Innate Immunity

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CELLULAR MORPHOLOGY
Coccus, Bacillus, Spirillum
Coccobacillus (football shaped)
Fusiform
CELLULAR ARRANGEMENT AND NUMBER
Strepto (Chain of 7+)
Staphylo (cluster)
Mono (singular)
Diplo (pair, e.g. Streptococcus pneumonia or Nisseria gonorrhea)
Trio (triplet)
Tetrado (quartet)
COLONIAL MORPHOLOGY
Mucoid, punctifoid, irregular, color (pigments in cytochromes)
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IMMUNOLOGY: Host defense for pathogenic bacteria
INNATE
Constitutive (always on)
ACQUIRED (Adaptive)
Inducible (arises in response
to organisms)
Non-specific (blind to particular organism)
Specific (responds
specifically to the organism)
Anamnesic (has memory)
Delayed response time
Less effective discrim.
Required when innate fails
Amnesic (no memory)
Swift response time
Effectively discriminates between self/non-self
First line of defense
Innate Inflammatory response:
Recruits more cells from local blood vessels
Induces clotting downstream to prevent spread
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ROUTES OF INFECTION
Mucosal Surfaces: Airway, GI, urogenital tracts (easier to infect)
External Epithelia: External surface, wounds & abrasions, insect bites
COMPONENTS OF IMMUNITY
1) Complement (made of proteins, circulates in plasma): Innate immunity
2) Humoral Immunity (made of antibodies; immunoglobin)
Adaptive. Made up of B Lympohocytes
3) Cell Mediated Immunity (directed by cells, mostly T lymphocytes)
Both innate and adaptive
4) Phagocytes (Made up of both innate and acquired phagocytes)
CONTROL OF IMMUNE RESPONSE is important.
If it goes overboard, your own immune system can kill you in a few hours!
* Know what the effectors are of immunity (What is it that effects the
mechanism that is directly doing the work?)
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THE IMMUNE SYSTEM CELLS: (Originate in the bone marrow)
1. Myeloid: tissue based and filled with granules = granulocytes
A. GRANULOCYTES
1) Basophils
2) Eosinophils
3) Neutrophils (PMN’s)
Short-lived, abundant in blood but not in healthy tissues
The major component of pus
B. DENDRITIC CELLS
C. MONOCYTES: innate functions, but guided by acquired functions
(like hardware waiting for software instructions)
1) Macrophages (in submucosa of lung, GI; liver, spleen) They
are long-lived, first on site, followed by PMN’s. Derived from monocytes, they
engulf and initiate inflammatory response by releasing cytokines and
chemokines to bring PMN’s to the site. Also initiate adaptive immune response
a) Super-killer macrophages
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MACROPHAGES AND PMN’S
Macrophages and PMN’s have cell-surface receptors that distinguish self from
non-self. They bind to the pathogen, surround it, pull it internally into its
phagosome (internal vacuole) where its lysosome granules release enzymes,
proteins/peptides, and the cell itself also creates acids, NO, O2-, and H2O2 to
kill the pathogen.
NOTE: Polysaccharide capsules of bacteria are not recognized by phagocyte
receptors, so the bacteria cannot be bound by them. Some bacteria inhibit the
effect of the phagocytes’ lysosomes, so they can grow inside a macrophage.
THREE ROLES OF INFECTION:
Delivers additional effector cells to site
Microvascular coagulation physically prevents spread to bloodstream
Promotes repair of injured tissue
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2. Erythroid
A. RBC’s
B. Megakaryocytes  Platelets
3. Lymphoid
A. Lymphoblasts
1) Bone Marrow
a) B Lymphocytes (lymphoblast receives signals and
matures in bone marrow)
2) Thymus
a) T Lymphocytes (lymphoblast receives signals and
matures in thymus)
i) CD4
ii) CD8
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INNATE IMMUNE MECHANISMS
1. Structural (First line of defense)
A. Integument (epithelium lines internal and external surfaces)
1) Keratin (dermis and epidermis)
2) NaCl (creates a high osmotic gradient)
3) Sebum (antimicrobial fatty acids)
4) pH (acid / base)
2. Mechanical
A. Gravity: Pushes fluids of head, bladder, etc downward toward
orifices; prevents entry of organisms.
B. Eyelids/ Conjunctiva: sebum, lysosyme, mechanical blinking
C. Mucocilliary Elevator: mucus/ cilia move debris out of lungs
NOTE: 109 organisms inhaled per deep breath, caught in nares, lung, eyelids
Mucus contains glycoproteins (mucins), prevents adherence.
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3. Biochemical
A. Lysosyme and Phospholipase A:
(Lysosyme is an enzyme that cleaves the crosslink in peptidoglycan)
(Phospholipase A digests phospholipids)
- present in tears, saliva, airway secretions, and mucus
- harms bacteria, but not humans
- pain and tears go together
B. Fatty Acids (on skin)
C. Acids and bile salts GI tract)
D. Enzymes (pepsin in stomach)
E. Antibacterial peptides
1) Cryptins made by Panth cells in sm. intestine
2) Surfactant Proteins A & D in lungs
Opsonization = To coat bacteria, aiding in phagocytosis
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4. Genetic: Many infections are species-specific
- receptor specificity (if no receptor, no infection)
5. Cellular
A. Non-pathogenic bacteria (normal flora) compete for nutrients with
pathogens, and secrete antimicrobial substances
B. Phagocytes (The effector cells of innate immunity)
1) Dendritic Cells (the “guardians”)
2) Neutrophils (PMN’S)
3) Monocytes
a) Macrophages
i) Superkiller macrophages
All phagocytes except Dendritic cells are controlled by cytokines.
Oxidative Killing (NO, O2-, H2O2, and OH-)
Non-Oxidative killing (antimicrobial peptides, Phospholipase A, lysosymes)
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Phagocytes grab bacteria and pull them in.
Dendritic cells don’t kill the bacteria; they just take them to the T lymphocytes
to report what they’ve found.
DENDRITIC CELLS
Have Toll-like receptors: TLR 1-10 in humans
They are pattern recognition receptors, can recognize signals in pathogen.
TLR 2 = peptidoglycan (PG) (in bacteria only)
TLR 3 = Viral double-stranded RNA
TLR 4 = Lipopolysaccharide (LPS) (in bacteria only) Requires a co-molecule
to trigger its signaling: LPS-binding protein in plasma = LBP. CD14 is a coreceptor that functions with LBP to recognize LPS.
TLR 6 = Endotoxin
TLR 9 = CpG immunostimulatory sequences of DNA (in bacteria only)
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SIGNAL TRANSDUCTION IN DENDRITES
Purpose: to allow DNA to express genes to respond to pathogen
1) The pathogen component binds to the receptor on the Dendritic cell
membrane.
2) MyD88 (which underlies the receptor and is within the Dendritic cell)
allows an inactive kinase (IRAK)i to become active (IRAK)a.
3) TRAF-6 becomes active and controls two transcription factors:
NfKB (promotes transcription of genes) and IKB (inhibits NfKB)
4) NfKB (Transcription factors) enters nucleus of cell
5) NfKB causes mRNA to activate by promoting appropriate cytokine gene
transcription (yielding corresponding mRNA)
6) mRNA leaves the nucleus as cytokine mRNA
7) Cytokine mRNA encounters ribosomes and Golgi apparatus, is translated
and processed, and cytokines are then packaged, and secreted outside of the
cell.
* Cytokines are proteins that cause other cells to take action and
modulate systems.
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FUNCTIONS OF DENDRITIC CELLS
1) Sense pathogen components
2) Produce cytokines
3) Phagocytize without killing, takes it to the lymph system to show T cells
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