consists of central and peripheral lymphoid tissues and

immune cells
antigens are individual components of substances that

enter or contact the body; the immune system recognizes these substances as being foreign interaction between components of the immune system and antigens is the immune response

A. Non-specific Immunity

- distinguishes self from non-self (unresponsiveness to bodys own tissues, preventing immune response to own cells), but doesnt differentiate between specific pathogens a) first line of non-specific defense includes skin and mucous membranes

b) second line of non-specific defense includes chemical signals molecules, anti-microbial substances, phagocytic and natural killer cells and fever associated with the inflammatory response (we will have a look at the Inflammatory Response later in the slide show)

- natural killer cells lymphocytes which are functionally and structurally different from other lymphocytes nonspecific (attack anything that is considered foreign) and are capable of destroying tumor cells and virus-infected cells; they do not need to be activated by other cells; they are inhibited by molecules present on normal host cells

B. Specific Immunity
develops over lifetime (it is acquired), distinguishes

between self and non-self and responds to specific foreign materials and pathogens lymphocytes (specific class of white blood cells) include: i) T cells (participate in cell-mediated immunity destroy antigen-bearing cells) ii) B cells (participate in humoral immunity B cells are transformed into plasma cells which produce and secrete antibodies; act against very specific antigens)

 memory response exists where specific immunity is

concerned with subsequent exposure to the same antigen, a heightened immune response is quickly produced response to commonly encountered microorganisms often goes unnoticed
self-limitation ability of lymphocytes to perform a

function for a brief period (destruction of pathogen) and then die or differentiate into non-active memory cells

Antigens

also known as immunogens substances that enter the body and are recognized as being foreign to the host and stimulate an immune response; recognized by receptors on immune cells and proteins antibodies (AKA immunoglobulins) antibodies are generated in response to antigens microbial antigens include bacteria, fungi, protozoa and parasites antigens may also be other agents like pollen, plant resins (ex. poison ivy), insect venoms; antigens are also found in transfused blood or transplanted organs (foreign protein molecules) antigenic molecules have a specific shape/configuration which is recognized by and bind to specific receptors on antibodies

Immune Cells 1. lymphocytes are primary cells for specific immunity; additional accessory cells (non-lymphoid) are required for recognition and activation of specific immune responses by T and B cells; lymphocytes are generated in bone marrow and mature in central lymphoid tissues (what are some examples of these?) 2. accessory cells include mononuclear phagocytes, dendritic cells and antigen-presenting cells (APCs) a) APCs and macrophages (phagocytes) present the antigen to T cells; cytokines (signaling molecules) stimulate T cells and B cells to divide multiple times, creating both effector cells (those responsible for destroying the antigen) and memory cells (for future use)

b) monocytes produced and released by bone marrow; migrate to many tissues for maturity into macrophages large cells with numerous vacuoles (ex. alveolar macrophages and those residing in lymph nodes); macrophages engulf/trap infectious agents until specific immunity agents and cells can be activated; they also break down large antigen molecules and present them to T cells for initiation of the immune response; macrophages also secrete cytokines, producing fever and priming and attracting T and B cells c) dendritic cells also present antigen to T lymphocytes found in lymphoid tissue and other areas where antigens enter the body; present in abundance on skin d) immunoglobulins antibodies proteins which are produced by activated B cells:

5 classes of antibodies: IgG 75% of antibodies anti-viral, anti-toxin, antibacterial; binds to macrophages and activates complement system (group of proteins which are activated during inflammatory response) IgA - found in secretions (saliva, sputum) and protects mucous membranes IgM involved in early immune response and activates complement system IgD found in B cells; aids in their maturation IgE binds to mast cells and basophils (see Inflammatory Response later in slide show); involved in allergic reactions and hypersensitivity reactions responsible for histamine release

Cytokines and the Immune Response

Cytokines - regulatory proteins produced in all phases

of the immune response made by and act upon immune cells act as signaling molecules which regulate mobilization, proliferation and division of leukocytes from bone marrow(white blood cells - see Inflammatory Response later in slide show); cytokines are produced by T cells and macrophages cytokines include interleukins 1-18 interleukin 1 stimulates acute phase of immune response, mobilizing neutrophils, produces fever and activates the vascular epithelial response to injury and invading substances (see Inflammatory Response later in slide show)

Mechanisms of the Immune Response

1. Active Immunity (AKA Acquired Immunity)

immunization or having had contact previously with a specific antigen takes a few days to weeks after first exposure to the specific invader to become fully developed

2. Passive Immunity

passed from mother to infant before birth or via injection with high concentrations of antibodies for specific disease (ex. gamma globulin used sometimes to treat immune deficiency disorders or hepatitis A postexposure to it)

3. Humoral Immunity
relies on presence of antibodies produced by B cells in

blood combination of antibody with antigen may result in:

a) clumping of cells b) neutralization of bacterial toxins and viruses c) destruction of pathogens d) complement system activation (see Inflammatory Response later in slide show) e) facilitation of phagocytosis

4. Cell Mediated Immunity

protects against viruses, intracellular bacteria and cancer

cells T cells and macrophages dominate

Regulation of the Immune Response

lack of self-regulation leads to allergic reactions or

autoimmune disorders (so, inappropriate immune responses) immune process is usually limited because destruction of pathogen ends response (foreign material no longer exists to stimulate response) and chemicals involved in the response (ex. cytokines) have short life span and are only secreted for short period; additionally, tolerance to own tissues (not recognized as foreign) prevents response to chemicals involved in the immune process

THE INFLAMMATORY RESPONSE Definition: bodys reaction to vascularized tissue injury; necessary for healing process to begin; also accompanies specific immune responses ** normally limited to local response; if response is more generalized life threatening
the suffix itis is added to the injured organ in naming the

inflammatory condition ex. pericarditis means inflammation of pericardium or bronchitis means inflammation of bronchi

 any type of tissue injury or invasion will trigger the

inflammatory response: a) physical/mechanical injury: impact, distortion, temperature extremes, etc. b) ischemic injury: decreased blood supply to tissue with subsequent decreased oxygen supply c) chemical injury: strong acids, strong bases, venom, allergic reactions d) biological invasion and any toxins they may secret to produce injury: viruses, fungi, bacteria, etc.
the basic process of the inflammatory response is the

always the same regardless of cause, but the degree of severity and its magnitude definitely varies

A. ACUTE INFLAMMATION immediate response to injury; non-specific in nature; aimed at removing and limiting the activity of injurious agents and at limiting the quantity of injured tissue
signs of acute inflammation:

localized redness swelling (edema) heat pain

these signs are only obvious for superficial injury; for deeper

organs, pain may be the only apparent sign; localized heat may also not be immediately obvious with inflammation of internal organs because temperature of deep organs is already core temperature less localized sign of inflammation (systemic manifestation) is fever chemical mediators of inflammatory response (pyrogens) enter circulatory system causing increased body temperature and metabolic rate by affecting the hypothalamic control centres for body temperature

A. Chemical Mediators of the Inflammatory Response

inflammation is precipitated by injury, but signs and

symptoms are caused by chemical mediators:

a) Histamine widely distributed throughout the body;

found in high concentrations in platelets, basophils and mast cells (see Cells Involved in Inflammatory Response); causes increased permeability of capillary membranes and dilation of vasculature; one of the first mediators of inflammatory response; also causes bronchial smooth muscle contraction (short, transient effect)

b) Plasma Proteases consist of kinins, activated complement proteins (see below) and clotting factors; ex. bradykinin - causes vasodilation, increased capillary permeability and pain; blood clotting system also contributes to vascular phase of inflammation (as stated above)

c) Complement System consists of plasma proteins; enhance inflammatory and immune responses in a cascade by exerting several different influences: i) guiding mast cells and basophils to site of injury or invasion ii) activating the above cells, causing release of other inflammatory mediators iii) causing cell membrane lysis of invading organism iv) presenting antigen-antibody complex to macrophages for phagocytosis

d) Prostaglandins lipid soluble molecules (fatty acids) produced secondary to the release of arachidonic acid from phospholipid (endothelial cell) membranes in response to injury; also released by mast cells and neutrophils - several types of prostaglandins exist (including one called thromboxane); contribute to vasodilation, increased capillary permeability, pain and fever - some prostaglandins also potentiate the effects of histamine; others promote platelet aggregation (clumping) and vasoconstriction - ASA (AKA Aspirin) or other NSAIDs (non-steroidal anti-inflammatory drugs) reduce inflammation and pain by inhibiting prostaglandin synthesis

e) Leukotrienes also lipid soluble molecules; released by leukocytes and mast cells and produced secondary to release of arachidonic acid from phospholipid membranes - they are complimentary to histamine (have similar functions - increased capillary permeability, etc.); these cause slow and sustained contraction of bronchial smooth muscle; like histamine, leukotrienes are also important mediators in asthma and anaphylaxis

f ) Platelet Activating Factor produced by endothelial cell membrane lipids causes platelet aggregation (clumping/gathering); acts to initiate inflammatory response (well see this later in the slide show); activates neutrophils and attracts eosinophils; also causes bronchospasm (again, asthma) g) Nitric Oxide gas released by injured endothelial cells vasodilator

B. White Blood Cells (Leukocytes) and Others Involved In the Inflammatory Response
1. Granulocytes (leukocytes covered in granules filled with inflammatory mediators) a) neutrophils - primary phagocytes that arrive at injury site first contain enzymes and anti-bacterial substances which destroy or degrade engulfed materials; also generate oxygen free radicals and nitric oxide (NO causes vasodilation); neutrophils have divided nuclei (several lobes) and are often referred to as polymorphonuclear cells; neutrophil count in blood increases greatly during early phase of inflammation (particularly with bacterial infection) mobilized from bone marrow

b) eosinophils increase in number in the blood during allergic reactions responsible for controlling release of chemical mediators from mast cells and other leukocytes c) basophils contain histamine and other inflammatory mediators; also involved in allergic responses d) mast cells are similar in function to basophils in that they also participate in inflammatory response; mast cells carry IgE immunoglobulins (antibodies) which play a large role in allergic responses and chronic inflammatory responses - mast cells reside within tissues (basophils are a type of white blood cell released into circulation by bone marrow)

2. Mononuclear Phagocytes (monocytes) largest of white blood cells, but only make up about 5% of total leukocytes; longer lifespan than granulocytes - responsible for actual destruction of antigen, signaling specific immunity processes and resolving inflammatory process (once antigen is gone, response normally ends) - monocytes migrate to injured site within a day or two of the initial insult or invasion - capable of engulfing a significant quantity of foreign material - play major role in chronic inflammation by walling off foreign material that can not be broken down and eliminated from the region (usually inorganic molecules) well deal with chronic inflammation later in the slide show

A/ Initial Response to Injury (how the acute inflammatory response begins) 1. small-diametered vascular structures are damaged (endothelial cells) 2. platelets in circulation adhere to and gather at site of damage (aggregation) 3. fibrin (insoluble plasma protein) forms clot to prevent further red blood cell loss 4. vasoconstriction occurs 2 release of platelet activating factor and thromboxane (one type of prostaglandin) from platelets and injured endothelial cell membranes ***#2,3 and 4 above occur in aid of limiting blood loss and in walling off injured area

B/ Acute Vascular Response (follows initial response to injury) initiated and controlled by chemical mediators released from cells or activated plasma proteins (mast cells, basophils, injured epithelial cells, lymphocytes, phagocytes, complement proteins) 1.vasodilation and increased capillary permeability, leading to hyperemia (increased blood flow, therefore increased nutrients and oxygen) and escape of fluid, clotting factors, leukocytes and antibodies (exudate) from vascular space to site of injury localized edema, causing redness and heat 2. flooding of the injured region with fluid causes dilution of any toxic agents present; with fluid shift, blood flow in capillaries slows down (blood becomes more viscous), furthering blood clotting helps to keep any infectious organism from spreading to adjacent regions or beyond 3. pain also occurs as result of exudate applying pressure to surrounding sensory nerve fibres

C/Cellular Response - sequence of events is as follows:

Pavementing Increased blood viscosity 2 fluid leaving vascular space (increased capillary permeability) caused by histamine, leukotriene and kinin release; leukocytes are attracted to, and start to move along, periphery of blood vessels in the injured region

Emigration Leukocytes pass through capillary walls into tissue spaces

Chemotaxis Leukocytes are guided to site of injury via cytokines (signaling cells), cellular debris and complement fragments

Phagocytosis Neutrophils (first) and macrophages engulf and degrade bacteria and cellular debris (if dead leukocytes remain at injury site pus formation)

B. CHRONIC INFLAMMATION may last for weeks, months or years; may develop from recurrent or progressive acute inflammatory process or from low grade responses that fail to bring on a significant acute inflammatory response - rather than an influx of neutrophils initially, infiltration of monocytes and lymphocytes occurs; additionally, fibroblasts (new connective tissue cells) may proliferate, causing scarring and tissue deformity

- examples of irritants resulting in this type of response in terms of lung tissue are talc, silica (sand particles if inhaled causes silicosis pulmonary disease) and asbestos (asbestosis if inhaled) inhalation of inorganic particulate causes inorganic alveolitis, AKA pneumoconiosis (a form of INTRAPULMONARY PARENCHYMAL DISORDER youll deal with these in patho!) - may also be caused by long term exposure to bacteria or fungi, so organic irritants (when inhaled, lead to a different class of INTRAPULMONARY PARENCHYMAL DISORDERS Hypersensitivity Pneumonitis youll cover these in patho as well!) - patients with recurrent pulmonary infection are also prone to this process (ex. cystic fibrosis, bronchiectasis again, patho)

i) non-specific chronic inflammation diffuse (generalized) accumulation of macrophages and lymphocytes at site of injury; leads to fibroblast proliferation with subsequent scar formation which may replace normal connective and functional tissues (ex: idiopathic pulmonary fibrosis once again, patho!)
ii) granulomatous inflammation granuloma is a small lesion formed by monocytes and lymphocytes; associated with foreign matter such as silica and asbestos (inorganic material) or micro-organisms such as those causing tuberculosis (Mycobacterium tuberculosis), or different types of fungi; these materials are not easily digested/broken down by phagocytes, and are not well controlled by other inflammatory mechanisms; the granulomas may become multinucleated giant cells that attempt to surround the foreign matter; the invading substance becomes encapsulated by connective tissue and is isolated

Systemic Manifestations of Inflammatory Response

inflammation normally remains localized; occasionally

systemic manifestations occur 2 release of chemical mediators of inflammation into circulation increase in white blood cell count, fever and inflammatory response occurring in other tissues/organs distal to initial site of injury or invasion systemic inflammatory response AKA SIRS; ARDS is a fantastic example of this particular process! a more widespread inflammatory response may result with increased capillary permeability throughout the body and global vascular smooth muscle dilation (what do you suppose happens to systemic blood pressure here?); may occur secondary to mediator release from a single severely injured organ, affecting other organ systems or by massive vascular invasion of pathogens (sepsis AKA bacteremia)