Download Immunity - Seattle Central College

Immunity
Vertebrate model
Cells
Innate
Adaptive
Immunity
• Innate: response to attack is always the same
– Mechanical mechanisms
– Chemical mediators
– Cellular response
– Inflammatory response
• Adaptive: response to attack improves with each
exposure
– Specificity
– Memory
Innate immunity
• Mechanical mechanisms
– Physical barriers prevent entry
• Skin & mucus membranes (Verts)
• Chitin exoskeleton (Arthro)
– Dilute invading army of pathogens & wash away
pathogens from surface
• Tears, saliva, urine
Innate immunity
•
Chemical mediators
– Some prevent entry to cells, kill bacteria, produce
inflammation
1. Complement proteins
•
•
•
~ 20 in plasma
normally inactive; activated by combining with parts of
bacterial cells or antibodies
Leads to chain rxn activation of neighboring compliments
& inflammation, phagocytosis, or lysis
Innate immunity
•
Chemical mediators
2. Interferons protect against viral infection (Vert)
•
•
Virus-infected cells release interferons (SOS signal)
Some bind to neighboring cells & stimulate neighbors to
produce & secrete antiviral proteins
–
•
Intiviral proteins inhibit production of new viral RNA
Some interferons activate macrophages and NKC
– Lysozyme digests prokaryote cell walls (Arthro)
– Low pH digestive sac digests some cells walls (Arthro
& Vert)
Innate immunity
• Cellular mechanisms
– White Blood Cells (Leucocytes) are most important
cellular components
• Attracted to invading bacteria and microorganisms
through chemotaxis
– Phagocytic cells
– Inflammatory cells
– Natural Killer Cells (NKC)
Leucocytes
•
•
Large; contain nuclei
Travelers in blood;
wandering militia
–
•
Distributed (via blood) to
body tissues where they
leave bloodstream and
crawl around
2 Jobs
1.
2.
Remove dead and dying
cells via phagocytosis
intercept & destroy
invaders
Leucocytes
G
A
Leucocytes divide labor
• Granulocytes: Leukocytes containing large
cytoplasmic granules; 3 types
1. Neutrophils: Most common
• Short-lived; 10-12 hours in blood
• phagocytize microorganisms & foreign substances in
tissues --> pus!!
2. Basophils: Least common
• release histamine & others promoting inflammation
• release heparin which prevents clotting
Leucocytes divide labor
• Granulocytes: Leukocytes containing large
cytoplasmic granules
3. Eosinophils: release inflammation suppressing
compounds (antihistamine)
– Produce chemicals that destroy worm parasites
Leucocytes divide labor
• Agranulocytes: Leukocytes lacking cytoplasmic
granules
– Lymphocytes: Smallest WBC; immune response; B & T
• produce antibodies & proteins to destroy foreign cells
• allergic reactions
• reject tissue grafts
– Monocytes: Largest WBC; become macrophages in
tissues
• Phagocytize bacteria, dead cells, cell fragments
• Present phagocytized particles to lymphocytes -> activation
Thrombocytes
• Majority of non-RBC formed elements
• Cell fragments
• Form platelets and release chemicals that
stimulate clotting
Innate immunity
• Phagocytic cells
– Neutrophils
• Small; first to enter infected
tissue from blood; ingest, then
die --> pus accumulation
– Macrophages
• Monocytes leave blood &
enlarge; arrive after neutrophils;
do most eating & cleanup
• Also hang out at “entry points”
(gate-keepers)
Innate immunity
• Natural Killer Cells (NKC)
– 15% of all lymphocytes
– Recognize tumor cells or virus-infected cells
(generalist killers)
– No memory; non-specific
– Kill via release of perforin (cell membrane lysis)
Innate immunity
• Inflammatory & anti-inflamatory cells: activated
through innate or adaptive immunity
– Basophils
• Motile WBC; enter infected tissue
– Mast cells
• Non-motile; Located in CT at “points of entry”
– Eosinophils
• Release enzymes that reduce inflammation (control)
Innate immunity
• Local inflammation
– Redness, heat, swelling caused by increased blood flow and
vascular permeability
– Chemicals and swelling activate pain receptors (what type of
receptors are these?)
• Systemic inflammation
– Red marrow increases neutrophil production
– Pyrogens stimulate fever by increasing heat production &
conservation
– Vascular permeability increases (why?)
Coordination of innate responses
• Inflammation, chemotaxis, phagocytosis
Lymphatic system
• Immune cells live in
lymphatic organs
• They monitor lymph &
blood and respond to
invaders
• Guard entrances to
the body, the torso &
major routes of travel
Adaptive immunity
• Lymphocytes
– Origin & development
– Activation & multiplication
• Antibody-mediated (humoral)
• Cell-mediated
Adaptive immunity
• Antigens stimulate adaptive immune response
– Self
– Foreign
• MHC molecules display antigens
• Lymphocytes
– Origin & development
– Activation & multiplication
• Types of Adaptive Immunity
– Antibody-mediated
• B cells; produce cells that make antibodies
– Cell-mediated
• T cells; cytotoxic (Tc) & helper (Th)
Antigens
• Foreign
– Unique components (proteins or polysaccharides)
of bacteria, viruses & their chemical byproducts
– Pollen, hair, foods are antigens that can produce
allergic response (overreaction of immune system)
• Self
– Produced by our bodies
• Used to recognize tumor antigens
Cells Develop in marrow & thymus
• Red marrow produces:
– B-cells: released into
bloodstream and migrate
to lymph organs
– Pre T-cells: migrate to
thymus & mature there
• Mature T-cells migrate to
lymph organs
B & T-cells
• Contain unique antigen receptors in their cell
membranes
– We each have thousands of different populations of B & Tcells, each with unique antigen receptors
• Cells are stimulated by binding of antigens to their
unique receptors
How are antigen receptors created?
• 1 receptor gene
contains many repeats
• Alternative splicing
creates enormous
diversity in variable
binding sites
• 1 gene codes for
potentially 1000’s of
receptors
MHC molecules display antigens
• MHC I: displays antigens
on infected cells
– All nucleated cells can do
this
– Tc cells bind & respond by
killing cell with perforins
MHC molecules display antigens
• MHC II: displays antigens
when a cell phagocytizes
a pathogen (APC cells)
– Only phagocytic cells do
this
– Tc cells bind and
autostimulate
– Th cells bind & stimulate Tc
& B cells & autostimulate
B-cell proliferation
• Once B and Th cells are
stimulated, they
produce two cells types
• Plasma – produce
antibodies
• Memory – hang out &
remember
Effects of Antibodies
• Direct: Antibodies bind antigens = inactivation
• Indirect: Activate Complement cascade
• Series of proteins that stimulate innate immune responses:
• Inflammation, Chemotaxis, Phagocytosis or lysis
Antibody production
• Differs following first and
second exposure to
antigen
– First exposure = primary
response
• B-cells bind antigen; produce
plasma cells (produce
antibodies) and memory Bcells
• Response time = 3-14 days;
disease symptoms develop;
SLOW
Antibody production
• Second exposure =
secondary response
– Memory cells quickly
produce plasma cells
and antibodies
– Shorter lag time
– More plasma cells &
antibodies produced
– RAPID response
precludes disease
symptoms = immunity
Th cell help adaptive immune response
• APC ingests, processes & displays antigen
• Th binds, autostimulates & stimulates B & Tc cells
Humoral response
• APC, Th, Tc & B cells
Tc contact kill infected cells
• Cellular response
• Perforin & granzymes digest infected cells