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! without it we would not survive till ! dispersed chemicals, cells and tissues
adulthood
! dispersal and transport via circulatory and
our body has many ways to prevent or to slow lymphatic systems
infections
two major kinds of mechanisms that protect the
Individual Susceptibilities body:
! physical & chemical barriers that work to c. sebaceous glands provides protective film
prevent entry of pathogens over skin
! internal cells & chemicals that attempt to d. acidity of skin secretions ('acid mantle')
remove pathogens if they get past the barriers inhibit bacterial & fungal growth
nonspecific – treats all potential pathogens the same f. Langerhans cells ( & Granstein cells) ! serve as
way antigen presenting cells
attempt to prevent entry of pathogens into body they expose skin antigens to T cells
skin is rarely, if ever, penetrated while intact line all systems that open to outside of body
only a few bacteria and parasitic worms (cercariae) can do a. secretes mucus
this
thick, sticky, traps pathogens
if skin is broken: staphs and streps are most likely to get in
b. in the nose nasal hairs help trap pathogens
Human Anatomy & Physiology: Body Defense & Immunity; Ziser Lecture Notes, 2014.4 3 Human Anatomy & Physiology: Body Defense & Immunity; Ziser Lecture Notes, 2014.4 4
c. many mucus membranes have cilia low flow ! bladder infection
in resp system move mucus out of system acidity also inhibits bacterial growth
d. stomach lining secretes gastric juices acidity also inhibits bacterial growth
contains HCl and enzymes; highly acidic (pH~1.2-3.0) but: some pathogens thrive in moisture and if they
occur in large enough numbers they are able to
kill and dissolve most bacteria and toxins penetrate eg. Treponema
except S. aureus and C. botulinum
Internal Cells & Chemicals
but: Helicobacter pylori neutralizes acids to grow in
stomach
may cause gastritis or ulcers 1. blood has nonspecific, antimicrobial chemicals that
help to fight invaders:
e. eye is protected by lacrimal apparatus
eg. transferrins – bind to Fe to inhibit bacterial growth
continual blinking flushes and wipes away
pathogens 2. Simple Phagocytosis
lysozyme in tears kills and dissolves some bacteria many WBC’s travel through blood and tissues and
(most G+ and some G- bacteria)
gobble up bacteria and foreign material
(lysozyme also found in sweat, saliva, and nasal
secretions)
mostly neutrophils and macrophages (formed from
monocytes)
f. saliva in mouth allows continual flushing of
bacteria to stomach migrate to area of infection
lysozyme kills and dissolves some bacteria monocytes enlarge on way to become
macrophages
g. urine provides continual flushing of bacteria
entering urethra
engulf and destroy circulating pathogens
Human Anatomy & Physiology: Body Defense & Immunity; Ziser Lecture Notes, 2014.4 5 Human Anatomy & Physiology: Body Defense & Immunity; Ziser Lecture Notes, 2014.4 6
[referred to as the reticuloendothelial system] not all microorganisms are killed once phagocytized
larger response that prevents spread of infection !increased blood flow to area
damage to body’s tissues causes: this allows defensive chemicals and clotting factors and cells
to move to the area
redness, pain, heat and swelling clot forms around area to prevent spread of infection
eg interferon
involves coordinated autonomic, neuroendorine
and behavioral response very high temperatures (>40º C) may be life
threatening
used by all vertebrates as acute phase reaction to
immune challenge 7. Complement Reactions
hypothalamic thermostat is reset usually to 1-4 foreign substance may trigger cascade
degrees above normal which activates complement proteins
=complement fixation
eg. 102.2 ºF
produced by pyrogens secreted by macrophages ~5% of all blood proteins (20 different ones) are
when exposed to certain pathogens complement proteins
the effects of complement activation are short has only very limited effects on cancer cells
lived
! they are quickly destroyed high doses have side effects:
fatigue, fever, chills, joint pain, seizures
malfunctions of system may result in some hypersensitivity
experimentally used to treat HIV, Hepatitis, genital herpes,
disorders
influenza, common cold
functionally, the third line of defense against infections most are large complex organic molecules (MW
>10,000), not normally found in the body
non innate, but adaptive: especially immunogenic:
foreign proteins
1. carefully targeted nucleic acids
some lipids
many large polysaccharides
! recognizes a specific foreign substance and
acts to immobilize or neutralize it but large simple molecules of many small repeating units (eg.
plastics) have little or no immunogenicity
2. amplifies the immune response, complement
reactions, etc against specific pathogen must be foreign to the host
!but may become so by attaching to the for viruses and other organisms that establish
body’s own proteins (=Haptens) themselves within body cells the immune system
uses a different process
eg. chemicals in poison ivy, animal dander,
some detergents, cosmetics, etc
the infected cells display major histocompatability
complex (MHC) molecules on their surface
actually, only certain parts of an entire antigen are
which bind to and display small peptides or
immunogenic
fragments of proteins that come from the
parasite
usually a small sequence of amino acids (~10)
that triggers an immune reactions
these MHC with foreign peptides form antigens
that can be recognized by antigen receptors
! = antigenic determinants (=epitopes)
on certain lymphocytes which identify and kill
infected cells, leaving healthy cells alone
most naturally occurring antigens have a variety of
antigenic determinants
The Immune Response
eg. large proteins have 100’s
The immune response (=specific immunity) involves
the interaction of two major processes in the
Antigen Processing
body, directed by two different kinds of
lymphocytes (WBC’s):
immune surveillance is a search for antigens
A. Antibody Mediated Immunity
uses a large population of white blood cells
(AMI; Humoral Immunity)
= lymphocytes
B. Cell Mediated Immunity
to control bacteria and large parasites immune system
(CMI;)
deploys soluble antigen receptors called antibodies
involves the release of proteins called antibodies plasma cells secrete antibodies
2,000 Ab/sec over few (4-5) days, then dies
B-Cell Development & Activation
memory cells do not secrete antibodies
1. by the time an infant is a few months old live for months or years
B lymphocytes (B cells) have completed the 1st
stage of their development: if later exposed to same antigen they can
develop into same kind of plasma cells and
manufactured in fetal liver secrete antibodies
they synthesize up to 100,000 antibody ie. they “remember” an earlier encounter with the
antigen
molecules that they hold in the cell
membrane Antibodies
2. The next stage of development occurs in lymph antibodies are proteins called immunoglobins
nodes and spleen and only occurs if B cell =gamma globulin of plasma proteins
encounters an antigen it recognizes:
each of us has ~ a billion different kinds of antibodies
a. specific B cells activated by exposure to an and each of these has a unique shape
antigen
each immunoglobin molecule consists of 4 polypeptide
!antigen binds to antibodies on cell chains joined together to form a “Y” shaped
membrane of B cell molecule
b. triggers clonal selection and multiplication each antibody has 2 or more combining sites
Human Anatomy & Physiology: Body Defense & Immunity; Ziser Lecture Notes, 2014.4 19 Human Anatomy & Physiology: Body Defense & Immunity; Ziser Lecture Notes, 2014.4 20
1st antibody released to blood by plasma cells
during primary response
! small concave areas at tip of arms of “Y” that attacks specific toxins eg. diptheria, tetanus,
are uniquely shaped and complementary to botulism toxin
the epitope blood group antibodies belong to this group
! cause agglutination
two long (=heavy, ~400 AA’s) chains and two short (=light, ~200
AA’s) chains linked by disulfide bonds Ig A
constant region ! same AA sequence for all in same class dimer
10-25% in serum
variable region ! =antigen binding sites (tips of Y) also found in body secretions:
mucus, saliva, urine, milk, tears
the body uses ~300 gene “pieces” to make >1 Billion different active against bacterial and viral infections
kinds of antibody molecules
inhibits attachment of parasites in gut
1st to encounter bacteria in GI tract
the amino acid sequence determines the specific passed to nursing child in mothers milk
shape of these polypeptide chains
Ig E
this unique shape allows a specific antibody to associated with allergies
causes certain WBC’s to release histamine
combine with specific antigen ! dilates capillaries
! constricts bronchi
Classes of Antibody Molecules:
Ig D
IgG very low concentrations in serum
most abundant antibody in plasma levels increase during chronic infections
75-80% of gamma globulin
also found in internal secretions formation of the antigen/antibody complex by B-cell
(synovial fluid, spinal fluid, peritoneal fluid)
effective against bacteria, viruses, and toxins
activity does not generally destroy the invader
plasma levels increase dramatically during
secondary responses ! it prepares it for destruction by
only Ig that can cross placenta non-specific phagocytosis (WBC’s)
triggering complement fixation
IgM CMI (T-cell activity)
largest of the antibodies
only found in blood
5-10% of plasma immunoglobins
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Human Anatomy & Physiology: Body Defense & Immunity; Ziser Lecture Notes, 2014.4 23 Human Anatomy & Physiology: Body Defense & Immunity; Ziser Lecture Notes, 2014.4 24
Cell Mediated Immunity
= CMI
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4. The next stage of development occurs only if T cell dampens activity of T and B cells
brings immune response to an end
encounters an antigen it recognizes:
iv. Delayed Hypersensitivity Cells
a. specific T cells activated by exposure to a
specific antigen (on a cell) chronic infections
cell mediated allergies
T-cells cannot recognize free antigens in the blood
generally need cell to cell contact to work
v. Memory Cells
eg. viral infected cell, cancer cell, bacterial cell
5. each T-cells secrete specific kinds of immunoactive
b. initiate clonal selection and multiplication of chemicals = cytokines (=lymphokines)
specific kind of T-cell
soluble chemical messengers by which cells of
c. differentiation into several cell types the immune system communicate with
each other
i. Helper T-cells (esp CD4 cells)
NOT antibodies
most prevalent of all kinds of T cells, 65%
directly helps T and B cells to function cytokines direct the activities of both B and
releases lymphokines:
! recruit lymphocytes T cells and phagocytes
! stimulate differentiation of lymphocytes
! help B cells recognize antigens Kinds of Cytokines
there can be no immune response without them
eg. chemotactic factor
ii. Cytotoxic T- cells (CD8 cells)
! attracts macrophages to invaders
directly kill specific target cells by lysis
especially effective against foreign cells, cancer cells, eg. macrophage activating factor
fungi , some protozoa and helminths
recognizes virally infected cells by viral antigens on ! tells macrophages to destroy antigen
cells surface gives them enhanced antibacterial activity:
increased metabolic activity
iii. Suppressor T-cells (CD8 cells) more lysosomes
increased phagocytosis
restricts rampant uncontrolled immune response
Human Anatomy & Physiology: Body Defense & Immunity; Ziser Lecture Notes, 2014.4 27 Human Anatomy & Physiology: Body Defense & Immunity; Ziser Lecture Notes, 2014.4 28
eg. lymphotoxin Interactions of AMI and CMI Systems:
! poison which kills any cell it contacts
requires direct cell contact both systems work together to increase the immune
response against specific foreign antigens
eg. migration inhibition factor
! attracts macrophages in inflammatory resonse eg. stimulate B-cells to differentiate into plasma cells
and produce antibodies
eg. Interleukin 2
! proliferation of TH cells
Neuroendocrine-Immune
eg. stress can activate parts of same pathway
Interactions
eg. mental state can influence the body’s resistance
all three systems are interconnected to disease: anxiety or psychological stress
increased severity of a cold
neural links:
hypothalamus! pituitary! adrenal! stress
neurons innervate immune system organs
such as spleen and lymph nodes >bld sugar ! reduced inflammatory response
Examples of interactions:
natural
acquired (=artificial)
active
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eg. gamma globulin to treat hepatitis, botulism, normal state of self tolerance breaks down due to:
snake bites, etc
Human Anatomy & Physiology: Body Defense & Immunity; Ziser Lecture Notes, 2014.4 39