Blood Part 2

Defends against eveyrthing without targetting specific pathogens. Included examples are intact skin, enzymes in saliva, tears, mucus, acidic gastric secretion (stomach), WBCs (mainly granulocytes and monocytes/macrophages).

Non-specific defenses (innate immunity)

The body’s targetted, adaptive immune responses that recognize/eliminate unique pathogens and foreign molecules (includes B- and T-cells).

Specific defenses (acquired immunity)

non-specific

no memory

fast (effect in seconds/minutes/hours)

handled by phagocytes (neutrophils and macrophages)

uses the complement system to defend (a system of proteins that circulate in the blood in an inactive state until triggered)

innate/natural immunity

specific

has memory

slow (days/weeks)

handled by lymphocytes (B- and T-cells)

uses antibodies and cytotoxic molecules (ex. killer T-cells) to fight off pathogens

acquired/adaptive immunity

List the pros (3) and cons (2) of the immune system

pros:

• defends against foreign invaders (bacteria, viruses)

• removes our own old/damaged/abnormal cells

• identifies and destroys abnormal or mutant cells

cons:

• exaggerated responses to “harmless” substances (allergies)

• autoimmune diseases (attacking “self immune system”)

___is a nonspecific, innate response to tissue injury. It can be triggered by cuts on skin surfaces, bullet wounds, injuries due to sun burn, infected sutures, during surgery, or infection of tonsils by cold virus.

inflammation

infammation usually has 3 purposes:

1. healing

2. destruction of “non-self” cells/pathogens

3. repair by fibrosis/scar tissue

list the 5 cardinal signs of inflammation and what causes them

1. redness (rubor)=a result of increased blood flow caused by histamines, etc.

2. swelling (tumor)=a result of increased blood flow caused by histamines, etc.

3. heat (calor)=a result of increased blood flow caused by histamines, etc.

4. pain (dolor)=a result of pressure on nerve endings caused by bradykinin and prostaglandin (PGE2)

5. loss of function

What are the effects of histamine on the vasculature (blood vessel walls)?

1. release of histamine

2. arteriole dilation (increased blood flow+heat to the area) due to histamine’s release.

3. expansion of capillary bed to accommodate for increased blood flow.

4. as a result the capillary bed becomes leaky; proteins (bradykinin, prostaglandins, complement proteins) and fluids in the vessels escape into the extracellular matrix to fight infection

5. as proteins leave the blood vessels, they alter the osmotic pressure in the interstitial space, drawing water out of the vessels and edema (swelling) results.

What are the cellular events associated with inflammation?

1. margination of WBCs: leukocytes move from the center of the blood vessel towards the edges (endothelium) due to increased blood flow.

2. tethering and rolling of WBCs: carbohydrate molecules on the WBC surface catch onto endothelial surface proteins (selectins). This tethers the WBCs to the vessel wall, causing them to roll.

3. activation of WBCs and endothelial cells: inflammatory chemicals (cytokines and chemokines) activate the endothelial cells+the WBCs, causing them to express new surface proteins and prepare for strong binding.

4. arrest/firm attachment of WBCs to endothelial cells: activation signal triggers anchoring proteins on the WBC to lock, stopping the WBC against the force of blood flow.

5. emigration/diapedesis: wBC squeezes betweeen adjacent endothelial cells by temporarily breaking/rearranging the tight junctions OR through transcellular migration.

6. chemotaxis of WBCs: once outside the blood vessel, the WBC migrates through the tissue towards the site of injury/infection.

7. Recognition and phagocytosis of foreign/”nonself” agents by WBC

Migration of neutrophils (macrophages) to the site of infection

chemotaxis and chemo-attractants

ability of WBCs to move against a concentration gradient (low→high) in respones to chemical factors (chemotactic factors).

chemotaxis

chemotactitc factors can include (4)

1. complement products (C5a)

2. chemokines (IL-8)

3. bacterial products

4. damaged membrane products (arachidonic acid metabolites)

What are PRRs?

Pattern Recognition Receptors. PRRs can be found on macrophages, epithelial cells, and dendritic cells. They help the phagocytes recognize common patterns.

What is the process of phagoctosis?

1. recognition of foreign body (using PRRs)

2. attachment to the foreign body (opsonization).

3. internalization (engulfing)

4. destruction of the “non-self” substance

the process of adding host factors to the outside of bacteria to enhance attachment and speed up the process of phagocytosis

opsonization

what are host factors, aka opsonins

factors made by the “self” or own body

what are the two types of opsonins

antibodies

complement proteins

____are the WBC that manufacture and release antibodies to fight infection.

plasma cells

how do antibodies work (3 steps)

1. antibody attaches to the bacterium (IgG)

2. antibody brings the bacterium to the phagocyte

3. the phagocyte recognizes the antibody covered bacterium and eats it.

___is the primary organ that produces and secretes most of the body's complement proteins into the blood.

the liver

how do complement proteins work (4 steps)

1. bacterium presence causes the complement protein to split into 1 big piece and 1 small piece

2. the big piece bonds to the bacterium, the small piece attaches to an effector cell

3. the complement-bacterium complex binds to the complement receptor on the effector cell.

4. the effector cell eats the bacterium and kills it.

There are 3 different ways of killing by neutrophils

1. oxygen dependent killing (inside neutrophils)

2. oxygen-independent enzymatic killers

3. suicidal killing (outside neutrophils)

what method refers to corrosive free radicals being produced to destroy a foreign body (superoxide anion O2-, hydrogen peroxide H2O2, myeloperoxidase produces HOCl. these act like bleach to kill the bacteria.

oxygen dependent killing.

give 3 examples of bactericidal proteins and enzymes that are oxygen-INDEPENT killers

lysozymes

lactoferrin

defensins

___act inside the cell by breaking bacterial cell walls

lysoyzmes

___act in the extracellular space by binding to iron in the plasma, preventing bacteria from using it to grow

lactoferrin

___acts outside the cell by poking holes into bacteria to kill it

defensins

____acts by bursting open, projecting its sticky DNA onto the bacteria and gluing it into place. eventually the bacteria that is glued in place breaks down.

Neutrophil extracellular traps (NETs)

Neutrophilic killing is destructive and indiscriminate (causes collateral damage to surrounding tissues). products produced during phagocytosis are also released extracellularly (lysosomal enzymes and oxygen-derived activated metabolites) as neutrophils die off, they accumulate at the infection site which appears as pus.

Functions of activated complement proteins can be represented by the acronym OIL:

Opsonization (coating pathogens)

recruits Inflammatory mediators (aka immune cells)

Lysis (killing by a membrane attack complex formation (MAC)) punches a hole into the bacterium

Outline the vascular and cellular events of the innate immune system during infection/inflammation

Vascular

1. bacteria triggers macrophage to release cytokines and chemokines

2. vasodilation and increased permeability of vessels cause redness, heat, swelling

3. inflammatory cells move into tissues, releasing inflammatory mediators that cause pain

cellular events

4. neutrophils in the bone marrow are released when needed to fight infection (can sense inflammation)

5. neutrophils enter the infected tissue to kill bacteria. they die in the tissue and are eaten by macrophages

there are two different lymphoid tissues that are made during lymphocyte development and selection, what are they called

primary lymphoid tissue: the structures in which b and t cells originated (bone marrow+thymus)

secondary lymphoid tissue: lymph nodes

in primary lymphoid tissue, lymphocytes differentiate and are educated. explain this further.

lymphocyte eduaction=stages where lymphocytes are exposed to the body’s own proteins. two sets of b and t cells are produced:

the first set binds to the body’s own proteins and are flagged as dangerous and destroyed

the second set recognize the body’s cell and proteins without binding to them

explain secondary lymphoid tissue

in the lymph nodes, lymphocytes encounter foreign antigens and matured b and t cells who recognize the antigen become activated

All lymphocytes (b and t cells) must be able to do the following 3 R’s

1. recognize antigens (foreign agents)

2. respond to the antigens (destroy them)

3. remember the first encounter so they can better respond next time they see the same antigen

Describe the general structure of an antibody

the two arms are called antigne binding sites. they bind to proteins and carbohydrates.

the stem of the antibody is the constant region. it is where the macrophage binds in opsonization

What happens to a B cell after it encounters its specific antigen? (HUMORAL immunity)

B cell recognizes antigen→makes copies of itself→copies become either plasma cells or memory cells

What is the fate of a B cell which turns into a plasma cell (fights infection) in HUMORAL immunity

1. antigen enters the body

2. antigen binds to the matching b cell receptor on a b cell (membrane bound recognition)

3. b cell become activated

4. b cell undergoes cloning

5. b cells differentiate/mature into plasma cells

6. plasma cells produce and secrete antibodies (soluble recognition)

7. antibodies circulate through the body and bind to the specific antigen

what is the fate of a b cell which turns into a memory cell (lives in lymph nodes) in HUMORAL immunity

1. antigen enters the body

2. antigen binds to the matching b cell receptor on a b cell

3. b cell becomes activated

4. b cell undergoes cloning

5. b cells differentiate/mature into memory cells

6. memory cells remain in the body for a long time

7. if the same antigen appears again, memory cells rapidly multiply and produce many plasma cells

8. plasma cells produce antibodies

plasma cells fight current infection, memory cells remain in the lymph notes for years or even decades

After a b cells produce an antibodies, the antibodies function in 3 ways in HUMORAL immunity

1. opsonization (mark for eating)

2. complement activation (OIL)

3. neutralization (blocking toxins)

decsribe how antibodies neutralize bacterial toxins in HUMORAL immunity

1. some bacteria produce toxins which bind to receptors on healthy cells and changes/damages the cell.

2. antibodies defend by binding to the toxin FIRST, which blocks it from binding to receptors on healthy cells.

3. then a phagocyte can engulf the antibody-toxin complex and destroy it.

There is another branch of acquired immunity called cellular immunity =___

acquired immunity involving t cells

t cells are especially important for (3)

viruses

cancer

transplants

the types of t cells involved in cellular immunity are (3). these are responsible for recognizing, responding, and remembering pathogens

helper t cells (recognize)

cytotoxic t cells (respond)

memory t cells (remember)

unlike b cells, t cells do not recognize free-floating antigens directly. they require the pathway to be:

antigen→antigen-presenting cell (APC) displays a piece of the antigen→t cell recognizes the displayed antigen→t cell becomes activated and responds

Describe the steps of antigen presentation to t cells

1. foreign antigen enters the body

2. an antigen presenting cell (APC) like a macrophage takes up the antigen

3. APC processes the antigen into smaller pieces

4. APC displays an antigen piece using a MHC protein

5. helper t cell recognizes the antigen-MHC complex

Describe the steps for a APC and helper t cell to trigger an immune response

1. APC displays an antigen on MHC which the t cell receptor recognizes

2. handshake: co-stimulatory molecules on APC bind to receptors on the t cell

3. APC releases cytokines which activate the t cell and direct its response

4. helper t cell is fully activated

Describe the two types of MHC proteins and where they are present

MHC I = on the membrane of cells with a nucleus

MHC II = on the membrane of specialized antigen-presenting cells like macrophages or dendritic cells

Differentiate between innate immunity, adaptive immunity, humoral immunity, and cellular immunity

Innate immunity: rapid, nonspecific protection from birth

adaptive immunity: targeted, long-lasting memory against specific pathogens. two types:

• humoral (antibody-mediated, b cells; is extracellular so occurs in body fluids/blood)

• cellular (cell-mediated, t help/cytotoxic cells; is intracellular so occurs inside infected host cells)

What are the two types of immune response

primary vs secondary

describe the pathway of primary immune response

1. foreign antigen A enters

2. matching b/t cells recognize it

3. cloning

4. plasma+memory cells develop

5. antibodies increase SLOWLY

describe the pathway of secondary immune response

1. familiar antigen A centers

2. memory cells recognize it

3. cloning

4. LOTS of plasma cells+antibodies are produced QUICKLY

what is the difference between active and passive immunity?

active=your immune system does the work

passive=you recieve antibodies that someone/something else already made and gave to you

describe the characteristics of active immunity

• acquired from exposure to the actual disease or an injection of an altered antigen (vaccine)

• immune system produces b/t cells→plasma+memory cells

• antibodies are self-generated

• takes weeks for the primary response but days for the secondary response

• can last months to years thanks to memory cells

describe the characteristics of passive immunity

• acquired from antibodies transferred through the placenta or breast milk

• antibodies are pre-formed in the mother’s body and work immediately (no cell cloning necessary)

• passive immunity only lasts a few weeks because no long-term immune memory can be transferred (memory cells only from acitve immunity)