week 10

Question 1

what are memory and regulatory T-cells

Answer 1

TH cells can differentiate into memory TH cells
○ Retain antigen affinity of the originally activated T cell
○ Used to act as later effector cells during reinfection
○ Not long lifecycle, able to clonally replicate and pass traits to next generations

Some naïve T cells differentiate into regulatory t cells
○ Don’t promote immune response but helps restore homeostasis
Lack of this associated with chronic inflammation

Question 2

What are MHC proteins

Answer 2

• Major histocompatibility complex glycoproteins
• These are the proteins that infected cells place antigens on to display to immune system
• Two types
  ○ MHCI
  § Display antigens on infected cell’s surface
  ○ MHCII
  § Display antigens on the surface of APCSs helper T cells use this intelligence to alert the army

Question 3

Initiation of cell-mediated response

Answer 3

• APCS that have phagocytosed a pathogen travel to the lymph nides to displayed captured antigen to T cells
• The binding of antigen-loaded MHCI or MHCII to T cell reports activated T cells, cell-mediated adaptive immune response begins
  Activated cytotoxic t cells can directly kill infected host cell

Question 4

Helper T cells + activation of the humoral response

Answer 4

• Some activated helper T cells help activate cytotoxic T cells, some interact with B cells
  
  • B cells found in the lymph nodes (agents of the humoral immune response)
    ○ Born in bone marrow, undergoes education there (no college)
  • Helper T cells are tubes between APC’s and B cells
  • Free-floating antigens from the microbe bind to B cell receptors, specific for epitope of that antigen (recognizing part)
  • If helper T cell presents the same antigen to B cell as the one already on its receptor, B cell becomes activated
    ○ Differentiates into plasma cell, a factory for antibodies

Question 5

B cell

Answer 5

• Each recognizes a particular epitope
  
  • Responds to infection by microbe
    Some activated B cells differentiate into memory B cells

Question 6

How do monocytes differentiate into macrophages and what are their roles

Answer 6

• Monocytes circulate in blood stream
  
  • Attracted by chemical signals (cytokines) to site of infection
  • Become sticky and roll on surface of blood vessel, squeeze through epithelial cells to move into tissue, differentiating into macrophages when traveling through blood vessels which secrete more cytokines
    ○ Macrophages=large structures that ingest many microbes simultaneously
    Patrolling resident macrophages

Question 7

what are dendrocytes

Answer 7

• Have long protrusions/finger-like projections that squeeze through tight spaces to sample microbes
  
  • Always growing and moving
    Increases surface area of cell
    APCs

Question 8

Cytokines, chemokines, interferons (language of immune system)

Answer 8

• Close-range acting hormone system
  
  • Allows cell communication
  • Signals danger
  • Some cytokines important for anti-inflammatory signals after danger passes, resetting homeostasis
    ○ Inflammation
    § Key part of innate immune response
    § Signs of acute inflammation: heat, swelling, redness, pain
    Pus: white blood cells, mostly neutrophils (dead)

Question 9

Role of Phagocytes as antigen presenting cells

Answer 9

• Macrophage and dendrocytes are also antigen presenting cells (APC)
  
  • Process the antigens they ingest, displays them on their T cells surface
    Forms link between innate and adaptive immune system

Question 10

Microbiome in the gut

Answer 10

• Peyer’s patches
  ○ Specialist sites within small intestine
  ○ Rich in “M-cells” that take up antigens or bacteria, once they exit, are taken up by macrophages
  ○ Sites of uptake of antigens in the gut for presentation to macrophages
  Check-in, helps body differentiate between friend and foe

Question 11

Bacterial capsules interfere with antigen recognition process

Answer 11

• Many pathogens have capsules to evade innate immune system
  
  • Can present things on surface to mask themselves, can hide major components of themselves, be slippery
  • Pathogens recognized by immune system by
    ○ Pattern Recognition Receptors (PRRs): cells that recognize invariant and essential microbial factors unique to the microbe
    They recognize MAMPS: Microbe associated molecular patterns

Question 12

PRRs I: The toll-like receptors (TLRs)

Answer 12

• Transmembrane receptors on some immune cells that recognize viral and bacterial products
  
  • On binding to ligand they stimulate cytokines to signal inflammatory response and induce macrophages to produce antimicrobial proteins and peptides

Question 13

PRRs II: The NODs and NOD-like receptors (NLRs)

Answer 13

• TLRs can only sense outside of host cell, external MAMPS
  
  • Internal (cytoplasmic) NOD liker receptors bind to MAMPS and
    ○ Activate cytokine production
    ○ Form a complex called an inflammasome that activates the adaptive immune response, triggers apoptosis
    Packages into apoptotic bodies

Question 14

Natural killer cells

Answer 14

Attack host cells that have bee overwhelmed by pathogens, not pathogens themselves
Infected cell signals an altered self response alert immune system by labelling itself as infected, becomes target for NK cells

• Large and granular
  
  • Not phagocytic
  • Lymphocytic, distinct from T and B cells
  • Main role: innate defense

Question 15

Mechanism of action
of NK cells

Answer 15

1. Infected host cell signal altered self response
   
   2. NK cells alerted by interferons of macrophage-generated cytokines
   3. NK cell binds to infected cell, punch holes in cell membrane using enzyme perforin (found in granules (membrane-bound so to not hurt NK cell itself) of NK cells
   4. Granzyme moves through pores and induces infected cell to undergo apoptosis, this way as to not release the pathogen into the environment

Question 16

Efferocytosis

Answer 16

• After infected cell undergoes apoptosis
  
  • A cascade of events take place
    ○ Apoptotic bodies are small enough from neutrophils to consume via efferocytosis
    ○ The neutrophils dispose of the apoptotic cell bodies along with intruder microbes
    Inflammation is minimal

Question 17

Adaptive immune response

Answer 17

• Branch of immune system that has a memory
  
  • Develops when needed
  • 2 types
    
    1. Cell-mediated immunity
       i. Teams of T-cells (T-lymphocytes) work to recognize antigens displayed on infected cells
       ii. Target infections in the body’s cells
    2. Humoral immunity
       i. Antibodies directly target microbial, invaders (B-cell response)
       ii. Target infections in the body’s fluid (humors)
  • Both are intertwined
  • This response is like a weapons cache that, together, can defend the body against foreign invaders (every pathogen known and unknown)
  • When missing=lethal mutation (ex. Boy in the bubble)

Question 18

Adaptive immunity

Answer 18

• Not born with develops over 3-4 days following invading microbe exposure
  
  • Immune system recognizes small pieces of a given antigen (called antigenic determinants or epitomes)
  • Antigen=can be too big to be recognized, so broken into small pieces
    Phagocytosis produces many epitopes to show the adaptive immune system (ex: zombie dog that shows what it has killed)

Question 19

Immunogenicity

Answer 19

Immunogenicity: effectiveness by which an antigen elicits an immune response

* Nucleic acids and lipids (lowest), carbohydrates, proteins (highest)
	○ Proteins most effective because of diverse structures (3D)
	○ Carbohydrates: more restricted in regards to shapes
	○ Nucleic acids and lipids: more conserved

Question 20

T-Cells

Answer 20

• Born with weapons cache (T cells born from hematopoietic stem cells in bone marrow)
  
  • From birth, naïve immune system capable of recognizing and responding to foreign epitopes while avoiding response to self
  • Each cells can recognize a slightly different epitopes, together can recognize all, once T-cells are matured, they develop unique T-cell receptor and in the thymus gland will learn
    This t-cell education in thymus happens before birth so they don’t react to own cells in the body

Question 21

Thymus college

Answer 21

• Testing cells’ ability to identify
  
  • Positive selection for their ability to respond to immune syste,’s commands
  • Tested for reactivity against self antigens in the thymus
    ○ Negative selection-displine
    ○ Are killed if they fail the test
  • 98% of the T cells are killed here
  • Shuts down after birth, becomes derelict by puberty
    Reserves of educated T cells are maintained by the body and reproduced at balanced rat

Question 22

2 types of effector T-cells

Answer 22

• Mature T-cells differentiate into
  
  1. Cytotoxic T cells (TC)/ CD8+ cells
     
     1. Are assassins
     2. Seeks and destroys cells that present noxious antigens (indicating they are infected)
  2. Helper T cells
     
     1. Intelligence officers
        Memorize databanks of antigens and to alert B-cells if circulating antigen is detected