Immunity Flashcards
What are some ways that bacteria are classified?
gram+/gram-
rods/ spheres
aerobic / anaerobic
What are 2 examples of gram+ bacteria that are spherical and aerobic? How are these bugs distinguished from one another?
Staph: in clusters
Strep: in chains and pairs
What are 2 bacteria that are gram +, in rods and anaerobic? How are they distinguished from one another?
Clostridium: spore forming
Propionbacterium: non spore forming
What are 2 bacteria that are aerobic, in rods and gram +? How are they distinguished from one another?
Bacillus: spore forming
listeria: non spore forming
What is an example of a bacteria that is gram -, in rods, and anaerobic?
Bacteroides
What are some examples of gram- bugs, in rods, aerobic, and grow on a complex media?
Legionella Haemophiulus Bordetella Brucella Campylobacter
What are some examples of gram- bugs, in rods, aerobic and grow on simple media?
Vibrio Escherichia Klebsiella Salmonella Shigella Pseudomonas
What is an example of a bug that is gram-, in spheres, and in pairs?
Neisseria
Aerobic
need O2 for oxidative phosphorylation
no O2= death
find on skin and lungs
Microaerobic
Need some O2 but alot of O2 will kill them
GI tract
Facultative anearobic
can use O2 if they have it, but can survive w/o it
Obligate anaerobic
cannot tolerate O2
Endotoxin
from gram - bacteria
release by bacteria after bacterial cell death
i.e. LPS lipopolysaccharide
Exotoxin
from gram+ bacteria
secreted from life bacteria
i.e. botulinum toxin, tetanus
How are gram+ and gram- bugs structurally different?
determined by cell wall
gram+: has a thick layer of peptidoglycan: stains purple
gram-: thick layer of peptidoglycan & outer membrane: stains pale
Plasmids and what they cause?
small piece of DNA: give bacteria super powers (i.e. ability to break down abx)
bacteria can transfer this power to other friends, even it it isn’t in the same species
-can cause abx resistance to spread quickly
All _____________ are intracellular while most __________ are extracellular
viruses
bacteria
How specific do host cells need to be for viruses?
Very: species specific and cell type specific
How do viruses work?
enter cell as viron w/ genetic material and a capsid (shell)
uncoats itself; exposes genetic material which then inserts into host cell DNA or RNA and uses the cell to make its own proteins
What are 2 positive aspects of viruses?
- gene therapy
2. 5% of our DNA is derived from viruses
What are 2 classifications of fungi? Describe them.
Molds: filamentous fungi grow as multinucleate, branching hyphae, forming a mycelium (ringworm)
Yeasts: grow as ovoid or spherical, single cells multiply by budding & division (histoplasma)
Candida albicans
fungi found in normal gut flora
causes opportunistic infections: thrush, yeast infections
Aspergillus spp.
highly aerobic fungi
cause of respiratory infections
worse in immunocompromised patients
most common nosocomial fungal infection
Tinea
general term for skin fungus: dermatophyte
Tinea capitis: head
cruris: groin (jock itch)
pedis: feet (athlete’s foot)
What are the 3 big categories of the innate immune system?
Mononuclear phagocytic system
Polymorphonuclear leukocytes/ Granulocytes
Lymphocytes
Monocyte
become macrophages when they leave the blood
What are the big players of the mononuclear phagocytic system?
macrophages:
Kuppfer: liver
Microglia: brain (don’t want these activated, usually in brain injury or stroke)
Dust cell: lung
Osteoclast: bone (not immune; aggregates of macrophages)
Dendritic cell
NOT macrophages; but part of mononuclear phagocytic system
i.e Langerhans cells on skin
“eat and run away”
What types of cells are in the polymorphonuclear leukocyte/granulocyte category
Neutrophil: most common WBC (97%)
Basophil
Eosinophil
Mast cell
What is the order of frequency of immune cells from most to least?
Neutrophils Lymphocytes Monocytes Eosinophils Basophils NEVER LET MONKEYS EAT BANANAS
What innate immune cells occur primarily in tissue, and not in blood?
macrophages
dendritic cells
mast cells
What are the 3 big categories of lymphocytes?
B cells
T cells
NK: natural killer cells
B cells: 2 types
plasma cells: make antibodies
memory cells: keep copy in case pathogen ever comes back
T cells: 4 types
Tc: cytotoxic T cells- CD8
Th1: helper T cells- CD4
Th2: helper T cells-CD4
Memory cells
What is the difference between humoral and cell mediated?
humoral: extracellular: all fluid outside cells; eg plasma, interstitial, synovial, mucus etc
cell mediated: intracellular: mostly viral infections
What is the difference btw innate and adaptive immune system?
innate: born with
adaptive: respond specifically to pathogens you’ve been exposed to
What are some examples of innate humoral immune responses?
humoral: myeloid cells–> immediate response
-neutrophils
-macrophages
-mast cells
-eosinophils
DOES NOT CHANGE
Non-host epitopes (part of protein that the immune cell can attach to)
-bacteria try to limit amount of epitopes
What are some examples of adaptive humoral immune respones?
change over time based on specific threats body has encountered
- B cells (also Th cells, APCs, Antigen presenting cells)
- produce antibodies that are very specific
- takes time to develop
What are some examples of innate cell-mediated immune responses?
NK cells: natural killer T cells
MHC existence
look for virally infected cells, not specific
What is an example of adaptive cell-mediated immune response?
Tc cells: cytotoxic T cells
if the cell is abnormal, it kills it
-specific but slower
MHC1-TCR
Macrophages
all over body, waiting for something to happen
responsible for innate response to trauma
-Engulf bacteria and release cytokines (chemical messangers btw cells, usually immune)
-trigger chemokines
-antigen presentation
Cytokines
chemokines
Cytokines: “magic fairy dust” released by macrophages
-do whatever they are supposed to do
-act as chemical messengers btw immune cells
-initiate inflammation
Chemokines: triggered by cytokines
-allow neutrophils to come kill bacteria
Dendritic cells
antigen uptake in peripheral sites
-antigen presentation in lymph nodes
Neutrophils
phagocytosis and activation of bactericidal mechanisms
short lived; become pus when they die
Eosinophils
killing of antibody-coated paraistes
Mast cells
release granules containing histamine and other active agents
How are cytokines and chemokines involved in inflammation?
released by macrophages after bacteria is found
- they act on vascular wall to increase permeability and cause vasodilation: causes redness, heat, swelling
- inflammatory cells can now migrate into tissue, releasing inflammatory mediators and cause pain
What happens at the arteriole during inflammation?
- arteriolar constriction
- transudate leaves: swelling
- mast cell degranulation: release histamine
What happens at the capillary during inflammation?
- endothelial cell contraction
- increased vascular permeability
- plasma proteins and neutrophils leak out
- platelet aggregation and adhesion
What happens at the venule during inflammation?
- emigration of neutrophils
- infiltration by macrophages
- fibrin deposiiont and fibrosis
What plasma systems are activated during acute inflammation?
Complement system
clotting system
kinin system
What 3 activities occur as a consequence of cellular injury in the acute inflammation cascade?
- mast cell degranulation
- activation of plasma systems (complement, clotting, kinin)
- release of cellular products
What are the s/s of acute inflammation?
Vasodilation: redness, heat vascular permeability: edema cellular inflammation: pus thrombosis: clots stimulation of nerve endings: pain
During inflammation, what 2 major things do mast cells do?
- degranulation
2. synthesis of eicosanoids
What pre-formed factors do mast cells degranulate?
Histamine
neutrophil and eosinophil chemtactic factors (attract these types of cells)
What products do mast cells stimulate the synthesis of?
Phospholipase A2–> removes arachiodonic acid 9AA) & eicosaphentaenoic acid (EPA) from plasma membrane:
- Cyclooxygenase–>prostaglandins (cause vascular effects and pain)
- 5-lipoxygenase–> Leukotrienes (vascular effects)
also makes platelet activating factor (vascular effects and platelet aggregation)
What blocks phospholipse A2 from breaking down the AA and EPA from the plasma membrane
steroids
What can be used to block the prostaglandins from the cyclooxygenase pathway?
NSAIDS; COX inhibitors
COX-1: multi fx
COX-2: inflammation specific
Describe the nature of leukocyte infiltrates in the inflammatory process, using an MI as example.
infarction= ischemic necrosis
- dead cardiomyoctes trigger inflammatory response
- edema occurs almost immediately: increased vasc. permeability
- Neutrophils respond early: ~ 1 day
- Monocytes come later; convert to macrophages; start repair process
- replace dead tissue w/ scar tissue
Macrophages can either ________ or __________
fight or build
Phagocytosis is a multistep process that involves diffusion of ____________ from a site of injury
chemotactic factors
What types of cells are involved in phagocytosis (opsonisation)?
macrophage, neutrophils,
How do neutrophils know where to go?
Diapedesis: movement of neutrophils through the opened intercellular junctions and into the tissue
From there, they move up the gradient to where there is the highest concentration of chemotactic factors (chemotaxis)
What is chemotaxis signaled by?
chemokines
What are the phases of phagocytosis?
- recognitions: non-host epitopes, bound antibody ( opsonisation) or complement (C3b): neutrophil adheres to the bacteria
- engulfment: by extensions of the neutrophil’s membrane (pseudopods)
- formation of phagosome: containing bacterium surrounded by neutrophil’s plasma membrane
- fusion of lysosomes w/ vacuole to form phagolysosome, lysosomes release their digestive enzymes & production of free radicals
- killing and breaking down of bacterium
What needs to be on the bacteria for the neutrophil to attach to it?
What is opsonisation?
PAMP: pathogen-associated molecular patterns: something on bacterium that looks different then the host cell;
Ab R: antibody receptor
opsonization: the process by which a pathogen is marked for ingestion and destruction by a phagocyte. Opsonization involves the binding of an opsonin, e.g., antibody, to an epitope on an antigen After opsonin binds to the membrane, phagocytes are attracted to the pathogen.
___________ are associated with the stages of inflammation. They mediate ____________ and the acquired _______________.
Cytokines; inflammation; immune response
What are the 4 stages of inflammation?
- initial response
- recruitment of cells
- Remove debris
- repair and regeneration
What happens in the initial response phase of inflammation?
Induce vessel leakage and endothelial adherence molecules
- first few seconds to minutes
- swelling starts
- endothelial adheasion: stops rolling neutrophils at site of injury = first line of defense; very short life span
What happens in the recruitment of cells phase of inflammation?
neutrophils are stopped close to damage site; diapedesis; and chemotaxis
-signal sent to body to send new neutrophils (bone marrow)
What happens in the remove debris phase of inflammation?
activate leukocytes; lymphocyte growth; antibody synthesis
What happens in the promote and regeneration phase of inflammation?
induce fibroblast growth and collagen production
What happens if we can’t fix the problem causing acute inflammation?
becomes chronic inflammation:
angiogensis: new blood vessels to area
mononuclear cell infiltrates
fibrosis (scar tissues)
Hematopoietic stem cells begin where?
bone marrow
Where do t-cells go?
thymus
What are the two types of t-cells
helper t cells
cytotoxic t cells
Where do b cells go?
bone marrow
T/B cells should not be ____________
self reactive
Where do t/b cells go to find their antigen?
secondary lymphoid organs (lymph nodes)
Once the t/b cells find their antigen they go through ______ and ________.
clonal selection and clonal proliferation
When are t/b cells considered active?
when they find their antigen
What happens if naive t/b cells don’t find their antigen?
they die
Somatic hypermutation
- b cells under go this as they replicate
- daughter b cells that bind better continue to expand, daughters that bind worse are discarded
- results in extremely specific b cells
T/F: T-cells also undergo somatic hypermutation.
False
T/F: T and B cells both make memory cells.
True
What are examples of primary lymphoid tissue?
thyroid and bone marrow
What ares of the body do not have lymph?
brain, kidney, and bone
What are some examples of secondary lymphoid tissue?>
lymph nodes, spleen, MALT (mucosal), GALT (gut)and BALT (bronchial)
Where are peyer’s patches found?
ileum of small intestines
What is an epitope?
-part of antigen that t/b cell will actually bind to
The more epitopes a bacteria has, this ________ chance a b cell will react to it.
increase
Epitopes are almost always a ________.
protein
B-cells are _______ but ______.
specific but slow
The constant region of the antibody determines what?
antibody class
IgM
- largest
- first to appear
- spleen is the major site
IgG
- most common in the blood
- 4 subclasses of IgG
IgE
allergies, found in tissues bound to mast cells
IgA
secreted in GI tract, GU tract, resp tract
Opsonization
- process by which a pathogen is marked for ingestion and destruction by antibodies
- greatly increases efficiency of phagocytosis
How are parasitic worms killed?
-worm is too big for ingestion so eosinophil degranulates to degrade it
T/F: A given B cell makes only 1 specific antibody
true
You do NOT want b-cells to be _____
self-reactive
Negative selection
keep the b-cells that don’t bind with self antigen
Primary exposure
- delayed response while naive b-cells look for antigen
- always start as IgM
i. e. flu shot
Secondary exposure
- much quicker
- bigger response
- mostly from IgG (possibly IgA or IgE)
- this is how vaccines work
Peyers Patches
- gut associated lymphoid tissue
- antigen is imported from lumen and presented to t/b cells
- plasma cells produce antibody that is secreted into the lumen - neutralized pathogens
What immunoglobin can cross the placenta?
- IgG
- protects fetus from pathogens
- relies on IgG
Breastfeeding
- IgG and IgA will be given to baby in milk
- provides protection against pathogens in GI tract
- bottle fed baby more likely to get infections
B lymphocytes may become plasma cells that produce free floating __________
antibodies
What are the 2 types of T lympocytes? Which one is part of the adaptive immune system?
helper: phagocytosis
cytotoxic: lysis of infected cell (adaptive)
What is the clonal diversity phase of T/b cells?
Where do they reside?
lymphoid stem cells from the marrow migrate to central lymphoid organs and differentiate (thymus=T cells, regions of marrow=b cells)
these cells are IMMUNOCOMPETENT, naive and have never encountered foreign antigens.
They migrate to secondary lymphoid organs (spleen, nodes) until antigen comes along
What happens when a T/B cell finds its antigen?
They become active
go through clonal selection and clonal proliferation—clonal expansion
What do B cells undergo that T cells don’t
somatic hypermutation
Daughter B cells that bind better to antigens continue to expand and ones that don’t die
=extremely specific B cells
What are primary and secondary lymphoid tissue?
Primary: thymus; bone marrow
Secondary: lymph nodes, speleen, MALT & GALT & BALT
Describe the structure of an antibody
Y shaped: 2 identical light (L) & 2 identical heavy (H) chains held together by disulfide bonds
- constant and variable regions:
constant: same for each antibody class
variable: differs from antibody to antibody
Antibodies always start as _____. Then they change based on _________
IgM
where they are needed
Generally, where do you find:
IgG
IgA
IgE
IgG: blood
IgA: secreted
IgE: mucosa
An antigen attaches to the ________ part of an antibody.
A macrophage attaches to the _________ part of an antibody.
variable
constant
If a B cell can’t find its antigen what happens?
What happens if it does fine its antigen?
It dies
It replicates
Everytime a B cell replicates, what happens?
the DNA that codes for the binding domain mutates
How are self-reacting B cells weeded out?
nurse cells throw self-antigens at the them, if the b cell responds it is killed
Describe the IgE mediated destruction of parasites
pieces of dead worm bind to naive B cell
The B cell undergoes clonal expansion, selection, proliferation
It becomes a IgE
IgE can bind to mast cell
The mast cell degranulates and releases eosinophil factor that attracts eosinophils
IgE variable region binds to worm
Eosinophils degrade the worm
What does a high # of eosonophils indicative of?
parasitic infection
What is an example of primary and secondary exposure in medicine?
vaccinations: inject antigens, train B cells against them, create memory cells that spring to action if antigen is ever encountered again
What is an MHC?
Major Histocompatibility Complex: T cell receptor
-cell that presents an antigen to a T cell
How is a T cell different from a B cell?
T cell has a variable binding site (like B cell), but only 1 binding site (B cell has 2)
T cell needs its antigen handed to it (B cell goes around searching for its antigen)
What 3 things does a T cell need to bind to its antigen?
- proper antigen
- correct TCR (receptor on T cell)
- MHC
How many MHCs are there? Where do you get them from? How many do you share w/ your sibling?
12: 6 from each parent
share 6 w/ sibling (typically)
What is the structure of Class I MHC?
Where are they found?
What are the 3 different types?
structure: single transmembrane chain (alpha) complexed w/ a B2 microglobulin
Found on all nucleated cells and platelets
3 types: HLA-A HLA-B HLA-C
What is the structure of Class II MHC?
Where are they found?
What are the 3 different types?
structure: 2 transmembrane chains (alpha and beta)
found: B cells, APCs, and some epithelial cells
types: HLA-DP, HLA-DQ, HLA-DR
What does MHC-1 react with?
What does MHC-II react with?
I: cytotoxic T cells (CD-8)
II: helper T cells (CD-4)
If a T cell reacts with an MHC-I, what has most likely infected the cell? What will happen to the infected cell after the T cell binds to the antigen?
virally infected, or cancer: the cell is making a foreign protein
The T cell will signal the MHC to die, or kills it
If a T cell reacts with an MHC-II, what type of protein is the antigen made out of? What will the T cell do?
antigen is exogenously derived, i.e. macrophage has ingested something foreign
Don’t want to kill macrophage; T cell will signal for help (don’t need to know further than this)
What decides if a transplant organ will be rejected?
MHCs/HLAs (same thing)
What are examples of APCs?
APC= Antigen Presenting cells
macrophages
dendritic cells
B lymphocytes
For MHC-IIs, what type of helper T cells respond to B-cells? macrophages?
B-cells: TH2
macrophages: TH1
If a T cell meets a macrophage w/ a foreign antigen, what does the T cell tell the macrophage to do?
Activates the macrophage and makes it more aggressive and phagocytotic
-essentially the T cell tells the macrophage to ramp up what it is already doing
If a T cell meets a B cell w/ a foreign antigen, what does the T cell tell the B cell to do?
T cell will activate the B cell–> leads to clonal selection, proliferation, expansion, etc.
What happens if a self-reactive B cell finds an antigen? Why is this mechanism good?
no T cell would recognize it and B cell wouldn’t go any further
This is a second checkpoint to avoid autoimmune problems
Where does T cell development occur?
thymus
What is the analogy for how T cells develop that Dr. Garman gave us?
You want to date someone that likes you but isn’t a stalker
Describe positive selection of T cells.
T cells must interact with one type of MHC; if it can’t then it will never bind.
This is how it will decide if it will become a CD8 or CD4 cell
During positive selection of T cells, are Th1 and Th2 cells differentiated yet?
no
Describe negative selection of T cells.
cell presents self-antigen; if it binds too tightly, we get rid of it (stalker)
-remove self reactive T cells
If a T cell passes both positive and negative selection in the thymus, what does it do then?
T cell leaves thymus as mature naive T cell
What is an immune privileged site? What are some examples?
somewhere that T cells don't go Placenta/fetus Testes, ovaries Eyes Brain Thymus
In lymph nodes, what occurs in the germinal centers located in the cortex?
B cells undergo clonal expansion
become enlarged/swollen when there is an infection because they become full of B-cells that have their antigens and are under going clonal exapnsion
Where in the lymph nodes, do T cells undergo clonal expansion?
paracortical area: btw cortex and medulla
Describe the role of dendritic cells in capturing antigens.
“they grab a small piece of antigen and run away”
- Immature dendritic cell picks up antigen in tissue and phagocytoses it (releases cytokines)
- after it meets antigen, it becomes mature and migrates to regional lymph node and presents the antigen to an immunocompetent T cell
What is the analogy that Dr. Garman gave us to describe natural killer cells?
“Illiterate Gestapo”
Describe how NK cells work. What do they check for?
check for MHC-I and accompanying surface proteins to make sure they look ok
-if MHCs are not there, too few, mutated or accompanying proteins not there: NK will kill that cell
MHCs are found on all ___________________ cells including leukocytes
nucleated
What do superantigens bind to? Is this reversible or irreversible?
binds random Th-cells w/ random MHC II cell
irreversible
Superantigens activate Th cells___________ of the TCR antigen specificity.
independently: they don’t fit into the receptor site, but still activate it
- This causes an over active immune response
What syndrome is an example of a superantigen?
TSST
How many types of hypersensitivities are there?
4: I-IV
Type I hypersensitivity are mediated by _________. They mainly mediate _____________ & _____________
IgE
allergies and anaphylaxis
What is the main symptom of type I hypersensitivities?
Mast cells are activated by IgEs: inflammation
VASCULAR PERMEABILITY & increased blood flow–> edema
Type II hypersensitivities are mediated by _____ which cause _________ to bind to our cells and cause immune response.
IgG (antibody of blood)
antibodies
What are some examples of Type II hypersensitivities?
blood transfusion reaction
hemolytic disease of newborn
Graves disease
Myasthenia Gravis
Type III hypersensitivities are mediated by _________ and occur when too much antigen and antibodies build up and form __________
IgG
immune complexes
What happens when immune complexes form?
they start sticking on blood vessels and cause vascular damage
What are some examples of Type III hypersensitivities?
Systemic lupus erythematous
necrotizing vasculitis
serum sickness
Type IV hypersensitivities are mediated by ____________
T cells (cytotoxic, Th1, or Th2)
What are some examples of Type IV hypersensitivities?
transplant rejection
Hashimoto’s thyroiditis
DM I
poison ivy
What are 3 sources of antigens? What kind of antigen does each type of hypersensitivity usually react with.
Allergy
Autoimmunity (self antigen)
Alloimmunity (some one elses antigens)
Type I: mostly allergy
Type II: mostly autoimmune; some alloimmunity
Type III: auto and alloimmunity
Type IV: all 3
What 2 things do you need to acquire an autoimmune disease?
genetic predisposition (usually HLA linked) & environmental trigger
w/ lupus (SLE), ____________ antibodies are produced that work against double stranded _______
antinuclear
DNA
When does SLE affect DNA?
During necrosis, when cells release DNA the antibodies bind to it and form immune complexes and we get vasculitis
What demographic of people are most likely to get SLE? What organ failure is a big risk for SLE?
African Americans in US are 8x more likely; F>M in their young 20s
Kidney failure
