ICL 1.0: Introduction to Innate Immunity Flashcards
what are the beneficial effects of the immune system?
- protection from invaders (extracellular and intracellular)
- elimination of altered self (tumors)
what are examples of intracellular invaders?
viruses
some bacteria and parasites
what are examples of extracellular invaders?
most bacteria, fungi and parasites)
what are some of the detrimental effects of the immune system?
- inflammation = discomfort
2. autoimmunity = damage to self
what did the smallpox vaccine do?
vaccination was first used against smallpox, a viral infection.
in 1979, after 3 years in which no case of smallpox was recorded, WHO announced that the virus has been eradicated
what is a pathogen?
any organism with the potential to cause disease
what is an opportunistic pathogen?
any organism that causes disease if the body’s defenses are weakened
in a normal, healthy situation, they wouldn’t cause disease
ex. HIV patients will be a lot more effected by viruses because HIV has lowered the number of T-cells in their body whereas normally, these viruses wouldn’t have done anything
what are the four kinds of pathogens?
- bacteria
- virus
- fungi
- parasites
what are some examples of bacteria? what diseases are they associated with?
- salmonella enteritidis = food poisoning
2. mycobacterium tuberculosis = tuberculosis
what are some examples of viruses? what diseases are they associated with?
- variola = smallpox
- influenza = flu
- HIV = AIDS
what are some examples of fungi? what diseases are they associated with?
- epidermophyton floccosum = ringworm
2. candida albicans = thrush, systemic candidiasis
what are some examples of parasites? what diseases are they associated with?
- trypanosoma brucei = sleeping sickness
2. plasmodium falciparum = malaria
what does a virus, bacteria, fungi and parasite look like?
slide 7
what is the 1st line of defense against a microbe?
innate immune system
block entry of pathogen into body
- skin
- mucous membranes (GI tract and airway)
what is the 2nd line of defense against a microbe?
innate immune system
if the microbe enters the body, internal defenses like phagocytes and complement kick in
which cells are phagocytes?
- neutrophils
- monocytes
- macrophages
what is the 3rd line of defense against a microbe?
adaptive immune system
specific immune defense like B cells and T cells
B cells = antibodies
T cells = cytotoxic T cells, helper T cells
what happens during the immediate stage of your immune defense response?
0-4 hours after exposed to microbe
mediated by the innate immune system
key molecules = complement, histamine, etc.
key cells = macrophages, mast cells, neutrophils
what are mast cells?
basophils in the tissue
what is the complement system?
part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and attack the pathogen’s cell membrane
what happens during the early stage of your immune defense response?
4-96 hours after exposed to microbe
mediated by the innate immune system
key molecules = complement, IL-1, TNFα, IL12, IFNα/β, MBP, CRP
key cells = macrophages, neutrophils, NK cells
what happens during the late stage of your immune defense response?
> 96 hours after exposed to microbe
mediated by the specific immune system
key molecules = IgM, IgG, IL2, IL4, IL12, IFNγ
key cells = T cells, B cells, macrophages
what are the three types of innate host defenses against infection?
- anatomical barriers
- humoral components
- cellular components
what are the anatomical barriers?
- mechanical factors
- chemical factors =
- biological factors
what are the humoral components of the immune system?
- Complement
- Coagulation system
- Cytokines
what are the cellular components of the immune system?
- Neutrophils
- Monocytes and macrophages
- NK cells
- Eosinophils
what parts of your body make up the “skin” part of the physical barrier against microbes?
- hair
- skin
- nails
what parts of your body make up the mucosal surfaces of the physical barrier against microbes?
- sinuses
- trachea
- lungs
- kidney
- bladder
- vagina
- stomach
- intestines
- eyes
aka the GI tract and respiratory tract
what are some of the mechanical factors that act as anatomical barriers?
- skin = squamous epithelium
- mucous membranes
- non-ciliated epithelium like in the GI tract; does peristalsis
- ciliated epithelium like in the respiratory tract; it’s a mucociliary elevator
- epithelium like in the nasopharynx; flushing activates tears, saliva, mucus and urine
what are some of the chemical factors that act as anatomical barriers?
- skin
- sweat = anti-microbial fatty acids - mucous membranes
- HCl = low pH
- tears and saliva = lysozyme and phospholipase A
- defensins in the respiratory and GI tract = antimicrobial
- sufactants in lungs = opsonin
what are some of the biological factors that act as anatomical barriers?
normal flora in skin and mucous membranes
they have antimicrobial substances and compete for nutrients and colonization
what does the complement system do?
It’s a very important part of the innate immune system!
- lysis of bacteria and some viruses
- opsonin
- increase in vascular permeability
- recruitment and activation of phagocytic cells
Complement proteins are produced by the liver; the most important is C3
what does the coagulation system do?
- increase vascular permeability
- recruitment of phagocytic cells
- Β-lysin from platelets; a cationic detergent
how do lactoferrin and transferrin work?
compete with bacteria for iron
how do lysozyme work?
they break down bacterial walls
what do neutrophils do?
- phagocytosis and intracellular killing
2. inflammation and tissue damage
what do macrophages do?
- Phagocytosis and intracellular killing
- Extracellular killing of infected or altered self targets
- Tissue repair
- Antigen presentation for specific immune response
what do NK and LAK cells do?
killing of virus-infected and altered self targets
what do eosinophils do?
kill certain parasites
what are the components of the immune system
- nonspecific = innate immune system which is made up of humoral and cellular parts
humoral = complement, interferone, TNF, etc.
cellular = macrophages, neutrophils
- specific = adaptive immune system which is made up humoral and cellular parts
humoral = antibodies
cellular = T cells and other effector cells
how can one single cell divide into such large array of
physically and functionally different type of cells?
different locations and different environments and different growth factors make the stem cell turn into different things!
which cells are antigen independent cells?
- RBCs
- platelets
- neutrophils
- macrophages
- NK cells
- CD8
- CD4
don’t need to be activated
which cells are antigen-dependent cells?
- cytotoxic T-cell
- TH1
- TH2
a bacteria or virus or some other antigen has to induce the change into these types of cells
without antigens, CTL, TH2, and TH1 cells won’t develop
what do a T cell, B cell, NK cell, macrophages, dendritic cell, and neutrophil look like?
slide 23
slide 25-27
what do lymphocytes do?
production of antibodies (B cells) or cytotoxic and helper functions (T cells)
what do NK cells do?
- kill cells infected with certain viruses
2. Produce INFγ to activate macrophages
what do plasma cells do?
they’re full differentiated form of B cells that secrete antibodies
what do neutrophils do?
phagocytosis and killing of microorganisms
They are the backups for macrophages!
But they do NOT present antigens to T-cells
what do dendritic cells do?
macrophages in the skin
they activate T cells and initiate the adaptive immune response
what do mast cells do?
expulsion of parasites from body through release of granules containing histamine and other active agents
what do macrophages do?
phagocytosis and killing of microorganisms
activation of T cells and initiation of immune responses
what is innate immunity?
keeps most people healthy for most of the time
however, some infections outrun the innate immune response
what is adaptive immunity?
the adaptive immune response adds to an ongoing innate immune response
increases the power and focus of the immune response, which provides a highly specialized defense against one pathogen
what are the differences between the innate and adaptive immune system?
- innate immune system
- self vs. non-self germline encoded
- antigen independent
- no memory response and no changes after 1st exposure
- immediate response; within minutes
- adaptive immune system
- self vs. non-self somatically selected
- antigen specific
- memory response
- latent response; days
which parts of the immune system involve innate immunity?
- epithelial barriers
- phagocytes
- complement
- nK cells
which parts of the immune system involve adaptive immunity?
- antibodies
2. effector T cells
what are the two parts of the innate immune response?
- recognition that a pathogen is present
2. kill and eliminate it
what are the steps involved in the innate immune response?
- healthy skin is not inflamed
- surface wound introduces bacteria which activates resident effector cells to secrete cytokines
- vasodilation and increased vascular permeability allow fluid, protein and inflammatory cells to leave blood and enter tissue
- the infected tissue becomes inflamed, causing redness, heat, swelling and pain
what are the signs of inflammation?
- heat
- pain
- redness
- swelling
what are some of the things that can develop as a side effect of the immune response?
- allergies
- contact dermatitis
- Celiac disease
- Graft-versus-host disease
- rejection of organ transplant
- autoimmune diseases
what is contact dermatitis?
a red, itchy rash caused by direct contact with a substance or an allergic reaction to it
many substances can cause such reactions, including soaps, cosmetics, fragrances, jewelry and plants
what is Celiac disease?
disruption of the gut because of hypersensitivity to wheat gluten
what is graft-versus-host disease?
when MHC-disparate transplanted BM attacks the skin, liver and intestines of the recipient
usually only happens with BM transplants
what are PAMPs?
PAMP = Pathogen-Associate Molecular Patterns
they are bacterial components or products that induce a host innate immune-response
what are some examples of PAMPs?
lipopolysaccharide (LPS), Gram -
peptidoglycan (PGN), Gram +
lipoteichoic acid (LTA), Gram +
N-formylated peptides (fMLP), both Gram - and Gram +
lipoarabinomannan (LAM), mycobacteria
what are PRRs?
PRR = Pattern Recognition Receptors
recognition of PAMPs by PRRs results in the activation of different Intracellular
signaling molecules which mediate inflammatory responses & drive T cell development which leads to activation of adaptive immunity
How does antigen presentation work in the innate vs. adaptive immune system?
the innate immune system can be activated by free antigens = pathogenic molecules detected freely in blood and tissue
the adaptive immune system requires antigen presentation = the pathogens must be engulfed by cells, broken down and the pieces of the protein are transported to the surface and the antigen is “presented” to T-cells for activation
What are cytokines?
Cell signaling proteins
They’re often released by immune cells and stimulate inflammatory response
What are the types of cytokines?
- Chemokines
- Interleukins
- TNF
- TGF
- Interferons
What are chemokines?
A cytokines that attracts immune cells = chemotaxis
What do interferons do?
Cytokines that interfere with viral replication
What is chemotaxis?
The process of attracting immune system cells
What are cluster of differentiation structures of the cell?
Cellular surface molecules found on many immune cells and are used to identify cell types
Some are used as receptor/cell binding sites
Which cells are in the innate immune system?
- Phagocytes = macrophages and neutrophils
- Complement
- NK cells
- Eosinophils
- Mast cells and basophils
How do the cells of the innate immune system recognize molecules that are foreign?
By looking for structures on pathogens called PAMPs = pathogen associated molecular patterns
PAMPs are patterns of molecules found on many microbes but not many human cells
Innate immune system cells recognize PAMPs by using pattern recognition receptors like toll-like receptors (TLRs)
Where are TLRs found?
TLR = toll-like receptors —> a type of pattern recognition receptor that recognizes PAMPs
They’re found on macrophages, dendritic cells and mast cells
What do TLRs do?
They’re PRRs that recognize PAMPs and then secrete cytokines which trigger an inflammatory response
What are some of the PAMPs that the innate immune system responds to?
- Endotoxin (LPS)
- Peptidoglycan cell wall
- Mannose
- Lipoteichoic acid on gram-positive bacteria
- Double stranded RNA
- Unmethylated DNA
What are endotoxins?
a PAMP also known as LPS
LPS is found in gram negative bacteria and can bind to LPS-binding protein found in the plasma - then that complex can bind CD14 on macrophages
CD14 binds LPS*****
Once CD14 is found, it triggers TLR4 which leads to cytokine production = IL-1, IL6, IL-8, TNF
What is the peptidoglycan cell wall?
a PAMP that the innate immune system recognizes
If bacteria get inside a macrophage, there are intracellular NOD receptors
Once peptidoglycan binds to NOD inside the macrophage, it induces the production of cytokines
What is mannose?
a PAMP that is a polysaccharide on bacteria/yeast
MBL (mannose-binding lectin) from liver binds to mannose and activates the lectin pathway of the complement activation
Why does the innate immune recognize double stranded RNA?
Human cells don’t have double stranded RNA but many RNA viruses have double stranded RNA
Why does the innate immune system recognize methylated DNA?
Most human DNA is methylated; unmethylated DNA is more common in bacterial DNA
How long do monocytes circulate in the blood?
3 days
When the monocytes enter tissue they become macrophages
What are liver macrophages called?
Kupffer cells
What are the three functions of macrophages?
- Phagocytosis
- Cytokine production = trigger inflammatory response
- Antigen presentation to adaptive immune system
What is phagocytosis?
When macrophages engulf pathogens into a structure called a phagosome
Phagosome inside the macrophage then merges with a lysosome inside the macrophage
lysosome has deadly enzymes which kills the virus or bacteria
What is inside macrophage lysosomes?
- Reactive oxygen species
NADPH oxidase produces superoxides and H2O2 which are toxic to pathogens
- Reactive nitrogen intermediates
NO + O2- —> ONOO- (peroxynitrite)
- Enzymes
Proteases, nucleases, lysozyme
How does tuberculosis effect phagocytosis?
It blocks the process of the phagosome fusing with the lysosome by modifying the phagosome so that it’s unable to fuse with the lysosome
This allows TB to proliferate inside the macrophage AND it’s protected from antibodies outside the macrophage that can’t get in!!
What is Chediak-Higashi Syndrome?
Rare immune deficiency syndrome
Results in failure of lysosomes to fuse with phagosomes during phagocytosis
People who have this have recurrent bacterial infections
What things activate macrophages?
- LPS from bacteria
- Peptidoglycan
- Bacterial DNA
- IFN-gamma from T-cells and NKC
- C5a protein from complement
What are some of the surface receptors on macrophages?
CD14 —> binds LPS on gram - bacteria
Fc receptor —> binds to Fc portion of antibodies
C3b receptor —> binds to C3b portion of complement proteins
Which 3 molecules allow macrophages to interact with T-cells?
MHCII binds to CD4 on T cells
B7 binds to CD28 on T cells
CD40 binds to CD40L on T cells
Which cytokines do macrophages release?
IL-1 and TNF-α
Both increase the synthesis of endothelial adhesion molecules which allows neutrophils to enter inflamed tissue
They also release IL-6, IL-8, and IL-12
What is IL-1?
It’s an endogenous pyrogen released by macrophages = causes fever
Acts on the hypothalamus and raises the set point in the body
What is TNF α?
It’s released by macrophages and can cause vascular leak and septic shock
It’s a cachetin because it inhibits lipoprotein lipase in fat tissue which reduces utilization of fatty acids and leads to cachexia - this is why people can become cachexic when they have an infection!
TNF α can cause DIC….
What does IL-6 do?
Causes fever
Stimulates acute phase protein production in liver like C-reactive proteins
What does IL-8 do?
Attracts neutrophils
What is IL-12?
Promotes TH1 T-cell development
Which cells are chemotaxins for neutrophils?
IL-8 from macrophages
C5a from complement system
What are opsonins?
They bind to foreign invaders and increase the likelihood it’ll be taken up by phagocytosis
A major opsonin for neutrophils is IgG — neutrophils have receptors for Fc portion of IgG antibody
Which surface molecules are on NK cells?
CD16
Binds Fc portion of IgG antibodies which enhances activity of NK cells
CD56
Also called NCAM and it’s commonly expressed on the surface of NK cells and aids in binding to other cells
