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Functions of a healthy functioning immune system
Surveillance, recognition, destruction
Innate, natural defenses
present at birth, provide nonspecific resistance to infection
Adaptive immunities
specific, must be acquired
First line of defense
any barrier that blocks invasion at the portal of entry – nonspecific
Second line of defense
protective cells and fluids; inflammation and phagocytosis – nonspecific
Third line of defense
acquired with exposure to foreign substance; produces protective antibodies and creates memory cells – specific
First line of defense: Physical barriers
Skin
Tears, saliva, urine flush out microbes
Defense of respiratory tract
• Mucous coat impedes attachment and entry of bacteria
• Nasal hair traps larger particles
Lysozyme
an enzyme that hydrolyzes the cell wall of bacteria, in tears
Some hosts are genetically _____ to the diseases of other hosts
immune
antigen
A substance that induces the production of antibodies
Antibodies
Proteins secreted by our immune cells that bind antigens
White blood cells (WBCs) include
Leukocytes and lympocytes
Granulocytes/Agranulocytes
innate capacity to recognize and differentiate any foreign material.
Lymphocytes
adaptive immunity and are used recognize and differentiate any foreign material
Nonself
is foreign material
Self
normal cells of the body
Pathogen recognition receptors (PRRs)
receptors on WBCs (ex: neutrophils)
epithelial cells for PAMPs (ex: toll-like receptors)
T-Lymphocytes and B-Lymphocytes/plasma cells are adaptive/innate immunity
adaptive
Basophils, eosinophils, neutrophil, macrophage, etc are adaptive/innate immunity
innate
Hemopoiesis/Hematopoiesis
production of blood cells
Stem cells
undifferentiated cells, precursor of new cells
Embryonic stem cells are
totipotent ~ can become any cell in the body
Hematopoietic stem cells are
multi-potent ~ can give rise to a limited number of cell types
Granulocytes
contain cytoplasmic granules, have lobed nucleus
Agranulocytes
do not contain granules, have unlobed rounded nucleus
Neutrophils
first immune cell to arrive upon infection, initiate inflammatory cascade upon encountering foreign material
Neutrophils makes up
55-90% of all immune cells
Eosinophils
• destroy eukaryotic pathogens particularly round worm infections
• IgE (antibody) mediated degranulation and allergy response
Eosinophils make up
1-3% of all immune cells
Basophils
release potent chemical mediators and IgE (antibody) in allergy responses
Basophils make up
0.5% of immune cells
Mast cells
• Nonmotile cells bound to connective tissue
• Participates in IgE mediated allergy responses
• Attract phagocytes to the site of infection
Monocytes, Macrophages, & Dendritic cells
kidney-shaped nucleus; highly phagocytic and can present antigens
Largest of WBCs
Monocytes, Macrophages, & Dendritic cells make up
3-7% of the immune cell population
Monocyte
earliest stage, pre-curser cell type to macrophages & dendritic cells
Macrophages
final differentiation of monocytes
Dendritic cells
trap pathogens and participate in immune reactions by “professional antigen presentation”
Sort from least phagocytic/ability to present antigens
monocytes, macrophages, dendritic
Lymphocytes make up
20-35%
Lymphocytes
specific immune response
Innate immunity: Natural Killer T Cells
kill pathogen infected host cells
Adaptive immunity - Humoral immunity: Memory B cells typically provide long/short lasting immunity
long
Adaptive immunity - Humoral immunity: Plasma B cells produce
antibodies
Cytolytic T cells
kill foreign cells
Helper T cells
modulate immune functions
T regulatory cells
down regulate the immune response
Memory T cells
long lived cells that will recognize pathogens later
Erythrocytes
develop from bone marrow stem cells, no nucleus, simple biconcave sacs of hemoglobin.
Platelets
formed elements in circulating blood that are not whole cells
Lymphatic System Purpose
1. Provides an auxiliary route for return of extracellular fluid to the circulatory system
2. Acts as a drain-off system for the inflammatory response
3. Renders immune surveillance, recognition, and protection against foreign material by trafficking immune cells
Lymphatic capillaries permeate all parts of the body except
CNS, bone, placenta, and thymus
Lymphatic Vessels
Functions to return lymph to circulation
Thin walls easily permeated by extracellular fluid which is then moved through contraction of skeletal muscles
Primary lymphatic organs purpose
generates the lymphocytes and early immune cells
Ex: Red bone marrow and thymus gland
Secondary lymphatic organs
site of educating lymphocytes and immune cells
Ex: lymph nodes and spleen
Red bone marrow
Site of blood cell production
Some white blood cells mature here (B cells)
More bones in children have red marrow and it decreases as we age
Thymus gland
Site of T cell maturation
Bilobed gland found in the thoracic cavity superior to the heart
Largest in children and shrinks as we age
Immature T lymphocytes move from the marrow to the thymus where they mature
The primary lymphatic organs are
Red bone marrow and thymus gland
Lymph nodes
Small, oval-shaped structures found along the lymphatic vessels filled with B cells, T cells, macrophages, and dendritic cells
Spleen
filters circulating blood to remove worn out RBCs and pathogens; structurally similar to lymph node
Gut associated lymphoid tissue (GALT)
Specialized lymphoid tissue in the gastrointestinal tract to increase rate of processing intestinal antigens
Examples of secondary lymphatic organs and sites of Antigen presentation
Lymph nodes, spleen, GALT
Second Line of Immune Defense (process)
1. Recognition by innate immune cells
2. Initiate Inflammation
3. Phagocytosis of foreign microbe or infected cells
4. Complement to increase phagocytosis and lyse microbial membranes
5. Interferon to alert a specific immune attack
Pattern Recognition Receptors (PRRs)
Proteins on the cell surface of innate immune cells and epithelial cells
Pathogen associated molecular patterns (PAMPs)
are unique molecules that identify microbes as non-self
• Lipolysaccharides
• Double stranded RNA
• Peptidoglycan
-molecules shared by microorganisms
Cells expressing PRRs then will secrete ______ & _______ chemical signals to alert the immune system
cytokines & chemokines
Cytokines
alert the immune system to distinguish the type of infection
Chemokines
chemical signal that will induce chemotaxis or trafficking of immune cells to the site of infection
Redness
increased circulation and vasodilation in injured tissues in response to chemical mediators
Warmth
heat given off by the increased blood flow, can lead to fever
Swelling
increased fluid escaping into the tissue as blood vessels dilate – edema; WBC’s, microbes, debris, and fluid collect to form pus (abscess); prevents spread of infection
Pain/soreness
stimulation of nerve endings
Diapedesis
migration of cells out of blood vessels into the tissues
Chemotaxis
migration in response to chemokines
Fever is initiated by
pyrogens
Fever (definiton)
Initiated by circulating pyrogens which reset the hypothalamus to increase body temperature; signals muscles to increase heat production and vasoconstriction
Exogenous pyrogens
products of infectious agents
Endogenous pyrogens
liberated by monocytes, neutrophils, and macrophages during phagocytosis
General activities of phagocytes
To survey tissue compartments and discover microbes, particulate matter, and dead or injured cells
To ingest and eliminate these materials
To extract immunogenic information (antigens) from foreign matter to present to other immune cells
Complement
blood proteins that work in concert to destroy bacteria and viruses
Complement (process)
Recruits phagocytes
Opsinize pathogen surfaces causing phagocytosis
Membrane attack complex
Membrane attack complex
makes holes in some bacteria and viruses that causes them to burst
Opsinization
binding of antibodies or complement proteins to the surface of infected cells or directly to the microbes.
Steps of opsinization
increases the rate of phagocytosis → increases antigen presentation → increases clearance of the microbe
Complement Pathways - Classical
activated by the presence of antibody bound to microorganism
Complement Pathways - Lectin pathway
nonspecific reaction of a host serum protein that binds mannose (sugar) on bacterial surface
Complement Pathways - Alternative
begins when complement proteins bind to cell wall and surface components of microorganisms
Binding of antibodies, mannose, or bacterial surface molecules activates…
Complement pathway
Interferon
Small protein produced by certain WBCs and tissue cells
Interferon alpha
lymphocytes and macrophages
Interferon beta
fibroblasts and epithelial cells
Interferon gamma
T cells
Interferons are produced in response to
viruses, RNA, immune products, and various antigens