Unit 2 - Innate Immunology Flashcards
What organ represents the largest organ of the human immune system?
Skin
What does the lymphatic system drain into?
Vena cava
- circulatory system
True or False:
Lymphatic system and circulatory systems use the same vessels
False
- they are separate systems that run in parallel
Describe the relationship between the heart, the capillaries, and the lymphatic system
- Heart pumps blood to capillaries
- Fluid leaks into the tissues
- Fluid is drained into lymph capillaries and returned to the heart
What are the two types of lymphatic tissue?
- Primary lymphoid tissue
2. Secondary lymphoid tissue
What are two examples of primary lymphoid tissue?
- Bone marrow
- Thymus
What are 2 examples of secondary lymphoid tissues?
- Spleen
- Lymph nodes
What is the FUNCTION of the primary lymphoid tissue?
MAKES the immune cells
- made in the bone marrow
- matures in the thymus
What is the FUNCTION of the secondary lymphoid tissue?
STORES the immune cells
What does bone marrow contain (the cells that differentiate into immune cells)?
Hematopoietic stem cells
What is the role of the thymus in the immune system?
Involved in the maturation of T-cells
What is the role of the lymph nodes (3)?
- Stores leukocytes
- Filters body fluids
- Detects evidence of infection (antigens, pathogens)
What is the role of the spleen in the immune system?
Filters blood to remove old red blood cells or pathogens in blood
What is the primary component of the cell wall of gram (+) bacteria?
Peptidoglycan
- absorbs gram stain and makes them show positive
Define innate immunity
Defense mechanisms present at BIRTH
Define adaptive/acquired immunity
Defense mechanisms acquired by exposure to pathogens
Which type of immunity tends to be specific? Non-specific?
Specific = acquired/adaptive Non-specific = innate
What is the first line of defense?
INNATE: Surface protection
- anatomical and physiological
- genetic barriers
- non-specific chemical barriers
What is the second line of defense?
INNATE: cellular and more specific chemical barriers
- mostly non-specific
- no immunological memory
What is the third line of defense?
ADAPTIVE/ACQUIRED: Specific immune response developed against individual pathogens
- memory for immunity
What are 2 examples of first line defenses?
- Skin
- Coughing
- Sneezing
- low pH
- Lysozyme
What are 2 examples of second line defenses?
- Phagocytosis
- Inflammation
- Fever
- Interferon
What are 2 examples of third line defenses?
- T-lymphocytes
- B lymphocytes
- Antibodies
What are some example of chemical barriers in the first line defense?
- Oil
- Salt
- Saliva
- Lysozyme
- Defensins
- Urine
What do lysozymes break down?
Break down CELL WALLS on bacteria (gram +)
- they target peptidoglycan
How is mucus is physical barrier in the first line defenses?
Epithelial cells secrete mucus
- traps pathogens to be flushed from the body
What is the mucociliary escalator?
The epithelial cells of the respiratory tract that have short hair-like cilia to brush mucus up and out of the tract
True or False:
Lungs should be germ-free
True
True or False:
Pathogens become highly specialized to a specific host, and genetic changes can bring about immunity
True
- this can be done by mutation
- for example: some ppl have 32 base pairs were deleted to create a partial resistance against HIV
True or False:
In order to be successful, pathogens have to overcome physical barriers
False
- must overcome physical, chemical and genetic barriers
Explain the methods used by Helicobacter pylori to overcome the physical, chemical and genetic barriers in humans
Physical = flagellum burrows into mucosal layer of the stomach Chemical = ammonia (from urea) neutralize stomach acid Genetic = well-adapted to survive in the human stomach
Explain what a microbiome does for the body
“Good” or resident microbes line our body and block other “harmful” pathogens from adhering
Why can antibiotics be bad for you?
They kill off bad bacteria AND “good” bacteria, leaving us vulnerable other bacteria (good/bad) taking up residence
What are the 7 methods of innate immunity?
- Physical barriers
- Chemical barriers
- Genetic barriers
- Inflammatory response
- Interferons
- Phagocytosis
- Complement
What immune system is active at birth? Which one takes time to develop?
Birth = INNATE
Takes time = ACQUIRED
What is centrifugation?
Components of blood separate when spun at high speed
What is blood plasma?
Blood minus cells
- it looks cloudy
What is blood serum?
Plasma minus clotting proteins
- it looks clear
What is the buffy coat?
The layer of WBCs after blood has been subjected to centrifugion
Where do RBCs, platelets and leukocytes come from?
The same stem cell
- Hematopoietic stem cell
What are the two lineages of leukocytes?
- Myeloid
2. Lymphoid
Which immune cells (leukocytes) are active at birth?
- All myeloid cells
2. One lymphoid cells (NK cells)
What is the function of leukocytes?
Recognize non-self cells
- like cells with cell walls
From the lymphoid lineage, what cells are innate and which are acquired?
Innate = Natural killer cells Acquired = everything else
What are the leukocytes that are part of the innate system that are derived from the myeloid lineage?
- Neurtrophils
- Basophils
- Eosinophils
- Monocytes
What are the 3 leukocytes derived from the lymphoid lineage?
- T cells (acquired)
- B cells (acquired)
- Natural killer cells (innate)
What is the name of the leukocyte system that resides in the network of reticular connective tissue?
Mononuclear phagocyte system
- this is between the cells and tissues
(formerly reticuloendothelial system)
What cells are made up of aneucleated cell fragments?
Platelet (Thrombocyte)
What are platelets produced by?
Megakaryocyte
When platelets are activated, what do they release?
Blood clotting agents
Define thrombocytopenia
Failure to form blood clots
Define thrombocytosis
Too many blood clots
- can lead to blood vessel blockage
What chemotactic agent do platelets release that cause other cells to move toward its source?
Platelet-derived growth factor
True or False:
Platelets help to fight off infections
False
- platelets release platelet-derived growth factor that attract leukocytes to the site - which DO fight off the infection
Phagocytes are cells that are part of which immune system (innate or acquired)?
INNATE immune system
Which phagocytes have special PRRs that are callled toll-like receptors (2)?
- Neutrophils
2. Macrophages
How do phagocytes tell the difference between “self-cells” and “non-self” cells?
Pattern recognition receptors (PRRs)
- can “feel” abnormal surface on non-self cells
What is the name for the abnormal surface of the invading cell, that the phagocyte will recognize with their PRRs?
Pathogen associated molecular patterns (PAMPs)
How are neutrophils able to chase down invading bacteria?
Chemotaxis!
What is the reason that RBCs don’t get eaten by neutrophils?
RBCs lack the pattern (PAMPs)
- therefore they don’t get eaten
Neutrophils have receptors on them that act as PRRs (Pattern recognition receptors), what are these receptors made up of?
Proteins
What happens to the bacteria after the PRRs bind with the PAMPs?
The phagocyte invaginates and “eats” the bacteria
What is the name of the cell compartment that is filled with toxins and enzymes?
Lysosomes
What is the name of the resulting somal body from the fusion of a phagosome and a lysosome?
Phagolysosome
What is the function of lysosomes?
Digest things!
- they are acidic
- they have digestive enzymes inside of them
What are the two mechanisms that phagocytes use to achieve intracellular killing?
- Oxygen dependent mechanisms
2. Oxygen independent mechanisms
Describe reactive oxygen species (respiratory burst)
- Oxygen is converted to superoxide (if we remove an electron
- Superoxide + water = H2O2 (hydrogen peroxide)
- If we break H2O2 in half … we get OH radicals (which are more toxic than H2O2)
- O2+ (superoxide), H2O2, OH and bleach are all found inside lysosomes
What is hypochlorite made up of?
Chlorine (Cl-) + Hydrogen peroxide (H2O2)
What are the 3 electrically charged proteins that are involved in oxygen independent mechanisms in phagocytes?
- Lysozyme
- Lactoferrin
- Protease
How do lysozymes damage membranes?
Lysozymes target the cell wall in gram (+) bacteria
What does lactoferrin do to bacteria?
It’s a protein that binds to iron
- bacteria are starved for iron
- this pulls the iron away from the bacteria
What does protease do to bacteria?
Breaks down proteins and peptides
What is the other name for neutrophils?
Polymorphonuclear cells (PMN cells)
What is the most abundant leukocyte in blood?
Neutrophils
Where are neutrophils mainly found in the body?
Circulating in the system (blood, to tissues, to lymph vessels)
What are two characteristics of neutrophils?
- Granulocyte
2. Phagocyte
What is the role of monocytes?
They circulate in the blood and enter tissues during infection
- they regulate the inflammatory response
What can monocytes differentiate into (2)?
Macrophages or Dendritic cells
What do macrophages promote (3)?
- Localized inflammation
- Immune response
- Custodial role (cleaning up debris)
What leukocyte is the bridge between the innate and adaptive immune systems?
Dendritic cells
Where are monocytes typically found (3)?
Lungs
Liver
Spleen
How are eosinophils and basophils different from neutrophils (in regards to the method killing foreign objects)?
Eosinophils and basophils RELEASE the contents of their granules to the EXTRACELLULAR SPACE
- neutrophils deal with the foreign object INSIDE (phagolysosome)
What are mast cells functionally equivalent to?
Basophils
True or False:
Mast cells are not granulocytes but have granules
True
- mast cells are not typically found in the blood, even though they have the same function
- this is how they were missed in the classification of granulocytes
True or False:
Mast cells are avid phagocytes
True
True or False:
Monocytes are granulocytes
False
- The cells that are granulocytes are neutrophils, basophils, eosinophils and mast cells
What do eosinophils target?
Multicellular parasite - that are too big to phagocytose
- therefore, release their toxins to EXTRACELLULAR space
What is frustrated phagocytosis?
The cell (eosinophil) DEGRANULATES to release toxins in the vicinity of the pathogen - histamine may also be released
What happens to the surrounding tissues if frustrated phagocytosis occurs?
Toxins will affect healthy “self” cells as well
- causing stress and maybe necrosis
What are some parasites coated in, that make eosinophils especially attracted to them?
IgE antibody
- results in antibody-dependent cell-mediated cytotoxicity (antibodies that are calling the WBCs to them)
Mast cells and basophils are quite different cells but perform the same function. What is that function?
Induce inflammation
Where are mast cells found? Where are basophils found?
Mast cells = connective tissue
Basophils = circulate in blood
What do mast cells and basophils release (2)?
- Histamine
2. Prostaglandins
If Basophils and mast cells are able to release histamine and prostaglandins, how do they store it in the cells?
Histamines = stored in the granules Prostaglandins = produced as needed
What are inflammatory cytokines?
Chemicals that coordinate the immune response
What are the two inflammatory cytokines (of basophils and mast cells)?
- Histamine
2. Prostaglandins
Which inflammatory cytokine has an immediate effect and which has a prolonged effect?
Histamine = immediate Prostaglandins = prolonged
True or False:
Phagocytes can end up being the host for a virus or endocytic parasite
True
- such as TB!
True or False:
Natural Killer Cells are lymphocytes that phagocytose their targets
False
- NK cells either lyse the target cell or induce apoptosis
How do natural killer cells (NK) kill their target cells (2)?
- Lyse the target cell (inject toxins into the cells)
2. Induce apoptosis (cause cells to kill themselves)
What is a cell that will NOT become a host for tuberculosis?
Natural killer cells
- because they do not phagocytose their target cells
- TB wants to be eaten to take over the host cell and hide in it
What is the name of the molecule that cells have on them that identify them as “self”?
MHC-1
- its a protein
What action will natural killer cells take if a cell does not have MHC-1 protein on it?
NK cells will KILL it!
What happens if a cell has the wrong MHC-1 protein on it’s cell surface?
NK cells will KILL it!
What kind of response will eosinphils produce?
A systemic response
- to a parasite or an allergy
What kind of response will basophils and mast cells produce?
A systemic response
- inflammation or an allergy
Which cells in the body perform phagocytosis (5)?
- Neutrophils
- Monocytes
- Macrophages
- Dendritic cells
- Mast cells
What lineage of WBCs do natural killers cells come from?
Lymphoid!
- not myeloid (that’s basically everything else)
Which WBCs will fight off a bacteria infection (4)?
- Neutrophil
- Monocyte
- Macrophage
- Dendritic cells
What are 4 characteristics of inflammation?
- Rubur (redness)
- Calor (warmth)
- Tumor (swelling)
- Dolor (pain)
What are the 5 stages of inflammation?
- Vasoconstriction (until clots forms)
- Chemokines (chemotaxis) - attract WBCs
- Cytokines (stimulate inflammation)
- Vasodilation (increase blood flow)
- Edema/swelling (accumulation of WBCs to fight infection
Why is it important that vasoconstriction is the first stage of inflammation?
Reduce the amount of blood lost
If the skin is punctured, what leukocytes will be there first? Second?
- Macrophages (residents of tissue)
2. Neutrophils (arrive from circulation)
What effects do cytokines have (3)?
- Vasoactive (ex: histamine)
- Chemotactic (ex: PDGF)
- Both!
What is the name of the cytokine released from platelets that cause leukocytes to come and help assist?
Platelet-derived growth factor
What are examples of cytokines that have vasoactive effects (4)?
- Histamine
- Serotonin
- Bradykinin
- Prostaglandins
What are examples of substances that have chemotactic effects (5)?
- Endotoxins
- Platelet activating factor
- Leukotrienes
- Mast cell chemotactic factors
- Bacterial peptides, PAMPs
What are 4 examples of chemical mediators that have both vasoactive and chemotactic effects?
- Complement components
- Cytokines (such as interferon and interleukin)
- Some products of arachidonic acid metabolism
- Platelet activators
Where is histamine primarily formed? Where is it stored? How quickly does it act?
- Formed by basophils and mast cells
- Stored in granules
- Acts rapidly
Where is prostaglanin formed? Where is it stored? How quickly does it act?
- Formed by basophils and mast cells
- Not stored - made as needed!
- Slow to act
What is serotonin primarily involved in?
Intestinal movements
- happy feelings after feeding
What is serotonin secreted by?
Platelets to induce blood clotting
What does bradykinin do?
Increases the sensation of pain and vasodilation
What is the relationship between vasodilation and leukocytes?
Dilation of the blood vessels increases the permeability for leukocytes
- SLOWED at the site
- BIND to the endothelial wall of the vessel
- ENTER the tissues
What two leukocytes are the primary WBCs that slow down, bind and enter tissues when there is vasodilation?
- Neutrophils
2. Monocytes
What do endothelial cells near the site of infection express, which cause leukocytes to stick to the vessel wall?
ICAMs
- intercellular adhesion molecules
What is the name of the process whereby ICAMs are expressed and leukocytes stick to the vessel wall?
Margination
What is the name of the process whereby leukocytes pass through the small holes in the endothelial cells in vessels?
Diapedesis
Once leukocytes are inside the tissues (after diapedesis) how do they know where to go?
Chemotaxis!
True or False:
Tumor necrosis factor (TNF) is a cytokine that is a pyrogen
True
True or False:
IL-1 is a cytokine that is a pyrogen
True
True or False:
IL-6 is a cytokine that is a pyrogen
True
True or False:
IL-8 is a cytokine that is a pyrogen
False!
- non-pyrogenic
True or Flase:
IL-12 is a cytokine that is a pyrogen
False!
- non-pyrogenic
What is the role of interferons?
Chemical (protein) produced by cells that are used to WARN other cells that one is infected by a VIRUS
- gives cells an opportunity to prepare themselves for battle
What do interferons cause other cells to produce?
Enzymes that will degrade the viral mess anger RNA
- preventing viral protein synthesis
What are the 3 cytokines that contribute to fever?
- TNF
- IL-1
- IL-6
What do pyrogens do to the body?
Raise the natural body temperature
What happens during a cytokine storm?
- Body is infected by an unrecognized pathogen
- Immune cells respond rapidly - producing cytokines
- Immune response leads to a positive feedback loop
- Patient dies due to the IMMUNE response - NOT the infectious disease
What can happen if you get a WBC stem cell transplant?
The transplanted WBCs recognize YOU as “non-self” and attack YOU!
= cytokine storm
Is the complement system part of the innate or adaptive immune response?
INNATE
What does the complement system do to foreign things in the body?
Poke holes in the surface of the foreign cell
True or False:
The complement system is vasoactive
True(ish)
- it is BOTH vasoactive AND chemotactic!
True or False:
Each protein in the complement pathway is a protease that activates the next protein in the pathway
True
True or False:
Only the classical pathway and MB-lectin pathways converge on C3 convertase
False
- ALL 3 pathways converge on C3 convertase
What does C3 convertase change C3 into?
C3a and C3b
(a = active)
(b = bound)
What does C3a do?
What does C3b do?
C3a = released and stimulated inflammation C3b = embedded in membrane
What does opsonization do?
Makes things more LIKELY to be phagocytized
- sugary donut vs. plain donut example
What does C3b become?
C5 convertase
What does C5a stimulate?
Chemotaxis
- attraction of neutrophils
What does C5b react with and what does it form?
Reacts with: C6, C7, C8 and up to 15 C9 proteins
Forms = membrane attack complex (MAC)
Which complement pathway requires antibodies to be present in order to be activated?
Classical pathway
What is the complement is responsible for inflammation?
C3a
Which complement is responsible for the attraction of neutrophils?
C5a
Which complement is responsible for opsonization?
C3b
Which complements are responsible for cell lysis?
C5b, C6, C7, C8, C9
What are the 4 steps involved to find out if a person has antibodies against hepatitis B?
- Serum is heated (antibodies are stable and complement is destroyed)
- HBV antigen and complement are added in a known amount
- If patient HAS antibodies for hep b it will sequester the complement
- Sheep RBC and anti-RBC are added - if the complement was not sequestered, lysis is observed
Which comlements are vasoactive (2)?
C3a and C5a
What is the name of the test to determine if a patient has certain antibodies?
Complement fixation test
