Immune response distinguishing self from nonself memory

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Immune response distinguishing self from
non-self memory Immunity all mechanisms
used by the body to protect itself against
all things foreign microorganisms or their
products foods, pollen, animal
hair/dander chemicals, drugs Immunity innate or
acquired
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Innate immunity all elements with which we are
born, always present, available on short
notice to protect non-specific Body surfaces
skin, mucous membranes Chemical
factors Fever Phagocytes blood
components Acquired immunity accidental or
intentional exposure to ANTIGENS system
with memory specific
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Host defense mechanisms A. Outer
barriers Skin keratin sweat (NaCl), sebum
(unsat. fatty acids) dead skin cells are
shed Mucous membranes mucus and ciliated
epithelium stomach - acid mucus -
prevent attachment entry intestinal tract,
lungs tears saliva - flushing
lysozyme saliva - aggregation of bacteria
urinary tract - urinary flow
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B. Phagocytosis cells in blood lymph
leukocytes active without exposure enhanced by
immune system
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Leukocytes Granulocytes basophils,
eosinophils, neutrophils Monocytes
Lymphocytes Phagocytes Neutrophils - most
numerous phagocyte chemotactic - drawn
where needed exit capillaries
short-lived Monocytes - large cells
leave bloodstream, enlarge to macrophages
long-lived, can divide Fixed macrophages
microglia (CNS), dust cells (lung) Kuppfer
cells (liver) Wandering macrophages
peritoneal cavity, lungs
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Non-phagocytic killing neutrophils act in
several ways 1. creating superoxide (O2-) and
H2O2 which are converted to hypochlorite
(bleach) 2. generating nitric oxide 3. forming
NETs neutrophil extracellular traps webs
of extracellular fibers formation due to
unique form of cellular suicide
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C. Blood factors Lactoferrin
Transferrin - iron binding proteins
Complement - family of 11 proteins act in
non-specific and specific responses non-specific
C3 C3a - chemotactic for
neutrophils C3b - attaches to bacterial
cell activated by LPS or bacterial glycoprot
eins activated by bacterial polysaccharides
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Inflammatory response tissue damage is one
trigger brings increase in phagocytes
neutrophils, macrophages phagocytes die,
release chemotactic factors Symptoms
erythema (rubror) edema (tumor) pain
(dolor) localized temperature increase
(calor) Triggers histamine bradykinin
prostaglandin
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Inflammatory response - highly integrated, non
specific Erythema histamine increases blood
flow to area via capillary dilation Edema
capillary dilation causes increased
permeability, fluid loss to tissues (histamine
may also contribute) Pain leukocyte death
releases bradykinin and prostaglandin
bradykinin lowers neuron threshold
prostaglandin enhances the effect
Temperature (localized) warm blood to
surface enhances phagocytosis, inhibits
bacteria Gradually fibrin deposition to
wall off area accumulation of dead cells -pus
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Fever - generalized prostaglandin from
leukocytes - LPS stimulates release
hypothalamus control center activated heat
conservation - restrict flow to surface heat
generation - shivering heat dissipation -
increase flow to surface perspiration
enhance phagocytosis inhibit bacteria
Aspirin! Inhibits prostaglandin secretion
results in acid secretion in stomach - ulcers
results in decreased blood clotting,
bleeding results in Reye syndrome (esp.
varicella and flu)
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Reyes Syndrome treatment varies protect
brain against damage from swelling
http//www.reyessyndrome.org
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Acquired immune response The Lymphatic System
Reticuloendothelial System (RES) Overlapping
organ systems Lymphatic lymphocytes
supporting structures RES macrophages related
phagocytes Lymphatic RES Bone marrow
Bone marrow Lymph nodes Lymph
nodes Thymus Thymus Spleen
Spleen Liver
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Bone marrow - stem cells which give rise to all
blood cells B lymphocytes - mature in bone
marrow T lymphocytes - mature in thymus
Macrophages Primary lymphoid organs Thymus
site of T lymphocyte maturation commitment to
respond to specific antigen receptor on cell
surface 5 survive Bone marrow site of B
lymphocyte maturation differentiation re
ceptor on surface
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Secondary lymphoid organs Spleen - trap
concentrate foreign antigens B lymphocytes 50
of spleen cells T lymphocytes 30-40 of spleen
cells Lymph nodes macrophages, B T
lymphocytes
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Immune System Response Antibody-mediated or
Humoral response B lymphocytes
Cell-mediated response T lymphocytes
(subpopulation)
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Antigen carbohydrate protein
nucleic acid? small molecules - if attached
to protein cell surface components (MHC,
ABO, LPS) Epitope reactive portion
face Heterophile antigen many faces
stronger response
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Fate of an antigen 1. Bloodstream to spleen
2. Lodge in epidermal, dermal or subcutaneous
tissue inflammatory response antigen (free
macrophages) to lymph nodes 3.
Gastrointestinal or Respiratory
tract macrophages lymphocytes
interact macrophages transport to other tissues
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Antibody structure 4 polypeptide chains
2 heavy, 2 light constant regions variable
regions Papain cut Fc Fab Antibody
classes - based on heavy chain IgA IgD IgE
IgG IgM
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Immunoglobulin G - IgG 80 of serum
antibodies cross walls of blood vessels,
placenta protect against bacteria, viruses,
toxins enhance phagocytosis
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Immunoglobulin M - IgM 5-10 pentamer first
antibody produced ABO reactive antibody
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Immunoglobulin A - IgA secretory antibody
tears, saliva, breast milk monomer in serum,
dimer in secretion prevent attachment to mucosa
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Immunoglobulin D -IgD surface receptor for B
lymphocytes Immunoglobulin E - IgE exaggerated
response bound to mast cells and basophils
histamine release
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ANTIBODY FORMATION B lymphocytes formed
mature in bone marrow maturation
produce antibody molecule, surface receptor
stimulation antigen binds receptor lymphocy
te activated by immune system
multiplication forms clone of cells, clonal
selection plasma cells - antibody
producers memory cells - wait Time
course primary response - delayed, short-lived
IgM first, then IgG secondary response -
anamnestic response, rapid, strong
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Role of other cells Macrophages - Antigen
Presenting Cell (APC) engulf antigen cut to
epitopes epitopes bond to MHC class II on
surface T cell with appropriate receptor
recognizes MHC epitope (CD4 receptor
on T cell) APC secretes Interleukin 1 (IL-1),
activating T cell T cell secretes other IL
molecules Il-2 IL-4 activate T cell,
causing proliferation release or IL-4
IL-5 B cell proliferates into Plasma and
Memory cells
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Antigen-Antibody Reactions Toxin -
neutralize Soluble antigen - precipitation Cells
- agglutination Activate complement -
complement fixation activate neutrophils initi
ate inflammatory response lyse cell Activate
phagocytosis opsonization
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Cell-mediated immunity T lymphocytes travel
to site to destroy antigen subpopulations
with same receptor, different function T
lymphocyte subpopulations Regulatory effects T
helpers (TH) T suppressors (TS) regulate
B cell, antibody production Inflammatory
effects TDTH release lymphokines induce
migration activation of monocytes and
macrophages Cytotoxic effects T cytotoxic
(TC) or killer T cells deliver lethal hit,
killing target cell
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CELL-MEDIATED IMMUNITY Protective
role immunity to infectious agents, esp. those
with intracellular stage fungi,
viruses tissue graft rejection cancer cell
Harmful role delayed hypersensitivity
reactions allergic contact dermatitis,
infectious allergy (tuberculin) (contact
dermatitis molecule skin protein carrier)
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Hypersensitivity Reactions Type I
anaphylaxis - mediated by IgE rapid response
blood vessel dilation, hypotension, shock
insect venom Type II cytolytic/cytotoxic
reactions - mediated by IgG, IgM bind to cell,
initiate complement cascade lysis Type
III immune complex reactions Ag-Ab complex in
tissues phagocytes attack, releasing
lytic enzymes hours Type IV delayed
hypersensitivity/cell mediated reactions
mediated by T cells which release
lymphokines macrophage accumulation and
activation begins 18-24 hr, peak at 24-48
hr rash of small pox, measles tuberculin
reaction
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Lymphokines macrophage chemotactic
factor macrophage inhibiting factor macrophage
activating factor (phagocytosis) mitogenic
factor interferon interleukins