Transcript anatomy presentation 1

Part 2: Lines of Defense and
Antibody Production
Sarah Weinsztok
Intro: Antibodies and Pathogens
• *What is a pathogen? An organism or virus
causing disease
• Specific antibodies combat pathogens when they
enter the body
▫ B cells produce antibodies
• Antibodies bind to microbes and mark them for
elimination
Immune System *Lines of Defense! First
line…
• The first 2 defense lines=nonspecific
• 1st defense line=external
▫ *Mucus and skin
• Mucus=a viscous fluid that traps microbes and other
particles
▫ Ex: trachea has mucus producing cells and cilial cells- trap
microbes via cilial beatings
▫ Mucus regions in body: nose, trachea, vagina, urethra
• Skin is touch, secretes lactic and fatty acids to kill
microbes
▫ Skin and mucus membranes provide hostile environments
for microbes- acidic skin pH via sweat glands to prevent
microbial colonization
▫ Antimicrobial proteins
 Ex: lysozyme- digests bacterial cell walls
Line of Defense 2: Phagocytosis
• We all know phagocytosis= cellular eating
▫ Ingestion of invading microorganisms by certain types of
white blood cells (aka phagocytes) which causes
inflammation=prevents microbial spread
• 2nd line=internal and nonspecific
• Ingest pathogens in the blood-large numbers at an
infection cite form pus
• *There are 4 leucocytes (white blood cells) that are
phagocytic…
Vertebrate v Invertebrate Defenses
• Exoskeletons of invertebrates act
like the skin and mucus
membranes of vertebrates,
providing an external barrier to
prevent intruders
• Hemolymph= insect equivalent of
blood
▫ Contains hemocytes-some ingest
bacteria by phagocytosis, or form
cellular capsules around bacteria
▫ Macrophage antimicrobial peptides
similar to those in hemocytes
• However, invertebrates lack cells
analogous to lymphocytes (which
do acquired immunity)
4 Phagocytic Leucocytes
• 1) neutrophils- most abundant (60%), attracted to and
enter infected tissue, engulfing and destroying microbes
▫ Downside-they self destruct, so life span=only a few days
• 2)macrophages: more effective, large, long lived cells
developing from monocytes, some migrate and some
permanently set in immune system
▫ More on this later in Gail’s powerpt, macrophages surround
and engulf microbe, forming a vacuole, and enzyme break
down microbe, expelling it via exocytosis
• 3) eosinophils-low activity but critical defense against
multicellular parasites
▫ Position themselves against parasites body and discharge
destructive enzymes
• 4)dendritic cells- ingest like macrophages do, but mostly
stimulate development of acquired immunity
Just another important defense
mechanism to remember…
• Becomes important as we move on
• NK (natural killer) cells
▫ Another innate defense
▫ Patrol body and attack virus infected body and
cancer cells
 Attaches and releases chemicals, which leads to
death via apoptosis
 Remember, apoptosis=programmed cell death
*3rd defense line, aka “The Biggie”:
Antibody Production
• 3rd and last line of defense=antibody production
▫ Internal and specific, or acquired
• *Antibodies v antigens?
▫ Antibodies are proteins that recognize and bind to specific antigens
▫ Antigens are foreign substances that stimulate production of antibodies;
can be a wide range of substances
▫ In layman’s terms, antibodies..good!, antigens…bad
• 2 branches of immunity here
▫ Humoral immune response= activation and clonal selection of B cells
▫ Cell mediated immune response= activation and selection of cytoxic T
cells
▫ Different branches because they respond to different threats!
▫ T cells are important, they respond to antigens in antigen presenting
cells, and in turn stimulate the activation of nearby B cells and cytoxic T
cells
Helper T Cells
• Helper T Cells= T cells have receptors in their plasma
membrane that bind to antigens presented by
microphages
▫ Recognized mostly with dendritic cells, macrophages, and B
cells
 Remember, there are many different types of these
lymphocytes mentioned earlier, they each recognize one
specific antigen and respond by forming a clone, which secretes
a specific antibody against the antigen
 So, Helper T’s lead to both Humoral and Cell mediated
immune responses
▫ Macrophage passes signal to helper T cell, changing it from
inactive to active state
• It is specific! T cells eliminate body cells infected by
viruses and other intracellular pathogens, and cancer
cells
Helper T’s help both humoral and cell
mediated immune responses
Cytotoxic T Cells and Cell Mediated
immune response
• CD8=surface protein that enhances interaction
between target cell and T cell
▫ Chemokines (more info in Gail’s slides) essentially
direct the migration of phagocytes
 Help promote activation of T cell into a killer cell (NK
remember?)
• CD8 binds to I MHC molecule (more later),
importantly it helps keep 2 cells in contact during
activation of T cell
• Death of an infected cell deprives pathogen of a
place to reproduce and exposes it to circulating
antibodies, which leads to its disposal
▫ Eliminate body cells infected by viruses, cancer cells,
and transplanted cells
Cytotoxic T cell binds to antigen
complex on the target cell,
which leads to the activation of
the cytotoxic T cells
Activated T cell releases
perforin molecules, which form
pores in target cell membrane,
and enzymes which enter target
cell via endocytosis
These enzymes initiate
apoptosis within target cell,
leading to fragmentation of the
nucleus, release of apoptotic
bodies, and cell death. The
newly released cytotoxic T cell
can move on to attack other
target cells
Cytotoxic T Cells and Viruses
• Cytotoxic T cells can work on malignant tumors by identifying
their distinctive molecules (antigens)
▫ Counter Ex. Epstein Barr Virus (associated with mononucleosis)
and others actually reduce I MHC molecules-they escape T cell
detection, but there is a backup
 NK cells can induce apoptosis in these certain viral cells
• *This shows a difference between bacteria and viruses, the
reason antibiotics are not effective in viruses
▫ Antibiotics=chemicals produced by microorganisms to
kill/control growth of other microorganisms. They block specific
metabolic pathways found in bacteria (without causing damage to
human cells because big difference in the individual cellular
makeups)
▫ Viruses reproduce and perform most functions using host cell’s
metabolic pathways, which are not affected by antibiotics. Viruses
carry out very few processes themselves, and so are not affected by
antibiotics, which block metabolic pathways in bad cells
Viruses Take Over Host Cells
B Cell Activation: Humoral Immune
Response
• An activated helper T cell with receptors for same antigen can then
bind to a B cell. T cells send signals to B- causing it to change from
inactive to active state
▫ Antigens in humoral immune response are typically proteins on bacterial
surfaces, or incompatible transplanted tissue or transfused blood cells
• Inactive B cells have antibodies in their plasma membrane, and if
they match an antigen, it binds to the antibody
• Stimulated by both an antigen and cytokines, B cell proliferates and
differentiates into a clone of antibody-secreting plasma cells and a
clone of memory B cells
▫ Plasma cells: activated B cells divide forming clones, become active with
a greater volume, large rER, they synthesize large amounts of antibody,
then are excreted by exocytosis
▫ Memory cells: B and T cell combination formed at the came time as
activated helper T cells and B cells, used when presented with a
challenging disease, provide long-term immunity to a disease
B Cell Activation Cont’d.
• When an antigen binds to receptors on surface
of B cell, cell takes in a few of foreign molecules
by receptor mediated endocytosis
▫ Then presents cell fragments to helper T cell,
which causes T and B cell-cell interactions
• T-dependent (stronger response of the two) or
T-independent antigen responses. Some
antigens require helper T cells along with B cells
to combat it, and the response from both is
stronger
Antibody Classes
• There are 5 types of
constant chains of
antibodies
▫ Tails of Y shaped
antibodies are
constant
▫ Head is specific to
recognize/ bind
with antigen
• Polyclonal vs
monoclonal
(explained later)
Antibody-Antigen Binding
• This binding leads to antigen disposal mechanisms:
▫ 1) viral neutralization- antibodies bind to certain proteins on a
virus surface-block ability to infect host
▫ 2) opsonization- bound antibodies enhance microphage
attachment to microbes, increasing phagocytosis (aka cellular
eating remember..)
▫ 3)agglutination- (clumping) of bacteria or viruses can be readily
phagocytosed by microphages
▫ 4)precipitation-antibodies cross-link soluble antigen molecules
dissolved in bodily fluids, forming immobile aggregates, disposed
of by phagocytosis
• Complement system-can form cascade system where each
component activates the next
• Membrane attack complex-pore forms in membrane, swells
and lyses-promote inflammation and stimulates phagocytosis
Antibody mediated mechanisms of
antigen disposal