chapter 16: nonspecific immunity specific vs. nonspecific responses innate nonspecific immunity...
TRANSCRIPT
Chapter 16: Nonspecific ImmunitySpecific vs. Nonspecific responsesInnate nonspecific immunityCells and tissues involved in immune responsesMolecular immunity
ComplementCytokinesInflammation
Physiological changesFeverMetabolism
Nonspecific vs. Specific Immune ResponseVertebrates (humans too) have two lines of
defense against invaders, nonspecific and specific immune response
The first line of defense is the nonspecific responseThese are physical barriers and physiological
defense mechanismsIt is called nonspecific because they are directed at
any invading organismSpecific immunity takes time to develop and is
only effective following the nonspecific response
Innate nonspecific immunityTissue barriers and nonspecific factors are important in
nonspecific immunityPhysical barriers
Skin - Sweat Mucous membranes - Saliva, tears, mucus Urine flow
Nonspecific antimicrobial factors Lysozyme - Destroys cell walls Beta-lysin - kills G+ Defensins - small, antimicrobial peptides Peroxidase - found in saliva and neutrophils Complement - Punch holes in bacteria Interferons - interfere with viral replication Lactoferrin - Competes with bacteria for iron
Structure of the skin
Complement cascade systemComplement is a series of proteins that are
activated by infection, and form an antimicrobial complex
Complement can be activated by three different pathways, the classical pathway (antibody based), the alternative pathway (endotoxin or cell wall activated), or the lectin pathway
Both result in the formation of a membrane attack complex that punches holes in the cell membranes of bacteria and other invaders (not viruses, why?)
The Classical PathwayAn antibody-antigen complex interacts with C1,
which produces an active enzyme that cleaves C2 and C4
The cleaved products of C2 and C4 (C4bC2a) produce an enzyme called the C3 convertase
The C3 convertase cleaves C3, producing C3bC3b is the C5 convertase, which cleaves C5 into
C5a and C5bC5b organizes C6, C7, C8, and C9 into the
membrane attack complex (MAC), which results in lysis of the bacterial cell
The alternative pathwayThe alternative pathway skips a few steps of
the classical pathwayC3b is produced in very low levels
spontaneously from C3C3b interacts with endotoxin and other
bacterial cell wall components and Factors B, D, and P to form C3bBb, which is an alternative C3 convertase, which produces more C3b, the C5 convertase
This produces C5b, which results in formation of the MAC
Lectin PathwayThe lectin pathway is very similar to the
classical pathway, except for activationActivation occurs when mannose binding
lectin (MBL) binds to mannose found on the surface of some bacterial cells (often part of LPS)
This then activates two proteins called MASP-1 and MASP-2, and all three stick togetherThis complex then cuts C4 and C2, and off we
go!
http://www.medicine.uiowa.edu/martinlab/complement.html
Chemical defense mechanismsCytokines are molecular messages between
cells that are important in the immune response as well as other communications between cells
There are many different kinds of cytokines, which act in specific ways to stimulate different aspects of the immune response
Some important cytokinesInterferons (INF)Interleukins (IL)Tumor necrosis factors (TNF)
CytokinesInterferons (IFN’s) - Antiviral proteins. Three
types are known IFN-alpha - produced by white blood cells (leukocytes);
antiviral IFN-beta - produced by tissue cells (fibroblasts);
antiviral IFN-gamma - produced by immune cells (T-cells);
antiviral, also involved in other immune responsesInterleukins (IL) - Function in many aspects of
the immune response. Will be discussed in subsequent chapters
Colony-stimulating factors - Cause a proliferation of certain cell types
Tumor necrosis factors (TNF’s) - Kill some tumor cells, also involved in other immune responses
InflammationThe first host response to invading organisms
(injury) is inflammationThere are four cardinal signs associated with
inflammationRednessHeatSwellingPain
The same sequence of events occurs in response to any injury, whether caused by invading bacteria, burns or trauma
The inflammatory responseDuring inflammation, C3a and C5a
(complement) cause the release of chemicals from tissue mast cell granules (histamine, leukotrienes, and kinins, in particular)
These chemicals increase permeability of the small capillaries, leading to increased blood flow
Circulating leukocytes (white blood cells) adhere to receptors on the inner walls of blood vessels and migrate out in response to chemical attractants (chemotaxis)Neutrophils show up first, then moncytes
(macrophages) and lymphocytes (pus)
http://www.biologymad.com/Immunology/inflammation.jpg
PhagocytosisPhagocytosis involves the process of phagocytic cells
engulfing and killing microorganismsStep one - Find the invader
Chemical products of microorganisms, components of complement (C5a) and phospholipids released by the mammalian cell are all chemoattractants for phagocytes
Step two - Attach and engulf C3b helps with this part (opsonization)
Step three - Kill, kill, kill Neutrophils contain granules, monocytes have lysosomes that
contain digestive enzymes that kill the invaderhttp://www.exploratorium.edu/imaging_station/gallery.ph
p?Asset=Human%20macrophage%20-%20phagocytosis&Group=&Category=Blood%20Cells&Section=Introduction
Physiological changes affect the immune response - FeverFever - Normal body temperature is closely
regulated, but in the case of infection, a higher setting is used to:Elevate the temperature above that preferred for
optimal growth of pathogensActivate and speed up a number of body defenses
Fever can be activated by the cytokine IL-1, which is released by phagocytic cells that have come in contact with microorganisms. It can also be activated by TNF-alpha
By slowing the growth rate of the bacteria, and increasing enzymatic activity of the immune response, fever helps speed clearing of an infection
Changes in iron metabolismThe ability to limit iron availability to
invading organisms is a major nonspecific defense mechanism
There are two important iron-binding proteins in bloodTransferrinLactoferrin
High iron levels in blood can increase the chances for infection
Cells involved in the immune responseAll blood cells (white blood cells =
leukocytes; red blood cells = erythrocytes and platelets) arise from a single precursor, the hematopoietic stem cell
Leukocytes are the cells primarily responsible for the defense of the body against microorganismsGranulocytes - Neutrophils, Basophils and
EosinophilsAgranulocytes –
Mononuclear phagocytes - Monocytes and macrophages
Lymphocytes – B, T, and NK cells
Natural Killer cellsNK cells are so named because they don’t
seem to require recognition of MHC (which we’ll learn about in the next chapter) and don’t have a TCR (ditto)
NK cells recognize (how, we’re not sure) our cells that are infected or have mutated, and kill them without being specific