Immune Systerm

7/30/2019 Immune Systerm

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The Immune SystemChapter 43

Animal Defenses

Two categories: Innate Immunity

Does not distinguish one infectious agent from another

Acquired Immunity Responds in specific ways to particular toxins, microorganisms, aberrant

body cells, and other substances marked as foreign molecules

Innate Immunity Two types ofInnate Immunity:

External Defenses First Line of Defense

Physical barriers (Epithelium) Skin Mucus membranes

Internal Defenses Second Line of Defense

Phagocytic cells Antimicrobial proteins

Both come into play when external defenses have been compromised

Acquired Immunity The Immune System

The third line of defense Comes into play if the first two lines of defense have been compromised

Specific defensive proteins called antibodies are produced by lymphocytes

First Line of Defense Physical Barriers

Skin Cannot normally be penetrated by bacteria and viruses

But, even minute abrasions allow their passage Secreations from sebaceous and sweat glands keep the

skin in a pH range of 3 to 5 (acidic) Kills most microbes

Microbial colonization is also inhibited by saliva, tears, and mucussecretions that continually bathe exposed epithelium

All of these secretions contain antimicrobial proteins An example is lysozyme, an enzyme that digests the cell walls of many bacteria.


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Mucus Membranes

Line digestive, respiratory, and genitourinary tracts Also prevents entry of harmful microbes Traps microbes and particles

In the trachea, ciliated epithelial cells sweep out mucus and trappedmicrobes

Prevents these from entering the lungs Exposes them to the acidic environment of the stomach

Kills most microbes Hepatitis A is an exception (can survive this)

Second Line of Defense Depends mainly on phagocytosis

The ingestion of invading organisms by certain types of white blood cellsPhagocytic Cells

Macrophages 5% of leukocytes Specialized cells that develop from monocytes Large, long-lived phagocytes Cells extend long pseudopodia, engulf the microbe into a vacuole which fuses with a

lysosome. Lysosomes kill in two ways

By generating toxins such as nitric oxide

By digetsing microbes with lysozyme

Evading Macrophages

Some microbes have outer capsules to which macrophages cannot attach Others, like Mycobacterium tuberculosis, are resistant to lysosomal destruction

Esinophils Only 1.5% of leukocytes

Help fight large parasitic invaderso e.g. Schistosoma mansoni (blood fluke)o They position themselves alongside the parasite and discharge destructive

enzymes from cytoplasmic granules

Neutrophils

60-70% of all leukocytes Usually the first to arrive

Attracted to chemical signals released by infected tissue Self-destruct while destroying invaders

Life Span is short


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Natural Killer Cells

Do not attack microbes directly They destroy infected cells

Typically those infected with viruses Also attack abnormal body cells that could become cancerous They attack the cells membrane and cause the cell to lyse

Antimicrobial Proteins

A variety of proteinsThey function in nonspecific defense

Attack microbes directly Or impede microbe reproduction Lysozyme and other antimicrobial proteins are known collectively as the

complement system

(including about 20 serum proteins)Interferons

Another set of proteins Nonspecific defense Secreted by virus-infected cells

Do not benefit the infected cell but induce neighboring cells to producechemicals that inhibit viral reproduction

Inflammatory Response Tissue damages leads to a localized inflammatory response

Could be injury Could be invasion by microbes

Capillaries Respond by Increased dilation Increased permeability Leads to increased redness, heat, and swelling

Histamine Release

Inflammation sets offhistamine release Histamine is released by special leukocytes called basophils and by mast cells in

connective tissue

Histamine triggers both increased dilation and permeability of nearby capillaries

Enhanced Blood Flow In addition to histamine, damaged tissues also release prostaglandins and

other substances the also promote blood flow to the injured site Enhances delivery of clotting elements

Blocks spread of microbes

Enhances migration of phagocytic cells


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Rapid Response to Invasion

Neutrophils are the first phagocytes to arrive Next are macrophages

Macrophages consume pathogens and their products Macrophages also consume damaged tissue cells and the remains of neutrophils

The dead phagocytic cells and fluids leaked from capillaries is called pus

Systemic Response If damage or infection is severe, a widespread non-specific

response may occurThis is called a systemic response The number of leukocytes in the blood may increase several-fold

within a few hours Feveris a systemic response

Increased body temperature

May be triggered by toxins or by pyrogens released from leukocytes Inhibits growth of some microbes Facilitates phagocytosis Speeds up repair of tissue

Septic Shock

An overwhelming systemic inflammatory response Characterized by

High fever Low Blood pressure

The most common form of death in U.S. Critical Care Units

Local Inflammation is an essential step toward healing Widespread inflammation can be devastating

Acquired Immunity The third line of defense The key cells of the third line of defense are lymphocytes

Two Main Types B Cells

Mature in Bone marrow

T Cells Mature in the Thymus

Both cell types circulate through the blood Both are concentrated in the

Spleen Live Other Lymphatic tissues


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Lymphocytes

Recognize and respond to particular microbes and foreignmolecules (antigens)This is called specificity

Antigens Viruses Bacteria Fungi Protozoa Parasitic worms Non-pathogens

Pollen Transplanted tissue

Antibodies

Proteins produced by B cells Each antigen has a unique molecular shape

Stimulates certain B cells to secrete antibodies to interact specifically with it

B and T cells recognize specific antigens through their plasma membrane-boundantigen receptors

Antigen Receptors

A single B or T cells has about 100,000 receptors, all with exactly the samespecificity

There is an enormous variety of B and T cells in the body, each withdifferent specificity

This allows response to millions of potential pathogens

Immune Response Antigens encountered many, many lymphocytes Only those with specificity for that antigen interact with it

This stimulates the lymphocyte to divide and differentiate intoto different clonal lines of cells

Effector Cells Short-lived cells that combat the same antigen

Memory Cells Long-lived cells bearing receptors for the same antigen

Eventually, a few cells give rise to thousands of new cellsallspecific to the invading antigen


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Immune Response

First exposure Primary immune response

About 10 to 17 days required for peak effector cell response

Second (and subsequent) Exposure Secondary immune response Response is faster (2 to 7 days) Magnitude is greater Duration is longer

Immunological Memory

The ability of the immune system to generate a secondary immuneresponse is called immunological memory Based on clones of long-lived B and T cells

Self vs. Non-Self Healthy immune systems do not attack healthy cells from their own body Lymphocytes originate from pleuropotent stem cells in the bone marrow or

liver of a developing fetus If they migrate to the thymus and mature there, then they become T cells If they stay in the bone marrow and mature there, then they become B cells

While B cells and T cells are developing, their antigen receptors are tested forpotential self-reactivity

If they are self-reactive, they are rendered non-functional or destroyed byapoptosis (programmed cell death)

This leaves only lymphocytes that react to foreign substancesAuto immune Diseases

A failure of self tolerance or recognitionThe bodys immune system attacks specific tissues within the body

Examples: Lupus Multiple Sclerosis Rheumatoid Arthritis

Recognizing Self

Cell surface glycoproteins identify individuals These are encoded by a family of genes called

major histocompatability complexes (MHC) Class I MHC

Found on almost every cell

Class II MHC Found only on specific cells, including macrophages, B cells, activated T cells, and those of the

thymus


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MHCs

For vertebrates there are numerous alleles for each class I and class II MHCgene

These produce the most polymorphic proteins known

Most of us are heterozygous for every one of our MHC genes These create a unique biochemical fingerprint for every one of usexceptidentical twins

MHC protein molecules capture and cradle fragments of intercellular proteinantigens and carry these to the cells surface

The MHC molecules present the antigen on the cell surface so that T cellreceptors can receive it

T Cells

Each responds to one type of MHC molecule Cytotoxic T Cells (TC)These have antigen receptors that bind protein fragments displayed by the bodies

Class I MHC molecules Destroy virally infected cells and tumor cells, and are also implicated in transplant

rejection

Helper T cells (TH)These have receptors that bind to protein fragments presented by class II MHC

molecules Once activated, they divide rapidly and secrete small proteins called cytokines that

regulate or help the immune response

The response of a T cell depends on the ability of MHC molecules topresent a protein fragment to it An MHC molecule can present of variety of peptides that are structurally similar Plus, we usually make two different MHC polypeptides per geneThus, chances are good that one fragment of any pathogen will be presented by MHC

molecules to our T cells, generating an immune response

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