into subclasses based on structure and function of the specific proteins IgM - Secreted during primary response IgG - Secreted during secondary response IgD - Receptors for antigens on B cells IgA - Found in external secretions IgF - Promote histamine release





Antibodies

• Structure of Antibodies Each antibody consists of two short

polypeptides, light chains, and two identical long chains, heavy chains.

- Antibodies with the same variable segments have identical clefts and therefore recognize the same antigen.




Antibodies

• Antibody Diversity Estimated human B cells can make

between 106 and 109 different antibody molecules.

Immune receptor genes are assembled by stitching together three or four DNA segments that code for different parts of the receptor molecule.

- Somatic Rearrangement- And a lot more…



Immunological Tolerance

• Immune response does not respond to the animal’s own tissue Immune system of an embryo is able to

respond to both foreign and self molecules- Loses ability to respond to self

molecules as development proceeds- If regained as adult result is autoimmune

disease


Active Immunity Through Clonal Selection• Binding of antigen to its receptor on the

lymphocyte surface stimulates cell division and produces a clone (clonal selection) of memory cells Primary Immune Response carried out by

“original cells from this proliferation Secondary Immune Response occurs

when body is again invaded by same pathogen/antigen and this time body starts with a large clone of lymphocytes that recognize the pathogen





Antibodies in Medical Diagnosis

• Blood Typing • (ABO System)

The immune system is tolerant to its own red blood cell antigens.

- People with type A blood make antibodies against the B antigen and vise-versa.

- People who are type AB do not produce anti-A or anti-B antibodies.

- People who are type O have both anti-A and anti-B antibodies.




• Rh Factor People who have Rh antigen are Rh-

Positive and people who do not have the antigen are Rh-Negative

- If a mother produces antibodies against the Rh factor and her second child is Rh-positive, the antibodies can cause hemolysis of the Rh-Positive red blood cells of the fetus

Erythroblastosis fetalis



• Monoclonal Antibodies Monoclonal antibodies exhibit specificity

for one antigenic determinant Animal is injected with an antigen, and

subsequently killed- B lymphocytes are then obtained from

the animal’s spleen and placed in incubation vessels

Hybridized with cancerous multiple myeloma cells




• Development of much more sensitive clinical laboratory tests Monoclonal antibodies react against one

specific antigen- Modern pregnancy tests


(hCG)


Evolution of the Immune System

• Bacteria Defend against viral invasion through

restriction endonucleases that degrade foreign DNA lacking specific DNA pattern

• Invertebrates Mark cell surfaces with self labels

- Employ negative test May not recognize cells that resemble

self marker as foreign



• Shared Elements of Invertebrate and Vertebrate Immune Responses Phagocytes Distinguishing Self from Non-Self Lymphocytes Immunoglobulins

- Antibodies in vertebrates- Lectins in invertebrates



• Vertebrates Modern vertebrate immune system first

arose in fish with jaws- Sharks are oldest surviving group

Have immune response much like that in mammals



T Cell Destruction: AIDS

• The AIDS retrovirus (HIV) mounts a direct attack on CD4+ T cells

• HIV’s attack on CD4+ T cells cripples the immune system in at least three ways: HIV-infected cells die only after releasing

replicated viruses HIV causes infected cells to secrete a

soluble suppressing factor that blocks other T cells from responding

May block transcription of MHC genes




T Cell Destruction: AIDS

• Treatment was limited to drugs that inhibit reverse transcriptase (AZT) Recently, protease inhibitors have become

available- Inhibit enzyme necessary for viral

assembly Like the influenza virus, HIV engages in

some form of antigen shifting, making it difficult to develop an effective vaccine.



Antigen Shifting

• Pathogen may defeat the immune system by mutating frequently so that it varies the nature of its surface antigens. By the time a significant number of

antibodies have been generated against one form of a protein, another form is already present in the population.

- Survives immunological attack and reproduces

- Trypanosomes/sleeping sickness


Autoimmunity and Allergy• Autoimmune diseases are produced by a

failure of the immune system to recognize and tolerate self antigens Results in the activation of autoreactive T

cells and production on of autoantibodies by B cells

More than 40 known human autoimmune diseases

Treated by suppressing immune system and/or antiinflammatory drugs (e.g. aspirin)


Autoimmunity and Allergy

• Allergy refers to particular types of abnormal immune responses to antigens - allergens Immediate Hypersensitivity - Due to an

abnormal B cell response to an allergen that produces symptoms within seconds or minutes, IgE involved

Delayed Hypersensitivity - Abnormal T cell response that produces symptoms within about 48 hours after allergen exposure


Autoimmunity and Allergy

• Mast cells initiate inflammatory response Release histamine causing capillaries to

swell- Widespread and excessive release of

histamine may cause Anaphylactic Shock (an uncontrolled fall in blood pressure)




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Chapter 57