Innate immune system lecture Flashcards
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.
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
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
Neutrophils
Most abundant and important in innate response
– Sometimes called polymorphonuclear neutrophilic leukocytes (PMNs)
Basophils
Involved in allergic reaction
Eosinophils
Important in expelling parasitic worms
– Active in allergic reactions
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
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
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
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”
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
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
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
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
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
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
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
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
Classical pathway
– Activation requires antibodies
* Antibodies interact complement C1
– Activates protein
* Leads to activation of all complex proteins
Inflammation from complement system
Complement components C3a and C5a induce
changes in endothelial cells changes in endothelial cells
* Effects vascular permeability associated with inflammation
Opsonization
– C3b binds foreign material
* Allows phagocytes to easily “grab” particles
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
Inflammation occurs in response to?
tissue damage * Four cardinal signs – Heat – Pain – Redness – Swelling * Loss of function – Fifth sign that can also be present
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
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
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.
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
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
