WEEK 2: INNATE AND INFLAMMATORY RESPONSE

Question 1

Differentiate between innate and adaptive immunity.

Answer 1

INNATE
*Immediate onset
*Short duration
*No memory
*Activity always present
*Non-specific
*Amplification insignificant

ADAPTIVE IMMUNITY
*Onset at approximately 3-4 days
*Long duration
*Has memory cells
*Activity normal silent
*Highly specific
*Can be amplified

Question 2

Describe the principles of innate immunity action.

Answer 2

1.Physical and mechanical barriers; epithelial anti-microbial substances produced at epithelial surfaces.

2.Phagocytic and killer cells
*Neutrophils, macrophages and natural killer cells.

3.Blood proteins
*Complement system

4.Circulating proteins
*Cytokines and chemokines

Question 3

State the cells of adaptive immunity.

Answer 3

T and B lymphocytes (cells).

Question 4

Outline the cells of the innate immunity.

Answer 4

*Neutrophils
*Mast cells
*Monocytes
*Basophils
*Eosinophils
*Dendritic cells

Question 5

Outline the WBC according to their relative abundance.

Answer 5

Never Let Monkeys Eat Bananas

Neutrophils, lymphocytes, Monocytes, Eosinophils, Basophils

Question 6

Outline the stages of Phagocytosis.

Answer 6

1.Attachment
2.Internalization ( ingestion)
3.Degranulation (phagolysosome0
4.Exocytosis

Question 7

State the functions of natural killer cells.
Describe 2 mechanisms on how natural killer cells.

Answer 7

*They recognize infected cells and stressed cells and cause aptosis.

1.
*Nk cells release a granule containing Perforin and Granzymes

-Perforin result in pore formation on the target cell and Granzymes results in aptosis.

*The granule will bind to the target cell FAS ligand.

2.
*Nk cells respond to IL-12 from the macrophages
*It will secrete INF-gamma which activates macrophages to kill and phagocytize microbes

Question 8

Outline the innate immunity recognizing strategies.

Answer 8

*Pattern Recognizing Receptors; soluble, membrane associated, cytosolic

ON PATHOGENS
*PAMPS: Pathogen associated molecular patterns
*DAMPS: Damage associated molecular patterns, released from damaged cells by trauma.

Question 9

Describe the complement system.

Answer 9

A display mechanism brought in play non-specifically in response to invading pathogen.

Question 10

State the 3 activation pathways for the complement system.

Answer 10

1.Classical pathway
2.Lectin pathway
3.Alternane pathway

Question 11

Describe the classical pathway

Answer 11

1.The antibody binds to an antigen on the surface of a pathogen, activating the C1 complement protein.

2.C1 acts a protease and cleaves C2 and C4 to form C4b2b formerly C4b2a.

3.C42b converts C3 into C3a and C3b, which forms a C5 convertase

Question 12

Describe the Lectin pathway.

Answer 12

Mannan-binding-lectin (MBL) binds to the carbohydrates on a pathogen.

Proteases bound on the other side of the MBL cleaves C4 into C4a and C4b.

C4b creates C3 convertase, and the rest of the steps happen identically to the classical pathway from the C3 convertase step.

Question 13

Describe the alternative pathway.

Answer 13

The pathogenic antigen (such as LPS) activates C3 so it creates a C3B complex.

Factor D cleaves the C3B complex so that C3bBb is created.

C3bBb is a C3 convertase, which converts more C3 into C3a and C3b

Question 14

What is the function of the following:
C3a
C3b
C5a
C5b

Answer 14

C3a, C5a: inflammation
C3b: Phagocytosis and opsonization
C5b: activate the membrane attack complex

Question 15

What is the following of the following:
C3a
C3b
C5a
C5b

Answer 15

C3a, C5a: inflammation.
C3b: Phagocytosis and opsonization.
C5b: activate the membrane attack complex.

Question 16

What is the membrane attack complex?

Describe how the MAC is initiated.

Answer 16

The membrane attack complex (MAC) or terminal complement complex (TCC) is a complex of proteins typically formed on the surface of pathogen cell membranes as a result of the activation of the host’s complement system.

1.MAC is initiated when the complement protein C5 convertase cleaves C5 into C5a and C5b.

2.Another complement protein, C6, binds to C5b.

3.The C5bC6 complex is bound by C7.

This junction alters the configuration of the protein molecules exposing a hydrophobic site on C7 that allows the C7 to insert into the phospholipid bilayer of the pathogen.

4.Similar hydrophobic sites on C8 and C9 molecules are exposed when they bind to the complex, so they can also insert into the bilayer.

5.C8 is a complex made of the two proteins C8-beta and C8 alpha-gamma.
-C8 alpha has the hydrophobic area that inserts into the bilayer.

6.C8 gamma induces the polymerization of 10-16 molecules of C9 into a pore-forming structure known as the membrane attack complex.

Question 17

What diseases are associated with the deficiency of the following complex?

1.C3 and Factor D
2.C3b-INA
3.Deficiency in early components of C1, C2 and C4
4.C1 inhibitor

Answer 17

1.Severe bacterial infection
2.Severe Neisseria infections
3.Systemic lupus erythmatons (SLE)
-Glomerulonephritis
-Polymyositis
4.Hereditary angioedema

Question 18

What are cytokines?

Answer 18

A group of non-enzymatic proteins and peptides, produced by a variety of cell type, able to modulate the behavior and the function of individual cells and tissues, including the immune system.

Question 19

Describe the 3 activity of cytokines action.

Answer 19

Paracrine: On the same cell
Paracrine: On nearby cell
Endocrine: Far away cell and transported by blood

Question 20

Describe the following cytokine activity.

pleiotropy
redundancy
synergy
antagonism

Answer 20

*One cytokine can have different effects on different cells.

*Different cytokines can have the same effect.

*Cytokines can be induce

*Cytokines can block each other.

Question 21

How do the different components of the innate immune system work together to eliminate different types of microbes?

Answer 21

Through the inflammation response.

Question 22

What is inflammation?

Answer 22

Processes involved in the disturbance of tissue homeostasis as a result of acute or chronic form of infection, stress, autoimmune reaction, tissue necrosis or mechanical injury or foreign bodies.

Question 23

Outline the goal of inflammation.

Answer 23

*Isolate, destroy inactivate the invaders.
*Limit tissue damage
*Remove debris
*Prepare for subsequent healing and repair

Question 24

Describe the process of inflammation.

Answer 24

1.A break in the skin introduces bacteria, which reproduce at the wound site.

2.Activated resident macrophages engulf the pathogens and secrete cytokines and chemotaxis.

3.Activated MAST CELLS release histamines.

-Histamine dilates local blood vessels and widens the capillary pores.

• Cytokines cause neutrophils and monocytes to stick to the blood vessel wall ( Marginalization).

4.Chemotaxins attract neutrophils and monocytes which squeeze out of the blood vessel well (Diapedesis) and migrate to the infection site.

NOTE: Neutrophils arrive earliest because they are more mobile than monocytes.

5.Monocytes enlarge into the macrophages.
*Newly arriving macrophages and neutrophils engulf the pathogens and destroy them.

6.Marking of the bacteria for destruction for destruction by opsonins.
-Phagocytes by means of TLR , recognize and subsequently engulf infiltrations that have standard bacterial cell wall components not found on human cell.

-Foreign particles are deliberately marked for phagocytosis ingestion by being coated with chemical mediators called OPSONINS

7.Leukolytic destruction of bacteria: Neutrophils and macrophages clear the inflamed area and toxic agents and tissue debris by phagocytic and non-phagocytic means.

8.Neutrophils die after phagocytizing 5-25 bacteria.
-Macrophages die after phagocytizing up to 100 bacteria.

Question 25

What is marginalization?

Answer 25

Cytokines cause neutrophils and monocytes to stick to the blood vessel wall.

Question 26

What is meant by diapedesis?

Answer 26

Chemotaxins attract neutrophils and monocytes which squeeze out of the blood vessel well.

The passage of blood cells through the intact walls of the capillaries, typically accompanying inflammation.

Question 27

What are the functions of opsonins?

Describe how opsonin’s work.

Answer 27

Enhance phagocytosis by linking the foreign cell wall ta o phagocytic cell.

One portion of the opsonin molecule binds non-specifically to the surface of an invading bacterium, whereas another portion of the opsonin molecule binds to the receptor specific for it on the phagocytic cell’s plasma membrane.

This link ensures that the bacterial victim does not get away before a phagocyte can perform its lethal attack.

Question 28

Describe pus formation.

Answer 28

This is whereby in an infected wound , a collection of phagocytic cells, both dead and living and dead tissue are liquidified by lysosomal enzymes released from the phagocytes and bacteria.

Question 29

Describe how the tissue is repaired.

Answer 29

Fibroblasts, connective tissue sell starts to divide rapidly in the vicinity and secrete large quantities of the protein collagen, which fills in the region vacated by the lost cells and result in the formation of a scar tissue.

Question 30

Describe the 5 classical signs of inflammation.

Answer 30

1.Redness: enhanced blood flow to the damaged tissue in order to deliver the macrophages and neutrophils
2.Heat: Enhanced blood flow to the damaged vessel.
3.Pain: Local distension within the swollen tissue and by direct effect of locally produced substances on the receptor endings on the receptor endings of neurons that supply the are
4.Loss of function: Due to pain
5.Swelling: Oedema due to leakage of plasma proteins from vasodilated blood arterioles.

Question 31

What is the local acute immune response (Systemic inflammatory response syndrome)?

How does it result in the following effects:
*Fever
*Production of large number of acute phase proteins in the liver
*Increased production of white blood cells (leukocytosis).

Answer 31

A variety of systemic changes in the host due to inflammation that enhance the ability of the innate immune system to eradicate infection and, in severe infections, can contribute to systemic tissue injury or death.

These changes are thought to be mediated by the endocrine actions of cytokines and are collectively described as the acute-phase response or the systemic inflammatory response syndrome.

*Local inflammatory response result in the release of IL-1, 6 and TNF-alpha which stimulate the release of PROSTAGLANDINS from the brain (hypothalamus) and result in fever.

The Pituitary gland releases ACTH which stimulate the adrenal cortex to release Corticosteroids which act on the liver and promote the release of acute phase proteins.

Local inflammatory response release IL-6 and TNF -alpha which stimulate the BONE MARROW to release A LOT OF LEUKOCYTES.

It also releases IL-1,6, TNF-gamma, LIF, OSM which stimulate the liver to release Acute phase proteins.

Question 32

Name the acute phase proteins which are activated by the
local acute immune response.

Answer 32

Fibrinogen
Mannose binding Protein
Complement complements
C-reactive protein (CRP)
Serum amyloid A (SAA)

Question 33

Outline the functions of the acute phase response.

Answer 33

*Enhance effectiveness of the inflammatory response

• Limit tissue damage and

*Promote healing