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N5315 Advanced Pathophysiology Inflammation, Altered Immunity and Infection. Complete Study Guide.

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N5315 Advanced Pathophysiology Inflammation, Altered Immunity and Infection Core Concepts Objectives with Advanced Organizers IMMUNE SYSTEM: FIVE TYPES The first four types are all ADAPTIVE  Cell-Mediated immunity  Humoral immunity  Acquired immunity (you may see it written as Active Acquired immunity)  Passive Acquired immunity {both natural & artificial} = (borrowed immunity)  Natural immunity (innate response/ genetic immunity, not from previous exposure, includes the Inflammation process and NK cells)  NK-cell=Natural killer cells= part of the Innate/Natural immune system, *in lecture and outline* They come from the lymphoid stem cell line, like regular T & B cells and are considered a T-cell type, but don’t differentiate further to become specific for any one antigen. They kill via cell lysis or apoptosis without the need for specific antigen receptors (more info later in notes)  Killer T-cells=Cytotoxic-cells, Tc (Cytotoxic-cells is what Dr. G labeled them on the organizer) These are in lecture and Organizer also. NOTE TO SELF ** NKT-cells=hybrid of the other two (not in lecture or outline) WHO CARES, don’t get confused Natural/Innate immunity (from book table 7-1 page 192) SKIP Not part of Dr. G outline or objectives The first line of Defenses  Occurs constantly (through our natural physical barriers like skin)  Book calls it Broadly specific aka, not specific!  No memory  Uses Epithelia cells (like skin) Peptides involved:  Defensins,  cathelicidins,  colectins,  lactoferrin,  bacterial toxins Protective factors include:  Cytokines, lysosomes  Low stomach PH  Low Urine Ph  Ciliary activity  Skin, mucous membranes Second line: Inflammation:* Immediate*  Broadly specific “Aka is Broadly activated by most anything, Damage to cell or any foreign antigen”  No memory Cell type used:  Granulocytes = (neutrophils/basophils/eosinophils, mast-cells) (all contain granules inside)  Monocytes/Macrophages (changes to Macrophages in tissue)  NK cells =Natural killers (also function as antigen presenting cells) stimulating=the T-B cell action  Platelets  Endothelial cells Peptides involved  Complement  Clotting factors  kinins Protective factors include:  Vascular response, vasodilation  Cellular components (the cell types listed above)  Secretory molecules or Cytokines (can be either pro-inflammatory, or anti-inflammatory)  Activation of plasma protein systems ADAPTIVE (AQUIRED) Immunity *passive &*active ( Humoral and cell mediated) Everything else Third Line defenses  Is initiated by the cells of the innate immune system NK=natural killers  Delay between primary exposure to antigen and maximum response  Immediate reaction on second exposure to antigen  Very SPECIFIC  Memory of antigens from T and B (lymphocytes memory cells) Cells type used:  T Lymphocytes from Cell mediated Immune system  B lymphocytes from Humoral Immune system  Macrophages/ Monocytes  Dendritic cells Peptides involved  Antibodies  Complement Protective factors  Activated T and B lymphocytes  Cytokines AND Antibodies DIFFERENCE BETWEEN CELL MEDIATED & HUMORAL T-CELLS or T-LYMPHOCYTES: come from Lymphoid Stem cells in the bone marrow. They migrate and further mature in the THYMUS. They are considered immunocompetent but are still not fully mature cells. They migrate to Spleen or Lymph nodes (or other secondary lymphoid organs) where they remain dormant until activated to undergo the 2nd phase of maturation. 2 nd phase of maturation= Clonal Selection occurs after they are stimulated by an Antigen Presenting Cell to further differentiate into a T-Cell with specific receptors for a specific antigen. (antigen presenting cell can be almost any cell that can process a given antigens inside the cell and then display a “marker” or /antigen-specific receptor on its surface that attracts the attention of the T-cells or other immune cells. Cell-Mediated immunity is that Immunity conferred by a variety of T-Cells with various functions. Immunity is active against cells infected with intracellular Bacteria or Viruses. It defends against:  fungal  parasitic infections  tumors  responsible for organ transplantation rejection. T-Cells or T-Lymphocytes, come in different varieties and are classified by “cluster of differentiation” CD for short. We need to know 4 types for the test. Some are commonly known by several names.  T-HELPER CELLS (CD4 /T4cells) (HELPERS) *Important * many functions This group of T cells helps the antigen-driven maturation of both B & T cells. They perform this task by facilitating & magnifying the interaction between APCs (antigen presenting cells) & the immune-competent lymphocytes. ACTIVATES o macrophages o B-cells, (activate B-cells with chemical messengers CYTOKINES to mature into plasma cells that can produce antibodies) o Cytotoxic T-cells o other T-helper/CD4 cells. RELEASES o lymphokines that begin the inflammatory process. o Subgroups of the T-helper cells/CD4 cells like, TH1 and TH2, release the lymphokines. *in lecture notes* MEDIATES o Mediates delayed hypersensitivity reactions such as the TB skin test. *from lecture notes*  CYTOTOXIC-T CELLS- (Cytotoxic cells/ CD8/T8cells/ T-killers/Tc) KILLS: Releasing cytotoxic chemicals that destroy the cell membrane Or inducing apoptosis o virus infected cells o tumor cells o allograft cells (transplant tissue) (from his lecture)  *Memory T-cells*: not on his outline organizer but in his lecture( page2) allow the host to remember antigens and respond quicker and more vigorously after the initial exposure. They live for many years and* can reproduce themselves  T-regulatory cells: slow or stop the immune response after invader is destroyed EXAMPLE OF HOW CELL MEDIATED IMMUNITY WORKS. Antigen enters host cell→ Macrophage  → antigen expressed on MCH (major histocompatibility complex) class II  → secretes Interleukin 1 to attract T- helper cells/CD4  → presents it to T-helper cell/CD4 cell  → T-helper/CD4 differentiates into Th1 & Th2 (these are sub groups of T-helper cells)  → Th1 (subgroup T-helper cells/CD4 cell) releases Interleukin 2 (IL 2)  → IL 2 activates CYTOTOXIC T-cells: (Tc), CD8, killer T’s, T8 Cells, all the same thing)  → Tc (Cytotoxic T-cells, CD8) connects with MHC class I receptor on invader  → Cytotoxic chemicals released → invader killed.  Th2 (subgroup of T-helper-cell /CD4-cell) releases Interleukin 4 (L4) → activates the Humoral immune system: AKA call the B-CELLS IN to do their job *Same Idea presented differently* T cell activation: begins with the binding of antigen to specific T cell receptors. The naïve T cell proliferates and differentiates into a functional (effector) T cell, whose functions include: (1) direct killing of foreign and/or abnormal cells, (2) assistance and/or activation of other cells, such as macrophages. The first function is carried out by a subclass of T cells, termed T cytotoxic lymphocytes. Activation of macrophages is performed by a special subset of Th cells. Additional T cells develop into T-regulator cells that regulate the immune response in order to avoid inadvertently attacking self-antigens or to avoid over activation of the immune response

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N5315 Advanced Pathophysiology
Inflammation, Altered Immunity and Infection
Core Concepts Objectives with Advanced Organizers
IMMUNE SYSTEM: FIVE TYPES



The first four types are all ADAPTIVE

 Cell-Mediated immunity

 Humoral immunity

 Acquired immunity (you may see it written as Active Acquired immunity)

 Passive Acquired immunity {both natural & artificial} = (borrowed immunity)

 Natural immunity (innate response/ genetic immunity, not from previous exposure,
includes the Inflammation process and NK cells)




 NK-cell=Natural killer cells= part of the Innate/Natural immune system, *in lecture and outline*
They come from the lymphoid stem cell line, like regular T & B cells and are considered a T-cell type, but
don’t differentiate further to become specific for any one antigen. They kill via cell lysis or apoptosis
without the need for specific antigen receptors (more info later in notes)

 Killer T-cells=Cytotoxic-cells, Tc (Cytotoxic-cells is what Dr. G labeled them on the organizer) These are
in lecture and Organizer also.


NOTE TO SELF ** NKT-cells=hybrid of the other two (not in lecture or outline) WHO CARES, don’t get confused

,Natural/Innate immunity (from book table 7-1 page 192) SKIP Not part of Dr. G outline or objectives

The first line of Defenses
 Occurs constantly (through our natural physical barriers like skin)
 Book calls it Broadly specific aka, not specific!
 No memory
 Uses Epithelia cells (like skin)
Peptides involved:
 Defensins,
 cathelicidins,
 colectins,
 lactoferrin,
 bacterial toxins

Protective factors include:
 Cytokines, lysosomes
 Low stomach PH
 Low Urine Ph
 Ciliary activity
 Skin, mucous membranes

Second line: Inflammation:* Immediate*
 Broadly specific “Aka is Broadly activated by most anything, Damage to cell or any foreign antigen”
 No memory
Cell type used:
 Granulocytes = (neutrophils/basophils/eosinophils, mast-cells) (all contain granules inside)
 Monocytes/Macrophages (changes to Macrophages in tissue)
 NK cells =Natural killers (also function as antigen presenting cells) stimulating=the T-B cell action
 Platelets
 Endothelial cells
Peptides involved
 Complement
 Clotting factors
 kinins
Protective factors include:
 Vascular response, vasodilation
 Cellular components (the cell types listed above)
 Secretory molecules or Cytokines (can be either pro-inflammatory, or anti-inflammatory)
 Activation of plasma protein systems


ADAPTIVE (AQUIRED) Immunity *passive &*active (Humoral and cell mediated) Everything else
Third Line defenses
 Is initiated by the cells of the innate immune system NK=natural killers
 Delay between primary exposure to antigen and maximum response
 Immediate reaction on second exposure to antigen
 Very SPECIFIC
 Memory of antigens from T and B (lymphocytes memory cells)
Cells type used:
 T Lymphocytes from Cell mediated Immune system
 B lymphocytes from Humoral Immune system
 Macrophages/ Monocytes
 Dendritic cells
Peptides involved
 Antibodies
 Complement
Protective factors
 Activated T and B lymphocytes
 Cytokines AND Antibodies

,DIFFERENCE BETWEEN CELL MEDIATED & HUMORAL

T-CELLS or T-LYMPHOCYTES: come from Lymphoid Stem cells in the bone marrow. They migrate and further
mature in the THYMUS. They are considered immunocompetent but are still not fully mature cells. They migrate to
Spleen or Lymph nodes (or other secondary lymphoid organs) where they remain dormant until activated to undergo
the 2nd phase of maturation.
2nd phase of maturation= Clonal Selection occurs after they are stimulated by an Antigen Presenting Cell to further
differentiate into a T-Cell with specific receptors for a specific antigen. (antigen presenting cell can be almost any
cell that can process a given antigens inside the cell and then display a “marker” or /antigen-specific receptor on
its surface that attracts the attention of the T-cells or other immune cells.

Cell-Mediated immunity is that Immunity conferred by a variety of T-Cells with various functions. Immunity is
active against cells infected with intracellular Bacteria or Viruses.
It defends against:
 fungal
 parasitic infections
 tumors
 responsible for organ transplantation rejection.

T-Cells or T-Lymphocytes, come in different varieties and are classified by “cluster of differentiation” CD for short.
We need to know 4 types for the test. Some are commonly known by several names.

 T-HELPER CELLS (CD4 /T4cells) (HELPERS) *Important * many functions
This group of T cells helps the antigen-driven maturation of both B & T cells. They perform this task by
facilitating & magnifying the interaction between
APCs (antigen presenting cells) & the immune-competent lymphocytes.

ACTIVATES
o macrophages
o B-cells, (activate B-cells with chemical messengers CYTOKINES to mature into plasma cells that can produce antibodies)
o Cytotoxic T-cells
o other T-helper/CD4 cells.

RELEASES
o lymphokines that begin the inflammatory process.
o Subgroups of the T-helper cells/CD4 cells like, TH1 and TH2, release the lymphokines. *in lecture notes*

MEDIATES
o Mediates delayed hypersensitivity reactions such as the TB skin test. *from lecture notes*


 CYTOTOXIC-T CELLS- (Cytotoxic cells/ CD8/T8cells/ T-killers/Tc)
KILLS: Releasing cytotoxic chemicals that destroy the cell membrane
Or inducing apoptosis

o virus infected cells
o tumor cells
o allograft cells (transplant tissue) (from his lecture)

 *Memory T-cells*: not on his outline organizer but in his lecture( page2)
allow the host to remember antigens and respond quicker and more vigorously after the initial exposure.
They live for many years and* can reproduce themselves

 T-regulatory cells: slow or stop the immune response after invader is destroyed

, EXAMPLE OF HOW CELL MEDIATED IMMUNITY WORKS.
Antigen enters host cell→ Macrophage
 → antigen expressed on MCH (major histocompatibility complex) class II
 → secretes Interleukin 1 to attract T- helper cells/CD4
 → presents it to T-helper cell/CD4 cell
 → T-helper/CD4 differentiates into Th1 & Th2 (these are sub groups of T-helper cells)
 → Th1 (subgroup T-helper cells/CD4 cell) releases Interleukin 2 (IL 2)
 → IL 2 activates CYTOTOXIC T-cells: (Tc), CD8, killer T’s, T8 Cells, all the same thing)
 → Tc (Cytotoxic T-cells, CD8) connects with MHC class I receptor on invader
 → Cytotoxic chemicals released → invader killed.
 Th2 (subgroup of T-helper-cell /CD4-cell) releases Interleukin 4 (L4) → activates the
Humoral immune system: AKA call the B-CELLS IN to do their job

*Same Idea presented differently*
T cell activation: begins with the binding of antigen to specific T cell receptors. The naïve T cell proliferates and
differentiates into a functional (effector) T cell, whose functions include: (1) direct killing of foreign and/or
abnormal cells, (2) assistance and/or activation of other cells, such as macrophages. The first function is carried out
by a subclass of T cells, termed T cytotoxic lymphocytes. Activation of macrophages is performed by a special subset
of Th cells. Additional T cells develop into T-regulator cells that regulate the immune response in order to avoid
inadvertently attacking self-antigens or to avoid over activation of the immune response




EXAMPLE OF: ACTIVATION OF HUMORAL IMMUNITY / B-CELL immunity /
G.E.M.A.D antibodies creation

 B-cells stimulated by release of IL4
 B-cells differentiate into plasma cells that produce Antibodies and memory B-cells.
 Plasma cells produce antibodies ( IgG.IgE.IgM.IgA.IgD) that will bind to the antigen and
form: antigen-antibody complexes
 Memory B-cells will act during secondary immune response and will remember the
antigen and respond quicker in initiating the immunoglobulin (Ig- G.E.M.A.D) creating
process.
 Present antigen antibody complex to the cell mediated immune system


*Same Idea presented differently*
B cell activation occurs when an immune-competent B cell encounters an antigen for the first time, only those cells
with specific BCRs complimentary to that antigens determinant sites are stimulated to proliferate & differentiate
(clonal selection), resulting in multiple copies of that particular B-cell. The differentiated B-cell becomes a plasma
cell & can be found in the blood, secondary lymphoid organs (sleep & lymph nodes), & some inflammatory sites.
Each plasma cell is a factory for antibody production & is dedicated to the secretion of a single class or subclass of
antibody with one variable region & therefore specificity against one antigenic determinant.

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