Chap 16 Flashcards
Nonspecific defenses of the host
Innate immunity
Mature cell that releases antibodies
Plasma cell
Cells that make up innate immunity
-Basophil
-Eosinophil
-Mast cell
Granulocytes
-Basophil
-Eosinophil
-Mast cell
-Neutrophil
Both innate and adaptive cells
-Neutrophil
-Monocyte
-Dendritic cell
- Natural Killer cell
Adaptive immunity cells
Plasma cell
B cell
T cells
Types of T cells
-T helper
-Cytotoxic T cells (lymphocytes)
-T regulatory cell
Agranulocyte with many surface projections
Dendritic cells
Releases histamines that cause inflammation
Basophil
Kills parasites with oxidative burst
Eosinophil
Antigen-presenting cells; produce antibacterial peptides
Mast cell
Phagocytizes bacteria and fungi
Neutrophil
Precursor to macrophages. Some macrophages can be fixed in certain organs while others wander tissues, causing inflammation. All perform phagocytosis.
Monocyte
In skin and respiratory and intestinal mucosa, phagocytizes bacteria and presents antigens to T cells
Dendritic cell
Kills cancer cells and virus-infected cells
NK cell
Recognizes antigens and produces antibodies
Plasma cell, B cell
TH (T helper cell)
secrete cytokines
They are CD4+ cells that bind MHC class II molecules on APCs.
Helper T cells
recognize and kill specific “non-self” cells. They are CD8+ cells that bind to MHC class I molecules. T
Cytotoxic T lymphocyte CTL
Cells are CD4+ cells that destroy cells that do not correctly recognize “self” cells.
T regulatory cells
measure leukocytes in the blood
White blood cell (WBC) counts
High WBC counts may indicate
bacterial infections, autoimmune diseases, or side effects of medications
Low WBC counts may indicate
viral infections, pneumonia, autoimmune diseases, or cancers
Normal WBC range
5,000-10,000 WBCs per cubic milimeter or 5.0-10.0 x 10^9 WBCs per liter
Normal neutrophils percentage
60-70%
Normal lymphocytes percentage
20% to 25%
Normal monocytes percentage
3% to 8%
Normal Eosinophils percentage
2% to 4%
Normal basophils percentage
0.5% to 1%
Immunity
ability to ward off disease
Susceptibility
lack of resistance to a disease
Innate immunity
defenses against any pathogen; rapid, present at birth
Adaptive immunity:
immunity or resistance to a specific pathogen; slower to respond, has memory component
Toll-like receptors (TLRs)
on host cells attach to pathogen-associated molecular patterns (PAMPs)
TLRs bound to PAMPs induce
the release of cytokines from the host cell that regulate the intensity and duration of immune responses
First line defenses
Skin
Mucous membranes
Innate (Non-specific) Defenses
- First-line defenses
- Phagocytosis
- inflammation
- Complement system
Two main divisions of adaptive defense
- humoral immunity
- Cell-mediated immunity
Antigen presenting/processing cells aid in
activation of adaptive defenses
humoral immune response
consists of the activity of B cells and the antibodies they produce
Cell-mediated immunity
host defense used to fight intracellular pathogens and abnormal body cells such as cancer cells.
Protagonists of cell-mediated immunity are
T lymphocytes
Helper T cells
secrete cytokines to activate other cells of the immune system
Cytotoxic T cells
attack infected cells directly
Dermis
inner portion made of connective tissue
Epidermis
outer portion made of tightly packed epithelial cells containing keratin, a protective protein
Shedding and dryness of skin inhibits
microbial growth
Mucous membranes
Epithelial layer that lines the gastrointestinal, respiratory, and genitourinary tracts
Mucus
viscous glycoproteins that trap microbes and prevent tracts from drying out
Lacrimal apparatus
drains tears; washes eye
Ciliary escalator
transports microbes trapped in mucus away from the lungs
Earwax
prevents microbes from entering the ear
Urine
cleans the urethra via flow
Vaginal secretions
move microorganisms out of the vaginal tract
Other physical factors
Peristalsis, defecation, vomiting, diarrhea
Sebum
forms a protective film and lowers the pH (3–5) of skin
To what level does sebum lower pH?
3-5
Lysozyme
in perspiration, tears, saliva, and urine destroys bacterial cell walls
gastric juice
destroys most bacteria and toxins
pH of gastric juice
1.2-3.0
Low pH (3–5) of vaginal secretions inhibits
microbes
pH of Vaginal secretions
3-5
Normal microbiota
compete with pathogens via microbial antagonism (competitive exclusion)
microbial antagonism
(competitive exclusion)
Competitive advantage for space and nutrients
normal microbiota
Produce substances harmful to pathogens
normal microbiota
Alter conditions that affect pathogen survival
normal microbiota
Commensalism:
one organism benefits while the other (host) is unharmed
Probiotics
live microbial cultures administered to exert a beneficial effect
Formed Elements in Blood
Cells and cell fragments suspended in plasma
Types of formed elements in blood
Erythrocytes (red blood cells)
Leukocytes (white blood cells)
Platelets
How are formed elements created?
Created in red bone marrow stem cells via hematopoiesis
Granulocytes
leukocytes with granules in their cytoplasm that are visible with a light microscope
Neutrophils
phagocytic; work in early stages of infection
Basophils
release histamine; work in allergic responses
Eosinophils:
phagocytic; toxic against parasites and helminths
60-70% of leukocytes
function: Phagocytosis
Neutrophils
Basophils percentage
(0.5-1%)
Basophils function
Production of histamine
Eosinophils percentage
2-4%
Eosinophils function:
Production of toxic proteins against certain parasites; some phagocytosis
Agranulocytes
leukocytes with granules in their cytoplasm that are not visible with a light microscope
Monocytes
mature into macrophages in tissues where they are phagocytic
Dendritic cells found in
found in the skin, mucous membranes, and thymus; phagocytic
Lymphocytes
T cells, B cells, and NK cells; play a role in adaptive immunity
Monocytes percentage
3-8%
Function of monocytes
Phagocytosis (when they mature into macrophages)
Dendritic cells function
phagocytosis and initiation of adaptive immune responses
Lymphocytes percentage
20-25%
NK cells function
Destroy target cells by cytolysis and apoptosis
T cells function
Cell-mediated immunity
B cells function
Produce antibodies
Lymphatic system components
Lymph, lymphatic vessels, lymphoid tissue, and red bone marrow
Lymphatic system contains which cells?
lymphocytes and phagocytic cells
Lymph carries microbes to
lymph nodes
What happens at lymph nodes
lymphocytes and macrophages destroy the pathogen
Act against all pathogens; not specific to a given pathogen
Innate defenses
recognize a specific pathogen
Adaptive defenses
must be activated by APCs before they can work
adaptive, specific defenses
Examples of adaptive defenses
antibodies, cytotoxic cells
Innate and adaptive defenses make it very difficult for pathogens to
penetrate, colonize and cause disease
Phago:
from the Greek, meaning eat
Cyte
from the Greek, meaning cell
Fixed macrophages
are residents in tissues and organs
Free (wandering) macrophages
roam tissues and gather at sites of infection
Chemotaxis
Chemical signals attract phagocytes to microorganisms
Adherence
Attachment of a phagocyte to the surface of the microorganism
Ingestion
Opsonization: microorganism is coated with serum proteins, making ingestion easier
Digestion
Microorganism is digested inside a phagolysosome
The Mechanism of Phagocytosis steps
- Chemotaxis
- Adherence
- Ingestion
- Digestion
Ingestion of a solid - such as a microorganism or cellular debris by a eukaryotic cell
Phagocytosis
Used by some protozoans for obtaining nutrients
Phagocytosis
Used by certain cells of the immune system to fight infection
Phagocytosis
Examples of phagocytes
Macrophages, neutrophils
Movement of a cell towards or away from a chemical stimulus
Chemotaxis
Phagocytes use pseudopods to
move towards microorganisms or damaged cells at the site of infection. Arrive only minutes after infection
Chemotactic chemicals that attract phagocytes include:
- microbial products
- Components of damaged cells
- Chemicals released by other white blood cells
- Peptides derived from the complement system
The plasma membrane of phagocytes usually attaches to glycoproteins on the microorganism’s surface. This process is called ____________.
adherence
Adherence is made easier through
opsonization
opsonization
antibodies or complement proteins from the host coat the microbe’s surface, serve as handles so phagocyte can more easily attach to the microorganism.
Opsonins
proteins that coat the microbe are called
pseudopods fuse, forming a sac called a
phagosome
The phagosome enters the cytoplasm where it fuses with
lysosomes
Digestion of most bacteria within lysosome is complete within
10-30 mins
elimination (exocytosis)
after phagocytosis,
Phagolysosome fuses with the plasma membrane and expels the contents
Some of the contents of the phagolysosome may also be presented on the cell membrane through a process called
antigen processing and presentation
Phagocytes are able to detect foreign cells by looking for molecules on
the surface of those invaders that are not found on the human body
look for a specific antigen on the surface of invaders
adaptive defenses
When immune surveillance cells such as macrophages are looking for invaders, they search for surface molecules that are not found on host surfaces, such as
peptidoglycan
capsules protect microbes because
they’re made of polysaccharides similar to molecules found on host cells.
When a macrophage encounters an encapsulated bacterium
It doesnt recognize it as foreign and ignores it
Examples of encapsulated bacterium
Streptococcus pneumoniae, common cause of bacterial pneumonia
are all bacteria killed after being swallowed by a phagocyte
no
how does the tuberculosis bacterium survive phagocytosis?
by preventing the fusion of lysosome and phagosome. This keeps digestive enzymes away from the bacterium
These two bacteria can actually escape the phagosome and live within the cytoplasm of the phagocyte
shigella and listeria
Some microbes are not affected by lysosomal activity
Leishmania, a protozoan, can resist lysosomal enzymes
inhibit the pathway that leads to oxidative killing within a phagocyte
legionella and some staphylococci
Some bacteria actually reproduce within the
phagocyte
Capable of hiding from host defenses by changing surface antigens ___________.
frequently
Changing surface antigens can result from
mutations, genetic recombinations
Viruses that frequently exhibit genetic recombination
RNA viruses such as:
influenzavirus, HIV
Trypanosoma causes
sleeping sickness
has a surface glycoprotein that undergoes frequent changes
Trypanosoma
Complement
group of proteins that when activated, undergoes a series of reactions leading to inflammation, opsonization and cell lysis.
Some bacteria simply invade complement by
covering the binding sites with a capsule
Other bacteria have peptidases that
destroy key complement proteins and block the cascade
mimic a control molecule that the human body uses to keep complement inactive when it is not needed.
Neisseria and some viruses
Produce molecules called leukocidins
1.Pseudomonas,
2.group A streptococci
3.bacterial pathogens.
Leukocidins cause
destruction of phagocytes, such as neutrophils and macrophages.
Species of Neisseria that cause meningitis and gonorrhea secrete an enzyme called
IgA protease
IgA protease destroys
a class of antibodies called IgA that are located in mucous membranes
meningitis and gonorrhea are less likely to be detected in which regions
mucous membranes
Examples of pathogens that can cause generalized suppressions of the immune system
HIV, measles and several viruses
How do viruses cause generalized suppression
suppress activity of cytokines, or reproduce within macrophages and T cells.
Superantigens role in invasion
toxins that distract adaptive defenses, causing them to produce a non-specific exaggerated response, and fail to respond to the actual invader
Signs and symptoms of inflammation:
pain, redness, immobility, swelling (edema), heat
Function of inflammation
Destroys injurious agent or limits its effects on the body
inflammation repairs
and replaces tissue damaged by the injurious agent
Inflammation activates
acute-phase proteins by the liver
Acute phase proteins by the liver cause
vasodilation and increased permeability of blood vessels
acute-phase proteins
Serum proteins whose concentration changes by at least 25% during inflammation.
Histamine
- Vasodilation
- Permeability
- Smooth muscle contraction
Kinin
A substance released from tissue cells that causes vasodilation.
Prostaglandin
A hormonelike substance that is released by damaged cells, intensifies inflammation.
Leukotrienes made by
- produced by mast cells and basophils
Leukotrienes produced by
mast cells and basophils
Leukotrienes cause
increased permeability of blood vessels
Leukotrienes help
phagocytes attach to pathogens.
cytokine
A small protein released from human cells that regulates the immune response; directly or indirectly may induce fever, pain, or T cell proliferation.
Histamine comes from
Mast cells, basophils, platelets
kinins come from
Blood plasma
Prostaglandins come from
damaged cells
Leukotrienes come from
Mast cells and basophils
complement comes from
blood plasma
cytokines come from
fixed macrophages
Effects of histamine
Vasodilation & increased permeability of blood vessels
effects of kinins
chemotaxis by attracting neutrophils
effects of prostaglandins
intensify the effects of histamine and kinins, and help phagocytes move through capillary walls.
Effects of leukotrienes
increase permeability of blood vessels and help attach phagocytes to pathogens
effect of complement
stimulates release of histamine, attracts phagocytes and promotes phagocytosis
effect of cytokines
vasodilation and increased permeability of blood vessels
First step of inflammation
histamines, kinins, prostaglandins, leukotrienes and cytokines are released by damaged cells
step 2 of inflammation
blood clot forms
step 3 of inflammation
Abscess starts to form
Step 4 of inflammation
margination- phagocytes stick to the endothelium
step 5 of inflammation
phagocytosis of invading bacteria occurs
Things that can trigger inflammation
sunburn, chemical burns, cuts, microbial infections
Inflammation is a type of
general, nonspecific, defensive response
Three main functions of inflammation
- Destroy agent causing injury
- Limit the effects of the agent on the rest of the body
- Repair or replace damaged tissue
certain components of the complement system can also stimulate the release of ______
histamines
histamines can result in
vasodilation
Vasodilation results in
more blood (more phagocytes), more oxygen, and more nutrients being delivered to the site of injury.
increased blood flow also results in
redness, heat and some of the pain associated with inflammation.
What has a direct effect on the capillaries in the area of the injury?
histamines, prostaglandins and leukotrienes
Cause the walls of the capillaries to become leakier
histamines, prostaglandins and leukotrienes
Leaky capillaries cause
more fluid to leave the capillary and enter tissue spaces, causing swelling or edema
Increased blood flow delivers
phagocytes such as monocytes and neutrophils to the scene.
phagocytes stick to the walls of the blood vessels in a process called
margination
After margination, the cells squeeze through the gaps in a process called
Diapedesis or emigration
within about an hour of tissue damage, the phagocytes begin to
destroy the invading microorganisms by phagocytosis.
After engulfing large numbers of microorganisms and damaged tissues,
the phagocytes die, forming pus
other components of the blood lead to the formation of ______ _________ which seal off the site of injury
blood clots
final stage of inflammation is
tissue repair
The increased delivery of nutrients and oxygen aids in
tissue repair
sticking of phagocytes to blood vessels in response to cytokines at the site of inflammation
margination
Phagocytes squeeze between endothelial cells of blood vessels via
diapedesis
tissue repair cannot be completed until
all harmful substances are removed or neutralized
Stroma
is the supporting connective tissue that is repaired
Parenchyma
is the functioning part of the tissue that is repaired
regenerated epidermis
parenchyma
Regenerated dermis is
Stroma
Fever
Abnormally high body temperature
Hypothalamus is normally set at
37 C
cause the hypothalamus to release prostaglandins that reset the hypothalamus to a higher temperature
cytokines
The body maintains the higher temperature until
the cytokines are eliminated
crisis
The phase of a fever characterized by vasodilation and sweating.
As body temperature falls (crisis),
vasodilation and sweating occurs
How is fever beneficial?
Damaging pathogens
Fevers increase the temperature of infected tissues to a level that damages pathogens.
Impairing pathogen replication
The systemic temperature increase caused by a fever can make it harder for pathogens to replicate if they have spread.
Complement system is made of
Serum proteins produced by the liver that enhances the immune system in destroying microbes
The complement system acts in
a cascade in a process called complement activation
Proteins are designated with
uppercase C and numbered in order of discovery
Activated fragments are indicated with
lowercase a and b
set of proteins that circulate in the blood serum
complement system
When the complement system is activated these proteins destroy foreign cells by
cytolysis
the complement system also activates
the inflammatory response, and assists in phagocytosis
The main components of the complement system are called
C1 through C9
Complement can be activated through 3 different pathways
- Classical pathway
- Alternative pathway
- Lectin patway
first activation pathway of complement system to be discovered
Classical pathway
The classical pathway begins when
a pair of antibodies attaches to antigens on the surface of a bacterium
Antigens can be
proteins or large polysaccharides on the surface of a bacterium
The antibodies bind and activate
C1
C1 then cleaves
several copies of C2 and C4
Together, the C2a and C4b fragments form
an enzyme that cleaves C3, activating the complement system
was named so because it was discovered after the classical pathway
Alternative pathway
Classical pathway requires antibodies specific to the
invading microorganism
The alternative pathway requires
three complement proteins called factor B, factor D and factor P
Factor P stands for
properdin
Factors B, P, & D are attracted to
microbial cell-surface material such as the lipid-carbohydrate complexes of certain bacteria and fungi
Together with C3, these proteins (B,P,D) result in the cleavage and activation of
C3 proteins
C3 proteins in turn activate the
rest of the complement system
Most recently discovered pathway of complement activatio is the
lectin pathway
What stimulates the production of lectins?
Macrophages ingest materials through phagocytosis, they release chemicals that stimulate the production of lectins
carbohydrate binding proteins
lectins
The lectins bind to
distinctive patterns of carbohydrates on the surface of certain bacteria and viruses.
the lectins themselves can act as
opsonins for phagocytosis, but also activate C2 and C4
the activation of C2 and C4 leads to the activation of C3 which
leads to the activation of the rest of the complement pathway
Step 1 classical pathway
Antibodies bind to antigens, activating C1
Step 2 classical pathway
C1 splits and activates C2 and C4
Step 3 classical pathway
C2a and C4b combine and activate C3
C3a functions in
inflammation
C3b functions in
cytolysis and opsonization
Step 1 alternative pathway
C3 present in the blood combines with factors B, D, and P on microbe surface
step 2 alternative pathway
C3 splits into C3a and C3b, functioning the same as in the classical pathway
What happens in the lectin pathway ?
Macrophages ingest pathogens, releasing cytokines that stimulate lectin production in the liver
Mannose-binding lectin (MBL) binds to
mannose, activating C2 and C4
C2a and C4b activate
C3, which functions the same as in the classical and alternative pathways
cytolysis
The destruction of cells, resulting from damage to their cell membrane, that causes cellular contents to leak out.
Activated complement proteins create a membrane attack complex (MAC) leads to
cytolysis
Promotes attachment of a phagocyte to a microbe
Opsonization
Activated complement proteins bind to mast cells, releasing histamine
inflammation
Outcomes of complement activation
- Cytolysis
- Opsonization
- Inflammation
The complement system is another way the body
fights infection and destroys pathogens
This component of innate immunity
“complements” other _______ _________.
immune reactions.
The cascade can be activated by
a pathogen directly or by an antibody–antigen reaction
Together these proteins destroy microbes by
cytolysis, (2) enhanced phagocytosis, and (3) inflammation
C3a and C5a act as
chemotactic factors, attract phagocytes to the site of infection.
C3a and c5a also bind to
mast cells , release histamine and cause inflammation. also relase other chemicals
C3b acts as an
opsonin, coating the invading cell
This coat makes it easier for the phagocyte to
adhere to the invading cell during phagocytosis
C5b binds to C6 and C7 which attach to the
plasma membrane of the invading cell
C8 and several C9 molecules bind to the C5b, C6, C7 complex and
forming a cylinder shaped membrane attack complex
MACs make holes in membrane causing
water and ions to leave, cytolysis, killing the cell
regulation of complement
Regulatory proteins readily break down complement proteins, minimizing host cell destruction
Complement and disease
Lack of complement proteins causes susceptibility to infections
Evading the complement system
Capsules prevent complement activation
Interferons
Cytokines produced by cells; have antiviral activity
IFN-α and IFN-β
produced by cells in response to viral infections; cause neighboring cells to produce antiviral proteins (AVPs) that inhibit viral replication
IFN-γ
causes neutrophils and macrophages to kill bacteria
Antiviral Action of Alpha and Beta Interferons (IFNs) step 1
Viral RNA from
an infecting virus
enters the cell.
Antiviral Action of Alpha and Beta Interferons (IFNs) step 2
The virus induces the host cell to
produce interferon mRNA
(IFN-mRNA), which is translated
into alpha and beta interferons.
Antiviral Action of Alpha and Beta Interferons (IFNs) step 3
Interferons make contact with uninfected
neighboring host cells, where they bind either
to the plasma membrane or to nuclear
receptors. Interferons induce the cells to
synthesize antiviral proteins (AVPs).
Antiviral Action of Alpha and Beta Interferons (IFNs) step 4
AVPs degrade viral mRNA and
inhibit protein synthesis—and
thus interfere with viral replication.
Iron-Binding Proteins
- Transferrin
- Lactoferrin
- Ferritin
- Hemoglobin
Transferrin found in
blood and tissue fluids
Lactoferrin found in
milk, saliva, and mucus
Ferritin found in
Liver, spleen, and red bone marrow
Hemoglobin found in
located in red blood cells
Bacteria produce
siderophores
siderophores compete with
iron-binding proteins
Antimicrobial Peptides
Short peptides produced in response to protein and sugar molecules on microbes
What do antimicrobial peptides do?
Inhibit cell wall synthesis
Form pores in the plasma membrane
have a Broad spectrum of activity
antimicrobial peptides
Genetic resistance
Confers a selective survival advantage
E.g., sickle cell trait and Plasmodium falciparum
Age
Confers a selective survival advantage
E.g., sickle cell trait and Plasmodium falciparum
Observing healthy protocols
another factor that helps prevent infection
20-25%
Lymphocytes
3-8%
Monocytes
2-4%
Eosinophils
0.5-1%
Basophils
60-70%
Neutrophils
viral infections, pneumonia, autoimmune diseases, or cancers
Low WBC
bacterial infections, autoimmune diseases, or side effects of medications
High WBC
PAMPs stand for
pathogen-associated molecular patterns (PAMPs)
Innate or adaptive: 1. First-line defenses
Innate
Innate or adaptive: 2. Phagocytosis
Innate
Innate or adaptive:
3. inflammation
Innate
Innate or adaptive:
4. Complement system
Innate
Innate or adaptive:
4. Complement system
Innate
found in the skin, mucous membranes, and thymus; phagocytic
Dendritic cells
T cells, B cells, and NK cells; play a role in adaptive immunity
Lymphocytes
Destroy target cells by cytolysis and apoptosis
NK cells
Opsonization:
microorganism is coated with serum proteins, making ingestion easier
(IFN-mRNA), which is translated
into
alpha and beta interferons.
(IFN-mRNA), which is translated
into
alpha and beta interferons.
Arrive only minutes after infection
Phagocytes
Complement activation leads to
inflammation, opsonization and cell lysis.
A substance released by tissue cells that causes vasodilation, capillary permeability, and smooth muscle contraction.
Histamine
Activates acute-phase proteins by the liver
Inflammation
Serum proteins whose concentration changes by at least 25% during inflammation.
Acute phase proteins
A substance released from tissue cells that causes vasodilation.
Kinin
Leukotrienes cause
increased permeability of blood vessels
Leukotrienes help
help phagocytes attach to pathogens.
A small protein released from human cells that regulates the immune response;
Cytokine
directly or indirectly may induce fever, pain, or T cell proliferation.
Cytokine
Help phagocytes attach to pathogens
Leukotrienes
increase permeability of blood vessels and help attach phagocytes to pathogens
Leukotrienes
stimulates release of histamine, attracts phagocytes and promotes phagocytosis
Complement
cause neighboring cells to produce antiviral proteins (AVPs) that inhibit viral replication
IFN a and IFN b
