The Immune System

what are the functions of the immune system?

competition for survival, protection against assimilation, protection against organ damage and aid repair, protection against parasitism, regulation of integrity

what are the benefits of the immune system?

protection from invaders, elimination of altered self (cancer), differentiation between foreign and self

what are the detrimental effects of the immune system?

discomfort (inflammation, allergies) and disease (autoimmunity)

what is immunity?

the body's ability to protect itself from its own defective cells as well as from bacteria, viruses, and other pathogens

what does immunity consist of?

lymphoid tissues, immune cells, chemicals that coordinate and execute responses

what are the 2 lines of defense in the body?

physical and chemical barriers, immune response

what is innate immunity?

• broad specificity, recognizes pathogens-associated molecular patterns (PAMP) and damage-associated molecular patterns (DAMP)
• fast response

what is acute inflammation?

red, warm, swollen, pain, cytokine-mediated

what are characteristics of acquired immunity?

• adaptive immunity
• specific immune response
• slow first response takes days
• memory
• cell-mediated vs humoral (antibody-mediated) immunity

what physical barriers are used in innate immunity?

skin, gut, lung, etc.

what physical barriers are used in adaptive immunity?

none

what soluble factors are there in innate immunity?

many proteins and non-protein secretions

what soluble factors are there in adaptive immunity?

immunoglobulins (antibody), cytokines

what cells are involved in innate immunity?

• phagocytes, NK cells
• eosinophils, innate
• lymphoid cells, mast cells

what cells are involved in adaptive immunity?

• T and B cells
• lymphocytes

what are characteristics of adaptive immunity?

• antigen dependent and specific
• has a lag period
• development of memory

what are characteristics of innate immunity?

• antigen independent
• no time lag
• not antigen specific
• no immunologic memory

what is the body's first line of defense?

epithelium: protective barrier of skin and mucous membranes

what is the purpose of salivary glands and glands in airways?

secrete mucus and immunoglobulins to trap and disable inhaled/ingested pathogens

why is the pH of the stomach so low?

it helps destroy swallowed pathogens

what are the components of the lungs in the immune system?

ciliated pseudo-stratified columnar epithelia

what are the functions of the lungs in the immune system?

elimination of dust, allergens, and microorganisms

what are the components of the GI tract in the immune system?

columnar epithelia

what is the function of the GI tract in the immune system?

acidity

what are the functions of the nasopharynx in the immune system?

flush, lysozyme

what are the components of the nasopharynx in the immune system?

mucus, saliva, tears

what is the lymphatic system?

network of vessels, cells, and organs that carries lymph

what is lymph?

similar to blood, without RBCs

what are characteristics of the lymphatic system?

• doesn't circulate cyclically
• flows from periphery toward heart
• empties into bloodstream

what are the functions of the lymphatic system?

returns extracellular fluid to bloodstream, drains areas of inflammation, surveillance for foreign materials

what is the thymus?

• site of T cell development

• produces T lymphocytes

what are examples of diffuse lymphoid tissue?

tonsil, gut-associated lymphoid tissue (GALT), bronchus-associated lymphoid tissue (BALT), clusters of lymphoid tissues

what is included in encapsulated lymphoid tissues?

lymph nodes and the spleen

what are characteristics of lymph nodes?

• gland-like structure that lies along lymph and blood vessels
• packed with T and B cells, also contain macrophages
• major areas in armpits, groin, and neck

what is the function of lymph nodes?

filter and survey materials from lymph

what is the spleen?

structure similar to lymph nodes, but circulates blood instead of lymph

what is the function of the spleen?

defense against blood borne bacteria

what are the primary lymphoid tissues in the lymphatic system?

thymus and bone marrow

what are the secondary lymphoid tissues in the lymphatic system?

encapsulated and diffuse lymphoid tissues

where are organs and tissues of the lymphatic system positioned?

wherever pathogens most likely enter

how are leukocytes grouped?

by morphology (granulocytes, agranulocytes), phagocytosis (phagocytes), antigen presenting cells (APCs)

what are the functions of splenic macrophages in the spleen?

• clearance of senescent RBCs by red pulp macrophages
• clearance of blood-borne particulate antigens by marginal zone macrophages

what are the functions of intestinal macrophages in the small intestine?

• recognition and removal of enteric pathogens
• tolerance to food antigens and microbiota

what is the function of subcapsular sinusoidal and medullary macrophages?

antigen capture and presentation to B cells

what is the function of langerhans cell?

phagocytosis and antigen presentation

what are the functions of basophils/mast cells?

release chemicals that mediate inflammation and allergic responses

what are the functions of eosinophils?

destroy invaders, particularly antibody-coated parasites

what are the functions of neutrophils?

ingest and destroy invaders, initiate resolution of inflammation

what are the functions of monocytes/macrophages?

ingest and destroy invaders, antigen presentation, immune system control

what are the functions of lymphocytes/plasma cells?

specific responses to invaders, including antibody production

what are the functions of dendritic cells?

recognize pathogens and activate other immune cells by antigen presentation

what is reticular connective tissue?

• found between organs/other tissues within the reticuloendothelial system
• provides scaffold for macrophage movement

what is the reticuloendothelial system?

• aka mononuclear phagocyte system
• heterogeneous population of phagocytic cells (primarily macrophages/monocytes)

what role do macrophages play in the reticuloendothelial system?

• survey for foreign intruders
• put at skin and in respiratory, GI, and UG tracts
• samples filtering organs of lymphatic system

what is a macrophage?

white blood cell responsible for killing microbes

what is the process through the reticuloendothelial system?

→ some pathogens bind directly to phagocyte receptors
→ phagocytosis brings pathogens into immune cells
→ phagosome contains ingested pathogen and lysosome contains enzymes and oxidants
→ lysosomal enzymes digest pathogens, producing antigenic fragments
→ encapsulated bacteria are coated with antibodies: bacteria with capsules must be coated with antibodies before phagocytes can recognize and ingest them
→ antibodies bind to phagocytes receptors, triggering phagocytosis
→ antigen-presenting macrophage displays antigenfragments on surface receptors

what are some nonspecific defense of innate immunity?

phagocytes ingest foreign material, NK cells kill infected and tumor cells, innate lymphoid cells, cytokines

what is the process of phagocytes ingesting foreign material in innate immunity?

→ pattern recognition receptors (toll-like receptors) for PAMPs and DAMPs
→ chemokines and other chemoattractants
→ extravasation
→ pus
→ opsonins

what is extravasation?

allows for leaving of the blood vessel to the tissue

what are opsonins?

antibodies and plasma proteins that tag particles/coat pathogens to be recognized and ingested by phagocytes

what is the process of NK cell killing?

→ NK cells target virus-infected cells and induce apoptosis
→ NK cells attack some tumor cells
→ NK cells and other lymphocytes secrete antiviral cytokines, including interferons
→ interferon-⍺ and interferon-β produced by infected cells
→ prevent viral replication
→ interferon-𝛾 activates macrophages and other immune cells

what are lymphocytes?

the innate counterparts of T cells

what are characteristics of lymphocytes?

• secretes cytokines that respond to pathogenic tissue damage
• affect subsequent adaptive immunity
• lack antigen specific receptors
• tissue resident, not found circulating in blood

what are characteristics of innate lymphoid cells?

• can induce cell death
• 3 subtypes: ILC1, ILC2, ILC_3

what does ILC_1 do?

secretes IFN𝛾, kills target cells

what does ILC_2 do?

secretes IL-5, IL-9, IL-13, amphiregulin

what does ILC_3 do?

produces IL-22 and IL-17

what do cytokines do?

enhance/stimulate the inflammatory response

what are the general functions of innate lymphoid cells?

block infection, tissue repair, promote tolerance

what are the detrimental effects of innate lymphoid cells?

promote disease (e.g. allergy, cancer)

what is chemotaxis?

neutrophils attract to bacterial chemical products like the peptide fMLP

what is inflammation?

• reaction of innate immunity
• sequence of specific physiological behaviors that occur in response to a nonspecific agent

what does inflammation act to?

neutralize/destroy offending agent, restrict tissue damage to smallest possible area, alerts body to threat of tissue injury, prepare injured area for healing

what are cardinal signs of acute inflammation?

heat, redness, swelling, pain, loss of function

what are mediators?

acute-phase proteins produced by the liver that help enable the inflammatory response

what is histamine released by?

mast cells and basophils, inflammatory mediators, vasodilators

what are chemokines?

chemoattracted cytokines

what complements mediators?

cell lysis/chemoattractants

what are characteristics of cytokines and chemokines?

• small, usually glycosylated and secreted peptides
• involved in direct development, maturation, localization, and life span of immune cells
• bind to specific, high-affinity receptors on target cells
• play an essential role in regulating both adaptive and innate immunity

what can be said about the expression of cytokines and their receptors?

tightly regulated, usually stimulate transient responses (autocrine, paracrine, endocrine)

what do cytokines exhibit?

pleiotropism, redundancy, synergy, antagonism

what is bradykinin?

serum protein, inflammatory mediator, vasodilator that promotes pain sensation, stimulates pain receptors,

what are characteristics of complement proteins?

• activated in a cascade reaction
• make up 10% of circulating plasma proteins

what do the 3 activation pathways of complement proteins result in?

opsonization, inflammation, membrane attack complex formation and cell lysis

what are complement effects?

combination of antibody and complement can kill bacteria and is shown to lyse human RBCs

what is the process of complement effects?

→ complement proteins insert themselves into the membrane of a pathogen, creating pores
→ water and ions enter the pathogen cell through the pores of the membrane attack complexes
→ cell swells and lyses

what are acute phase proteins?

liver proteins that act as opsonins and that enhance the inflammatory response

what are chemotaxins?

molecules that attract phagocytes to a site of infection

what are cytokines?

proteins released by one cell that affect growth/activity of another cell

what are pyrogens?

fever-producing substances

what are antibodies?

proteins secreted by B lymphocytes that fight specific invaders (immunoglobulins, 𝛾-globulins)

what are complements?

plasma and cell membrane proteins that act as opsonins, cytolytic agents, and mediators of inflammation

what are C-reactive proteins?

opsonin that activates complement cascade

what are granzymes?

cytotoxic enzymes that intiate apoptosis

what is heparin?

an anticoagulant

what is histamine?

vasodilator and bronchoconstrictor

what are interferons (IFN)?

cytokines that inhibit viral replication and modulate the immune response

what are interleukins (IL)?

• cytokines secreted by leukocytes to act primarily on other leukocytes
• IL-1 mediates inflammatory response and induces fever

what are kinins?

plasma proteins that activate to form bradykinin

what are lysozymes?

an extracellular enzyme that attacks bacteria