The Innate Immune System Flashcards
what is the difference between infection and disease?
if the number of infecting organisms is small and the immune system is effective, a person will not get sick
to cause disease, a pathogen must: breach host defenses, survive innate defense mechanisms, multiply
what are the physical barriers to infection?
skin (contains keratin)
mucous membranes (epithelial cells tightly connected, supports barrier function, selectively permeable)
lungs (mucociliatory escalator to remove small particles, microbes are trapped in nose and cilia lining upper airway)
what does SALT stand for?
Skin Associated Lymphoid Tissue
what does GALT stand for:
Gut Associated Lymphoid Tissue
what are primary lymphoid organs?
factory for lymphoid cells
what are secondary lymphoid organs?
stations for antigen encounters
what are complements?
set of proteins made by the liver
complement antibodies in the killing of bacteria
circulate in blood, enter tissue all over body
circulate as inactive forms and are proteolytically cleaved to activate
what are the three complement activation pathways?
classical
lectin
alternative
how do all complement pathways converge?
LYTIC
what are the components of the alternative pathway?
C3b - acts as an OPSONIN (proteins that coat pathogens)
C3a and C5 - anaphylotoxins, direct immune cell traffic to where it’s most needed
MEMBRANE ATTACK COMPLEX - punch holes in target cells, killing them
what are cytokines?
molecules secretes by a cell that can effect other cells
ex. interferon, which act as an alarm bell, helping other cells nearby fend off the virus
what molecule is found in the gut?
high concentration of DEFENSINS
higher concentration in close proximity to the crypts of the epithelium
secreted from crypts
keeps out even normal microbiota
what defence cells are found in white blood cells?
polymorphonuclear leukocytes
monocytes
macrophages
dendritic cells
mast cells
lymphocytes
1 litre of human blood contains 6 billion WBCs
what do myeloid bone marrow stem cells differentiate into?
PHAGOCYTES
why are bacterial cells hard to catch?
REPULSION
bacterial cells carry a negative charge, so do phagocytes
C3b binds to the surface of proteins, making it easier for phagocytes to bind
describe NEUTROPHILS
capture pathogens with NETs
sense and invader and spews a latticework of chromatin and antimicrobial compounds
prevents spread of the pathogen
allows rapid phagocytosis
what can interfere with NETosis?
a CAPSULE
what are monocytes?
differentiate into macrophages
circulate in the blood stream
attracted to by cytokines to where they are needed
differentiate while travelling through blood vessels
what are macrophages?
large structures that can ingest many microbes at once
can also be found in organs
ex. kuppfer cells in the liver, langerhans in the skin, microglia in the brain, alveolar macrophages in the lung
what are dendrocytes?
finger-like projections, give cells a bigger surface area
posess long protrusions that can squeeze through tight spaces into samples
what is inflammation?
a key part of the innate immune response
signs: heat at site, edema, redness, pain, altered function (cell is dealing with infection)
what is pus?
dead neutrophils
why is long term inflammation bad?
extremely hard to kill some microbes - have a thick cell wall and slow reproduction time
ex. mycobacterium tuberculosis, fish tank granuloma, chrones disease
describe phagocytes as antigen presenting cells?
process the antigens they ingest and display them on their surface for T-cells
link between innate and adaptive immune system
what are peyer’s paches?
specialist sites within the small intestine
rich in “M-cells”, uptake of antigens in the gut to present to macrophages
help body differentiate between friend and foe
how do pathogens evade the immune system?
CAPSULES - slippery, stain with India Ink
ex. strep. pneumoniae, neisseria meningitidis, bacillus anthracis
how are pathogens recognized by the immune system?
specialized set of receptors that recognize INVARIANT and ESSENTIAL microbial factors that are UNIQUE to the immune system
called: PATTERN RECOGNITION RECEPTORS
recognize: MICROBE ASSOCIATES MOLECULAR PATTERNS
do NOT discriminate between good and bad
what are Toll-like receptors?
TRANSMEMBRANE receptors on some IMMUNE cells that RECOGNIZE VIRAL AND BACTERIAL PRODUCTS
ligand bonding (molecule that binds to another molecule to send signals between cells): stimulate CYTOKINES to signal inflammatory response
induce macrophage response
what are NODs and NOD-LIKE RECEPTORS?
used if pathogen is INSIDE a host cell
bind to MAMPs and activate cytokine production
form an INFLAMMASOME that activates apoptosis (“good” cell death)
what are the types of cell death?
NECROSIS: “bad” cell death, leakage of cellular components, triggers cell death
APOPTOSIS: packages up nicely, phagocytosis of cells and fragments
how many toll-like receptors are there?
SEVEN
**MISSING 7 and 8
1,2,4,5,9 –> recognize BACTERIA
3 –> recognize viruses
6 –> recognizes mycoplasma
LGDLFDU
OUTSIDE CELL
how many NOD-like receptors are there?
FOUR
1 –> grame NEGATIVE bacteria
2-4 –> bacteria
CPPF
INSIDE CELL
what are inflammasomes?
protein complexes that allow rapid secretion of cytokines
what are NATURAL KILLER CELLS?
NOT PHAGOCYTIC
large and granular
role in innate defense
ATTACK HOST CELLS THAT HAVE BECOME OVERWHELMED BY PATHOGENS
describe the mechanism of NKCs
ALERTED by interferons or cytokines
infected host signals an ALTERED SELF response
NK cell binds to infected cell, punches holes in membrane
GRANZYME moves through pores, triggers APOPTOSIS
what is EFFEROCYTOSIS?
allows dying cell to be neatly packaged before death
small enough for neutrophils to consume via EFFEROCYTOSIS
neutrophils dispose of apoptotic cell bodies WITH intruder microbes
inflammation kept to a minimum
what is the adaptive immune system
branch with MEMORY
what are the types of adaptive immune?
T-cells: RECOGNIZE antigens on infected cells, TARGET infections
B-cells: ANTIBODIES target invaders, target infections of the body’s fluids
like a WEAPONS CACHE
describe adaptive immunity
develops 3-4 days following exposure to invading microbe
recognizes small pieces of a given antigen - EPITOPES, produced by PHAGOCYTOSIS
what are HAPTENS?
a molecule that is too small to elicit an immune response, must be BOUND to another molecule to act as an antigen
what macromolecules elicits the best immune response?
IMMUNOGENICITY
- Proteins –> greatest diversity in shape
- Carbs
- Nucleic acids and lipids
describe T-cell education
happens in the THYMUS
begins shortly before birth
thymus shrinks as we grow older
as cells mature, they develop a T-cell RECEPTOR –> each receptor recognizes a different antigen
describe “thymus college”
T-cells must be able to identify MHC peptides, tested for reactivity against self-antigens
understand commands, well disciplined
98% of T-cells are KILLED
what are the types of “effector” T-cells?
CYTOTOXIC T-cells: trained ASSASSINS, destroy cells presenting noxious antigens
HELPER T-cells: memorize databanks of antigens and ALERT B-cells if a circulating antigen is detected
what are MEMORY t-cells?
retain antigen affinity
act as effector cells during reinfection
short lifecycle, replicate
hazy memory over time, why we need booster shots
what are REGULATORY t-cells?
RESTORE HOMEOSTASIS after infection
lack of these cause chronic inflammation
what are MHC proteins?
the proteins infected cells place on antigens to display to the immune system
infected cell loads antigen to show they are infected
allows T-cells to recognize self vs antigen
what is MHC1?
display antigens on the SURFACE of the infected cell
what is MHCII?
display antigens on the surface of APCs
what is the initiation of cell-mediated reponse?
APCs that have phagocytosed a pathogen travel to lymph nodes to display captured antigens to display captured antigens
binding of antigen loaded MHCs to receptors activates T-cells, cell-mediated adaptive immune response begins
cytotoxic T-cells can directly kill an infected host
describe t-cell deployment
travel to LYMPH NODES
otherwise, t-cells and APCS will not find each other
4x10^11 t-cells in body
10 T-cells will recognize same pattern - CLONOTYPE
describe helper T-cells and the humoral response
some T-cells activate B-cells
B-cells undergo education in bone marrow, only recognize 1 antigen epitope
B cell activates when a helper T-cell presents the same antigen to a B-cell as the one on its receptor
what do B-cells differentiate into?
PLASMA cells
live 4-5 days, but produce 2000 antibodies per second
what is B cell and T-cell tolerance
ANTIGEN DOSE
if the antigen does is over the threshold value, B and T cells become overstimulated, do not respond
realize it is not killing you
describe the anatomy of an antibody
forms a T shape
top is antigen binding site (F(ab))
pepsin cleavage site in the middle
Fc fragment at the bottom
what binds antibodies together?
disulfide bonds
how many polypeptide chains are in an antibody?
4 - 2 heavy, 2 light
what are constant regions?
conserved amino acid sequences
5 heavy chain types: alpha, mew, gamma, delta, epsilon (defines antibody class)
2 light chain types: Kappa, lambda
what is an isotype?
defines various chains belonging to a SPECIES
what is an allotype?
differences in the constant region shared by some, but not all, members of a species
what is an idiotype?
differences in hypervariable region within an individual
REMEMBER: idiots are hyper
what is IgG?
simplest, smallest, most ABUNDANT
4 classes
binds and opsonizes microbes
neutralizes viruses
activates classical pathway
what is IgA
secreted antibody my MUCOSAL surfaces
found as a DIMER –> can bind 4 antigens
secretory piece wrapped around both molecules during secretion
found in tears, breast milk, mucose
IgM
can be found as MONOMERS on B-cells
most commonly found as a pentamer
can bind to 10 antigens
FIRST antibody detected during infection
what is IgD?
trace amounts, in blood
monomeric on surface of B-cells
does not bind to complement
what is IgE?
trace amounts in blood
more prominently of surface of mast cells and basophils
cells degranulate and amplify immune response
AMPLIFY body’s response to invaders
what are allergies
IgE triggers release of chemicals such as histamines from mast cells or leukotrienes
harmless antigens perceived as threats
what is anaphylaxis?
severe form of an allergy
excess histamine triggers smooth muscle contraction in lungs, weakens junctions between cells lining blood vessels
epipens: block process of degranulation. deliver spinephrine
describe complement as part of adaptive immunity
alternative pathway: C3b binds to bacteria –> forms MAC
antibodies made activate complement through the classical pathway
what is the classical pathway?
C1 complex binds Fc region
C1 cleaves C4 and C2 –> rejoin to make C3 convertase
C3 cleaves into C3a and C3b
C3B JOINS C3 CONVERTASE TO MAKE C5 CONVERTASE
convertase cleaves C5 to C5a and C5b
C5b forms MAC
how is the lectin path similar?
lectins produced in liver, bind to sugars on bacterial cells
trigger formation of C3 convertase
same as classical pathway
why do we need 3 pathways?
people missing pathways susceptible to blood-borne illnesses –> shape shifting pathogens
change antigens regularly to elude immune system
ex. Neisseria meningitidis, neisseria gonorrhoeae, salmonella typhi
what are the components of the gut microbiome?
- epithelial barrier: studded with T-cells
- Dendritic cells: between epithelial cells to sample antigens
- M cells also sample antigens
sIgA –> coats microbita components considers a threat
where are there the most TLRs?
on the lumen facing side of epithelial cells (see more antigens)
less on basal side
