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Flashcards in Innate immune system lecture Deck (28):
1

Specificity & Memory

Specificity
– Innate response lacks specificity
Memory
– Innate response lacks memory
– Innate immune response blocks 99.9% of
microbial attempts to infect human body.

2

First line of defense are barriers that shield interior of body from external surroundings
- Anatomical barriers include?

skin and mucous membranes
– Provide physical separation
– Membranes bathed in antimicrobial secretions

3

Normal Microbiota

– Defined as microorganisms found growing on body surfaces of healthy individuals body surfaces of healthy individuals
– Not technically part of immune system
* However, provides significant protection
– Protects through competitive exclusion
* Covers binding sites
– Pathogens can’t bind
* Competes for nutrients
– Nutrients unavailable for pathogens

4

Neutrophils

Most abundant and important in innate response
– Sometimes called polymorphonuclear neutrophilic leukocytes (PMNs)

5

Basophils

Involved in allergic reaction

6

Eosinophils

Important in expelling parasitic worms
– Active in allergic reactions

7

Mononulcear phagocytes

Constitute collection of phagocytic cells called mononuclear phagocyte system
– Include monocytes
* Circulate in blood
* Macrophages differentiate from monocytes
– Present in most tissues
* Abundant in liver, spleen, lymphnodes, lungs and peritoneal cavity

8

Dendritic cells

Branched cells involved in adaptive immunity
– Function as scout in tissues
* Engulf material in tissue and bring it to cells of adaptive immunity

9

Lymphocytes

Involved in adaptive immunity
– Two major groups
1) B lymphocytes
– B cells
2) T lymphocytes
– T cells
– Another type
3) Natural killer
– Lacks specificity of B and T cells

10

In order for immune system to respond, cells must
communicate with environment and with each other

- Cell surface receptors are the “eyes” and “ears” of the cell
- Cytokines are the “voice”
- Adhesion molecules act as the “hands”

11

Surface receptors are?

– Membrane proteins to which signal molecules bind
– Receptors specific to molecule to which it bonds
* Binding molecules called ligands
– When ligand binds, receptor becomes modified and sends signal to cell
* Cell responds by initiating some action

12

Cytokines are

bind to surface receptors and regulate cell function
– Numerous cytokine classes
1) Chemokines – important in chemotaxis important in chemotaxis
– Enhance ability of cells to migrate to appropriate site in body
2) Colony stimulating factors – Important in multiplication and differentiation of leukocytes
– During immune response, directs immature leukocytes to correct maturation pathway
3) Interferons – important in control of viral infections
– Also associated with inflammatory response
4) Interleukins – produced by leukocytes
– Important in innate and adaptive immunity
5) Tumor necrosis factor – kill tumor cells
– Instrumental in initiation of inflammation

13

Adhesion molecules are

– Allow cells to adhere to each other
– Responsible for the recruitment of phagocytes to
area of injury
* Epithelia cells lining blood vessels produce adhesion
molecules that catch phagocytes as they pass by
– Cause phagocytes to slow and leak out of vessels to area
of injury

14

Toll-like receptors (TLR) and NOD proteins

– Pattern recognition receptors
– TLR allow cells to “see” molecules signifying presence of microbes outside the cell
– TLR found in variety of cell types
* Recognize distinct “danger” compounds
– Signal is transmitted
* Results in change of gene expression of cell
– NOD proteins do same for inside cell

15

Complement system is composed of

nine proteins
- C1 – C9
– Numbered as discovered, not order of activation
* Certain proteins split into “a” and “b” fragments after
activation
– C3 can spontaneously split to C3a and C3b
* Insures enough C3b for activation of alternative pathway
– Activation of complement leads to major protective
outcomes
1) Inflammation
2) Opsonization
3) Lysis of foreign cells

16

Complement system is a Series of proteins circulating in blood and fluids

Circulate in inactive form Circulate in inactive form
– Augment activities of adaptive immune response
– Stimulation of inactive proteins initiates cascade of
reactions
* Results in rapid activation of components
– Three pathways of activation
1) Alternative pathway
2) Lectin pathway
3) Classical pathway

17

Alternative pathway

– Quickly and easily initiated
– Relies on binding of complement protein C3b to cell surface
* Initiates activation of other compliment proteins
– Allows formation of complement complex
– C3b always circulating in blood

18

Lectin pathway

– Activation requires mannan-binding lectins binding lectins
(MBL)
– Pattern recognition molecules
* Detect mannan
– Polymer of mannose
* Found in microbial cells
– MBL attaches to surface
* Activates complement proteins

19

Classical pathway

– Activation requires antibodies
* Antibodies interact complement C1
– Activates protein
* Leads to activation of all complex proteins

20

Inflammation from complement system

Complement components C3a and C5a induce
changes in endothelial cells changes in endothelial cells
* Effects vascular permeability associated with inflammation

21

Opsonization

– C3b binds foreign material
* Allows phagocytes to easily “grab” particles

22

Lysis of foreign cells

Complexes of C5b, C6, C7, C8 and multiple C9
spontaneously assemble
* Forms donut-shaped structure called membrane attack
complex (MAC)
* Creates pores in membrane
* Most effective on Gram-negative cells
– Little effect on Gram-positive cells

23

Inflammation occurs in response to?

tissue damage
* Four cardinal signs
– Heat
– Pain
– Redness
– Swelling
* Loss of function
– Fifth sign that can also be present

24

Factors that initiate inflammatory response

– Microbial products trigger toll-like receptors of macrophages
* Causes release of pro-inflammatory cytokines
– Microbial cell surface can trigger complement
* Leads to the production of C3a and C5a
– Tissue damage results in enzymatic cascade
* Cascades initiate inflammation

25

The inflammatory process Initiation leads to a?

cascade of events
* Results in dilation of blood vessels, leakage of fluid from vessels and migration of leukocytes and phagocytes
– Leakage of phagocytes from blood vessels called diapedesis
– Certain pro-inflammatory mediators cause the diameter of blood vessels to increase
* Results in increased blood flow
– Increased blood flow responsible for cardinal signs of inflammation

26

Outcomes of inflammation

– Intent is to limit damage and restore function
* Inflammation itself can cause considerable damage
– Release of toxic products and enzymes from phagocytic cells is responsible for tissue damage
– If inflammation is limited to area of injury, damage is usually local
– If inflammation results in delicate systems, consequences are more severe
* Inflammation around brain and spinal cord can lead to
encephalitis.

27

Apoptosis

– Programmed cell death
* Destroys cell without eliciting inflammatory response
– During apoptosis, cells undergo changes to signal
macrophages
* Cells are engulfed without triggering inflammatory
cascade

28

Fever One of the strongest indicators of infection Especially of?

bacterial infection
* Important host defense mechanism
* Temperature regulation center of body responds to fever inducing inducing substances called pyrogens
– Fever-inducing cytokines termed endogenous pyrogens
– Microbial products termed exogenous pyrogens
* Resulting fever inhibits growth of pathogens by
– Elevating temperature above maximum growth temperature
– Activating and speeding up other body defenses