Immune System

The immune system is the body’s response to

disease and injury.

Functional system rather than organ system

Two types of Immune Response:

Non-specific response (innate immunity): Basically just

recognizes foreign vs native

Specific response (acquired immunity)

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Innate: structural defenses; responds to non-specific

foreign substances

Present before any exposure to pathogens and is

effective from the time of birth

Adaptive: responds to specific foreign substances

Antigen-antibody relationship (acquired immunity)

Vaccinations depend on this

Involves lymphocytes (B, T and plasma cells)

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Originates in bone marrow

Rich supply of hematopoietic stem cells

Asymmetric cell division (one daughter stays in bone marrow)

Lymphoid and Myeloid lineage cells begin and are released from here

Differentiation into lymphoid

stem cells in the bone marrow – General B cells mature in the bone marrow

Differentiation into lymphoid

stem cells in the thymus – General T cells mature in the thymus

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Migration

Migration of mature general B and T cells to secondary lymphoid organs:

Lymph nodes

Spleen

Tonsils

External body surfaces (intestinal, respiratory, urinary, reproductive)

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Skin Physical barrier to microbes

Keratin resistant to most bacterial enzymes & toxins

Secretions are acidic pH 3-5

Mucosa Physical barrier & produces a variety of protective chemicals

Gastric mucosa Very acidic & produces proteolytic enzymes

Saliva & lacrimal fluid contain lysozyme

Mucous Traps bacteria & moves them away from epithelial surface

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Phagocytes

Macrophages: derived from monocyte

Free Macrophages: Roam through tissues

Fixed Macrophages: e.g. In liver & brain

Ingest cellular debris, foreign material, bacteria, fungi

Neutrophils: Ingest pathogens

Eosinophil: Weakly phagocytic of pathogens. Attack

parasites

Mast Cells: Phagocytic of various bacteria

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Phagocytes attach to their prey via surface receptors and engulf them, forming a

vacuole that fuses with a lysosome

Pseudopodia surround

microbes.

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Microbes are engulfed

into cell.

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Vacuole containing

microbes forms.

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Vacuole and lysosome

fuse.

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Toxic compounds

and lysosomal enzymes

destroy microbes.

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Microbial debris is

released by exocytosis.

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Microbes

MACROPHAGE

Vacuole Lysosome

containing

enzymes

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Natural Killer Cells:

Small population of large granular lymphocytes

Non specific for “non-self”

Not phagocytic: attack is by release of perforins that

perforate the target cell plasma membrane.

Shortly after perforation the target nucleus disintegrates.

Release chemicals that enhance the inflammatory response

Attack virus-infected body cells and cancer cells

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Inflammation

Tissue response to injury

Triggered by injury – trauma, heat, chemical irritation, infection, etc.

Beneficial effects Prevents spread of injury

Disposes of cellular debris & pathogens

Promotes repair

Signs of inflammation Redness

Heat

Swelling

Pain

Loss of function 12

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Antiviral proteins: Not virus specific.

Some cells produce & release interferon (IFNs) when invaded by virus

Released IFNs stimulate nearby cells to produce proteins (PKR) that interfere with viral replication by disrupting protein synthesis

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Complement – a group of plasma proteins (30) that

are activated in the presence of foreign substances

Complement activation

Enhances both innate & adaptive defenses

Enhances & amplifies inflammation

Bacteria & some other cell types are lysed

Innate & adaptive mechanisms

work together in a cohesive

fashion

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Specificity: directed at specific targets

Systemic: not restricted to initial site of infection / invasion

Memory: after initial exposure & activation, a more rapid & more vigorous response is made to subsequent exposures to pathogens (secondary response)

Components:

Humoral Immunity: (antibody mediated immunity) provided by

antibodies floating free in body fluids

Cell mediated immunity: Lymphocytes directly attack specific

invaders by lysis or indirect attack by initiating inflammation

and/or activating other lymphocytes & macrophages

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Antigen-

binding

sites Antibody A

Antigen

Antibody B Antibody C

Epitopes

(antigenic

determinants)

An antigen is any foreign molecule

That is specifically recognized by lymphocytes and

elicits a response from them

A lymphocyte actually recognizes and binds

To just a small, accessible portion of the antigen called

an epitope

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The body is populated by two main types of lymphocytes

Which circulate through the blood

B lymphocytes (B cells) and T lymphocytes (T cells)

The plasma membranes of both B cells and T cells

Have about 100,000 antigen receptor that all recognize the

same epitope

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B cell receptors consists of two identical heavy chains and two

identical light chains linked by several disulfide bridges.

Bind to specific, intact antigens

Are often called membrane antibodies or membrane immunoglobulin

Antigen-

binding

site

Antigen-

binding site

Disulfide

bridge

Light

chain

Heavy chains

Cytoplasm of B cell

A B cell receptor consists of two identical heavy chains and

two identical light chains linked by several disulfide bridges.

(a)

Variable

regions

Constant

regions

Transmembrane

region

Plasma

membrane

B cell

C C

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Antigen-

Binding site

b chain

Disulfide bridge

a chain

T cell

A T cell receptor consists of one α chain and one b

chain linked by a disulfide bridge.

(b)

Variable

regions

Constant

regions

Transmembrane

region

Plasma

membrane

Cytoplasm of T cell

Each T cell receptor consists of two different polypeptide chains (one α

chain and one b chain) linked by a disulfide bridge.

V V

C C

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MHC molecules are encoded by a family of genes called the major histocompatibility

complex

Infected cells produce MHC molecules which bind to antigen fragments and then are

transported to the cell surface in a process called antigen presentation

T cells bind to small fragments of antigens that are bound to normal cell-surface

proteins called MHC molecules

A nearby T cell can then detect the antigen fragment displayed on the cell’s surface

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T cells: recognize and destroy tagged antigens and proliferate

Cytotoxic T cells bind to antigen on plasma membrane of target cells and directly destroy the cells

Helper T cells activate B cells, cytotoxic T cells, Natural Killer cells and macrophages

Remaining cells can respond to secondary exposure

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APCs: Macrophages & B lymphocytes

Antigen Presenting Cells (APCs) ingest foreign material,

then present antigenic fragments on their cell surface

where they are recognized by T-cells T-cells: respond to antigen only if it is displayed on plasma membrane.

Interactions between APCs & lymphocytes and

lymphocyte-lymphocyte interactions are critical to

immune response

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B cells: recognize antigens, proliferate and produce

specific antibodies.

Differentiate into plasma cells- to produce more

antibodies

Differentiate into memory cells- keep antibodies in

supply for activation from second encounter by same

antigen

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B cells recognize

antigens,

Differentiate into plasma cells- produce more antibodies

Differentiate into memory cells- keep some for later

proliferate,

and produce specific antibodies.

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Active humoral immunity: B-cells encounter & respond to antigen to

produce an antibody

Naturally acquired: natural exposure to antigen (i.e. infection)

Artificially acquired: vaccines; dead/attenuated or fragmented pathogen

injected to elicit an immune response

Bestow immunity without disease; primary response

Booster shots (secondary response); intensify response

Shortcomings – adverse reactions & the immunity is less durable (poor memory) &

has less cell mediated component

Passive humoral immunity: Introduced “non-native” antibody

Natural: maternal antibody crosses the placental barrier conferring temporary

immunity to the baby (degrades after a few months)

Artificial: antibodies harvested from an outside source given by injection

protect from immediate threat but no memory is formed (antitoxins,

antivenins, gamma globulin, etc.)

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Types of Acquired Immunity

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Certain antigens on red blood cells (RBCs)

Determine whether a person has type A, B, AB, or

O blood

Antibodies to non-self blood types

Already exist in the body

Transfusion with incompatible blood

Leads to destruction of the transfused cells

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ABO Type Per Cent

O +ve 48%

-ve 4%

A +ve 24%

-ve 2%

B +ve 17%

-ve 1%

AB +ve 4%

-ve 0.3% 30

If an individual is transfused with an incompatible blood

group, destruction of the red blood cells (RBCs) will occur.

This may result in the death of the recipient.

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Recipient-donor combinations

Can be fatal or safe

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Blood Group Antigens

(on RBC surface)

Antibodies

(in plasma)

Transfuse with

group

A A Anti-B A or O

B B Anti-A B or O

AB A and B none AB, A, B or O

O None Anti-A & B O

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Another RBC antigen of next importance is the Rh type.

A blood group system with many antigens, one of which is D.

Rh refers to the presence or absence of the D antigen on the RBC.

Creates difficulties when an Rh-negative mother carries successive

Rh-positive fetuses

Unlike the ABO blood group system, individuals who lack the D antigen do not naturally make antibodies.

Production of antibody to D requires exposure to the antigen.

The D antigen is very immunogenic, i.e., individuals exposed to it will very likely make an antibody to it.

For this reason all individuals are typed for D, if negative must receive Rh (D) negative blood. 34

Pathogenesis

Fetomaternal Hemorrhage

Maternal Antibodies formed against Paternally derived antigens

During subsequent pregnancy, placental passage of maternal IgG antibodies

Maternal antibody attaches to fetal red blood cells

Fetal red blood cell hemolysis

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MHC molecules

Are responsible for stimulating the rejection of tissue

grafts and organ transplants

The chances of successful transplantation are

increased

If the donor and recipient MHC tissue types are well

matched

If the recipient is given immunosuppressive drugs

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Allergies are exaggerated (hypersensitive) responses To certain antigens called allergens

An acute allergic response sometimes leads to anaphylactic shock A whole-body, life-threatening reaction that can occur within

seconds of exposure to an allergen

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The immune system loses tolerance for self and turns against

certain molecules of the body

Rheumatoid arthritis

Is an autoimmune disease that leads to

damage and painful inflammation of the

cartilage and bone of joints

Other examples of autoimmune

diseases:

Systemic lupus erythematosus

Multiple sclerosis

Insulin-dependent diabetes

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An inborn or primary immunodeficiency

Results from hereditary or congenital defects that

prevent proper functioning of innate, humoral,

and/or cell-mediated defenses.

An acquired or secondary immunodeficiency

Results from exposure to various chemical and

biological agents

Range from temporary states to chronic diseases

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Acquired Immunodeficiency Syndrome

(AIDS)

People with AIDS

Are highly susceptible to opportunistic infections

and cancers that take advantage of an immune

system in collapse

Because AIDS arises from the loss of helper T

cells: Both humoral and cell-mediated immune

responses are impaired

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Growing evidence shows

That physical and emotional stress can harm

immunity

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