L9 Flashcards
Innate Immunity
Not antigen specific
Adaptive Immunity:
Antigen specific
The immune response develops with an
“innate” phase early after infection and with an “adaptive” later phase.
Innate immune response is
is ancient.
involves barrier defenses
involves cells that are NOT antigen specific.
- Physical barriers (Epithelial and Mucosal surfaces)
The skin acts as our first line of defense against invading organisms.
Mucosal surfaces (another important first line of defense)
The flushing action of tears and saliva helps prevent infection of the eyes and mouth.
Desquamation of
skin epithelium also helps remove bacteria and other infectious agents that have adhered to the epithelial surfaces.
Movement due to cilia or peristalsis helps to keep
air passages and the gastrointestinal tract free from microorganisms.
The trapping effect of
mucus that lines the respiratory and gastrointestinal tract helps protect the lungs and digestive systems from infection.
- Chemical barriers: Fatty acids in sweat
inhibit the growth of bacteria.
- Chemical barriers: Lysozyme and phospholipase found in
tears, saliva and nasal secretions can breakdown the cell wall of bacteria and destabilize bacterial membranes.
- Chemical barriers: The low pH of sweat and gastric secretions prevent
growth of bacteria.
- Chemical barriers: Defensins (low molecular weight proteins) found in the
lung and gastrointestinal tract have antimicrobial activity
- Chemical barriers: Surfactants in the lung
act enhance antigen clearance
- Biological barriers: The normal flora of the skin and in the gastrointestinal tract can
prevent the colonization of pathogenic bacteria by secreting toxic substances or by competing with pathogenic bacteria for nutrients or attachment to cell surfaces.
Immune Cells: Aliases are
white blood cells and leukocytes
All leukocytes are derived from
hematopoietic stem cells in bone marrow.
Myeloid cells are leukocytes derived from a
myeloid progenitor cell
Dendritic cells granulocytes monocytes
Granulocytes
Basophils
Eosinophils
Neutrophils
Monocytes in circulation differentiate
into
macrophages in tissue
Lymphoid cells are
leukocytes derived from lymphoid progenitor cells.
Natural Killer cells are innate
immune cells.
T cells and B cells are adaptive
immune cells.
Natural Killer Cells: Comprise
5-15% of leukocytes.
Natural killer cells: Primary job is to
kill virally infected and tumor cells. The can also produce cytokines (specifically IFN-γ) for macrophages early in infection. They are lymphocytes, but they are not antigen-specific.
Neutrophils
phagocytic cells
large cells
50-75% of blood leukocytes in humans
often the first cells to respond to “trouble”
neutrophils contain
arsenal of lysozymes and antibiotic proteins
neutrophils nucleus
characteristic multilobed nucleus
neutrophils rapidly respond to
rapidly respond to chemotactic agents
neutrophils produce
produce chemotactic agents for other leukocytes
neutrophils phagocytose invading
microorganisms or particles
Eosinophils:
Minor cell type, comprises 1-5% of total leukocytes in human blood. They are a type of granulocyte, and play a prominent role in response to parasitic infections (also involved in allergic reactions and asthma).
eosinophils They induce their function by
degranulating and releasing:
eosinophil cationic protein
- major basic protein
- eosinophil peroxidase
- reactive oxygen and reactive nitrogen intermediates
Basophils & Mast Cells: basophils comprise
0.2 % of blood leukocytes (very low numbers)
Basophils & Mast Cells: mast cells are very
similar and are found in tissues (not blood)
Basophils & Mast Cells: principal trigger is
IgE mediated surface receptor cross-linking
Basophils & Mast Cells: release multiple
inflammatory mediators
Basophils & Mast Cells: = histamine is
primary mediator
Basophils and mast cells; protective during
INFflammation but pathological role in allergy
An essential part of the inflammatory response is the
recruitment of innate immune cells to sites of infection and inflammation. These cells are part of the first line of defense in the innate immune system:
Natural killer (NK)–
NK cells can nonspecifically kill virus infected and tumor cells. important in nonspecific immunity to viral infections and tumor surveillance. FIRST RESPONDER!!
Eosinophils –
Eosinophils have proteins in granules that are effective in killing certain parasites. Involved in inflammatory and allergic responses ( particularly in the skin and airway)
Neutrophils –
Polymorphonuclear cells (PMNs) are recruited to the site of infection where they phagocytose invading organisms and kill them intracellularly. Can contribute to tissue damage during inflammation. FIRST RESPONDER!!
Macrophages –
main function is phagocytosis and intracellular killing of microorganisms.
capable of killing infected or altered self target cells
contribute to tissue repair/wound healing
act as antigen-presenting cells, which are required for the induction of specific immune responses.
Dendritic Cells –
main function is antigen processing and presentation to T-cells. Critical cell in initiating the adaptive immune response
Monocytes/Macrophages: monocyte —>
macrophage (in tissue) in tissue
Monocytes/Macrophages: 5-10% of
blood leukocytes
Monocytes/Macrophages: ARE
phagocytic cells
Monocytes/Macrophages: have characteristic
large nucleus
Monocytes/Macrophages: very large cell,
10 - 20 µm in diameter
Monocytes/Macrophages: produce
chemotactic agents for other leukocytes
Monocytes/Macrophages: contain arsenal of
lysozymes and antibiotic proteins
Monocytes/macrophages: phagocytose
microorganisms, particles, & tumor cells
Monocytes/macrophages: extremely important for
antigen presentation
extremely important for clearance of dead cells & debris
Dendritic Cells:
Phagocytic cells (less predominant than neutrophils, monocytes, macrophages) are primarily responsible for phagoytosing microbes, and presenting peptide antigens to lymphocytes. Thus, they are generally referred to as antigen presenting cells (or professional antigen presenting cells).
Monocytes/Macrophages and Dendritic Cells have an
additional important function:
Cytokines: Proteins produced by many different
cell types that mediate inflammatory and immune reactions. Cytokines are principal mediators of communication between cells of the immune response.
Chemokines: A large family of structurally
homologous, low molecular weight cytokines that stimulate leukocyte movement and regulate the migration of leukocytes from the blood to the tissues.
The dendritic cell is the principal cell type that links the
innate immune response to the adaptive immune response (macrophages can do this too)
Cytokine Producers Phagocytic Cells (but more specialized toward antigen presentation)
Periphery
Innate
Lymph Node
Adaptive
Lymphocytes derived from
hematopoietic stem cells in the bone marrow, that differentiate into lymphoid progenitor cells.
Lymphoid progenitors give rise to
B lymphocytes that mature in the bone marrow and T lymphocytes that mature in the thymus
Lymphocytes :
20-50% of blood leukocytes
B cells, T cells, NK cells
Lymphocytes; relatively small,
6 - 10 µm in diameter
Lymphocytes: produce
produce chemotactic agents to attract other leukocytes
produce cytokines to activate or inactivate other leukocytes
extremely important for adaptive immunity:
immunologic specificity
immune regulation
immune memory (basis for vaccines)
Adaptive immunity is comprised of both a
humoral arm and a cell-mediated arm.
Why are both arms needed? - adaptive immunity
Use different mechanisms to attack pathogens
humoral primarily effective against extracellular microbes
cell-mediated primarily effective intracellular pathogens
How do we tell immune cells apart?
Cluster of Differentiaton (CD) Markers
CD3+ cells are
T cells
CD3+CD4+ cells are
CD4+ T cells (or Helper T cells)
-CD3+CD8+ cells are
CD8+ T cells (or Cytotoxic T Cells)
An antigen (Ag) is any
substance that can be specifically bound by a cell of the adaptive immune system
Immunogen
- an antigen that ellicits an immune response
Tolerogen-
induces immunological tolerance or immune non-responsiveness
Allergen-
an antigen that causes an immediate hypersensitivity (allergic) reaction
Endogenous Antigen
Antigens generated within the cells of the body as a result of normal metabolism or viral infection
Proteins encoded for by genes of viruses
Abberant proteins encoded for by mutated genes (e.g. cancer cells)
Endogenous antigen - These are antigens presented by
APCs to CD8+ T cells
Exogenous Antigen
Antigen directly entering the body from the environment Inhaled antigen (e.g. cat hairs, pollen) Ingested antigen (e.g. shellfish protein, peanuts) Injected antigen (e.g. splinter, injected vaccine
Exogenous antigen - These are antigens presented by
APCs to CD4+ Tcells
Anatomy of Lymphocyte Activation
Microbe infects host
Microbe is taken up by APC at site of infection
APC enters lymph circulation and into LN
Naïve T and B cells enter LN from circulation
How do immune cells get into lymphoid organs?
no antigen
If no antigen is being presented, T cells leave and re-enter circulation.
How do immune cells get into lymphoid organs?
antigen present
If antigen is present, immune cell is activated prior to exiting and going to site of peripheral infection/inflammation
Controlling Leukocyte Entry into Peripheral Sites:
Physiochemical Variables:
Blood flow (shear force)
Post-capillary venules have less shear force and thin vessel wall
Controlling Leukocyte Entry into Peripheral Sites:
Physiochemical Variables
Electrostatic interactions
Net (-) charge on endothelia and inflammatory cells
Repulsion under physiological conditions
Electrostatic grasping can occur after injury/infection due to changes in charge distribution
Cellular adhesion molecules for
lymphocyte homing
Toll-like receptors are
HIGHLY CONSERVED across species.
TLRs were first described in drosophila and are almost identical in all species including humans.
TLRs are also known as
pattern recognition receptors
They recognize molecules that are broadly shared by pathogens but distinguishable from host molecules, collectively referred to as pathogen-associated molecular patterns (PAMPs)
Consequences of TLR ligation affect both
innate and adaptive immunity
