The immune system

THE IMMUNE SYSTEM

IMMUNOLOGY AND THE IMMUNE SYSTEM

• Immunology– Study of the components and function of the immune system

• Immune System – Molecules, cells, tissues and organs which provide non-specific

and specific protection against• Microorganisms• Microbial toxins• Tumor cells

– Crucial to human survival– Antigens :– Molecules from a pathogen or foreign organism that provoke a

specific immune response.

The Invaders . . .

• Bacteria

• Viruses

• parasites such as fungi, protista, & worms

worm trichura.jpg

http://www.hhs.gov/asphep/presentation/images/bacteria.jpg

http://www.skidmore.edu/academics/biology/plant_bio/lab13.FUNGI.html

Types Of Immune System

• Immune response– Innate (non-specific)– Adaptive (specific)

• Primary • Secondary

• These two systems perform many of their functions by cooperative interactions

Defense Mechanisms

Chapter 21, Immune System 6

Immunity: Innate (nonspecific)

• immunity an organism is born with.• system responds quickly and consists of:

– First line of defense – intact skin and mucosae prevent entry of microorganisms

– Second line of defense – antimicrobial proteins, phagocytes, and other cells

• Inhibit spread of invaders throughout the body• Inflammation is its hallmark and most important

mechanism


Immunity: Adaptive (specific) defense system

– Third line of defense – mounts attack against particular foreign substance.

– Immunity that an organism develops during life time.

– Develops only after exposure to including agents such as microbs, toxins, or other foreign substances.

• Takes longer to react than the innate system• Works in conjunction with the innate system

First line of defenses / innate immune system

• The body’s 1st line of defense against pathogens uses mostly physical and chemical barriers such as :

• Skin- acts as a barrier to invasion• Sweat- has chemicals which can kill different pathogens.• Tears – have lysozymes which has powerful digestive abilities

that render antigens harmless .• Saliva – also has lysozymes• Mucus – can trap pathogens, which are than sneezed,

coughed, washed away, or destroyed by chemicals • Stomach acids – destroys pathogens .

Body Coverings: The Skin


Epithelial Chemical Barriers

• Epithelial membranes produce protective chemicals that destroy microorganisms– Skin acidity (pH of 3 to 5) inhibits bacterial growth– Sebum contains chemicals toxic to bacteria– Stomach mucosae secrete concentrated HCl and

protein-digesting enzymes– Saliva and lacrimal fluid contain lysozyme– Mucus traps microorganisms that enter the

digestive and respiratory systems


Respiratory Tract Mucosae

• Mucus-coated hairs in the nose trap inhaled particles

• Mucosa of the upper respiratory tract is ciliated– Cilia sweep dust- and bacteria-laden mucus away

from lower respiratory passages

1st line of defense (Respiratory and Digestive System

• The respiratory passage is lined with mucous

• Cilia also lines the respiratory passage

• There is mucous in the respiratory passage that traps invading microbes and other foreign debris with the cilia.

• Acids in the stomach and protein digesting enzymes destroy most of the invading microbes carried into the body with food.

Immune System Overview: Goals

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Second line of defense

• If a pathogen is able to get past the body’s first line of defense, and an infection starts , the body can rely on it’s second line of defense .


Internal Defenses (Second Line of Defense)

• The body uses nonspecific cellular and chemical devices to protect itself

1. Phagocytes 2. natural killer (NK) cells3. Inflammatory response enlists macrophages,

mast cells, WBCs, and chemicals4. Antimicrobial proteins in blood and tissue fluid

• Harmful substances are identified by surface carbohydrates unique to infectious organisms

Leukocytes• also called white blood cells are large opaque blood cells that engulf invading microbes. They can also produce antibodies.– They have a nucleus (so different

from red blood cells)– The size of the nucleus and the

types of granules that can be found inside of them can be used to classify them into different classes of leukocytes.

• Granulocytes: have cytoplasmic granules and are made in the bone marrow.

• Agranulocytes: do not have a granular cytoplasm and are also made in the bone marrow, but then modified in the lymph nodes.

Nonspecific Phagocytosis

NeutrophilsMonocytesEosinophils

NeutrophilsMonocytesEosinophils


1. Phagocytes

• Macrophages are the chief phagocytic cells• Free macrophages wander throughout a region in search

of cellular debris• Kupffer cells (liver) and microglia (brain) are fixed

macrophages• Neutrophils become phagocytic when encountering

infectious material• Eosinophils are weakly phagocytic against parasitic

worms• Mast cells bind and ingest a wide range of bacteria


Mechanism of Phagocytosis

• Microbes adhere to the phagocyte• Pseudopods engulf the particle (antigen) into a

phagosome• Phagosomes fuse with a lysosome to form a

phagolysosome• Invaders in the phagolysosome are digested by

proteolytic enzymes• Indigestible and residual material is removed by

exocytosis


Mechanism of Phagocytosis

Figure 21.1a, b

Natural killer cells

Lymphocytes, such as NK cells, are characterized by their large nuclei that actively absorb Wright stain and therefore appear dark colored under a microscope.


2. Natural Killer (NK) Cells• Cells that can lyse and kill cancer cells and virus-infected

cells• Natural killer cells:

– Are a small, distinct group of large granular lymphocytes – React nonspecifically and eliminate cancerous and virus-

infected cells– Kill their target cells by releasing perforins and other

cytolytic chemicals– Secrete potent chemicals that enhance the

inflammatory response


3. Inflammation: Tissue Response to Injury

• The inflammatory response is triggered whenever body tissues are injured – Prevents the spread of damaging agents to nearby

tissues– Disposes of cell debris and pathogens– Sets the stage for repair processes

• The four cardinal signs of acute inflammation are redness, heat, swelling, and pain

Inflammatory Response

Histamine & prostaglandins released

Capillaries dilateClotting begins

Chemotactic factors attract phagocytic cells

Phagocytes consume pathogens & cell debris


4. Antimicrobial Proteins

• Enhance the innate defenses by:– Attacking microorganisms directly– Hindering microorganisms’ ability to reproduce

• The most important antimicrobial proteins are:– Interferon– Complement proteins

Interferon

• Protein secreted by a cell currently infected by a virus

• Interferon warns the neighboring cells of the impending viral infection

• The neighboring cells synthesize proteins that will block the virus from hijacking the cell DNA replication machinery


Interferon (IFN)

Figure 21.4


• Complement helps destroy pathogens• in three ways:• 1. Enhanced inflammation.• Complement proteins are• involved in and amplify the inflammatory response• because certain ones can bind to mast cells (type of• white blood cell in tissues) and trigger histamine• release, and others can attract phagocytes to the scene.• 2.

Complement Pathways


2.Some complement proteins bind to the surface ofpathogens already coated with antibodies, whichensures that the pathogens will be phagocytized by aneutrophil or macrophage.3. Certain other complement proteins join to form amembrane attack complex that produces holes in thesurface of some bacteria and viruses. Fluids and saltsthen enter the bacterial cell or virus to the point that itbursts .

Complement systems

Formation of membrane attack complexes


• Abnormally high body temperature in response to invading microorganisms

• The body’s thermostat is reset upwards in response to pyrogens, chemicals secreted by leukocytes and macrophages exposed to bacteria and other foreign substances

Fever


• High fevers are dangerous as they can denature enzymes

• Moderate fever can be beneficial, as it causes:– The liver and spleen to sequester iron and zinc

(needed by microorganisms)– An increase in the metabolic rate, which speeds

up tissue repair

Fever

Adaptive Immunity

• Immunity that an organism develops during lifetime

• Develops after exposure to antigens• Invovles the activity of lymphocytes• Includes 3rd line of defense

Adaptive Immunity (Specific immunity)

• Specificity

• Memory

• Ability to distinguish b/w self vs non-self

• T and B cell

Types of Adaptive Immunity

1. Antibody-Mediated Immunity (AMI) or Humoral Immunity– B lymphocytes

2. Cell-Mediated Immunity (CMI) or Cellular Immunity– T lymphocytes

Note: B and T cells ……..blood, lymph, lymphoid tissues such as spleen, lymph nodes etc.

Cell-Mediated Immune Response

• T cells

• Immune resoponse to infected cells( viruses, bacteria and parasites (Pathogens) within cells)

• Defense against cancer and transplant cells


T-Lymphocytes

• Helper T cells – secrete CYTOKINES help B cells Tc cells to divide• Cytotoxic T cells (killer T cells) Kill infected body cells• Memory T cells remain in body

How do T cells know a cell is infected?• Infected cells digest some pathogens and MHC

proteins carry pieces to cell surface• Antigen Presenting Cell (APC)• Alerts Helper T cells

MHC proteins displaying foreign antigens

infectedcell

T cell with antigen receptors

TH cell

Macrophages

Antigen-Presenting Cells

– B cells– Dendritic cells– macrophages

Helper T Cells (TH)

• bind to other white blood cells that have previously encountered an antigen– stimulate proliferation of other T cells– Stimulate B cells that have already become bound

to antigen

• Without TH, there is no immune response


The central role of Helper T Cells (Boss)

Chapter 21, Immune System 46Figure 21.17a

Cytotoxic T Cell (Tc)

• Destroys infected body cells– binds to target cell– secretes perforin protein

• punctures cell membrane of infected cell– apoptosis


Cytotoxic T cells

Killer T cellbinds to

infected cell

• Destroys infected body cells– binds to target cell– secretes perforin protein

• punctures cell membrane of infected cell– apoptosis

infected celldestroyed

Cytotoxic T cell

1

Accessoryprotein

Class I MHCmolecule

Infectedcell

Antigenreceptor

Antigenfragment

Cytotoxic T cell

1 2

Accessoryprotein

Class I MHCmolecule

Infectedcell

Antigenreceptor

Antigenfragment

Perforin

Pore

Gran-zymes

The killing action ofcytoxic T cells on an infected host cell.

Cytotoxic T cell

31 2

Accessoryprotein

Class I MHCmolecule

Infectedcell

Antigenreceptor

Antigenfragment

Perforin

Pore

Gran-zymes

ReleasedcytotoxicT cell

Dyinginfected cell

Figure 23.11 (1 of 2)

CMI

• Human Immunodeficiency Virus– virus infects and destroys helper T cells

• helper T cells don’t activate rest of immune system: killer T cells & B cells

• AIDS: Acquired ImmunoDeficiency Syndrome– infections by opportunistic

diseases– death usually from – “opportunistic” infections

• pneumonia, cancers

HIV & AIDS

HIV infected T cell

ANTIBODY-MEDIATED (HUMORAL) IMMUNITY

• targets extracellular microorganisms (Bacteria and viruses circulating in the blood)

• B-lymphocytes (B cells)………. Antibodies • Antibodies… extracellular fluids and surface of B

cells

Pathogen

1

Antigen-presentingcell Antigen

fragment

Class IIMHC

molecule

Antigenreceptor

Accessoryprotein

Helper T cell

Pathogen

1 2


fragment

Class IIMHC

molecule

Antigenreceptor

Accessoryprotein

Helper T cell

B cell

Cytokines

Activatedhelper T cell

Pathogen

31 2


fragment

Class IIMHC

molecule

Antigenreceptor

Accessoryprotein

Helper T cell

B cell

Cytokines

Activatedhelper T cell

Memory B cells

Plasma cellsSecreted

antibodies

Antibody-mediated (humoral) immunity = AMI

• 1- Macrophages phagocytize a pathogen and present an antigen to a matching helper-T cell

• 2- At the same time, some pathogens contact B-cells matching the pathogen’s antigens

• The helper-T cells multiply, secrete lymphokines which stimulate the B-cells to multiply and specialize into plasma cells

• The plasma cells secretes antibodies

The Nature of Antibodies

• Globular proteins called immunoglobulins• Basic antibody structure has 4 polypeptide chains

– 2 identical light chains– 2 identical heavy chains

• Regions of heavy and light chains– Variable– Constant

Antibody Molecule

antigen binding sites

antigen

light chains heavy chains

Immunoglobin Classes

IgM1st response to antigenCan’t cross placenta

IgGMost common formCrosses placenta (passive

immunity to fetus)

IgASecreted from mucus membranesIn colostrum

IgDB cell activationCan’t cross placenta

IgEHistamine reactions

and allergies (mast cells, basophils)

Types of Immunity

Active ImmunityNatural active immunity - acquired due to infectionArtificial active immunity – vaccination

Passive ImmunityNatural passive immunityplacenta to the fetusColostrumArtificial passive immunityInjection of immune serum

Types of Acquired Immunity

Summary

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QUESTIONS PLEASE

The immune system

Science

immune system overview

digestive system

line of defense respiratory

immune system immunology

innate system works

specific immune response

line of defense intact

line of defenses