23 Innate immunity

Question 1

1) Recognize and eliminate damaged and dead host cells
2) Stimulate the adaptive immune responses and influence the nature of the adaptive response
Are the functions of the ___

Answer 1

Innate immune system

Question 2

Enable recognition of foreign microorganisms

Answer 2

Receptors

Question 3

___ are mounted to eliminate the foreign microorganisms

Answer 3

Effector components

Question 4

o Receptors are encoded in the germline
o Limited diversity
o Pattern recognition receptors (PRRs)
 Recognizes structures shared by various microbes

Answer 4

Innate immune system receptors

Question 5

o Epithelial barriers and secreted antimicrobial proteins are always present and do not need to be activated
o All other components of the innate immune system must be

Answer 5

Effector functionsd of the innate immune system

Question 6

o Activated by sequential proteolysis (activation)
o Activation is inhibited by regulatory proteins that are present on normal host cells and absent from microbes (minimize damage to host cells)

Answer 6

Complement system

Question 7

Cleaves complement component 3 (C3), which releases C3b and C3a as products.

Answer 7

C3 convertase

Question 8

Stimulates mast cell degranulation, thus triggering an immune response. Attracts phagocytic cells to the site of inflammation

Answer 8

C3a

Question 9

• The larger of the two elements formed by the cleavage of complement component 3. ___ covalently bonds to microbial cell surfaces within an organism’s body. Binds with the C3 convertase, forming the C5 convertase

Answer 9

C3b

Question 10

Cleaves complement component 5 (C5), releasing C5a and C5b as products

Answer 10

C5 convertase

Question 11

Diffuses away from the C5 convertase reaction and attracts phagocytic cells to the site of inflammation

Answer 11

C5a

Question 12

Stays bound to the surface of the microorganism and continues the complement cascade (ends with the creation of a pore in the surface of the microorganism –the membrane attack complex)

Answer 12

C5b

Question 13

Allows liquids, electrolytes, and other cellular components to exit/enter the microorganism, causing cell lysis

Answer 13

Membrane attack complex (MAC). Note: formation of the MAC is not effective against microorganisms that have a protective layer of carbohydrates, or an extra-thick membrane

Question 14

Loss of liver function (e.g. alcoholic cirrhosis or chronic hepatitis B) leads to decreased complement protein synthesis and reduced complement function  patients are predisposed to infections caused by ___ bacteria

Answer 14

Pyogenic bacteria

Question 15

Part of the adaptive immune response (b/c antibodies are necessary to detect antigen on the pathogen surface and eventually form C3 convertase

Answer 15

Classical pathway

Question 16

C3 is normally around (normally hydrolyzed). However, C3 may become attached to the surface of microorganisms, attracting factor B (which gets cleaved and attracts factor D which also gets cleaved). The end cleavage product is the C3 convertase

Answer 16

Alternative pathway

Question 17

The mannose-binding lectin (MBL) is made by the liver. It is able to bind lectin (which is bound to carbohydrates of the microorganism membrane). It attracts C2, and C4, and the end cleavage product is C3 convertase.

Answer 17

MB-lectin pathway

Question 18

Attaches to the surface of the microorganism, attracting C5b, C6, C7, C8, and C9 (forms the membrane attack complex, which lyses the pathogen)

Answer 18

C3b

Question 19

May also be recognized by the C3b receptors of phagocytic cells, causing opsonization and phagocytosis

Answer 19

C3b

Question 20

Allows for removal of antigen-antibody complexes and aids the B cells to identify pathogens

Answer 20

Cooperation w/ adaptive immune system

Question 21

Inactivates protease activity of C1. This inhibits the classical pathway. A deficiency in C1 inhibitors leads to upregulation of the classical pathway (hereditary angioedema). In this disease, there are increased C3a, C4a, and C5a concentrations, leading to excessive inflammation, vasodilation, and vascular permeability, leading to edema

Answer 21

C1 inhibitor

Question 22

Disease resulting from upregulation of the classical pathway. There are increased C3a, C3a, and C5a concentrations, leading to excessive inflammation, vasodilation, and vascular permeability, leading to edema

Answer 22

Hereditary angioedema

Question 23

Binds to C4b and C4b, limiting the formation of C3 and C5 convertases. A deficiency leads to increase C3 and C5 convertase formation. This leads to complement-mediated hemolysis (paroxysmal nocturnal hemoglobinura is the resulting disease and is due to increased RBC lysis)

Answer 23

Decay accelerating factors

Question 24

Disease caused by deficient decay accelerating factor levels, and the resulting increase in C3 and C5 convertase formation

Answer 24

Paroxysmal nocturnal hemoglobinura

Question 25

Patients w/ C5-C9 complement deficiencies have increased susceptibility to only certain types of infections ( ___ and ___ infections)

Answer 25

Meningococcal & Neisseria-gonorrhea

Question 26

A phagocytic cell w/ a C3b receptor will increase its recognition of the pathogen to which the C3b protein is bound. Note: iC3b or Ab individually will enhance phagocytosis of the pathogen. However, both iC3b and Ab together will enhance phagocytosis of the pathogen even more

Answer 26

Opsonization (enhanced phagocytosis)

Question 27

1) Formation of the MAC 2) Opsonization 3) inflammation

Answer 27

Functions of the complement system

Question 28

Stimulated by C3a and C5a. All below factors are involved:  Contraction of smooth muscle  Increase vascular permeability  Increase expression of cell-adhesion molecules (CAM) on endothelial cells  Activate mast cells and basophils to produce inflammatory mediators (i.e. histamine, Tumor necrosis factors (TNFa))  C5a: acts directly on phagocytic cells to increase adhesion and extravasation

Answer 28

Inflammation

Question 29

A variety of ROSs are generated (toxic to microorganisms). Hydrogen peroxide, hydroxyl radicals, activated halides (Cl-, I-, etc), and NO are all used

Answer 29

Oxygen dependent killing

Question 30

Lysosomal enzymes and acidic pH destroy the microorganism.

Answer 30

Oxygen-independent killing

Question 31

Defect –NADPH oxidase activity (inability to form hydrogen peroxide). Consequence: Lack of oxidative burst and defective bactericidal activity. Leads to buildup of macrophages that are not able to kill microorganisms (granulomas)

Answer 31

Chronic granulomatous disease

Question 32

Defect –Myeloperoxidase (lack of hypochlorite production). Consequence: phenotype is mild b/c of the presence of other reactive oxygen species that can handle microorganisms

Answer 32

Myeloperoxidase deficiency

Question 33

May be activated by pathogens (lipopolysaccharides and mannose in the microorganism membrane) themselves or by the cells of the immune system.

Answer 33

Macrophages

Question 34

A macrophage that has been activated by an antigen will increase in size and in its capacity for phagocytosis. It will also produce and secrete more cytokines that are normally produces by macrohpages

Answer 34

Hyperactivated macrophage

Question 35

A macrophage that has been activated by T cells or NK cells (interferin-gamma mediated) will have enhanced expression of antigen presentation (increased expression of MHC2). They will also have increased phagocytic capacity

Answer 35

Primed macrophage

Question 36

T/F. Activated macrophages secrete a number of cytokines that promote inflammation (IL-1 and TNF-alpha)

Answer 36

True

Question 37

1) Inhibition of fusion w/ the lysosome 2) Prevention of acidification of endosomes 3) Escape the endosome 4) Prevent presentation of antigen 5) Therefore, a bacteria that would’ve normally developed in the extracellular space now develops inside macrophages

Answer 37

Mechanisms developed by pathogens to enter and survive inside macrophages

Question 38

o About 70% of cells in the blood (most abundant cells in the blood) o Shorter half-life compared to macrophages (b/c they are too dangerous to keep around for long) o Attracted to the site of inflammation by interleukin-1 and TNF-alpha (both are secreted by macrophages), C5a, and by microorganisms (lipopolysaccharides) o Function: phagocytosis

Answer 38

Neutrophils

Question 39

Defect –integrin beta chain/CD18 (type 1) and selectin (type 3). Consequence: poor adhesion of neutrophils to endothelium. Leukocytes also have poor adhesion. Therefore the endothelium is affected (low quality integrin attached) so are several cells involved in the immune response

Answer 39

Leukocyte adhesion deficiency

Question 40

The process by which leukocytes and circulating plasma proteins are brought into sites of infection and activated to destroy and eliminate the offending agents

Answer 40

Inflammation

Question 41

Function to induce apoptosis in infected host cells (w/ virus, bacteria, or cancerous cells) and damaged cells o Different than T-CD6 cells in that there is no T-cell receptor (no education) o Markers: CD16 (Fc-IgG), CD56. Found on the surface of these cells o Migrate to tissues (roll, stop, enter) o Recognize target cells by checking the balance b/t kill vs. non kill signals  Kill signals: e.g. foreign molecules (lipopolysaccharides –LPS)  Non-kill signals: e.g. MHC1  Activated by interleukin 2 (IL2 –stimulates proliferation of all T cells), interferon (IFN alpha & IFN beta) o Cytokine production: e.g. IFN-gamma, for differentiation of Th1 cells (helper T cells)

Answer 41

Natural killer cells

Question 42

consists of changes in cells that prevent virus replication and increase susceptibility to killing by lymphocytes, thus eliminating reservoirs of viral infection o A cell that has been infected by a virus will synthesize interferon which travels to neighboring cells, activating the IFN receptors and thus activating the antiviral response. The below are functions of the antiviral response  Cells whose IFN receptors have been activated synthesize antiviral proteins that sit in the cytosol. Thus they are “ready for” the invasion of viral proteins and will degrade any viral proteins that end up in their cytosol o Other functions:  Increase antigen presentation (increase MHC1 expression)  Induce chemokine release to recruit lymphocytes  Activates NKC

Answer 42

Antiviral defense

Question 43

The link b/t innate and adaptive immunity o (NOT macrophages) Take up bacterial antigens in the skin (and tissues) and move to enter a draining lymphatic vessel o Bearing antigen, these cells enter the draining lymph node where they settle in the T-cell areas

Answer 43

Dendritic cells

Question 44

Not formed in host cells b/c of a protective response (specialized molecules) that prevents these holes from forming in the membrane

Answer 44

Membrane attack complex

Question 45

As a result of infection, these cells increase in concentration in the blood

Answer 45

Neutrophils

Question 46

What is the order in which immune cells are activated during an infection?

Answer 46

1) Resident macrophages are activated first 2) Neutrophils are the first cells recruited to the site of infection by macrophage cytokines 3) Monocytes are then recruited so that they can differentiate into more macrophages 4) Lymphocytes are then recruited to deal with the infection

Question 47

___-gamma is involved in the interplay b/t macrophages & NK cells. ___ type-1 (alpha or beta) Is involved in the antiviral response

Answer 47

Interferon (IFN)

Question 48

* Innate immune response: LPSs found on the surface of bacteria can activate the system. Neither antibodies nor T cell receptors are involved * Adaptive immune response: The most potent means of activating this sytsem. This occurs when antibodies bind to the antigen at the surface of a cell. This exposes the Fc region of the antibody in a way that allows the first complement protein (C1) to bind

Answer 48

Activation of the complement system

Question 49

Complement peptides. Ex: C3a, C4a, and C5a

Answer 49

Anaphylatoxin

Question 50

Review the diagrams

Answer 50

Do it