Innate Immune System

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Innate Immune System

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Physical barrier-integrity of the mucosa and skin
Cells-Neutrophil, macrophage, dendritic cell
Soluble Factors-Receptors, Lysozyme, NOD, TLR

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Innate Immune System

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Is the first line of defense and takes care of 99.9% of all pathogens, bacteria or viruses

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Skin

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The most difficult barrier to penetrate is composed of two layers the Dermis and the Epidermis

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Dermis

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contains tightly woven fibrous connective tissues

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Epidermis

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Composed of many layers of epithelial cells.
Outermost sheets of cells embedded with keratin makes skin water-repellent

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Antimicrobial substances of the innate immune system-these are the soluable factors

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Lysozyme
Peroxidase
Lactoferrin
Defensins

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Lysozyme

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Enzymes that degrade peptidoglycan and is found in tears, saliva, blood and phagocytes

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Peroxidase

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Found in saliva, body tissues and phagocytes.
Breaks down hydrogen peroxide to produce reactive oxygen

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Lactoferrin

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Sequesters iron from microorganisms. Iron essential for microbial growth. Found in saliva, some phagocytes, blood and tissue fluids.

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Defensins

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Short proteins that attach and kill.
Antimicrobial peptides inserted into microbial membrane.
Found on mucous membranes and in phagocytes.

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Normal Flora

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Not technically part of immune system however, provides significant protection. Protects thru competitive exclusion by covering binding sites and competes for nutrients.

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Blood Cells

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are made in the bone marrow.

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Blood Cells

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RBC's - aka erythrocytes, carry oxygen in blood
Platelets - fragments of megakaryocytes, important component in blood clotting
WBC's - aka Leukocytes, important in host defense, and divided into four categories.

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WBC's

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Divided into 4 categories:
Granulocytes
Dendritic Cells
Mononuclear phogocytes
Lymphocytes

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Blood Cell formation

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Hematopoiesis

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Blood Cells

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including immune cells originate from hematopoietic stem cells in bone marrow

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Blood Cells stimulated to differentiate by colony-stimulating factor

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Red Blood Cells
Platelets
Granulocytes - Eosinophil, basophil and neutrophil
Monocytes - macrophage and dendritic cell

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Granulocytes

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Eosinophil
Basophil
Neutrophil

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Monocytes

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Macrophage
Dendritic Cell

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Macrophage

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mononuclear phagocytes
A close second in defense system

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Granulocytes

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Contain cytoplasmic granuals.
and are divided into three types Neutrophils
Basophils and
Eosinophils

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Neutrophils

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Most abundant and important in innate response system
sometimes called PMN's for Polymorphonuclear neutrophilic leukocytes.

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Basophils

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are involved in the allergic reaction

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Eosinophils

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Important in expelling parasitic worms. and Active in allergic reactions

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Mononuclear phagocytes

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Last one week
are a collection of phagocytic cells called the mononuclear phagocyte system.
Include monocytes in the blood that differentiate to macrophages in most tissues

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Macrophages

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Abundant in the liver, spleen, lymph nodes, lungs and peritoneal cavity

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Dendritic Cells

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Branched cells involved in adaptive immunity
Function as scout in tissues
Engulf material in tissue and bring it to cells of adaptive immunity

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CD4 Cells

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Hang out in areas of danger under the mucosal surfaces, captures and presents to immune response system

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Dendritic Cells

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will capture a piece of the bacteria and break it down into chunks of 6-9 amino acids (epitopes), going into the lymph node and hold it in the HLAII receptor showing it to the lymphocyte that recognizes the antigen with TCR T receptor for that specific antigen. The CD4 then recognizes both the Dendritic cell and the T Lymphocyte releasing a second signal of IL-I called interleukyne 1. With both signals the T-lymphocyte will start replicating making clonal replication CD4T Lymphocytes.

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CD4 T Cells

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are to make antibodies by finding a B Lymphocyte.
The CD4 T Cell will hold the antigen and the B Cell will capture the antigen = 1st signal.
CD4 cells then recognize both cells and release the IL-2 which is the second signal for the B cell to activate, divide and multiply.
Out of these cells few will become plasma cells that make antibodies and the others cells become memory cells so that the process is cut in half next time this particular pathogen is encountered.

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Secondary Immune Response

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Takes half the time of the normal process due to memory cells that keep a memory of the same pathogen.

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Lymphocytes

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are involved in the adaptive immunity system.

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Two major groups of Lymphocytes

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B Lymphocytes aka B cells
T lymphocytes aka T cells

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another type of lymphocyte

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natural killer cells and lacks the B and T cell specificity

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Cell Communication

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In order for immune system to respond cells respond with receptors as the eyes and ears and
Cytokines are the voice
Adhesion molecules are the hands

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Surface Receptors

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Membrane proteins to which signal molecules bond
Binding molecules are called Ligands

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When the Ligand Binds

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receptor becomes modified and sends signal to cell

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Cytokines

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bind to surface receptors and regulate cell function and have numerous classes

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Cytokines

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Chemokines
Colony stimulating factor
Interferons
interleukins
Tumor necrosis factor

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Chemokines

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important in chemotaxis
Enhance ability of cells to migrate to appropriate site in body

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Colony Stimulating Factor

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important in multiplication and differentiation of leukocytes
During immune response, directs immature leukocytes to correct maturation pathway.

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Interferons

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Important in control of viral infections
also associated with inflammatory response

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Interleukins

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produced by leukocytes important in innate and adaptive immunity

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Tumor necrosis factor

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kill tumor cells instrumental in initiation of inflammation process.

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Adhesion molecules

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allow cells to adhere to each other
Responsible for the recruitment of phagocytes to area of injury.
Epithelial cells lining blood vessels produce adhesion molecules that catch phagocytes as the pass by

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Sensor System

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Toll-like receptors TLR and NOD proteins
allow cells to see molecules signifying presence of microbes outside the cell. NOD proteins allow to see inside cell.

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Complement System

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Series of proteins circulating in blood and fluids.
Alternative pathway
Lectin pathway
Classical pathway

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Alternate pathway

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is an early warning that an invader is present. The Alternate pathway relies on C3b binding to cell surfaces allowing other complement proteins to subsequently attach and form a complement activating complex. The drop of pH triggers the alternative pathway.

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Lectin pathway

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activation requires mannan-binding proteins. MBL's are pattern-recognizing molecules the body uses to detect mannan, a ploymer of mannose often found on microbial cells.

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Classical pathway

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activation requires antibodies, a compnent of adaptive immunity. When antibodies bind to antigen they can then interact with the same complement component involved in activating the lectin pathway which leads to activation of other proteins.

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Complement system

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C1 thru C9 proteins.
activation of the complement system leads to major protective outcomes such as:
Inflammation
Opsonization and
Lysis of foreign cells

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Inflammation

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Complement components of C3a and C5a induce changes in endothelial cells effecting vascular permeability associated with inflammation

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Opsonization

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C3b binds foreign material allowing phagocytes to easily grab particles