unit 8 micro Flashcards
innate immunity is:
initial defenses to prevent infection
non-specific: defenses act in response to all pathogens
built in mechanisms: structures/chemicals are present at birth
no memory: same response regardless of prior exposure
adaptive immunity is:
response to pathogens
specific: defenses act in response to one type of bacterial strain or virus
builds up over time: requires exposure to antigens
has a memory: strong response with a second exposure to the same antigen
first line of defense consists of
initial barriers to pathogens to prevent entry and colonization
second line of defense is
a response to infection once the first line has been bypassed
physical factors in first line
barriers that prevent entry OR processes that remove microbes from the body surface
barriers include
skin: tightly packed epithelial cells that contain keratin
mucus membranes: contain epithelial cells bound by tight junctions; line nose, mouth, lungs, urinary and digestive tracts
mucus is produced to
cover and protect the cell layers, and to trap debris and microbes
endothelia is
tightly packed cells lining the urogenital
one well known example is blood brain barrier, which contains very tight cell junctions preventing pathogens from entering the CNS
mechanical action is then used to
flush mucus-trapped microbes out of the body
mucociliary escalator in the lungs use cilia to propel mucus out of the lungs, which is then swallowed or coughed/sneezed out
shedding of skin cells
flushing action of urine, tears
normal flora
through competitive inhibition, our microbiome prevents the growth of other microbes by out-competing pathogens for nutrients and by taking up spaces that can be colonized
chemical factors (1st)
substances or enzymes continuously produced by body cells.
sebum
produced by sebaceous glands in the dermis to seal off pores of hair follicles
production of oleic acid by
normal flora to create a mildly acidic environment on the skin to inhibit pathogen colonization
what in saliva, sweat and tears can break down bacterial cell walls
lysozyme
what antibodies that protect the respiratory tract
IgA
what in saliva (salivary amylase), lower digestive tract (pancreatic enzymes)
digestive enzymes
name chemical defenses involved in the second line of defense
antimicrobial peptides (AMPs), plasma protein mediators: acute phase proteins & complement proteins & cytokines & inflammation-eliciting mediators
AMPs are (antimicrobial peptides)
group of chemicals with broad-spectrum anti-microbial activity
some are produced continuously and some are produced in response to pathogen infection
some are produced by body cells and some are produced by normal flora
examples: cathelicidin, dermicidin, histatin
plasma protein mediators are
proteins found in the blood that play a role in the nonspecific innate immune response
acute phase proteins are
produced in the liver and secreted into the blood in response to inflammatory molecules
examples of acute proteins
different examples with different methods of inhibiting or destroying microbes, such as ferritin, fibrinogen, mannose-binding lectin
complement proteins are
group of proteins that circulate in inactive forms in the blood
activated in a cascade allowing for a rapid response to infection
method 1 of complement proteins
classical complement activation:
- antibody binds to bacterium
- C1 protein is recruited and activated & C3 protein is recruited and activated
method 2 of complement proteins
mannose-binding lectin:
- mannose-binding lectin binds to. carbohydrates on microbial surface
- C3 protein is recruited and activated
method 3 of complement proteins
alternative activation:
- C3 protein is directly recruited and activated
upon activation, C3
splits into 2 separate proteins C3a & C3b
outcome 1: opsonization
C3b protein coats the microbe, which makes the microbe more easily identified by macrophages
outcome 2: cytolysis
- C3b recruits and activates C5 protein
- C5 splits into 2 separate proteins, named C5a & C5b
- C5b recruits and combines with C6, C7, C8 & C9 proteins to form a membrane attack complex, which inserts into the cell membrane causing extracellular fluid to rush in, leading to microbial cell lysis
outcome 3: enhanced inflammation
C3a & C5a combine together and binds to mast cells, leading to increased production of histamine by mast cells
how do microbes avoid the complement system
presence of a capsule inhibits opsonisation and prevents insertion of the MAC, gram-negative cells can alter the structure of the outer membrane to prevent insertion of the MAC, gram-positive cocci can release an enzyme that breaks down C5 protein
cytokines are
soluble proteins that act as communication signals between cells
in the immune response, cytokines are
important to stimulate production of other chemical mediators or to promote cell functions
3 main types of cytokines
interleukins - modulate many parts of immune system
chemokines - recruit white blood cells to sites of infections, tissue damage and inflammation
interferons - important for our defenses against viral replication (can be produced in the lab and used as treatment for viral infection but have significant side effects)
inflammation-eliciting mediators
contributes to the inflammation response
examples of inflammation-eliciting mediators
histamine - produced by mast cells
leukotrienes - longer lasting effects than histamine
prostaglandins - also plays role in fever
bradykinin - increases vascular permeability leading to edema
cellular defenses involved in the second line of defense
granulocytes & agranulocytes
granulocytes are
white blood cells with lobed nuclei and granules in the cytoplasm
mast cells
reside in tissues to produce histamine
basophils
produces histamine in response to allergic reactions
neutrophils
elimination and destruction of bacteria through direct phagocytosis or through the production of extracellular traps (NETs)
eosinophils
protect against protozoan and helminthic infections by releasing degradative enzymes
agranulocytes are
white blood cells with no granules in cytoplasm
agranulocytes use
nonspecific mechanisms to recognize abnormal body cells. upon recognition, NK cells will induce apoptosis in these abnormal body cells
apoptosis
programmed cell death
after movement into body tissue
monocytes will differentiate into dendritic cells and macrophages
phagocytosis:
1. extravasation (diapedesis) of leukocytes to site of infection
- site of injury leads to release of inflammation-elicitors and cytokines
- through positive chemotaxis, phagocytes leave the blood stream through capillaries and enter tissues through process called extravasation
- neutrophils usually arrive first, followed by monocytes (which differentiate into macrophages)
phagocytosis:
2. pathogen recognition
-attachment of the phagocyte’s plasma membrane to the surface of the microorganism through the interaction of PAMPs on the pathogen with receptors on the phagocytes
PAMPs are
pathogen-associated molecular patterns
PRRs are
pathogen recognition receptors
examples of PAMPs
peptidoglycan, flagellin, lipopolysaccharides, lipopeptides
pathogen recognition can be enhanced by
opsonization
phagocytosis:
pathogen degradation
- pseudopods form around the microbe and a phagosome is made (phagocytic vesicle)
- a lysosome containing hydrogen peroxide and several enzymes, fuse with the phagosome to form a phagolysosome
- microbe is then digested
- indigestible material (waste) are excreted by exocytosis
how do microbes avoid phagocytosis
- presence of capsule inhibits adherence of the phagocyte to the pathogen
- some pathogens can release molecules that leads to phagocyte death
- some pathogens use phagocytosis as a mechanism for entry into the cells, and then replication inside the phagocytes
- formation of biofilms - phagocytes are unable to detach pathogens from a biofilm
acute inflammation in 2nd line
- immediate response to injury is vasoconstriction, which leads to the narrowing of blood vessels to minimize blood loss
- this is followed by vasodilation and increased vascular permeability
- phagocytes are then recruited due to tissue damage and release of chemicals such as histamine
- pus is formed as damage tissue and pathogens are cleared
- eventually tissue repair begins
5 signs/symptoms of inflammation
swelling, heat, redness, pain, altered function
chronic inflammation in 2nd line
occurs when the immune system is unable to clear pathogen
when this occurs, tissue damage can occur, such as the formation of granulomas
body temperature is regulated by
hypothalamus
As a result of bacterial or viral infections
a series of chemicals are
released, eventually leading to the production of prostaglandins that
leads to elevated body temperature
Fever can enhance the immune system by:
inhibiting the growth of many pathogens & stimulating the release of iron-sequestering compounds from the liver
during fever:
vasoconstriction of the blood vessels occur, marking the skin appear pale & leads also to shivering and an increase in metabolism
when fever breaks:
Vasodilation is stimulated, leading to release of heat from body
Complications of fever in situations where the immune response is too strong:
Tissue and organ damage, tachycardia, metabolic acidosis, dehydration,
seizures, delirium, coma
Antigens are found on pathogens and can stimulate the immune system. Examples
include:
bacteria: cell wall, flagella, fimbriae
viruses: spikes, fibres, envelope
Specific regions on antigens where antibodies bind to
epitopes
protein antigens
are generally more potent
carbohydrate antigens
can only stimulate the humoral immune defense
lipid and DNA antigens
least antigenic
antibodies are also called
immunoglobulins and are produced by the immune system to target antigens
5 classes of antibodies
IgG, IgM, IgA, IgD, IgE
most abundant in the body
IgG
found in respiratory secretions
IgA
aids in allergic responses and defense against parasites
IgE
cellular immunity involves
T cells & main target is to kill infected body cells and to boost the overall immune response
humoral immunity involves
B cells & main target is to kill extracellular antigens
describe how a T cell library is formed
hematopoietic (stem) cells are formed in bone marrow
half of these will migrate to the thymus and eventually become naive T cells
naive helper T cells contain
T-cell receptor (TCR) capable of binding to a specific epitope & CD4 co-receptor
naive cytotoxic T cells contain
T cell receptor capable of binding to a specific epitope & CD8 co-receptor
activation of helper T cells
- pathogen/antigen is phagocytosed by a
phagocyte (macrophage or dendritic cell)’ - Inside the macrophage, a protein complex called
MHC-II combines with the antigens - The MHC-II combined with the antigens are then
presents on the plasma membrane
4.The macrophage is now called an antigen-presenting cell (APC)
- The corresponding TCR on a naïve helper
T cell binds to the displayed antigen,
partially activating the naïve helper T cell - The CD4 co-receptor on the naïve helper T
cell also binds to the displayed antigen to
anchor the TCR-antigen complex - The APC releases cytokines which further
activates the naïve helper T cell - Once activated, the naïve helper T cell will
proliferate through mitosis and then differentiate into different types of cells (3)
memory T cells
function to remember the antigen. Should the antigen be encountered again, these cells will rapidly switch to cytotoxic T cells
T helper 1 (TH1)
stimulate other cells in the immune response
T helper 2 (TH2)
function to stimulate the humoral immunity
Cytotoxic T cells are activated
in the same way as helper T cells, with a few key
differences:
o Recognition of antigens are presented on MHC-I, not MHC-II
Anchoring is done by a CD8
co-receptor
Naïve cytotoxic T cells differentiate
into effector cytotoxic T cells
o Assistance from cytokines secreted
by TH1 cells leads to
longer-lasting effects
Once activated, effector cytotoxic T cells will release:
o perforin to create pores in the target cell
o granzymes, which are proteases, which will enter the
pores and induce programmed cell death (apoptosis)
describe how a B cell library is formed
• Hematopoietic (stem) cells are formed in the bone marrow
• Half of these cells remain in the bone marrow and eventually become B cells
o Each B cell is coated with IgM antibodies, capable of binding to a single epitope
T-dependent B cell activation
- The IgM antibodies of an
inactive B cell binds to a
foreign antigen - The IgM-antigen complex is
then internalized into the
inactive B cell - Inside the B cell, the antigen is combined with MHC-II and the antigen is then presented onto the B cell plasma membrane
- The B cell becomes an antigen-presenting cell (APC)
- A corresponding TH2 cell
(previously activated in cellular
immunity) binds to the presented antigen - After binding, the TH2 cell releases cytokines which activates the B cell
- Once activated, the B cell will proliferate through mitosis and then differentiate into
different types of cells (2)
plasma cells . . .
which secrete IgM antibodies initially, and later secrete
the longer-lasting IgG antibodies
memory B cells
which remember the antigen. Should the antigen be
encountered again, these cells will rapidly switch to plasma cells to secrete antibodies
T-dependent B cell activation is a
longer-lasting and leads to memory
T-independent B cell activation
- This usually occurs with T-independent antigens (e.g.
carbohydrate) which are sufficient to provide the first signal for activation - The B cell is directly activated through binding of
the IgM antibody to the foreign antigen - Once activated, the B cell will proliferate through mitosis, and then differentiate into plasma cells, which secrete IgM antibodies; no memory cells are made
• This response is short -lived and requires boosting from
innate immunity pathways such as the complement pathway
neutralization
the binding of antibodies to epitopes to prevent attachment to cells
opsonization
the coating of a pathogen to enhance phagocytosis
agglutination
the cross-linking of antigens to create large clumps
complement
activation of the complement cascade
antibody-dependent cell-mediated cytotoxicity
enhanced killing of pathogens that are too large to be phagocytosed
active, natural immunity
immunity gained from illness and recovery
active, artificial immunity
vaccination
passive, natural immunity
antibodies passed through breast milk or placenta
passive, artificial immunity
transfer of antibodies harvested from an individual or animal
describe the function of vaccinations
The deliberate exposure of a person to an antigen to trigger a primary response without the person feeling the effects of the pathogen
• Therefore, when they actually encounter the pathogen, a secondary response occurs
herd immunity is
when there are too few susceptible individuals for a disease to spread effectively
• This can be done by vaccination programs to reduce the number of susceptible individuals
• Susceptible individuals cannot be vaccinated for a variety of reasons, such as too young or allergic to a vaccine
ingredient
live, but attenuated (weakened) organisms vaccine
- Can still replicate, meaning boosters are not needed
- Increased challenges for storage and transport
- Example: chickenpox
inactivated, dead organisms vaccine
• No risk of severe infections, but boosters are often needed
• Useful for vaccination programs for developing countries (easy to store and
administer)
• Example: influenza, hepatitis A vaccine
subunit vaccines
contains only the key antigens of a pathogen
- Produced through genetic engineering or isolation from a degraded pathogen
- No protection against antigenic variation
- Example: hepatitis B, HPV
toxoid vaccines
contains inactivated toxins; pathogens themselves are not included
- Least amount of side effects, but does not prevent infection by pathogen
- Example: botulism, tetanus, pertussis
conjugate vaccines
synthetic vaccines that combine carbohydrate antigens with larger
proteins to stimulate both cellular and humoral immunity
- More expensive to produce
- Example: meningitis
nucleic acid vaccines
nucleic acid is injected; cells take up the nucleic acid and
use it as a template to make protein antigens
example: west nile vaccine (horses), covid-19 (pfizer, moderna)
