Innate and Adaptive Immunity

Immunity

• The ability of the body to defend itself against "unfamiliar" microorganisms
• Immune cells use antigens to identify cells as either "self" or "non-self."
• Immunity consists of innate and adaptive defenses

Innate Defenses

• A nonspecific defense mechanism initiated quickly in the body
• Exposure to pathogens does not have to occur for an innate response
• Physical barriers and cells initially encounter pathogens
• The main role is preventing infection
• Includes surface barriers and internal cells and chemicals

Surface Barriers

• Physically prevent pathogens from entering the body, for example the skin
• Keratin resists weak acids, bases, and bacterial enzymes
• The acid mantle, made of sweat and sebum, is slightly acidic and inhibits bacterial growth
• Mucous membranes line body cavities open to the exterior, like digestive, respiratory, and reproductive tracts
• Mucus traps dirt, debris, and microorganisms but cannot protect from deeper penetrating infection
• Nasal hairs trap microorganisms, preventing lower infection
• Cilia propels trapped microorganisms away from the nasal cavity and respiratory tract
• The stomach secretes very acidic gastric juices, with a pH of 1.5-3
• Acidity in the vagina prevents bacteria and fungal growth in the reproductive tract
• Tears/saliva cleanse the eyes and mouth
• Tears/saliva contain lysozyme, which destroys bacteria
• Acidic urine physically removes bacteria during urination

Internal Cells and Chemicals

• Used when surface barriers are breached
• Surface barriers like skin and mucous membranes can suffer physical damage causing entry points
• Pattern recognition receptors are proteins on cells of the innate immune system
• They recognize potentially harmful surfaces through molecules on pathogens, and not on normal human cells

Natural Killer (NK) Cells

• Targets cancerous and virus-infected cells
• Nonspecific: one NK cell can kill almost any virus if it comes into contact
• NK cells don't phagocytize
• Directly contact target cells and induce apoptosis
• NK cells release perforin, creating pores in the target cell membrane
• Apoptosis, or programmed cell death is different from lysis, which could spread infection

Phagocytes

• Neutrophils target bacterial cells and macrophages to engulf and destroy pathogenic cells/substances
• Neutrophils become phagocytic when encountering a pathogen, using defensins to cause lysis
• Macrophages are large and voracious
• Free macrophages travel to seek pathogens
• Fixed macrophages stay put inside tissue of a particular organ

Limits to Phagocytosis

• Pathogens are resistant to phagocytic lysosomes
• Additional enzymes released in a respiratory burst causes the release of large amounts of free radicals and oxidizing chemicals
• Capsules around some bacteria prevent phagocytes from "recognizing" them
• Opsonins used as a solution
• It's a substance that binds to the pathogen surface so phagocytes recognize and bind easily, like antibodies/complement
• Pathogens may simply be too large
• Release of toxic chemicals kill surrounding cells and damage healthy cells
• Benefits of destroying infectious agents outweigh destroying healthy cells because they can be replaced

Tissue Response to Injury

• Inflammation is a nonspecific localized response involving cells and chemicals
• Signs and symptoms include redness, heat, swelling, pain, and impaired function
• Benefits of this response prevent spread of pathogens, dispose of cell debris/pathogens, alerts immune system and allows tissue repair
• Inflammation begins when inflammatory chemicals are liberated at an injury site, for example:
• Histamine released by basophils causes vasodilation and increases permeability of local capillaries
• Kinins derived from plasma protein kininogen cause vasodilation, attracts leukocytes, and induces pain
• Prostaglandins generated by neutrophils, basophils, mast cells, promotes vasodilation, neutrophil chemotaxis, and induce pain
• Phagocytes flood to defend after inflammation begins
• Neutrophils and macrophages undergo a 4-step mobilization process before defending:
• Leukocytosis occurs as white blood cell count significantly increases
• Injured/damaged cells release leukocytosis-inducing factors
• Margination happens as they cling to the inside of capillary walls in the injured area
• Diapedesis sees it squeeze between cells of the endothelial wall instead of entering blood first
• Chemotaxis uses inflammatory chemicals as chemotactic agents, and WBC use positive response to locate injury site
• Positive chemotaxis moves cells toward a higher concentration of a chemical substance

White Blood Cell Mobilization

• Neutrophils are mobilized and arrive at the injury site first
• Monocytes take longer but transform into macrophages replace dead/worn-out neutrophils
• Macrophages dispose of cellular debris like pathogens/dead body cells

Antimicrobial Proteins

• Innate chemicals attack microorganisms/ interfere with their reproduction
• Interferons produced by infected cells protect surrounding noninfected cells
• Diffuse into healthy cells -> synthesizes proteins that degrade viral RNA so viruses cannot replicate
• Complement of ~20 plasma proteins synthesized by the liver is inactive until needed
• Has important roles in inflammatory reactions
• Activation leads to a massive release of inflammatory chemicals
• They complement innate defenses, stimulate phagocytes to clear debris/damaged cells, and can lyse or kill bacteria/cells

Innate Defense: Fever

• A body-wide systemic response to pathogens
• Abnormally high body temperature
• Leukocytes and macrophages release pyrogens causing reset of the hypothalamus
• Normal body temperature is 98.6 degrees
• Low-grade fever is 99-100.4 degrees for 24+ hours
• Fever over 103 degrees is concerning, especially in children
• Causes the liver and spleen to store more Fe+, withholding it from bacteria since it is needed for growth, and increases the metabolic rate of tissue cells speeding up repair

Adaptive Defenses

• A defense system more specific than innate, yet slower to respond
• Cells must be exposed to an antigen before reacting
• There are two features:

Humoral Immunity

• Antibodies present in body fluids circulate freely, mark, and temporarily inactivate target cells
• B lymphocytes are the primary defensive cells here

Cellular Immunity

• Lymphocytes directly attack/defend by killing target cells
• Release chemicals which increase inflammatory response and activate macrophages
• Includes T lymphocytes

Differences from Innate Defenses

• Adaptive defense uses lymphocytes, identifying specific pathogens
• Adaptive defense is systemic, using "memory" to quickly recognize/destroy pathogens before infection

Adaptive Defenses: Antigens

• Any substance that mobilizes the adaptive defense system
• The immune system recognizes “self” versus "non-self” by binding/recognizing antigens
• Can be complete or incomplete

Complete Antigens

• Immunogenic: stimulates lymphocyte proliferation and immune response
• Can react with activated lymphocytes and antibodies
• Foreign molecules may act as antigens -- proteins, polysaccharides, lipids, and nucleic acids

Haptens

• Incomplete and generates immune when attached to a protein carrier
• If bound, the immune system may recognize it as "non-self” and trigger allergies

Antigenic Determinants

• Lymphocytes/antibodies bind to antigenic determinants on the antigen surface, even though antigens have many determinants
• Lymphocytes and antibodies recognize only one antigenic determinant.

Self-Antigens (MHC Proteins)

• Body cells are self-antigens
• Present on an individual basis
• MHC proteins are glycoproteins on cell surfaces
• Genes determine the combination of this complex, making identical sets between individuals unlikely
• MHC proteins hold an antigen
• MHC protein + self-antigen = no immune response

Adaptive Defense: Cells

• Includes B and T lymphocytes

Lymphocyte Maturation

• All lymphocytes must mature to launch an immune response through specific steps:
• Originate from hematopoietic stem cells in red bone marrow
• "Educated" on immunocompetence, where lymphocytes recognize a single antigen, and self-tolerance
• B and T cells colonize lymphoid organs and are seeded to circulate
• Exposure to antigen leads to clonal selection
• Proliferation is when an activated lymphocyte replicates to form the same type

Effector and Memory Cells

• Effector cells are the lymphocytes which actively respond a stimulus to fight off an infection
• Memory cells are long-lived and "remember" a previous infection, launching a strong immune response if it is encountered again

Antigen-Presenting Cells (APCs)

• Act as a bridge between immune systems
• Includes dendritic cells that transport antigen, macrophages activated by T cells, and B lymphocytes presenting antigens to helper T cells

B Lymphocytes and Humoral Immunity

• Plasma releases antibodies for specific antigens
• Has four steps:
• A primary response that activates a cell by binding an antigen
• Clonal selection for cells that recognize an antigen
• Differentiating the cells into plasma for secreting, and memory cells

Secondary Immune Response

• Triggered if there is another exposure to the same antigen
• Immune system acts faster, secondary responses are more effective and prolonged
• Antibody concentration is much higher
• Memory B cells are long lasting

Active/Passive Humoral Immunity

• Active humoral immunity happens when B cells encounter a stimuli and produce antibodies to act against said stimuli in response
• In natural acquisition this is from infection
• In artificial is through the use of vaccines
• Passive humoral immunity supplies bodies with antibodies, and B cells aren't introduced to antigen so memory cells aren't produced
• In natural is from mother to fetus
• Artificial passes from an immune donor

Antibodies

• Known as immunoglobulins (Ig)
• Antibody has antigen-binding site for different classes such as:
• IgM secreted during primary response
• IgA found in body secretions prevents bacteria to enter epithelial surfaces
• IgD for B cell antigen receptor
• IgG the main antibody as part of primary and secondary response
• IgE mediates allergic and inflammatory response
• Plasma cells can switch which antibody is produced with the same antigenic determinant

Four Mechanisms of Antibody Actions

• Neutralization blocks specific sites, and no longer binds to receptors
• Agglutination has multiple antigen binding sites, clumps together and is easy access for phagocytes
• Precipitation where soluble molecules are clumped to settle
• Complement uses multiple antibodies binding and effects are antigens lysing, increased inflammatory response and promotes phagocytosis

T Lymphocytes and Cellular Immunity

• Two main functions: attacking cancerous cells/virus and mediates response
• T cells can't "see" antigens, so activation takes place through the MHC
• Binds if it displays a self-antigen

Types of Lymphocytes

• They help humoral immunity with functions of production, stimulating destruction, and innate systems with white blood cells
• Cytotoxic, this directly kills cells that bind a target and releases perforin or granzyme to trigger functions
• Regulatory T cells dampen immune and the response for prevention

Cellular vs Humoral

• They target cells directly and bind, cytotoxic cells need specific self antigen before function

Homeostatic Imbalances

• Includes immunodeficiencies
• Acquired, it's a disease affecting functions
• Autoimmune is one where systems can't determine and destroys
• Rheumatoid arthritis is multiple types, but treated drugs suppress the system and provides infection
• Congenital, impairs production and has effects
• Can also be aided through bone marrow transplant

Respiratory System Functions

• Supplies oxygen, disposes of carbon dioxide
• Consists of ventilation, the breathing process, and external respiration for lungs; transport gasses
• Tissues in body exchange

Respiratory Anatomy Zones

• Conducting has passages to the nose; transports and do not gas exchange for support
• Respiratory are exchange and found in bronchioles
• Has nasal, air cavity for rate
• Pharynx has tone of 3 regions for functions
• Closes to split passages
• Larynx that does closing off

Larynx

• Consists of cartilage and maintains
• Vocal cords make the sound and surrounded while expanding, creates sound
• Trachea consists of fibers and support, this maintains
• When contracts the diameter makes the force to be expelled in such cases
• Bronchi help reach with restricted zones

Anatomical Aspects

• To supply, blood, connect, tissue
• Organs, and gas to exhaling that can be done in certain ways for pressure
• Alveoli are thin and connected with walls made of something
• Three cells for exchange that is a must and protect.