edapt 5: innate defenses

non-specific processes

- a fever, or pyrexia, is an abnormal increase in the body's core temperature - fevers typically present during infection and inflammation and are cause by signaling molecules called pyrogens - two types of pyrogens

C3a and C3b

- activate a cascade of events to form a ring called the membrane attack complex - this complex forms a hole in the target cell and causes cytolysis

classical pathways

- activates only after an antigen-antibody complex is formed and is part of adaptive immunity

exogenous pyrogen

- agents originating outside the body, bacterial toxins, antigen-antibody complexes, and glycolipids from bacteria and viruses

alternative and lectin pathways

- are both part of innate immune system - bind directly to tumor cells and pathogens without the need of antibody-antigen complexes

seven steps of phagocytosis

- chemotaxis is the first step where the phagocytic cells are stimulated to move as a response to chemicals secreted by pathogens - adhesion: bacteria and viruses produce telltale signs that phagocytes may target. this recognition facilitates the binding of phagocytes to the microbe - engulfment: plasma membrane of the phagocyte extends to form pseudopods that surround and engulf the bacteria by a process called endocytosis - the vesicle that results from engulfment is called a phagosome - a phagolysosome is formed after fusion of the phagosome with a lysosome - killing and destruction: enzymes from the lysosome destroy the bacteria - release: residues of killed microbes are released from the cell

C3b

- coats microbial cells in process called opsonization, this enables the process of phagocytosis by making this microbe more appealing

interferons

- diffuse to nearby cells and induce production of antiviral proteins that inhibit the synthesis of viral particles - although the infected cells are not able to clear virus, they warn other cells that stop replication of the virus once it enter s - fever enhances the action of IFNs in causing apoptosis of the infected cells and stimulating adaptive immunity

first line of defense: mucus membrane

- digestive, respiratory, urinary, and reproductive tracts are open to the exterior and can act as a portal of entry for pathogens - the upper layer of mucus membrane is made up of tightly packed cells that continuously shed - mucus produced by cells in the epithelial layer of the mucus membrane trap pathogens - hair in the nasal cavity filters inspired air of large particles - cilia, found on pseudostratified ciliated epithelium of the respiratory tract, move mucus (laden with microbes and particles) to where it may be expelled by coughing or sneezing or where it may be swallowed - urine and secretions from the stomach and vagina are acidic and prevent microbial growth - the flowing action of urine, swallowing defecation, and vomiting are additional processes that retard growth and enhance the elimination of microbes - the lacrimal apparatus produces tears that wash away and clear irritating substances and microbes. tears, like sweat, also contain lysozyme

which type of white blood cell increases with parasitic worm infections

- eosinophils

components of second line of defense

- eosinophils - fever - macrophages - inflammation

physical barriers of first line of defense

- epidermis - perspiration - sebum - mucus membrane

a pyrogen induces _____ in body

- fever

inflammation

- generalized local defensive response to trauma and infection - the purpose of inflammation is to limit the spread of the pathogen and destroy it, remove debris, and initiate repair - there are four classic/cardinal signs of inflammation > rubor: > calor > tumor > dolor

non-phagocytic killing

- granulocytes, specifically neutrophils and eosinophils, along with natural killer cells destroy pathogens by releasing chemicals, such as perforins and granzymes, in their vicinity - neutrophils are attracted towards bacteria and, when in the immediate vicinity, they degranulate releasing superoxide and hypochlorite (active component of bleach) to destroy the pathogen. They are the first to arrive as a response to injury. The killing zone created by this burst also destroys the neutrophils but is more rapid and efficient in clearing pathogens than the phagocytic action of this granulocyte - high numbers of eosinophils are found in mucus membranes and are active during parasitic worm infections, allergies, and inflammatory reactions. Parasitic worms, too large to be destroyed by phagocytosis, are killed by lysozyme, hypochlorite, and superoxide released by these granulocytes. Eosinophils also release a histaminase enzyme that suppresses the action of histamine from mast cells. This is important to keep the inflammatory responses in control and localized to the appropriate region - lymphocytes have 3 types: > T and B lymphocytes and NK cells > the first two lymphocytes have special markers on their membrane to respond to specific antigens, thus providing adaptive immunity and do not play a role in innate immunity. NK cells lack the specific markers of T and B lymphocytes, they attack a variety of targets, but are especially good at identifying and attacking cancerous cells and cells infected by viruses > NK cells release perforins, which punch holes in the target cell's membranes, and granzymes, which induce programmed cell death

first line of defense: sebum

- helps keep skin pliable, reducing the chances of tear and abrasions which can compromise this barrier - lowers skin pH to a level inhibitory to many bacteria

during inflammation, basophils release an anticoagulant called _______ and a vasodilator called ______

- heparin - histamine

fever

- increases the effectiveness of interferons and phagocytes, inhibits multiplication of bacteria, increases metabolism, and stimulates immune reactions

when tissue is subjected to trauma it releases cytokines that stimulate the release of neutrophils from the bone marrow

- inflammatory chemicals like histamin (vasodilator), heparin (anticoagulant), and bradykinin are released by basophils that cause vasodilation and hyperemia (increase in blood flow) at the site of inflammation - margination: selectin, a cell adhesion molecule, is produced that causes margination/adhesion of neutrophils to the wall of blood vessels - diapedesis: histamine dilates the blood vessels increasing the gaps between endothelial cells. neutrophils squeeze through this narrow gap in a process called diapedesis - chemotaxis: neutrophils migrate towards the damaged site in response to chemicals secreted by bacteria - phagocytosis: bacteria are engulfed and killed

_______ are secreted by cells infected with viruses, alerting neighboring cells and protecting them from becoming infected

- interferons

non-specific antimicrobial proteins

- interferons are antimicrobial proteins produced and released by virally infected cells, especially leukocytes - complement is a group of 30 inactive plasma globulins produced by the liver that play a very important role in both innate and adaptive immunity

complement

- is a group of 30 inactive plasma globulins produced by the liver that play a very important role in both innate and adaptive immunity - they complement the action of antibodies - there are three different pathways that lead to complement activation: > classical > alternative > lectin - all 3 pathways, results in cascade of events enhances chemotaxis, phagocytosis, inflammation, and the destruction of cells via membrane attack complexes - each pathway results in splitting the C3 into the C3a and C3b -

components of third line of defense

- lymphocytes - cell-mediated immunity - humoral immunity - antibodies

saliva contains this chemical that destroys bacteria ______

- lysozyme

non-specific chemical defenses include

- lysozyme - lactic acid in sweat - skin's acidic pH - stomach hydrochloric acid

the second line of defense includes

- macrophages, inflammation, interferon, natural killer cells

during inflammation neutrophils stick to the walls of blood vessels by a process called ______

- margination

the most numerous phagocytic wbcs that have multilobed nuclei are

- neutrophils

which type of white blood cell perform both phagocytic and non-phagocytic killing

- neutrophils

what enhances activity of other anti-microbial immune cells and proteins

- non-specific processes, fever, and inflammation

dolor

- pain caused by the stimulation of nerve endings

which of the following are cardinal sign of inflammation?

- pain, swelling, heat, redness

phagocytes

- plays a vital role in both innate and adaptive immune responses - this process occurs in seven steps

endogenous pyrogen

- polypeptides secreted by neutrophils and macrophages - example: interleukin-1

rubar

- redness caused by increased circulation and vasodilation in injured tissues

first line of defense uses ciliated cells on the lining of the ______

- respiratory tract

pyrogens

- signaling molecules - two types > exogenous > endogenous - raise the set point of hypothalamic neurons that regulate body temperature to a higher temperature - as a result, the onset of fever is often accompanied by thermogenic responses, such as shivering - after pathogens have been death with, the concentration of circulating pyrogens declines and the normal thermoregulatory set point reestablishes itself. this is often referred to as 'breaking' the fever and is often accompanied by sweating, though the fever may return if the infection is stil present

components of first line of defense

- skin - mucosal membranes

tumor

- swelling from increased fluid escaping into tissues (edema)

first line of defense: perspiration

- the high-level of salt in sweat inhibits pathogen growth - sweat creates acidic environment - sweat has lysozyme which destroys bacteria cell walls

first line of defense: epidermis

- the top layers of the epidermis are rich in keratin protein which provides a tough barrier and prevents the entry of pathogens - these are shed frequently to wash off the pathogens that may have colonized. - epidermal dendritic cells phagocytize pathogens - skin has chemicals, like demicidin, that defend against pathogens - keratinocytes produce antimicrobial peptides called defensins

phagocytic killing

- three leukocytes that are involved are monocytes (become macrophages), neutrophils, and eosinophils. The action of these cells is enhanced by fever - monocytes are the largest of all leukocytes and have a kidney- or u-shaped nucleus and are widely distributed. - from blood, these agranulocytes migrate to connective tissues and become macrophages - the three specialized macrophages are microglial cells in nervous tissue, alveolar macrophages in the lungs, and kupffer cells in the liver - neutrophils are active phagocytes of bacteria - eosinophils phagocytize antigen-antibody complexes. eosinophils also combat parasites too large to be phagocytized by swarming the parasite and releasing various toxins

calor

- warmth from the increased flow of blood