Innate Immunity

1. Innate (nonspecific)

2. Acquired (specific)

1. First line of defense

2. Second line of defense

a surface protection composed of anatomical and physiological barriers that keep microbes from penetrating sterile body compartments

• 1. Physical barriers
• 2. Chemical barriers
• 3. Genetic barriers

Response time: 1st responder

Recognizes pathogens by predetermine patterns; toll-like receptors (TLR's)

No memory

Response time: 2nd to respond, clears infection

Learns each pathogen individually as it’s encountered

Memory to previously encountered pathogens

• 1. Skin (line of defense)
•      •Keratin
•      •Epithelial cells tightly packed
•      •Sebum

• 2. Mucous membranes
•      •Layer of epithelial cells
•      •Secrete mucous
•      •GI, GU, & Respiratory Tract

Non specific

1.Lacrimal Apparatus: tears

2.Saliva

3.Cilary Escalator

4.Perspiration: lysozyme

5.Urine

6.Defecation

7.Vomiting

Genetic differences in susceptibility can exist within members of one species.

Organisms that are considered normal to be present

• What do they do? 
• 1. Competitive exclusion
• 2. Microbial antagonism

• they produce harmful waste products, they take up space, they take nutrients, they
• can alter the pH, etc

• the normal microbiota has
• an ability to kill or injure a different microbe -due to a property your normal flora has

Cells of the Innate Immune System

• 1.Hematopoiesis
• 2. Stem Cells
• 3. Blood cells

refers to production of blood cells from stem cells

an immature cell that can differentiate into specialized cells (stem cell = undifferentiated cell)

1. RBC’s / Erythrocytes

2. Platelets – regulates blood clotting when there is injury

3. WBC’s - referred to as Leukocytes

4. Granulocytes

5. Agranulocytes

are the site of lymphocyte maturation where t-cells and b-cells mature.

occurs in the bone marrow and the thymus

-are the locations where the lymphocytes will meet the pathogen - sort of the command center 

-the lymphnodes and spleen

•Lymphatic vesicles

•Primary lymphoid organs

•Secondary lymphoid organs

• – Neutrophils 
• – Monocytes
• – Basophils 
• – Macrophages
• – Eosinophils 
• – NK Cells

–Phagocytosis

–Inflammation

–Fever

• –Antimicrobial substances such as Complement
•      •Complement

–Cytokines

• there are toll like receptors on the surface of cells. they are single membrane receptor protein. nonspecifically help us interact with bacteria when it does this it activates other things to occur such as production of various interleukin. *Toll like markers that can
• nonspecifically interact with pathogens.
• When the TLR4 recognizes and interacts with the LPS of a gram negative bacteria its going to signal other molecules such as cytokines and interleukins to come into play

Phagocytes engulf & destroy microbes

• -The two main types of white blood cells involved in phagocytosis:
• • Neutrophils
• • Macrophages

• - They squeeze through your capillaries to control tissue to help clear up infections
• - made in the bone marrow
• - Make up about 60% of the wbc’s
• - travel through the blood and are shortlived
• - Effective
• - Released in large quantities during infection
• - Dead neutrophils is pus

• - made in bone marrow
• - when traveling in the blood we refer to it as monocytes
• - Longer lived than neutraphils and larger

Macrophages will cut up the pathogen and display the pathogen on their surface and then lymphocyte will come and recognize that.

• when the bacteria is engulfed by a phagocyte it will be contained in a vacuole. the phagocyte has little vacuoles that contain lysosomes which has lytic enzymes.
• phagolysosome = where the lysosome will fuse with the phagosome.
• the phagosome contains the bacteria. lysosome then destroys the bacteria and then eject the debris. phagolysosome can take 10 - 30 minutes to kill the bacteria.

1.Block adherence

2.Escape to the cytoplasm

• 3.Block fusion of the phagosome
• & lysosome

- Various microorganisms have various ways of avoiding phagolysosome

- Tuberculosis prevents phagolysosome; resides in and infects the macrophages

• - Some bacteria can escape to the cytoplasm
• to escape being engulfed.

- Some can also kill the phagocyte

4 signs of inflammation - Redness, Warmth, swelling, and Pain

- Acute inflammation - intense but shortlived

- Chronic inflammation - not as intense but carried out over a long period of time

1.Vasodilation & increased permeability of blood vessels (wbc’s go in)

• 2.Phagocyte migration & phagocytosis - how can they get there? with vasodilation &
• increased permeability of the blood.

3.Tissue repair

Step 1 - Vasodialation

• • Histamine
• • Kinins 
• • Prostaglandins
• • Leukotrines

contributes to inflammatory response & causes constriction of smooth muscle

proteins in blood that affect BP and attract phagocytic granulocytes to injured area

• Hormone-like substance plays part in inflammation.  Intensify effect of histamine & kinins. Help phagocytes move through capillary
• walls. First discovered in the prostate

produced by mast cells. Contribute to most features during allergic reaction

Has interstitial spaces

More fluid and antimicrobial chemicals

Diapedesis - Monocytes squeeze through interstitial space

• expansion in the vessels and with expansion you can allow things to come out and patrol.
• For example platelets and monocytes

Prostaglandins and leukotrines

vasodilation, increasing blood flow to the site of a cut

squeeze through walls of blood vessels (diapedesis)

antimicrobial chemicals and clotting proteins to see into damaged tissue but also results in swelling, pressure on nerve endings, and pain

Phagocytes migrate to the site and devour bacteria

Undifferentiated stem cells repair the damaged tissue

Overall Goal:  Repair damaged site

–Bystander damage: you generally want inflammation but for some things like spinal injury it causes more damage

–Septic shock: blood poisoning

Definition: increase in internal body temperature to levels that are above normal 

It is a systemic Response to Infection

Caused by: Infection from bacteria, their toxins or viruses.

• Complement (C’) - Complement protein is
• found in the blood

Made by leukocytes to kill microbes – nitric oxide (NO), superoxide, hydrogen peroxide, defensins, transferrins, interferons

–some cytokines have antimicrobial properties (ex. interferons) but in general are molecules released from leukocytes to communicate with other cells and coordinate immune responses

• 30 proteins made by the liver which
• circulate in the blood and are only functional when activated

Activation is a cascade of ordered interactions between these proteins

1.Lysis of the microbe

2.Increased inflammation

3.Increased phagocytosis through opsonization

• 1) Antibody binds to bacteria
• 2) C1 binds to Ab
• 3) C1 cleaves C4 & C2
• 4)C4b C2b binds and cleaves C3
• 5) C4b C2b C3b binds and cleaves C5
• 6) C5b binds C6, C7, C8
• 7) C5b C6 C7 C8 bind many molecules of C9
• creating a hole in the bacteria cell membrane
• lysing the cell. This is the membrane attack
• complex

-Does not involve antibody.

-c3 binds directly to proteins on the pathogen

-Does not have c1, c2, c4.

-It begins with c3

•Mannose-binding lectin (MBL) also released from the liver

•Binds to microbe to trigger series of events

lysis of the cell

• Occurs through MAC that occurs when c5b
• binds to c6 c7 c8 c9 to form MAC that lysis the cell

Increasepermeability of the blood vessel due to c3a or c5a

• where c3b binding on the surface of the bacteria so that it draws the phagocyte towards it to be
• engulfed.

• c3a and c5a bind to a mast cell causing degranulization. This degranulization is
• evident by the result of the release of histamine which causes inflammation

•IFN-a & IFN-b: cause cells to degrade mRNA to block protein synthesis in an attempt to halt viral replication

•IFN-y: Activates neutrophils and macrophages to kill microbes by causing:

–Increased phagocytosis

• –Increased production of antimicrobial molecules such as NO, hydrogen peroxide, &
• superoxide

• Major role in controlling acute illness,
• ex. colds & flu

• Side effects: nausea, fatigue, headache,
• vomiting, weight loss, & fever