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MicroBio > Immunology - Guest Speaker > Flashcards

Immunology - Guest Speaker Flashcards

1
Q

The ~1500 known pathogens are tremendously diverse…

A
  • HIV
  • Streptococcus pnemoniae
  • Aspergillus fumigatus
  • Nestor americanus
  • however pathogens and non-pathogens can be very similar
  • we are covered & filled with microbes to which we should respond

in class notes

  • bacterial pathogens, worms,
  • many diff. pathogens yet immune system knows how to distinguish all over the
  • your body also had to know what is a pathogenic gene vs. which is not and then act accordingly
  • chromes dieases is when your immune system identifies the normal micrbos as being harmful (over reacting)
  • the deeper we go down the diagram in slide 5 the more intense it becomes
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2
Q

Additional challenges facing the immune system:

A
  • Microbes replicate very quickly
  • Microbes evolve very quickly
  • Immune system has to react to virtually any pathogen but not react to self
  • Immune responses have to clear infected tissues without causing too much damage to the host
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3
Q

Innate vs Adaptive Immunity

A

SLIDE 8
-slide summaries innate immunity (first couple of hrs after infection) vs adaptive

innate- gene-coded sequence, most cells can partipate in it

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4
Q

Anatomy of the immune system: systemic immune system

A

Bone marrow: site of hematopoesis and B cell development

Thymus: site of T cell development

Spleen: where T cells and B cells are activated when infection is in the blood; also filters blood and removed damaged RBCs

Lymph nodes: sites where B cells and T cells are activated when infection occurs in tissues

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5
Q

Mechanical and physical barriers to infection

A

Mechanical: Skin, tight junctions, flow of fluid, flow of mucus

Chemical: acidity, enzymes

Microbiological: normal (commensal) flora (if you get rid of too much good flora than it can cause you to get sick)

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6
Q

What happens when pathogens cause an infection in the body?

A
  1. Bacterial pathogen enters through a cut in the skin: Redness, swelling, pain, heat: Inflammation
  2. Influenza virus enters through the respiratory tract Fever, muscle aches: cytokines and prostaglandins
  3. Intestinal parasite enters through the mouth and takes up residence in the gut mucosa: Abdominal cramping: smooth muscle contractions for parasite expulsion

these responses are caused by actions of the innate immune system

-know what phagocytosing is (seem on slide 14)

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7
Q

Three roles of professional phagocytes

A
  1. Kill pathogens
  2. Initiate inflammatory response
  3. Initiate and influence adaptive immune response
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8
Q

Macrophages traffic phagocytosed and endocytosed particles to the lysosome

A 
Red = lysosomes
Green = Candida (yeast)
yellow = colocalization (showing every single one of the candidas inside a lysosomes)

-lysosomes are important for protecting us against pathogens

SLIDE 17

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9
Q

Characteristics of the lysosome

A
  • Protons acidify the environment and activate hydrolases
  • Proteases: digest cell wall proteins
  • Glycosidases: cleave cell wall sugars
  • Lipases: cleave cell wall lipids

Do not have learn all this list but know they are regulated by low pH and in lysosomes

  • Metabolite transporters pump essential metals and other nutrients out of the lysosome
  • Antimicrobial peptides are found in the lysosome and are active at acid pH
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10
Q

Antimicrobial peptides make holes in pathogens membranes

A

Brucella pseudomallei treated with antimicrobial peptides

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11
Q

The oxidative burst of macrophages and neutrophils

A

SLIDE 20

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12
Q

Oxidative Burst

A
  • Neutrophils kills microbes by producing reactive oxygen species, demonstrated here with the dye nitroblue tetrazolium (NBT)
  • toxic chemistry right on a pathogen
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13
Q

Neutrophils kill pathogens with extruded “nets” composed of DNA and protein

A 
Neutrophil Elastase (green),  DNA/histones (red), vital dye (blue)  
-nets are made when DNA gets spilled out and that then "catches" pathogen
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14
Q

Inflammation promotes the entry of immune cells into infected tissues

A
  • increased blood flow: redness, heat
  • increased vascular permeability: swelling
  • These changes make it easier for plasma proteins and cells to pass out of the blood and into the site of an infection
  • marco phages are important for telling us that we have an infection
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15
Q

Two strategies for sensing pathogens

A

SLIDE 25

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16
Q

Pathogen Associated Molecular Patterns (PAMPs):

A

-invariant components of pathogens recognized by the innate immune system

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17
Q

Common features of PAMPs

A
  • Conserved among many pathogens
  • Not found on human cells
  • Difficult for the pathogen to alter
  • Alert the immune system that a microbe is present
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18
Q

Toll Like Recetors (TLRs) survey the extracellular space and endosomes/lysosomes

A

SLIDE 28

-in normal function you dont have DNA and RNA floating around … so nucleic acid usually means it is a pathogen

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19
Q

Sensing PAMPs results in the production of inflammatory cytokines

A

Cytokines: soluble proteins that diffuse through blood and activate other cells

Canonical inflammatory cytokine: Tumor necrosis factor alpha (TNF-α)

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20
Q

Inflammatory cytokines enhance an ongoing immune response

A
  • Proteins are produced (chemokines) that attract immune cells: macrophages, neutrophils
  • Blood vessels become “sticky” for specific immune cells
  • Vasodialation increases blood flow to the inflamed site (heat, redness)
  • blood vessels become leaky and plasma enters tissues (swelling)
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21
Q

Recognition of viral PAMPSs activates the Type I Interferon Response

A

slide 37

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22
Q

Transcriptional targets of type I IFNs include Intrinsic antiviral factors

A

SLIDE 33

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23
Q

What about large multicellular pathogens like worms?

A
  • Recognition of components from worms (ex chitin) initiate effector functions that act to kill and expel worms:
  • “Weep and Sweep”: increased mucus production, smooth muscle contraction (histamine from macrophages and mast cells)
  • Macrophages secrete chitinases and proteases, eosinophils degranulate toxic granules onto the surface of the worm.
24
Q

What if these innate responses do not control infection?

A

Adaptive Immunity

25
Q

Principles of Adaptive Immunity

A

-Evolved only in vertebrates – suggests that cellular and anatomic complexity makes adaptive immunity advantageous

  • Mediated by T-cells and B-cells (therefore two cell types)
    - T-cells are used in
  • Allows a strong immune response to be targeted to a specific pathogen
  • Long-lived memory T-cells and B-cells provide immunological memory that minimizes the impact of subsequent infections with the same pathogen.
  • Allows vertebrates to counter newly evolving pathogens.
26
Q

Activation of T and B cells during an immune response: general principles

A
  • Dendritic cells at the site of infection migrate to lymph nodes (reasons why it is called that is because of all the dendrites around it)
  • Dendritic cells activate “naïve” T cells
  • B cells receive a signal from antigen via their antigen receptor in the lymph node
  • A subset of activated T cells “help” B cells to become activated
  • Activated T leave the lymph node and travel to the site of infection
  • Activated B cells produce antibody in the lymph nodes and at the site of infection
27
Q

Slide 49

A
  • marcophage (is MCH II)
  • CD4 support every single function of the immune system
  • HIV kills all your CD4T cells and that then affects your marcophage, etc. and it is super devastating :(
28
Q

Effects of TLR stimulation on dendritic cells

what makes a dendritic cell “decide” to migrate from the tissue to a draining lymph node?

A
  • Increased presentation of antigen on the cell surface: peptides complexed with MHC molecules. (Major Histoic Complexes)
  • Expression and secretion of cytokines that influence the differentiation and activation of T cells.
  • Migration from tissues to draining lymph nodes through an afferent lymphatic vessel.
29
Q

Lymphocytes constantly recirculate via theblood and the lymphatic system

A

Slide 42

30
Q

T cell receptor (TCR) diversity allows for recognition of virtually any pathogen

A
  • Antigen: any molecule that specifically binds either a B cell receptor or a T cell receptor leading to activation of the cell.T cell antigens are peptides.
  • Diversity is generated at the antigen binding site by genetic recombination events targeted to the TCR gene
  • any protien from any pathogen can be recognized by a t-cell
  • *for classical t-cells the antigen is ALWAYS a protien *
31
Q

T cells recognize protein antigens “presented” by MHC (HLA) molecules

A
  • MHC I are expressed on almost every cell type in the body
  • MHC II are expressed on professional antigen presenting cells (Dendritic Cells, Macrophages, B cells)
  • there are two MCH types because they live in two diff places…the cyctosol (virsus) and the endosomal/lysosomal
  • dendritic cells are the ones at are involved with MCH
  • dendritic act similar to the marcophages
32
Q

MHC I and MHC II present antigen from different cellular compartments

A
  • MHC I is expressed on almost every cell type in the body.
  • MHC I binds and presents antigens derived from the cytosol.
  • it is particulary imporant in helping virus fight antogins
  • proteasome degrades petidies or protien (i didn’t hear what she said
33
Q

MHC I and MHC II present antigen from different cellular compartments

A
  • Expression of MHC II is restricted to immune cells: macrophages, dendritic cells, B cells.
  • MHC II binds and presents antigens derived from the endosomal/lysosomal network.
  • the peptides are presented in surface in both the MCH’s (I and II)
34
Q

T cell receptor “recognizes” antigen presented by MHC I or MHC II on the surface of the DC

A
  • > 1 billion T-cells in the body
  • Each T cell has a unique receptor with specificity for a particular antigen presented by MHC
  • T cells specific for an antigen find dendritic cells presenting that antigen!
35
Q

Clonal expansion of activated T cells

A

-T cells proliferate, leave the lymph node and migrate to site of infection

36
Q

CD4 T cells are master regulators of the immune response

A

Although their only effector function is to secrete cytokines these cytokines are key to the immune response!

- Required for B cell production of antibodies
- Aid in activation of immune effector cells    - Help activate CD8 T cells

CD4 T cells tailor the immune response for the particular pathogen

37
Q

Presentation from different compartments relates to the function of CD8 and CD4 T cells

SUMMARY

A

CD8 T cells:

  • important for killing cells that are infected with a virus
  • viruses replicate in the cytosol
  • MHC I presents antigens from the cytosol
  • they recognize viruses that are produced from MHC 1

CD4 T cells:

  • Important for activating macrophages (extracellular pathogens)
  • Important for activating B-cells (extracellular pathogens)
  • MHC II presents antigens from endocytosis
  • MHC II only present on Dendritic cells, B cells, and macrophages
  • t-cells just keep circulating your body looking for an infected nuggets
  • t-cells need an MCH for it to get active (or something like that)
38
Q

The B cell receptor (BCR) is a membrane bound antibody molecule

A

Diversity is generated at the antigen binding site by genetic recombination events targeted to the BCR
Antibodieses are released upon B cell activation as extracellular molecules

39
Q

Antibodies and B cell receptors directly bind antigen

A
  • B cells can recognize virtually any type of antigen: protein, nucleic acid, carbohydrate, drugs, etc (while t-cells only recognize viruses)
  • B cells can recognize antigen on the surface of a pathogen or soluble antigens such as a protein toxin
  • it has this shape cuz it allows it to recognize antigen on many surfaces cuz it has hella shapes CHECK SLIDE 56 for reference (a lot more flexibiliy in how and what it can recognize unlike a T-cell)
40
Q

“Lock and Key” binding of antibody to antigenic epitopes

A

-Each B cell receptor/antibody recognizes only one antigen: specificity

41
Q

B cells are activated by binding antigen to B cell receptor but require CD4 T cell help

SKIPPED IT CUZ MORE THAN WHAT WE NEED TO KNOW

A

Signal 1:B cell binds a specific antigen using its B cell receptor

Signal 2: T cell recognizes antigen presented by the B cell and sends a signal

-Both signals are required for optimal B cell activation

42
Q

The sole purpose of a B cell is to make ANTIBODY

A
  • Upon activation B cells differentiate into plasma cells or memory cells
  • Plasma cells secrete large amounts of antibody
  • Memory cells are long lived and respond if the infection is encountered again
43
Q

B cells can make 5 types of antibody

Just really just know concepts

A

-First antibody made is always IgM Isotype switching occurs later and changes the isotype

-

44
Q

Antibodies improve over the course of an immune response: somatic hypermutation

A
  • During B cell activation mutations are targeted to the regionof DNA that encodes the antigen binding site of the antibody
  • New antibodies are made with different binding affinity for antigens
  • B cells that make antibodies that bind antigen strongly are signaled to survive
  • Over the course of the immune response higher affinity antibodies are produced
  • CD4 cells also help secerte CD8 cells
45
Q

Characteristics of memory cells

A
  • memory cells are more sensitive to antigen
  • larger population of memory cells than naïve for a particular antigen
  • memory B cells have high affinity antibodies ready to go
  • memory T cells patrol the peripheral tissues
46
Q

Types of vaccines

IMPORTANT to know them and the differences and look at what they do

A

•Live, attenuated vaccines
-take virsus and weaken it but still something
- these are the most ideal but they are not alway safe
•Inactivated vaccines
•Subunit vaccines
•Toxoid vaccines
-antibody response to a toxin
•Conjugate vaccines
-take a piece of the pathogen and try to get a reponse
•DNA vaccines
•Recombinant vector vaccines

47
Q

Linked recognition of antigen is highly efficient

A
  • Physical linkage of the peptide recognized by the T cell with the antigen recognized by the B cell is most efficient
  • Antigens that are recognized by BCR are 10,000x more efficiently presented by MHC II
  • During an infection B-cells often internalize whole pathogens ensuring linked recognition
  • What about vaccination with pathogen components?
48
Q

Exploiting linked recognition for vaccine design

A

-Hib vaccine against H. influenzae type B is a conjugate of bacterial polysaccharide and tetanus toxoid protein

49
Q

Derek Vetter

A
  • he has skit
  • he lived in a bubble and only had to live in there until he was 12
  • he died of leukemia after getting a bone marrow transfer from his sister b/c the bone marrow contained a trait that causes cancer which his sister’s immune system could control, but his couldn’t.
50
Q

slide 9

A

hematopoietic stem cell are involved in bone marrow transfer

51
Q

innate cells

A

-dendritic cell
-macrophage (know that this is)
-neutophil
SLIDE 13

52
Q

how to t-cells travel?

A
  • lymph would is made to make it easier to a t-cell to recognize
  • t-cell travel through the lympatic system (travel through all the lymph nodes and then go back to the circulatory sisterm… lymph node they get activate t-cells and sent back to the circulatory system to target pathogens.
53
Q

-t-cells function

A
  • many functions main function is to interact with other cells and make a change in some way
54
Q

CD8 T-cells

A
  • activated by the dentirites

- kill infected cells and spare those without infections (IT IS VERY SPECIFIC)

55
Q

what three things do antibodies do

A
  • neutralize - they bind with the pathogen so that it can not infect us
  • opsonize- promotes margophages to digest a pathogen and thus kill it
  • activate complement-lysis and ingestion
56
Q

Breast feeding

A

-gives IgA to babies

MicroBio (8 decks)

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