Chapter 21 Immune System

The Skin & Mucus Membranes

What external physical barriers does the body have as a first line of defense for the immune system?

Epidermis

• Physical Barrier

• Continual shedding of the squamos cells on the surface of the skin cells removes bacteria and fungi

• an infection rarely occurs if the barrier of the skin is not broken

Mucus Membranes

• These membrames line the body cavities

• They secrete mucus

• The muscu lubricates the surface of the membrane and traps microbes and foreign particles

• Ciliated cells then sweep the trapped particles toward the surface

Lacrimal Apparatus

• Tear gland of the eyes (function to make tears)

• Tears lubricate the eyes and with teh aid of the eyelids, prevent microbes from becoming established on the eye

• Tears also wash away foreign particles, like dust

Chemotaxis

• The movement of a white blood cell in response to a chemical gradient

• Chemical comes from the bacterial or damaged cells

Adherence

• Phagocyte attaches to the bacterua or foreign material

Ingestion

• This is just the process of endocytosis

Digestion

• Vesticles containing the particle or microbe is formed

• Lysosomes bind and pous enzymes into the vesicle

• microbe or particle is oxidized

Macrophages

• Derived from Monocytes

• An irregularly shaped cell that is amoeboid in nature

• They are found in many body tissues, either freely roaming or fixed within tissues such as lymph nodes

• They are the first line of defense when pathogens breach the body’s barrier defense

Microphages

• Derived from Neutrophils and Eosinophils

• Neutrophils - contain granules of histamine which influence blood vessel diameter

• They are the primary pathogens-killing cell of the inflammatory process

• Eosinophils - less abundant

• Used to defend against parasitic infections

Natural Killer Cells

• Derived from Lymphocytes

• Lymphocytes that destroy intruding microbes and some tumor cells

• Found in the spleen, lymph nodes, red bone marrow, and blood

• Must have direct contact to kill

• Kill by making the bacteria leaky to intracellular contents

Interferons

• Proteins produced by body cells infected with a virus

• The proteins travel to nearby cells and stimulate those cells to produce antiviral proteins

• Proteins interfere with viral replication

 Complement System

• Composed of over 30 proteins that made in the liver

• These proteins will bind to bacterial cells and:

  • Attract phagocytes 

  • Stimulate phagocytosis

  • Destroy plasma membranes

  • Promote inflammation

Inflammatory Response

• Anything that damages tissues can cause inflammation

  • Injury or infection

• Four characteristics: Heat, Redness, Pain, Swelling

• Acute Inflammation

  • Short term, unless cause of inflammation is not dealt with

• Chronic Inflammation

  • Ongoing - caused by foreign bodies, ongoing defense against pathogens (like allergies), autoimmune diseases

• Inflammatory Respose Types:

  • Tissue Injury

  • Vasodilation

  • Increased Vascular Permeability

  • Recruitment of Phagocytes

Tissue Injury

• Injured cells stimulate mast cells to secrete cytokines (substances secreted by immune cells) 

• Releases

  • Histamine

  • Leukotrienes

  • Prostaglandis

Histamine

• Stimulates vasodilation

• Causes increased blood flow to the damaged tissue

• Causes increased permeability of local capillaries, so plasma leaks out to form interstitial fluid 

• This causes the swelling associated with inflammation

Leukotrienes

• Attract neutrophils from the blood by chemotaxis

• Also increases vascular permeability
  

Prostaglandins

• Cause vasodilation by relaxing vascular smooth muscle

• A major cause of the pain associated with inflammation

Vasodialation

• Cytokines, such as histamine, increase the diameters of local capillaries

• The result is increased blood flow, which is responsible for the heat and redness of inflamed tissue

• Permits increased blood flow to the site of inflammation

 Increased Vascular Permeability

• Stimulates, there is increased permeability of the local capillaries

• This causes plasma to leak into the interstitial space

• Resulting in the swelling, or edema, associated with inflammation 

Recruitment of Phagocytes

• Leukotrienes attract neutrophils from the blood to the site of injury

• Macrophages are recruited to clean up any debris

• When infections are severe

  • Neutrophils are attracted in large numbers

  • They phagocytize the pathogens and subsequently die

  • The accumulated cellular remains are visible as pus

Adaptive (Specific) Immune Response

• Immunity acquired to a specific antigen only after you have been exposed to it

  • Includes as immunological memory which protects us from getting diseases repeatedly from the same pathogen

• Self Recognition

• Uses the lymphocytes, T-cells and B-cells that develop the ability to recognize foreign antigens

Self Recognition

It has the ability to distinguish self-antigens, which are commonly present in the body, from foreign antigens

T-cells

• Are important because they function against abnormal cells and cells with internal pathogens

• Cell-mediated immunity

B-Cells

• Functions against antigens and pathogens in body fluid

• Antibody-mediated immunity (part of B-cells)

Active Immunity

• Develop in response to antigens exposure

• Naturally Acquired - exposure to environmental antigens

  • Like having chickenpox as a child

• Artificially Acquired - develops after being given as antigen

  • Vaccines 

 Passive Immunity

• Transfer of antibodies from another source

• Naturally Acquired - antibodies transferred directly from a person

  • Newborns receive first antibodies from mother 

• Artificially Acquired - given specific antibodies to fight infection 

  • Receiving rabies shot after being bitten by possibly rabid animal

Specificity

• Specific defense is activated by specific antigen 

• Receptors on T cells and B cells designed to only recognize a specific antigen 

Versatility

• System must be ready to defend against any foreign antigen at any time

• Millions of antigens in the environment

Memory

• must "remember" previously encountered antigens

• Allows for faster and stronger response during subsequent exposures

Tolerance

Immune system ignores self-antigens

Antigens

• Are usually large and complex molecules on the surface of cells and pathogens

• Characteristics

  • Are molecules that can stimulate an immune response

  • May stimulate cells to produce antibodies or the making specific T cells

  • Ability to react with these specifically produced antibodies or T-cells

• Must be “presented” on the outside of the cell membrane to be recognized by a T cell

T-Cell Receptors

• Are composed of two chains of amino acids, each with two regions - variable and constant

  • The constant region is close to the membrane and has a sequence that is relatively constant between receptors

  • The variable region is further away from the membrane and has an amino acid sequence that varies between receptors 

Class 1 MHC Proteins

• All nucleated cells produce antigens that are transported to the cell membrane and displayed on MHC 1 proteins

• If the cells are healthy, and the antigens are normal, the T-cell ignores them

• If cells are unhealthy, or have non-self antigens, the T-cell will activate and destroy the cell

• Why organ recipients must take anti-rejection meds

Class 2 MHC Proteins

• Antigens presenting cells (APCs) process antigens

• APCs include macrophages, B-cells, and dendritic cells 

• APCs are located in regions of the body that are likely invasion routes for pathogens, such as the skin, respiratory, and digestive tract

First Signal

• Antigen receptors on the surface of the T-cell recognize and bind to antigen fragments presented by MHC 

Second Signal

• Molecules on the surface of the helper T-cell and on the surface of the antigen presenting cell cause the cells to bind to each other temporarily 

• Binding by these molecules is the second signal

Differentiation and Specialization

• T-cell divides several times and changes into a more highly specialized cell

Proliferation

• The specialized cells reproduce many times to produce an army of cells to attach to the pathogen

Helper T-Cells

•  Activated by Class II MHC proteins

• Function to stimulate the proliferation of other T and B cells that are already bound to the antigens

Cytotoxic (Killer) T-Cells

•  Activated by Class I MHC proteins

• Only T-Cells that directly attack and kill other cells

• Move around the body looking the specific antigens

Regulatory T-Cells

• Activated by Class I MHC proteins

• Function to suppress the activity of T-Cells and B cells

• Thought to shut off the immune response after the job is done

• Use to be called Supressors

Memory T-Cells

• Recognize the original invading antigen

• Permits faster response when the antigen is encountered in the future

Sensitization

• Antigens enter B cell by endocytosis

• Then displayed on surface by Class II MHC protein

Activation

• Helper T-cell binds to MHC complex

• Releases cytokines, activating B cells, stimulating cell division and promoting B cell development into plasma cells

Cell Division & Differentiation

• Plasma Cells - make and secrete large numbers of antibodies

• Helper B cells and Memory B cells - Similar in function to T cell equivalents

Immunoglobulins (Antibodies)

• Y shaped molecule composed of four polypeptide chains

  • Heavy chains - two chains each with about 450 amino acids and small carbohydrates

  • Light chains - two chains each with about 220 amino acids

• Each antibody has two variable regions on one end which function as antigen binding sites

  • Binds to only a specific portion of an antigen, forming the antigen-antibody complex

Functions of Antibodies

• Neutralization

  • Bind to viruses and toxins, preventing them from attaching to cells

• Agglutination and precipitation

  • Can link to antigens on multiple cells, binding them together

• Activation of complement system

  • Allow complement proteins to bind to and destroy the antigen

• Attracting and Enhancing phagocytosis

  • Attract more phagocytes and make them easier to engulf

• Stimulate Inflammation

  • Stimulate mast cells, helping non-specific immunity
    

Primary response

• Initial immune response

• Takes longer because process must start from beginning

Secondary Response

• Memory B cells can respond faster than B cells during initial exposure

• Increases speed and strength of immune response

• Memory cells can help this response even years after initial exposure