Lecture 12

Immune System in healthy person serves to?

• Surveil the body

• Recognize foreign material

• Destroy this foreign material

• Must be able to differentiate “self” from “nonself”

Define Markers (Antigens)

Proteins or sugars that lets the body determine if something is “harmful”

Define Lymph:

Plasma like liquid carried by lymphatic circulation

What does Lymph transport?

White blood cells

Lymphatic vessels transport what?

Lymphatic Fluid (Lymph)

Primary lymphatic organs is the site of?

Immune cell creation and where they mature

Red Bone marrow is what for long bones?

Internal matrix

Red bone marrow is the site of?

• blood cell production including B and T lymphocytes

• B-Cell maturation

Thymus is the site of?

T-Cell maturation

Secondary lymphatic organs is the site of?

Where immunity action takes place

Lymph nodes cluster around?

Lymphatic vessels

Lymph Nodes Function:

• Filter out material in the lymph

• Provide appropriate immune cells

Spleen function:

• Filter for blood (as opposed to lymph)

• Remove worn out RBCs

• Also filters pathogens from blood

Tonsils are the active source for?

Lymphocytes

All cells in blood originates from?

Hematopoietic stem cell

What are Leukocytes?

White blood cells

2 types of Leukocytes:

Agranulocytes + Granulocytes

Two types of Agranulocytes:

Monocytes + Lymphocytes

Define Monocytes:

Blood phagocytes that rapidly leave the circulation

Monocytes mature into what 2 cells?

Macrophages + Dendritic Cells

Define Macrophages:

Large phagocytic cells; high capacity for kill microbes and cleaning up dead cells

Define Dendritic Cells:

Resides in tissues + MPS process foreign matter and presents it to lymphocytes

Lymphocytes differentiate into:

• T cells

• B cells

• Natural Killer cells

• Natural Killer T cells

• Gamma-delta T cells

Name the 4 Granulocytes:

• Neutrophils

• Basophils

• Eosinophils

• Mast cells

Define Neutrophils:

Short-lived phagocytes in blood; active engulfers + killers of bacteria

Define Basophils:

Functions in inflammatory events

Define Eosinophils:

Active in protozoal, helminth, and inflammatory reactions

Define Mast Cells:

Specialized tissue cells similar to basophils that trigger local inflammatory reactions, such as allergic symptoms

Name 2 Non-Leukocytes:

1) Red blood cells (RBCs)

2) Platelets

Define RBCs:

Carries O2 + CO2

Define Platelets:

Involved in blood clotting, inflammation, and destruction of blood-borne bacteria

Host Defenses are a combination of? What do they consist of?

• Combination of innate non-specific protections and adaptive, specific protections

• Consist of the three lines of defense (First, Second, Third)

Define first line of defense:

Physical and chemical barriers that impede entry

5 Main Examples of First Line of Defense:

Skin,

Mucous Membranes,

Lysozymes,

Vomiting + Defecation

pH

Define Skin:

Thicker in some places (hands, feet, etc.)

+ sloughs off

Define Lysozymes:

• tears, blinking, and saliva

• breaks down cell walls

Pathogens evading the first time include?

Giardia and Entamoeba,

Necator (hookworm);

Plasmodium

Giardia and Entamoeba Function:

• colonize the small intestine and colon

• Failure of GI chemical defenses (acid, mucus)

Necator (hookworm) function:

Penetrates intact skin

Define Plasmodium:

Bypasses all external defenses via a vector

Define second line of defense:

Generalized defense (body is responding, not just physical defenses)

4 things involved in Second Line of Defense:

• Phagocytosis

• Inflammation

• Fever

• Antimicrobial products

Define Phagocyte:

Eating cell

Define Neutrophils:

general purpose phagocytes

Define Phagocytosis:

Physical process of engulfment

→ Attack and dismantling of foreign cells

Phagocytosis can be what?

Isolated event or as part of the orchestrated events of inflammation

5 Events of Phagocytosis:

Chemotaxis,

Ingestion,

Phagolysosome formation,

Destruction,

and Excretion

Define Chemotaxis:

Phagocytes → Region of inflammation aka injury site

• B/c attracted by stimulant products from parasite + host tissue

Define Adhesions: No PRR or PAMPs

Phagocytes use their PRRs (Pattern Recognition Receptors) to recognize + stick to PAMPs (pathogen-associated molecular patterns) on foreign cells

Define Engulfment and Phagosome Formation:

Phagocyte in contact w/ targeted foreign cell:

→ Sends seudopods to enclose cells or particles in a pocket

→ Internalizes them in a vacuole = phagosome

→ Results in more cytokines → amplifies innate response

Define Phagolysosome Formation and Killing:

→ Lysosomes quickly move + fuse to phagosome = phagolysosome

→ Granules containing antimicrobial chemicals are released into the phagolysosome to poison and then dismantle ingested material

Define Destruction:

Two separate systems of chemicals destroy microbes in the phagolysosome:

• Oxygen-dependent systems (respiratory burst, or oxidative burst).

Define Elimination:

Small bits of indigestible debris are released from macrophage by exocytosis.

Define Inflammatory Response:

Complex Reaction to Injury

Inflammation Response function:

Mobilize and attract immune components to the site of injury

Inflammatory Response is set in motion to?

Repair tissue damage, localize, and clear away harmful substances

→ Destroy microbes and block their further invasion

Define Diapedesis:

Migration of white blood cells from blood vessels into tissues

Name 4 Stages of Inflammation:

1) injury/immediate reaction

2) Vascular reaction

3) Edema and pus formation

4) Resolution/scar formation

Define Stage 1 of inflammation - injury/immediate reaction:

• early changes in vasculature near damaged tissue

• changes are controlled by 

  • nerves

  • chemical mediators

  • cytokines released by blood cells

  • tissue cells

  • platelets in area

What happens in quick succession during Stage 2 of inflammation - vascular reaction?

Blood vessels in the vicinity dilate, constrict, and then dilate again

• Vasodilation increases blood flow, facilitating immune components, causes redness and warmth.

• Vasoconstriction allows bad stuff to go out

Define Stage 2 of inflammation - vascular reaction

Blood vessels walls to contract:

• Form gaps that blood-borne components can move into extracellular spaces. Fluid that escapes: “exudate”

Define Stage 3 of Inflammation - Edema + Pus Formation:

• Accumulation of exudate causes swelling and hardness aka edema:

  • Contains plasma proteins and cellular debris

  • Content determines appearance

• >1 hour, neutrophils arrive, responding chemotactically to signaling molecules

How does Stage 3 of Inflammation - Edema + Pus Formation content determines appearance?

• Clear (serous)

• Red blood cells (RBCs)

• Pus (composed white blood cells (WBCs), phagocytosis debris) 

Define Part 1 of Stage 4 of inflammation - resolution/scar formation:

• Macrophages leave blood vessels via diapedesis

• Differentiated stem cells divide and repopulate to replace those that were damaged.

Define Part 2 of Stage 4 of inflammation - resolution/scar formation:

Final step: repair 

• Depending on tissue type and damage, results either 

  • complete resolution to healthy tissue 

  • formation of scar tissue

What defense is a fever apart?

Second line of defense

A fever is what? Not just?

Important component, not just a side effect

Define fever:

Abnormally elevated body temperature

Body temperature is controlled by? Normal body temp?

Controlled by hypothalamus of brain ~ 37 C

What initiates a fever?

Pyrogens

Pyrogens function:

• Increase heat production

• Low grade <101F; High 104 to 106F; >104 can cause serious damage on the host

What are 4 benefits of a raising body temp during fever?

• Physical signs of fever

• Inhibits multiplication of temperature sensitive microbes

• Reduces iron

• Increases metabolism and stimulates immune system

What have Hippocrates believed a fever was?

Thought it was the body burning off bad things

Name the 4 Antimicrobial products:

• Interferons

• Complement

• Antimicrobial peptides

• Restriction factors

Define Interferon:

Small proteins produced by certain WBCs and tissue cells

Interferon function:

Bind to cell surfaces and induce changes in expression

Define Complement:

Invokes Cascade reaction aka sequential set of reactions

Cascade Reaction involves how many proteins? How many stages?

30 some odd proteins;

Four stages

Result of Cascade Reaction:

Lysing of the cell

Antimicrobial peptides includes + function:

• Short peptides

• Defensin - inserts into cell membranes of bacteria

• Make pores and then lyse

Define Host restriction factors:

Molecules that limit virus multiplication

3 ways Pathogens can evade the second line:

1) Phagocytes engulf cells (Phagocytosis)

2) Cyst wall physically walls the parasite off from phagocytes and inflammatory signals

3) Coats outer surface with host-derived molecules aka stealing the host's own antigens to disguise itself → prevents complement recognition