Immunology- Welcome!

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Immunology- Welcome!

• Where were headed today
• Get a feel for what immunology covers
• A bit of history
• Some coverage of Chapter 1 2

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The Broad Overview

• The question is not why to we get sick and die?
  But how do we manage to survive at all??
• Observations
• We get sick, often recover
• Some illnesses impart immunity
• We sometimes get reactions to things
• Some people get sick more than others

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Immunology addresses these observations

• How we respond to become immune
• Recognize self from non-self
• Why we have allergies- rxns to things
• Why some people are prone to illness
• Practical areas
• Vaccines, immunotherapy against cancer, allergy
  treatments, transplants, etc.

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Characteristics of the Immune System (BRIEF!)

• Some parts are non-specific- indeed some things
  that help do so incidentally.
• Others are specific
• Recognize self from non-self
• React to non-self, thus we tolerate self.
• Theres a MEMORY of the reaction

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A bit of history

• Ancient observations
• Chinese- 1100 AD- use mild forms of smallpox to
  infect infants- variolation
• Lady Mary Montagu- from Turkey to England, 1718
• Edward Jenner- cowpox-smallpox- 1799
• Pasteur- vaccines against anthrax and rabies (why
  you should take vacation)

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More history

• Emil Von Behring, Shisaburo Kitasato Immune
  serum- specific killing of microbes, passive
  immunization against diphtheria, tetanus
  developed
• Jules Bordet complement (Nobel Prize 1919)
• Metchnikoff, 1882- phagocytosis

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More History

• Koch- Major early microbiologist- discovered
  causative agent for TB, TB rxn (Mantoux) test
• Peter Medawar, MacFarlane Burnet, Niels Jerne,
  1950s- clonal selection theory
• Susumu Tonegawa- generation of antibody diversity

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On to the broad overview

• Innate immunity- broad topic
• Adaptive immunity

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Die, you worm!
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Specific and non-specific responses (5e)
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Immunology Chapter 12- the Broad Overview

• Adaptive Immunity- Humoral and cellular
• Characteristics
• The players
• Humoral Response Fig 1-10
• STUDY THIS FIGURE!!!!!!

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Characteristics

• Antigenic specificity 
• Diversity respond to LOTS of different antigens
• two types antibody, or humoral, and cellular
  responses.
•  memory- faster stronger 2nd time 
• self/non-self-no inappropriate responses we
  tolerate ourselves.

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The players

• lymphocytes and antigen presenting cells.
•  Lymphocytes round little cells in blood and
  lymph nodes white blood cells 2 types
•   B lymphocytes Antibody production
• Mature in the bone marrow. Have membrane-bound
  antibody, that reacts with a particular antigen.

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• T lymphocytes arise in the bone marrow, mature
  in the thymus.
• Surface molecules that react with antigen- T-cell
  receptors.
• Need the action of a second molecule/cell type
  that presents Ag MHC proteins on Antigen
  Presenting Cells- APCs

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The Players (contd)

• APC's B cells, macrophages, dendritic cells
  have MHC II on surface to be recognized by Th
  cells.
•  Antigen is internalized and reexpressed-
  recognized along with the MHC II. Also provides
  a costimulatory signal.
• Finally- a virally infected cell also presents Ag
  - MHCI

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Production by clonal selection (1-10)
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Cell Mediated Response

• Activation of Th and Tc cells
• Exogenous and endogenous Ag presentation
• Think VIRUSES
• Th cells help lots of other cells- B cells,
  Macrophages, Tc cells- help is direct and by
  cytokines.

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When Things go wrong

• Allergies
• Autoimmune disease
• Transplantation problems
• Cancer??
• Immunodeficiency- natural and acquired

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Chapter 2 Cells and Organs of the immune system

• Where were going
• Lots of details- see learning objectives!
• Types of cells- functions, and some surface
  proteins
• Phagocytosis details
• Primary and secondary lymphoid organs
• Structure of a lymph node- some terms

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The war metaphor (unapologetic)

• Cells- soldiers
• Primary lymphoid organs training camp
• Secondary lymphoid organs war zone.
• Capture/destroy some antigens
• Present antigen to the proper cells
• Stimulate the proper cells (usually B cells)
• Produce the proper antibody
• The cells Hematopoiesis, toti, multi, uni-potent
  cells

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Differentiation is a matter of cytokine
environment, and stromal cells (later)
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Control is Complicated

• We make 3.7 X 1011 WBCs a DAY!!!!!
• The right types
• Production can change 10-20X upon bleeding or
  infection!!!
• One factor apoptosis
• Neutrophils programmed to live 1-3 days
• B cells- life span determined by stimulation.

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Bcl-2 inhibits apoptosis, so were lowering an
inhibitor counteracted by increased sensitivity
to cytokines, /cause receptors are up.
B cell lymphomas when BCL-2 is overactive!
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Stem Cells- we can find them!
Remove the differentiated cells
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Lymphoid cells

• T, B, null small- naïve large-
  stimulated-lymphoblasts
• Cant tell by looking! We differentiate by the
  surface molecules Table 2-5, but dont bother

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Lymphoid cells- Proteins to learn

• B cells surface antibody- 105/cell
• MHC II- capable of exogenous Ag presentation
• Ligands to Tcells
• Th and Tc
• TCR
• Th CD4
• Tc CD8
• Molecules for cell-cell interactions

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NK Cells

• No B or T-cell receptor
• Naturally kill tumor cells/virally infected
  cells
• Low MHCI levels
• ADCC- antibody-dependent cell-mediated
  cytotoxicity

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Macrophages!

• Phagocytic, long-lived, Ag-presenting, secretory
• AKA
• blood monocytes- precursor
• connective tissue- histiocytes
• liver-Kupffer cells
• brain microglea
• lungs alveolar Mphages
• kidneys mesangial cells

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Activated by LPS, IFN gamma
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Chemotaxis Adherance/opsonization Ingestion,
digestion Exocytosis
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Killing the bacteria 3 ways Oxygen Dependent
Killing Respiratory burst- NADPH oxidase- NADPH
202 ---gt NADP H 202-. This is
superoxide. turns into H202 w/ superoxide
dismutase 202- 2H---gt H2O2 O2 this can then
react with myeloperoxidase to make hypochlorite.
H2O2 Cl- ----H2O H OCl- uses up lots of
oxygen and NADPH the cell sometimes goes
anaerobic, making lactic acid- which helps the
process. Pentose phosphate shunt repenishes
NADPH Nitrogen products mphages respond to LPS,
muramyl di-peptide- the building block of
bacterial membranes- and IFN gamma, which comes
from T cells, and start making NO and other
reactive N products. NO is a byproduct of
arginine metabolism Oxygen independent killing
lysozyme defensins peptides that poke holes in
membranes. various hydrolytic enzymes- break up
proteins, lipids, etc.
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Other Myeloid cells

• Neutrophils- other major phagocyte
• Short lived (1-3 days), no Ag presentation
• Better phagocytes than m-phages
• Chemotactic- leave the blood by extravasation
• Inflammatory upon death
• Eosinophils Also phagocytic, less important,
  granules important for parasite killing
• Basophils- like mast cells degranulate in an
  allergic response.

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Dendritic cells

• Multiple lineages (fig 2-11)
• Langerhans cells skin
• Interstitial organs
• Interdigitating thymus

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Organs of the Immune System

• Primary Bone Marrow and Thymus- the training
  camp- competent B and T cells produced here.
• Secondary Lymph nodes, MALT, Spleen, various
  cells lurking under our skin.

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Positive and selection MHC I or II -
loss of self-reactive cells
The thymus
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Secondary Lymph organs

• Various levels of organization
• Follicles, primary and secondary
• Lymph nodes
• Spleen
• Peyers patches
• Langerhans cells lurking beneath your skin
• Catch, trap, present ag stimulate B cells Th
  cells produce antibody, including memory
  response.

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Primary follicles- unstimuated Dendritic naïve
B cells
Ag activated differentiation, affinity
maturation (memory, improved Ab producing cells)
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Ag meets Dendritic cells in the marginal zone
brought to the PALS T cells are activated, B
cells are activated, The primary follicles become
secondary
Processing RBCs
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MALT

• LOTS of surface area!- 20X 20M- gt 2X the size of
  my house!
• MALT- tonsils, appendix, Peyers patches
• Same pattern- trap, present, stimulate B Tcells,
  produce Ab in primary and secondary response.
• We massively tolerate gut bacteria- ????

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Finally- skin

• Langerhans cells cruise underneath the skin
• When the engulf Ag, the migrate to nearest lymph
  node.
• Intraepidermal lymphocytes
• Primitive- react to very few antigens- may
  protect against common bacterial antigens.

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Wrap-up- see learning objectives!

• Terms- stem cells types, myeloid and lymphoid
  lines, major functions of cells.
• Phagocytosis- process
• Primary and secondary lymph organs.
• Primary- selection in the thymus- and -
• 20 lymph organs- follicles, lymph nodes
• Structure of lymph node, what goes on inside,
  sources of lymphocytes
• Spleen structure, MALT, m-cells, langerhans
  cells, maybe intraepidermal lymphocytes.