Primary FunctionPrimary Function

To Protect the body from invaders.To Protect the body from invaders. Specific and Non Specific MechanismsSpecific and Non Specific Mechanisms Cellular as well as chemical attacks are Cellular as well as chemical attacks are

mounted against the pathogens!mounted against the pathogens! Antigen – the identified enemy.Antigen – the identified enemy. Specific cellular soldiers include the B Specific cellular soldiers include the B

cells and T cells.cells and T cells. Non-specific cellular soldiers include Non-specific cellular soldiers include

MacrophagesMacrophages

Perks if the Immune SystemPerks if the Immune System

The immune system Ha s the ability to The immune system Ha s the ability to recognize self from non-self.recognize self from non-self.

Small number of genes used to make a Small number of genes used to make a vast array of recognition structures.vast array of recognition structures.

Responds to pathogens and not Responds to pathogens and not pollen(usually)pollen(usually)

Has memory.Has memory.

Horse

Lining of the Trachea

Mucus secreting cells( orange ) trap microbes

Cilia( yellow ) sweep microbes into mucous

First Line of DefenseFirst Line of Defense

Skin provides a physical as well as a Skin provides a physical as well as a chemical barrier.chemical barrier.

Mucous containing enzymes like lysozyme Mucous containing enzymes like lysozyme trap and kill organisms.trap and kill organisms.

Acidic environment of the stomach kills Acidic environment of the stomach kills bacteria.bacteria.

However Hepatitis A can survive the gut However Hepatitis A can survive the gut and can spread through this means.and can spread through this means.

Second Line of DefenseSecond Line of Defense

If the invader makes it past the skin then non If the invader makes it past the skin then non specific cellular recruits are brought in.specific cellular recruits are brought in.

Inflammation ensues.Inflammation ensues. The primary function of the inflammatory The primary function of the inflammatory

response is to provide a means for these cellular response is to provide a means for these cellular recruits to get to the damaged area.recruits to get to the damaged area.

The response is initiated by chemicals released The response is initiated by chemicals released by damaged cells.by damaged cells.

Second Line PlayersSecond Line Players

MacrophagesMacrophages Natural Killer CellsNatural Killer Cells EosinophilsEosinophils Neutrophils-first to arrive and are also Neutrophils-first to arrive and are also

phagocytic but tend to self destruct and phagocytic but tend to self destruct and only last a few days.only last a few days.

BasophilsBasophils Mast CellsMast Cells

MacrophagesMacrophages

PhagocyticPhagocytic Differentiate from Differentiate from monocytes.monocytes. Secret super oxides and nitrous oxide to kill Secret super oxides and nitrous oxide to kill

bacteria.bacteria. Secrete lysozymes and work as a clean up Secrete lysozymes and work as a clean up

crew for cellular debris.crew for cellular debris. Are strategically placed in the body(spleen, Are strategically placed in the body(spleen,

lymph nodes and connective tissue)lymph nodes and connective tissue) Tuberculosis can live and reproduce in Tuberculosis can live and reproduce in

macrophages.macrophages.

MacrophageMacrophage

Phagocytosis of Bacteria by a Phagocytosis of Bacteria by a MacrophageMacrophage

Notice that macrophages have psuedopodia

Where Macrophages Hang Out in Where Macrophages Hang Out in the Bodythe Body

EosinophilsEosinophils

Kill larger parasites like the blood Kill larger parasites like the blood fluke(Schistosoma mansoni).fluke(Schistosoma mansoni).

Limited phagocytic abilities.Limited phagocytic abilities. Shoot cytoplasmic toxic granules at the Shoot cytoplasmic toxic granules at the

parasite and cause it to lyse.parasite and cause it to lyse.

Natural Killer CellsNatural Killer Cells

Do not directly attack microorganisms.Do not directly attack microorganisms. Kill virally infected cells and abnormal cells Kill virally infected cells and abnormal cells

like cancer cells.like cancer cells. Destruction of a virally infected cell causes Destruction of a virally infected cell causes

interferon to be released and protect interferon to be released and protect neighboring cells from viral infection.neighboring cells from viral infection.

Chemical Fighters of the First Line Chemical Fighters of the First Line of Defenseof Defense

Chemokines attract the cells of the non-specific Chemokines attract the cells of the non-specific response. (Chemotaxis)response. (Chemotaxis)

Pyrogens induce fever to kill pathogen.Pyrogens induce fever to kill pathogen. Septic shock is a systemic non specific response Septic shock is a systemic non specific response

and can kill the patient in 24 hours. and can kill the patient in 24 hours. Septic shock can result in high fevers and a drastice Septic shock can result in high fevers and a drastice

potentially lethal drop in blood pressure.potentially lethal drop in blood pressure.

Complement System: a group of proteins that Complement System: a group of proteins that lyse microbes.lyse microbes.

The Inflammatory ResponseThe Inflammatory Response

Primary function is to increase the Primary function is to increase the local blood supply to the affected local blood supply to the affected areas.areas.– Precappilary atriolesPrecappilary atrioles dilate to increase dilate to increase

blood supply coming from the heart.blood supply coming from the heart.– Post capillary veniolesPost capillary venioles constrict to keep constrict to keep

the blood in the damaged area. This the blood in the damaged area. This causes swelling(edema) and redness.causes swelling(edema) and redness.

– Interstitial fluidInterstitial fluid (fluid between cells) also (fluid between cells) also moves into the area because moves into the area because macrophages reside there.macrophages reside there.

Signals That Initiate the Signals That Initiate the Inflammotory responseInflammotory response

Basophils and Mast cells produce Basophils and Mast cells produce histamine.histamine.

Histamine causes blood vessels to Histamine causes blood vessels to dilatedilate

ProstaglandinsProstaglandins are also produced by are also produced by damaged tissue. Iniates pain.damaged tissue. Iniates pain.

Clotting is a sign of repair and Clotting is a sign of repair and platelets are involed.platelets are involed.

The Inflammatory ResponseThe Inflammatory Response

NeutrophilNeutrophil

Third Line of DefenseThird Line of Defense

Specific responseSpecific response Cellular components that recognize and destroy Cellular components that recognize and destroy

specific antigens.specific antigens. The specific attack is launched by:The specific attack is launched by:

B CellsB Cells T cellsT cells

Antigenic receptorsAntigenic receptors are proteins embedded in are proteins embedded in the plasma membrane of B cells and T cells that the plasma membrane of B cells and T cells that recognize specific antigensrecognize specific antigens

B cells may produce B cells may produce antibodiesantibodies..

Genetic Basis for SpecificityGenetic Basis for Specificity B and T lymphocytes bear about 100,000 B and T lymphocytes bear about 100,000

receptors for antigen with the exact same receptors for antigen with the exact same specificity.specificity.

As undifferentiated T and B cells gain specificity As undifferentiated T and B cells gain specificity they link together several segments of antibody they link together several segments of antibody genes to create unique peptides that make up genes to create unique peptides that make up the antigen receptors. the antigen receptors.

This occurs before the effector cell has seen the This occurs before the effector cell has seen the antigen.antigen.

This allows the immune system to respond to an This allows the immune system to respond to an enormous variety of antigens. enormous variety of antigens.

Selective Response

Humoral response Cell mediated Response

B Cells T Cells

Antibodies Activate other cells

Memory Cells

Free Floating anitgens Infected Cells

i

Clonal SelectionClonal Selection

Clonal SelectionClonal Selection

43-06-RoleOfBCells.mov

Clonal SelectionClonal Selection

Primary Immune ResponsePrimary Immune Response

Occurs the first time the body is exposed Occurs the first time the body is exposed to the antigen.to the antigen.

Takes 10-17 days after antigen exposure Takes 10-17 days after antigen exposure to create the maximum effector response.to create the maximum effector response.

Specific B cells and T cells generate Specific B cells and T cells generate plasma cellsplasma cells that produce antibodies. that produce antibodies.

These cells clear antigen from the body.These cells clear antigen from the body.

Secondary Immune ResponseSecondary Immune Response

On the second exposure to the same On the second exposure to the same antigen a more rapid response occurs(2-7 antigen a more rapid response occurs(2-7 days) due to memory.days) due to memory.

The response is greater and lasts longer.The response is greater and lasts longer. Antibodies have a higher affinity for the Antibodies have a higher affinity for the

antigen.antigen. Known as Known as immunological memory.immunological memory.

Where do Lymphocytes Develop?Where do Lymphocytes Develop?

Lymphocytes develop from Lymphocytes develop from pluripotent pluripotent stem cells.stem cells.

Lymphocytes that migrate from the bone Lymphocytes that migrate from the bone marrow to the Thymus become T cells.marrow to the Thymus become T cells.

Lymphocytes that remain in the bone Lymphocytes that remain in the bone marrow become B cells.marrow become B cells.

Primary Verses Secondary Primary Verses Secondary ResponseResponse

How Lymphocytes Distinguish How Lymphocytes Distinguish “Self” From “Non-self”“Self” From “Non-self”

Newly differentiated lymphocytes that Newly differentiated lymphocytes that react with receptors on body cells are react with receptors on body cells are made non-functional or programmed for made non-functional or programmed for cell death (cell death (apoptosisapoptosis).).

Failure of these to recognize self from Failure of these to recognize self from non-self leas to auto immune diseases like non-self leas to auto immune diseases like Multiple Sclerosis.Multiple Sclerosis.

Major Histocampatibility Major Histocampatibility Proteins(MHCProteins(MHC))

MHC proteins are present on body cells MHC proteins are present on body cells that distinguish the cell as “self”.that distinguish the cell as “self”.

T cells react with these proteins to T cells react with these proteins to facilitate a specific response.facilitate a specific response.

There are two main classes of MHC There are two main classes of MHC proteins.proteins.

B lymphocyteB lymphocyte

MHC ProteinsMHC Proteins

Class I MHC proteins are found on almost all Class I MHC proteins are found on almost all nucleated cells.nucleated cells.

Class II MHC proteins are found on specialized Class II MHC proteins are found on specialized B cells activated by T cells, some macrophages B cells activated by T cells, some macrophages and cells that make up the interior of the thymus.and cells that make up the interior of the thymus.

MHC proteins are polymorphic and there are MHC proteins are polymorphic and there are many alleles for MHC proteins.many alleles for MHC proteins.

It is highly unlikely (with the exception of It is highly unlikely (with the exception of identical twins) that any two individuals have the identical twins) that any two individuals have the same MHC proteins.same MHC proteins.

Two Main Types of Cells that Two Main Types of Cells that respond to MHC Proteinsrespond to MHC Proteins

Antigen Presentation

MHC I MHC II

Cytotoxic T Cells T Helper Cells

Attack infected cells Involve antigen presenting cells

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Cell Mediated Response and Cytotoxic T Cell Mediated Response and Cytotoxic T CellsCells

More on MHC II and Helper T CellsMore on MHC II and Helper T Cells

Antigen presenting cells (APC) ingest the Antigen presenting cells (APC) ingest the antigen, break it down and present pieces antigen, break it down and present pieces of the antigen on its surface in the context of the antigen on its surface in the context of MHC II proteins.of MHC II proteins.

An additional protein called CD-4 An additional protein called CD-4 enhances the binding of the helper T cells enhances the binding of the helper T cells to the APC.to the APC.

APC Cells may be specialized APC Cells may be specialized macrophages or B cellsmacrophages or B cells

MHC II and Helper T CellsMHC II and Helper T Cells

When Helper T cells bind to the APC:When Helper T cells bind to the APC: Clones of activated helper T cells proliferate.Clones of activated helper T cells proliferate. Activated T helper cells secrete Activated T helper cells secrete Interleukin II.Interleukin II.

• Causes B cells that have seen the antigen to Causes B cells that have seen the antigen to differentiate into plasma cells.differentiate into plasma cells.

APC also secrete APC also secrete Interleukin IInterleukin I that stimulated that stimulated T cells to secrete interleukin II.T cells to secrete interleukin II.

Action of Cytotoxic T CellsAction of Cytotoxic T Cells

Cell Mediated responseCell Mediated response

T Dependent Verses T Independent T Dependent Verses T Independent AnitgensAnitgens

T Dependent antigensT Dependent antigens are antigens that are antigens that stimulate cause T cells to stimulate B stimulate cause T cells to stimulate B cells.cells.

T Independent anitgensT Independent anitgens are antigens that are antigens that that do not involve T cells and stimulate that do not involve T cells and stimulate the production of plasma cells.the production of plasma cells. Usually polysacharrides form bacterial Usually polysacharrides form bacterial

capsules, parts of the flagella or toxins.capsules, parts of the flagella or toxins. Elicits a weaker response with no memory Elicits a weaker response with no memory

cells.cells.

T Dependent AntigensT Dependent Antigens

Antibody Structure and FunctionAntibody Structure and Function

Epitopes ( antigenic determinates)Epitopes ( antigenic determinates) are are accessilble parts of the antigen that bind to accessilble parts of the antigen that bind to the antibody.the antibody. One bacterial cell can be bound to as many One bacterial cell can be bound to as many

as 4 million antibodies.as 4 million antibodies. There may be many different epitopes present There may be many different epitopes present

on a single pathogen.on a single pathogen. Antibodies are known as serum proteins Antibodies are known as serum proteins

called called Immunoglobulins.Immunoglobulins.

Antigens Can Have Many EpitopesAntigens Can Have Many Epitopes

ImmunoglobulinsImmunoglobulins

Consists of 4 polypeptide chains.Consists of 4 polypeptide chains. Two constant heavy chains and two variable Two constant heavy chains and two variable

light chains.light chains.• The variable region binds to the epitope.The variable region binds to the epitope.• The constant region determines what type of The constant region determines what type of

antibody it is.antibody it is.

Monoclonal antibodiesMonoclonal antibodies are manufactured in are manufactured in the lab for clinical use and research the lab for clinical use and research studies.studies.

Antibody StructureAntibody Structure

Types of ImmunoglobulinsTypes of Immunoglobulins IgM IgM - Largest and cannot cross the placenta with - Largest and cannot cross the placenta with

many sites. Involved in agglutination.many sites. Involved in agglutination. IgGIgG - Most abundant and small enough to cross - Most abundant and small enough to cross

the placenta. Usually the first to arrive.the placenta. Usually the first to arrive. IgA IgA - Found on mucous membranes and are - Found on mucous membranes and are

found in breast milk. Protect abaies from found in breast milk. Protect abaies from gastrointestinal infection.gastrointestinal infection.

IgDIgD - Found on the surface of B cells and most - Found on the surface of B cells and most like initiate plasma cell production.like initiate plasma cell production.

IgEIgE – Tails attach to basophils and mast cells – Tails attach to basophils and mast cells and trigger the release of histamine.and trigger the release of histamine.

Antibody Mediated Disposal of the AntigenAntibody Mediated Disposal of the Antigen Neutralization - Neutralization - Antibody binds and blocks the Antibody binds and blocks the

activity of the antigen.activity of the antigen. Opsonization – Opsonization – Antibody attaches to antigen and Antibody attaches to antigen and

facilitates phagocytosis by macrophages.facilitates phagocytosis by macrophages. Agglutination – Agglutination – Antibody clumps antigen Antibody clumps antigen

together and precipitates it out of body fluids and together and precipitates it out of body fluids and facilitaes phagocytosis by macrophages.facilitaes phagocytosis by macrophages.

Complement System – Complement System – antibodies bind to antibodies bind to complement proteins and chemicals are release complement proteins and chemicals are release to put holes in the pathogen membrane.to put holes in the pathogen membrane.

Immune Adherence- Immune Adherence- Antigen coated with Antigen coated with antibodies and complement proteins adhere to antibodies and complement proteins adhere to the walls of blood vessels immobilizing than for the walls of blood vessels immobilizing than for phagocytosis.phagocytosis.

Complement SystemComplement System

Allergies Activated HistamineAllergies Activated Histamine ReleaseRelease

T Cell With HIVT Cell With HIV

Active Verses Passive ImmunityActive Verses Passive Immunity

Active immunity individuals make their own Active immunity individuals make their own antibodies due to exposure to the antigen. antibodies due to exposure to the antigen. Lasting immunityLasting immunity Can be induced by vaccination.Can be induced by vaccination.

Passive immunity occurs when antibodies are Passive immunity occurs when antibodies are passed from one individual to another.passed from one individual to another. Temporary and an immediate fix (rabies).Temporary and an immediate fix (rabies). Occurs naturally from mother to infant (IgG and IgA)Occurs naturally from mother to infant (IgG and IgA)

Blood TransfusionsBlood Transfusions

The immune reaction of patients receiving the wrong blood The immune reaction of patients receiving the wrong blood type will agglutinate surface antigens present on red type will agglutinate surface antigens present on red blood cells. The result is lethal.blood cells. The result is lethal.

Mothers and Rh factors. If the Mother is Rh negative and the baby is Mothers and Rh factors. If the Mother is Rh negative and the baby is Rh positive, during delivery when fetal and maternal blood is Rh positive, during delivery when fetal and maternal blood is exchanged the mother will produce antibodies against the Rh exchanged the mother will produce antibodies against the Rh antigen.antigen.

The problem occurs during the second pregnancy with an Rh positive The problem occurs during the second pregnancy with an Rh positive fetus.fetus.

Remedy – the mother is injected with antibodies against Rh antibodies Remedy – the mother is injected with antibodies against Rh antibodies

AllergiesAllergies

Allergies - exaggerated response to Allergies - exaggerated response to environmental antigens.environmental antigens.

- - Usually involves IgE.Usually involves IgE.

- - Some of the IgE antibodies will attach Some of the IgE antibodies will attach themselves themselves to mast cells instead of pollen and on to mast cells instead of pollen and on subsequent subsequent exposures to pollen stimulate the release exposures to pollen stimulate the release of of histamine.histamine.

Anaphylactic Shock – a massive release of Anaphylactic Shock – a massive release of histamine causes a lethal drop in blood pressurehistamine causes a lethal drop in blood pressure

-Individuals at risk carry epinephrine.-Individuals at risk carry epinephrine.

Transplanted tissuesTransplanted tissues

Graft verses Host Disease – Rejection of Graft verses Host Disease – Rejection of transplanted tissues due to incompatible transplanted tissues due to incompatible MHC proteins.MHC proteins.

May remedied by the regeneration of the May remedied by the regeneration of the patients tissues in cell culture.patients tissues in cell culture.

Currently close MHC matches are sought Currently close MHC matches are sought out.out.

HIV BuddingHIV Budding

Immunodeficiency DiseasesImmunodeficiency Diseases Scid(severe combined immunodeficiency).Scid(severe combined immunodeficiency).

Genetic Genetic Missing the functional enzyme called adenosine Missing the functional enzyme called adenosine

deaminase(ADA)deaminase(ADA) Both branches of the immune system fail.Both branches of the immune system fail. Usually requires bone marrow transplant.Usually requires bone marrow transplant. Gene therapy is being tried to replace the ADA gene Gene therapy is being tried to replace the ADA gene

but the results are unequivocal.but the results are unequivocal. Hodgkins LymphomaHodgkins Lymphoma

A type of cancerA type of cancer Damages lymphatic system.Damages lymphatic system.

Acquired Immunodeficiency Disease(AIDS)Acquired Immunodeficiency Disease(AIDS) viralviral

AIDSAIDS Caused by a retrovirus called Human Caused by a retrovirus called Human

immunodeficiency virus.immunodeficiency virus.

Patients with AIDS are highly susceptible Patients with AIDS are highly susceptible to opportunistic infections.to opportunistic infections. Typically die of Typically die of pneumocystitis pneumocystitis

• Pneumocystis carinii Pneumocystis carinii (protozoan)(protozoan)

HIV Mode of InfectionHIV Mode of Infection

Two major strains- HIV-1 and HIV-2Two major strains- HIV-1 and HIV-2 Infects T helper (CD-4) cells.Infects T helper (CD-4) cells.

CD-4 along with a coreceptor called fusinCD-4 along with a coreceptor called fusin is its mode of entry.is its mode of entry. Fusin is usually a receptor for chemokines. Fusin is usually a receptor for chemokines.

Chemokines can suppress HIV-1 infection Chemokines can suppress HIV-1 infection because they compete with the virus for the because they compete with the virus for the receptor.receptor.

Some individuals are have defective receptors Some individuals are have defective receptors and are resistant to HIV infection.and are resistant to HIV infection.

HIV Replication in the HostHIV Replication in the Host

HIV makes DNA from RNA using reverse HIV makes DNA from RNA using reverse transcriptase and integrates itself into the transcriptase and integrates itself into the host chromosome.host chromosome.

As a provirus it continues to replicate its As a provirus it continues to replicate its viral proteins for the life of the host cell.viral proteins for the life of the host cell.

Evades the host cell in this way.Evades the host cell in this way.

HIV BuddingHIV Budding

HIV Infection StagesHIV Infection Stages

ArthritisArthritis