The Immune System

Class

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IntroductionVertebrates have three levels of defenses

1. The Integumentary System

Skin and mucous membranes provide first line of defense

2. Nonspecific (innate) Immune System

Acts very rapidly after onset of infection

3. Specific Immune System

Eliminates microbes that escaped the second line of defense

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Integumentary system

The skin is the largest organ of the body

Provides a nearly impenetrable barrier, reinforced with chemical weapons

Oil & sweat glands give skin a pH of 3-5

Lysozyme breaks bacterial cell walls

Also contains many normal floraNon-pathogenic microorganisms that out-compete pathogenic

ones

Composed of Epidermis, Dermis, and Subcutaneous layers.

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Mucosal Epithelial Surfaces

The digestive, respiratory and urogenital tracts are lined by mucous membranes

-Cells secrete mucus which traps microbesDigestive tract

-Salivary lysozyme; acidic stomachRespiratory tract

-Ciliary actionUrogenital tract

-Acidic urine

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Nonspecific Immunity

The nonspecific or innate immune system consists of cellular and chemical devices that respond to any microbial infection

-The response is quite rapid

Among the most important defenses are three types of leukocytes (white blood cells)

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LeukocytesMacrophages•Large, irregularly shaped cells•Kill microbes by phagocytosis•Mature from monocytes that enter tissues from the bloodNeutrophils•The most abundant circulating leukocytes•First to appear at site of damage/infection•Kill microbes by phagocytosis

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LeukocytesNatural killer (NK) cells•Destroy pathogen-infected and cancer cells by causing programmed cell death or apoptosis

• Produce perforins and granzymes• Immune surveillance

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The Inflammatory Response

Inflammation involves several body systems

1.Injured cells release chemical alarms, including histamine and prostaglandins

2.Cause nearby blood vessels to dilate and increase in permeability

3.Promote phagocyte accumulation •Hallmark signs = Redness, warmth, swelling, pain, and potential loss of function•Interleukin-1 (IL-1) causes fever.

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The Inflammatory Response

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ComplementThe complement system consists of about 30 different proteins that circulate in the blood in an inactive form

-Upon pathogen encounter, a cascade of activation occurs

-Some proteins aggregate to form a membrane attack complex (MAC) on surface of pathogen

Pore

Fluid

Membraneof invadingmicrobe

Complementproteins

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Interferon

Interferons (IFN) are proteins that play a key role in body defense

-Three major types: IFN-, IFN-, IFN-

-IFN- and IFN-are produced by almost all body cells in response to viral infection

-Induce degradation of viral RNA

-IFN- is produced only by T-lymphocytes and natural killer cells

-Protects from infection and cancer

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The Specific Immune SystemThe scientific study of immunity began with Edward Jenner in 1796

-Observed that milkmaids who had cowpox rarely experienced smallpox

-Inoculated individuals with fluid from cowpox vesicles to protect them from smallpox

Vaccination

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AntigensAn antigen is a molecule that provokes a specific immune response

-May be components of microorganisms or proteins/glycoproteins found on surface of red blood cells or transplanted tissue cells

A single protein may have many different antigenic determinants or epitopes

-Each can stimulate a distinct immune response

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Lymphocytes

Lymphocytes are leukocytes with surface receptors for antigenic determinants•Direct an immune response against either the antigen or the cell that carries it

When a naïve lymphocyte binds a specific antigen for the first time, it gets activated by a process called clonal selection•Produces a clone of cells: some respond immediately, others are memory cells

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Lymphocytes

B lymphocytes or B cells •Respond to antigens by secreting antibodies or immunoglobulins (Ig)•Participate in humoral immunity

T lymphocytes or T cells •Regulate other immune cells or directly attack cells that carry specific antigens •Participate in cell-mediated immunity

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The Specific Immune System

The four characteristics of the specific, or adaptive, immune response are:

-1. Specificity

-2. Diversity

-3. Memory

-4. Ability to distinguish self from non-self

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Acquisition of Specific Immunity

Immunity can be acquired in two ways•Active immunity results from activation of an individual’s own lymphocytes

• Pathogen infection or vaccination

•Passive immunity results from obtaining another individual’s antibodies

• Transfer of maternal antibodies across placenta

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Organs of the Immune System

All cells are created in a process called hematopoiesis.

Organs of the immune system consist of the:

•Primary lymphoid organs • Bone marrow and thymus

• Secondary lymphoid organs • Lymph nodes, spleen, and mucosal-

associated lymphoid tissue (MALT)

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Primary Lymphoid Organs

The bone marrow is site of B cell maturation•Each B cell has about 105 Ig molecules on its surface, all with the same specificity

• However, different B cells will have different specificities

•B cells recognize epitopes directly•Any lymphocytes that are likely to bind to self-antigens undergo apoptosis

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Primary Lymphoid Organs

The thymus is the site of T cell maturation•Each T cell has about 105 identical T-cell receptors, or TCRs on its surface

• Recognize epitopes only if they are combined with major histocompatibility complex (MHC) peptides

• Lymphocytes that cannot bind MHCs, or that bind self-MHC/self-peptide too tightly undergo apoptosis

•T cells come in two flavors—Cytotoxic T (Tc or CD8) and Helper T (TH or CD4)

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Immune Responses

The first encounter with a foreign antigen is called the primary immune response•Only few B or T cells can recognize antigen

The second encounter is called the secondary immune response•This time there is a large clone of memory cells that can recognize the antigen

• Immune response is more effective

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Exposureto cowpox

Time

Exposureto cowpox

IgMIgG

This intervalmay be years

Secondary response

Primary response

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Autoimmunity

The acceptance of self cells is known as immune tolerance

Autoimmune diseases are caused by the failure of immune tolerance•Result in activation of autoreactive T cells, and production of autoantibodies by B cells

• Cause inflammation and organ damage• Alleviated by corticosteroids and NSAIDs, including aspirin