Immunology

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Innate immunity and adaptive immunity

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Innate immunity mediates the initial defense against infections.
Adaptive immunity develops more slowly and mediates the later, more effective defense against infections.

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Innate immunity

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Also called natural immunity, innate immunity refers to the fact that this type of host defense is always present in healthy individuals.
First line of defense in innate immunity is epithelial barriers and the natural antibiotics present in epithelia.
If microbes do breath the epithelia and enter the tissues or circulation, they are attacked by phagocytes, specialized lymphocytes called natural killer cells, and several plasma proteins including proteins of the complement system.
Innate immune response enhances the adaptive immune response.

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Adaptive immunity

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Also called specific or acquired immunity, adaptive immunity is the type of host defense that is stimulated by microbes that invade tissues. It "adapts" to the presence of microbial invaders.
Adaptive immune system consists of lymphocytes and their products, such as antibodies.
Whereas innate immunity recognized structures shared by classes of microbes, cell of adpative immunity, primarily lymphocytes, express receptors that specifically recognize antigens produced by microbes.
Adaptive immune responses are triggered only if microbes or antigens breach the epithelial barrier and are delivered to lymphoid organs where they can be recognized by lymphocytes.

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2 types of adaptive immunity

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Humoral immunity
Cell mediated immunity

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Humoral immunity

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Mediated by antibodies produced by B lymphocytes.
Eliminates microbes and microbial toxins that are present outside of host cells, in the blood, and in the lumens of mucosal organs, such as the GI and respiratory tracts.
Antibodies cannot gain access to microbes that live and divide inside infected cells.

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2 signals to activate lymphocyte

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Ag binding to receptor on lymphocyte.
Signal from microbe and innate system.

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T cell

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Ag receptor will bind protein fragments on a MHC molecule on the Ag-presenting cell.
Used in cell-mediated immunity

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T cells are distinguished by:

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surface proteins called cluster of differentiation (CD).

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Types of T cells

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Helper T cell
Tc cell
Natural killer (NK) cells

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Helper T cell

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CD4+ cells
Help B cells produce Ab's and phagocytes to destroy microbes.
Secrete cytokines.

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Tc cells

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CD8+ cells
Kills cells harboring intracellular microbes.

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Natural Killer cells

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Mediate innate immunity.
No clonally distributed receptor as in B and T cells.

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Effector cells

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Lymphocytes and other leukocytes.
Effectors are in the innate and adaptive immune systems.

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Tissues of the immune system

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Generative - Primary or central lymphoid organs. T cells and B cells become mature.
Peripheral - Secondary lymphoid organs where the adaptive immune system responds to microbes. Includes the spleen, lymph nodes, mucosal and cutaneous immune system. Concentrates Ag, APC, and lymph in such a way to optimize the immune response.

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Cells of the innate immune system

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Phagocytes including macrophage, monocytes, and neutrophils

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Macrophage activating cytokine

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INF gamma
NK cells produce this cytokine in response to intracellular microbes.

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Complement system

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Circulating and membrane proteins used in the defense against microbes.
Series of proteolytic enzymes that are cleaved to the active form.
Complement fixation is a cascade event.

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3 pathways of complement system

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Alternative pathway
Classical pathway
Lectin pathway

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Alternative pathway

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Triggered by some complement proteins being activated on microbe surfaces.
Innate immune system.

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Classical pathway

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Triggered by Ab binding to microbe.
Humoral arm of adaptive immune system.

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T cells recognize what type of Ag?

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ONLY peptide fragments and only when displayed on special display molecules.

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Barriers to adaptive immunity

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Very low frequency of naive lymphocytes.
Different microbes need different adaptive immune responses.

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MHC

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Genetic locus responsible for the display molecules of the immune system.

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Where is the immune response initiated?

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Ag is concentrated by the APC in lymphoid tissue where the immune response is initiated.

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APC maturation

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Macrophages and epithelial cells secrete TNF and IL-1 in response to microbes. This helps dendritic cells round up, lose adhesion to epithelial and move to lymphoid tissue.
During the migration to the lymph node, the dendritic cell matures to APC which can activate T cells.

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MHC I

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CD8+ T cells
All nucleated cells
Cytosolic proteins

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MHC II

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CD4+ T cells
Professional APC's, macrophages. B cells
Proteins in intracellular vescicles.

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An MHC molecules displays how many peptides?

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One.
APC's can present many different MHC/peptides however.

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MHC II is synthesized where?

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APC synthesized MHC II in ER.

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Extracellular microbe presentation

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Extracellular microbes are captured by APC including B cells and macrophages and presented by MHC II to CD4+ T cells.

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Cytosolic Ag presentation

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Cytosolic Ag's are displayed by MHC I in nucleated cells.
Associated peptides are recognized by CD8+ T cells that differentiate into Tc cells to kill infected cells.

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B cell recognition

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Uses membrane bound Ab's to recgonize Ag's
DOES NOT REQUIRE PROCESSING.

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Activates NK cells

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IL-12

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Activates macrophages

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IFN-y - this cytokine is produced by NK cells which activates macrophages to kill phagocytosed microbes..

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Effector molecules of humoral immunity

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Secreted Ab's

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Structure of Ab's

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Consists of 2 heavy chains and 2 light chains forming a disulfide-linked complex.
Each chain consists of a V region and a C region.