Overview: From Innate to Adaptive Immunity

Question 1

1. Define: Pattern-recognition receptor, pathogen-associated molecular pattern, Toll-like receptor, damage-associated molecular pattern, and recognize their abbreviations.

Answer 1

First line of defense = skin and mucous membrane barriers  constantly replaced and rich in antibiotics (beneficial!). Then comes innate immunity that detects intruders and helps cause their inactivation, destruction, and removal.
Innate is fast, but recognizes a few specific molecular ‘motifs’ or patterns that stimulate the response.
PAMP = pathogen-associated molecular patterns. DAMP = damage-associated molecular patterns. Innate system can also recognize the absence of normal structures when they’re in abnormal places.
Most body cells have PRRs (pattern-recognition receptors); TLR’s are a type of this and they can recognize specific foreign molecular structures (10 different types). TLRs get activated when they bind a pattern, activate a signaling cascade that produces cytokines and chemokines, and cause inflammation. Receptors can be in or out of cell.

Question 2

2. Name some common foreign patterns recognized by TLR.

Answer 2

Ex: lipopolysaccharide in cell wall of gram-negative bacteria; peptidoglycan in cell wall of G-positive, ds RNA from viruses (receptors for these will be inside cell because that’s where dsRNA more likely to be found).

Question 3

3. Identify the transcription factor that is most commonly activated in inflammation.

Answer 3

All TLRs (except TLR3) use the IRAK pathway, which activates the ‘mother of all inflammatory transcription factors,’ NF-kB.

Question 4

4. Define cytokine and chemokine.

Answer 4

Cytokines and chemokines help cause inflammation by increasing blood vessel diameter, stickiness, and leakiness to obtain and efflux of fluid and phagocytic WBCs into the tissues  quick movement of defense and healing agents into damaged area. This helps localize body’s healing components to this area of the body. Going from a linear to exponential immune response to quickly/efficiently counter damage.
Chemokines cause chemotaxis of WBCs so they get attracted to area.

Question 5

5. Describe the function of the innate immune response.

Answer 5

Innate response causes vessels to dilate and become leaky so fluid and WBCs can leak into affected tissue, where WBCs can eat or ‘wall off’ foreign bodies. Limited in what it can recognize, but it is fast and generally takes care of problems before you notice it.

Question 6

6. Name the cell that forms the bridge between innate and adaptive immunity.

Answer 6

Dendritic cells aid in the transition from innate to adaptive immunity; found basically everywhere and are very good phagocytes so quickly eat up foreign agents in inflamed areas. Upon eating and inflammation caused by cytokines and chemokines, DC moves into nearest lymphatic channel into lymph node where adaptive immunity starts. DC presents piece of antigen to lymphocytes in node and the ‘correct’ one (epitope fits in lock and key manner) will divide very FAST to direct a response to this specific invader.
Note: because DC’s are activated by cytokines and chemokines, it’s important to remember that you can’t have an adaptive response if there wasn’t an innate response first.
Adaptive immune system contains lymphocytes (recognition) and phagocytes (eating).

Question 7

7. Discuss in principle the role T cells play in immunity.

Answer 7

T lymphocytes survey the surfaces of body’s cells and recognize antigens using their own receptors. T cell sees antigens presented on DC, proliferates, and daughter cells migrate to affected site where they release lymphokines that increase inflammation (attracts monocytes/macrophages).
T cells mature in thymus and can be helper or killer cells.
Helper cells:
-Th1 – recognizes antigen, makes lymphokine that attracts macrophages  inflammation
-Th17 – causes more focused and powerful inflammation
-Th2 – stimulate macrophages to become ‘alternatively activated’  walls off pathogens and helps heal
-Tfh – migrate from lymph nodes into B cell follicles  help B cells get activated to make Ig’s
Treg – make lymphokines and suppress activation/function of Th1, 17, and 2. Help keep things in check. Helper cells have CD4 molecular marker.

CTL (cytotoxic killer T cells) destroy body cells that have foreign/abnormal antigen on its surface; marked by CD8. Look for fragments on MHC Class I antigen-presenting molecule (found on dendritic cells and all other cells that are nucleated). CTL will deliver a lethal hit to cause target cell to commit suicide.

Antigen pieces are put on an MHC Class II molecule on the DC (or other ‘antigen presenting cells’) and that presents to T cells, which get activated.

Question 8

8. Describe some of the functions of antibodies.

Answer 8

IgG = most abundant. 2 IgG’s bind an antigen to activate complement system that enhances inflammation and pathogen destruction. Only type of antibody that can cross placenta. Neutralizes toxins or binds bacteria to phagocytes (because phagocytes have the Fc Receptor for IgG). 
IgM = even better at activating complement; first type of antibody to appear after exposure to new antigen. 
IgD = inserts into B cell membranes and acts as antigen receptor. 
IgA = found in secretions; associated with Secretory Component that makes it resistant to digestive enzymes. Aids in 1st line of defense at mucous membranes. 
IgE = attached to mast cells  make prostaglandins, leukotrienes, and cytokines. Can cause release of histamine  allergy, and aid with resistance to parasites.

Question 9

9. Give examples of immunopathology.

Answer 9

Type I = immediate hypersensitivity  make too much IgE to environmental antigen  allergic symptoms.
Type II = autoimmunity due to antibodies that react against the self. If antigen looks like self, immune response can destroy self on accident because antibodies get confused in what to bind.
Type III occurs when you make antibody against soluble antigen. The antibody-antigen complex can get trapped in capillary basement membrane  inflammatory response (like lupus, arthritis, etc.).
Type IV = T-cell mediated autoimmunity. Killer T’s out of control.
Chronic frustrated immune response = when antigen isn’t self, but it isn’t something you can get rid of.
AIDS = HIV-1 infects Th cells because can bind CD4 = loss of Th cells.

Question 10

10. Distinguish between “humoral” (antibody-mediated) and cell-mediated immunity in terms of: the types of lymphocytes involved, and the nature of the molecules they release when activated.

Answer 10

Humoral = antibody-mediated response, occurs extracellularly, involves B-lymphocytes (transform into plasma cells that secrete antibodies). Cell mediated immunity is when T lymphocytes get activated and consequently activate macrophages, NK cells, and cytotoxic T lymphocytes. Both responses release cytokines when activated.