Chapter 15: Innate and Adaptive Immunity
What is the main difference between the two mechanisms of adaptive immunity?
Humoral immunity acts on extracellular microbes, and cell-mediated immunity acts on intracellular microbes.
Elaborate on the mechanism adaptive immunity: humoral immunity:
Humoral immunity: mediated by antibodies that are produce by B lymphocyte cells; antibodies secreted into circulation and mucosal fluid, where they eliminate *extracellular* microbes and their toxins; stop microbes on mucosal surfaces and in blood from gaining access to and colonizing body tissues
Memory T lymphocyte
Lymphocyte with developed memory of foreign substance so repeat exposure to same microbe created a quicker and more vicious response
What are chemokines?
cytokines that stimulate migration and activation of immune and inflammatory cells. They are implicated in dx's such as RA, MS, Lupus, HIV, IBDs, allergic asthma, chronic bronchitis, and COPD.
How do B cells use antibodies?
They use membrane-bound antibodies to recognize a wide variety of proteins, polysaccharides, lipids, and small chemicals. Antigens maybe expressed on microbial surfaces or may be in soluble forms (toxins)
What are colony-stimulating factors (CSFs)?
cytokines that stimulate bone marrow pluripotent stem and progenitor cells to produce large numbers of platelets, erythrocytes, lymphocytes, neutrophils, monocytes, eosinophils, basophils, and dentritic cells. Recombinant CSF molecules are currently being used to increase success rates of bone marrow transplants. Therapies where stimulation or inhibition of immune response of cell production is desirable.
What are cytokines?
low-weight molecular regulatory proteins that produced by cells of innate and adaptive immune system that mediate many of actions of these cells; ex: interleukins (ILs) are made by leukocytes to act on leukocytes, and interferons (IFNs) interfere with virus multiplication
Describe dendritic cells and their functions.
Long, finger-like processes Most found as immature cells under epithelial tissue and in most organs, where posited to capture foreign agents and transport of lymphoid organs. Once activated, undergo complex maturation process as they migrate to regional lymph nodes Antigen-presenting cells and release signals to adaptive immune system
What lymphocyte is part of the innate immune system and is the first line of defense against viruses?
NK or Natural Killer cells Also have ability to recognized and kill tumor cells, abnormal body cells, and cells infected with intracellular pathogens, such as viruses and intracellular bacteria.
What are some defenses of the epithelial barriers?
Outside: cilia, hair, mucous, skin, sweat - acidic/antimicrobial Inside: heparin released to increase blood flow to injured area (release by basophils and mast cells); sweat glands
Antigens
Substances that elicit adaptive immune responses
What are T cells respond to?
They are responsible for cell-mediated immunity and the antigen receptors on most T cells only recognized peptide fragments of protein antigens. These antigens are bound to specialized peptide display molecules, MHC molecules, on the surface of antigen presenting cells.
What is unique about B cells?
They are the ONLY cells capable of producing antibodies, and therefore, they are the cells that mediate humoral response.
What do cytotoxic T cells do?
They destroy cells infected with intracellular pathogens.
How to B cells respond to antigens and other signals?
They differentiate into plasma cells which produce antibody. Secreted antibodies enter circulation and mucosal fluids, and bind to microbes before they can colonize body tissues.
What/where are the peripheral lymphoid tissues?
1. Lymph nodes: axillae, groin, neck, thorax, abdomen 2. Speen: LUQ of abdomen 3. Located around membranes lining, respiratory, digestive, and GU systems; musoca-associated lymphoid tissues or MALT
What are two types of cell-mediated immunity's t lymphocytes?
1. Cytotoxic T Cell 2. MCH-1: major histocompatibility complex-1 3. TCR: T-cell receptor
Major components of innate immunity
1. Epithelial cells/skin and mucous membranes 2. phagocytic leukocytes: neutrophils and macrophages 3. NK cells 4. Complement system: several plasma proteins
What are the two groups of lymphocytes of adaptive immunity?
1. Humeral immunity: B lymphocytes 2. Cell-mediated immunity: T lymphocytes
What are the three types of granulocytes and what are their functions?
1. Neutrophils: most numerous and impt cells in innate immunity; take up variety of microorgs by phagocytosis and destroy hem using degradative enzymes and other antimicrobial substances store in their cytoplasmic granules. 2. Eosinophils: impt defense against parasites that are too large to be ingested by macrophages and neutrophils 3. Basophils: release histamine and heparin in response to inflammation; involved in allergic reactions; allow neutrophils to get to infxn by increasing blood flow to area Relatively short-lived, a few days, but produced in greater numbers during immune response.
What are the two subset T cells and what do they do?
1. helper T cells: help B lymphocytes produce antibodies and help phagocytic cells destroy ingested pathogens 2. cyctotoxic T cells: kill or lyse intracellular microbes
Seven cells of innate immunity:
1. mast cells: receptors, nonspecific antigen binding; releases heparin to increase blood flow to site 2. dentritic cells: engulf antigens, digest antigens; puts epitope on MHC membrane; exits tissue into blood stream to bring debris to lymph and call adaptive immune system 3. neurtophils: phagocytic, engulfs pathogens 4. basophils: release histamine/heparin, dilated blood vessel, leaky capillaries, incr blood flow 5. eosinophil 6. NK cell: specialized receptor on cell that binds to infected cell or cancer cells, release powerful digestive enzymes to lyse cell; circulate in blood and respond to cytokines released 7. macrophage: largest phagocytic cell, engulfs anything harmful or pahtogenic
What functions do macrophages and dendritic cells have in common?
Both release several communication molecules that direct the nature of adaptive immune responses. Serve as impt intermediaries between two immune systems.
What does IgM do?
Circulates in bodily fluids; has 5 units to pull antigens together in clumps
Lymphocytes are often distinguished by what surface proteins?
Clusters of differentiation or CD proteins: 1. CD4+: follow to see progression of HIV infxn 2. CD8+: activated - cytotoxic T cells, recognize MHC Often recognized by a "cluster" of antibodies
A vaccination provides protection from innate immunity or adaptive immunity and why?
Adaptive b/c immunity develops exposure to the specific antigen. Antibodies produced to attack antigen if exposed again.
How does the adaptive immune system use the innate immune system?
Adaptive immune response amplifies and increases its efficiency by recruitment and activation of additional phagocytes and molecules of the innate immune system, at the effector stage of immunity.
What is the function that adaptive immunity has that innate immunity does *not* have?
Adaptive immune system capable of recognizing numerous microbial and non-infections substances and developing a unique specific immune response for each substance. Whereas, innate immune system can only recognize structures sheared by classes of microorganism.
Where doe the cells of the innate and adaptive immune systems originate from?
Bone marrow stem cells give rise to two main categories of WBCs: myeloid and lymphoid. The MYELOID progenitor is the precursor for most of the phagocytic cells of innate immune system: monocytes/macrophages, granulocytes, and dendritic cells. (NK cells from LYMPHOID lineage.) The LYMPHOID linage consists of lymphocytes of adaptive immune system and the *NK cells of innate immunity*.
What do innate and adaptive immunity have in common?
Both destroy an invading agent by using effector responses of phagocytosis and the compliment system; interactive, cooperative effort
Adaptive Immunity (specific)
later, but more effective immune response; focused recognition of each unique foreign agent
What are examples of when pathogens can penetrate the epithelial barriers
Burns, wounds, and deep lacerations
What can be found on T helper cells, attach to MHC II proteins, and differentiate in the thymus?
CD4 receptors
Describe the changes in immune response in the elderly.
Cell and humoral immune response declines. More susceptible to infection More evidence of autoimmune and immune complex disorders than younger ppl Higher incidence of cancer, 60-70% genetic, but environment is significant Vaccination less successful in immunization in elderly then young adults T and B cell show deficiencies in activation Thymus gland decrease in size therefore decreasing T cell production
Elaborate on the mechanism adaptive immunity: cell-mediated immunity:
Cell-mediated/Adaptive: defends against *intracellular* molecules like viruses with T lymphocyte cells; activate phagocytes to destroy microbes that have not been engulfed or kill any type of host ell that is harboring microbes
What are the more important properties of cytokines?
Cell-to-cell communication, they bind to specific receptors on the membrane surface of their target cells; short-lived, avoids excessive immune response Pleiotropic: ability of cytokine to act on different cells Actions may be local or systemic
What are the different immunoglobulins?
IgG IgA IgM IgD IgE
What do humoral immunity B lymphocytes do?
Differentiate into antibody production plasma cells that interact with and protect against microbes present in blood or on mucosal surfaces
What does IgE do?
Found on mast cells in tissues; starts inflammation; involved in allergy
Where to B and T lymphocytes originate from?
From the lymphoid progenitor in the bone marrow Antigen-specific lymphocytes of adaptive immune system
What is the most important function of dendritic cells?
Function as key antigen-presenting cells that initiate adaptive immunity responses by processing and presenting molecules of foreign antigens to B and T lymphocytes.
How does innate immunity communicate with adaptive immunity?
It communicates to lymphocytes involved in adaptive immunity that characteristics of the pathogen and information about its intracellular and extracellular location. It also stimulates and influences the nature of adaptive immune responses.
What does it mean if IgM antibodies are presents in a newborn's blood?
It means the baby had a congenital infection in the womb. The infection did NOT come from the mother, as IgM CANNOT cross placental barrier.
Innate Imm: Describe relationship between monocytes and macrophages.
Macrophages are part of monocytic phagocyte system, a family of phagocytic cells. They reside in almost ALL tissues, and are the MATURE form of monocytes. Monocytes circulate in the blood and continually migrate into tissue, where they differentiate into macrophages.
What are major histocompatibility complex (MHC) molecules? What is their role in organ transplant?
Membrane bound proteins encodes by a MHC gene locus that display peptides for recognition by T cells Initially they were thought to be antigens that evoked rejection of transplanted organs, but histocompatibility (tissue compatibility) molecules are now known as extremely important for induction and regulation of immune responses. MHC genes are the most polymorphic genes known, and it's almost impossible for two individuals to have identical MHC profiles. MHC alleles affect immune responses and susceptibility to number of diseases. It is important for donors and recipients to match closely, to prevent rejection.
Explain what pattern recognition is.
Microbes typically bear repeating patterns of molecular structure on their surface, and so the immune system recognizes pathogen-associated molecular patterns (PAMPs). The receptors that recognize them are pattern recognizing receptors (PRRs).
What are the central lymphoid tissues and functions?
Provide environment for immune cell production and maturation. 1. Bone marrow: site of B cell maturation 2. Thymus gland: maturation occurs for T-cells, stored in thymus/adipose tissue; after puberty, T cell production decreases, problem as we age if didn't build up immunity as child Thymus is fully formed and functional at birth.
What are the epithelial barriers of the innate immune system?
Provide physical and chemical barriers to external and internal environments; include: epidermis of skin and linings, GI tract, respiratory tract, and urogenital tract
What are the functions of macrophages?
Relatively long-lived cells; perform functions of innate and adaptive immune systems: 1. Phagocytosis: Engulf and kill invading microorganisms: impt first-line defense innate immunity 2. Dispose of pathogens and infected cells targeted for disposal by an adaptive immune response. 3. Antigen-presenting cells of adaptive immune response: process and present molecules of foreign antigens to the lymphocytes of adaptive immunity. 4. Help induce inflammation 5. Secrete signaling proteins that activate other immune cells and recruit them into immune response 6. General scavenger cells that clear dead cells and cell debris in the body
What are Human MHC proteins and their role in organ transplant?
They are called human leukocyte antigens (HLAs). These molecules play a role in transplant rejection and are detected by immunologic tests so they are commonly called antigens. Because class I and II MHC gene are closely linked on one chromosome, the combination of HLA genes is usually inherited as a unit, called a *haplo-type*. Everyone has two, one from each parent. In organ or tissue transplant, the closer the matching of HLA types, the greater the probability of identical antigens and the lower chance of rejection.
What is opsonization?
When soluble molecules coat particles, like microbes, to tag them for recognition by phagocytes. The coating materials are called *opsonins*. Opsonins are important in innate immunity and acute inflammation, and with activation of adaptive humoral immunity, IgG and IgM antibodies can coat microbes and act as opsonins by binding to receoptprs o neurtopils and macrophages. The adaptive immune response thus enhances the phagocytic func of innate cells.
What is a nosocomial infection?
a hospital-acquired infectin (HAI) infxn acquired in hospital or health care facility
Immune response
collective, coordinated response of cells and molecules of the immune system
Functions of innate immunity
can distinguish self from non-self, react against various microbial agents within minutes to hours of infxn, prevents est of infection and deeper tissue penetration from microorganism
What does IgG do?
circulates in body fluids, binding antigens
Innate immunity (non-specific)
first line of defense; early, rapid response of immune system; mechanisms in place before infection occurs
What does IgA do?
found in secretions on mucous membranes; prevents antigens from entering body
What does IgD do?
found on the surface of B cells; acts as an antigen receptor
Why is self-regulation in the immune system important?
prevents overreaction of immune system; involves antigens, antibodies, cytokines, regulatory T cells, and the neuroendocrine system. Tolerance of self-antigens helps prevent autoimmune reactions.
What type of chemical barrier dies skin provide?
skin has chemicals that create salty and acidic environment with antibacterial properties
What is the function of suppressor T cells?
to help regulate immune cells; negative feedback loop to decrease immune system