Anatomy and Physiology 2 Immune System

Fixed Macrophages

(Histiocytes) those located in certain tissues and organs of the body: liver lungs nervous system epidermis

Antiserum

(a solution containing antibodies) into the body from another person or animal that is immune to the disease

IgA

-2nd most abundant -monomers (in plasma) and dimers -(2 monomers joined together in body secretions) -15% of plasma antibody -found in mucus secretions made from plasma cells in mucus membranes - tears, saliva, intestinal mucus, seminal fluid, and colostrum

IgD

-4th in abundance, RARE -Found primarily on cell membranes of B Cells where they act as antigen receptors -Don't cross placenta

Three major types of human interferons:

-Alpha Interferons -Beta Interferon -Gamma Interferon

Characteristics of Antibodies:

-Antigen binding sites -Monomer -Antibody monomer -Immunoglobin (Ig) classes

Characteristics of Antigens cont.:

-Antigenic Determinate -Hapten

Artificially Acquired Immunity

-Artificially Acquired Active Immunity -Artificially Acquired Passive Immunity

Monocytes

-As infection progresses and subsides they become more predominant -Enlarge and develop into Macrophages (Wandering and Fixed)

B cell and Antigen interaction

-B cells activate when antigen reacts with specific antibodies on the surface

Mechanisms of Phagocytosis

-Chemotaxis -Adherence -Ingestion -Digestion

Antimicrobial Substances

-Complement (C) or the Complement System -Interferons

Three major effects of Complement which destroy microorganisms:

-Cytolysis -Inflammation enhancement -Opsonization (immune adherence)

Complement System

-Group of plasma proteins (approx. 20) are involved in lysis of foreign cells and enhancement of inflammation and phagocytosis -Nonspecific since these proteins are activated in response to any foreign cell -Proteins of complement are designated C1-C9 with various subcomponents

Helper T-Cells (T4)

-Have CD4 Protein on their cell membrane that recognize (and stimulated by) foreign T-Dependent Antigen on APC's (antigen presenting cells) -Also stimulated by Interleukin (4 or 12) (released by APC's) which activate them -Activated (sensitized) Helper T-Cells multiply, causing a clone of these cells to develop, which then releases Interleukin 2 (IL-2) and other cytokinins (lymphokines), helping to activate B-Cells with antibodies specific for antigen and other types of T-Cells

Types of T-Cells

-Helper T-Cell (T4) -Suppressor T-Cell -Cytotoxic T-Cells (Killer T-Cells or T8 Cells) -Delayed Hypersensitivity T-Cells -Memory T-Cells

Humoral

-Humor refers to body fluids -Involves antibodies dissolved in extracellular fluids (not within a cell) such as blood plasma, lymph, and mucus secretions -Antibodies produced and directed against a specific antigen when B lymphocytes (bone marrow derived) are exposed to the antigen in all lymphatic organs

Types of Immune Response:

-Humoral (Antibody Mediated) -Cellular (Cell Mediated)

Mechanical Factors

-Intact skin- multiple layers of closely packed cells -Lacrimal Apparatus- glands that produce tears and the structures that drain tears and protect eyes -Salivary- glands protect mucous membranes of the mouth -Mucus- secreted by cells lining respiratory and GI tract -Urine- flows through urethra and vaginal secretions, protects urinary and female genital tracts

Cellular

-Involves not antibodies but T Lymphocytes that have antigen receptors on their surfaces allowing them to recognize and react to an antigen that are specific -Different T Cells are specific for different antigens

IgG

-Monomers -Most prevalent, about 80% of antibody in plasma -Cross placenta to fetus -Complements the activity of the antibody

IgE

-Monomers (2 binding sites) -VERY RARE, about .2% -Found primarily on cell membranes of Mast cells and Basophils, and when they react with a specific antigen, they cause cells to release histamine and other chemicals - mediators (causing intensified inflammatory response)

Neutrophil

-Most abundant phagocyte -Most numerous in blood during EARLY stages of infection -Migrate to site of infection phagocytize microorganisms

Characteristics of Antigens:

-Most are large molecules; proteins, glycoproteins, lipoproteins, large polysaccharides

Naturally acquired immunity

-Naturally acquired active immunity -Naturally acquired passive immunity

Specific (Adaptive) Defenses - third line of defense

-Naturally acquired immunity -Artificially acquired immunity -Types of Immune Responses- humoral and cellular

Actions of Phagocytic Cells- Phagocytes

-Neutrophils -Monocytes

Neutralization

-Of toxins by antibodies blocking their active sites -Inactivation of viruses by antibody combining with them and preventing their attachment to host cells- preventing their replication -Immobilization of bacteria by an antibody attaching to Flagella of mobile bacteria, preventing their spread

Non-Specific (Innate) Defenses- second line of defense

-Phagocytosis -Natural killer cells (NK) -Inflammation (local) -Fever (systemic) -Antimicrobial substances

Activated B cell multiplies and produces a clone of:

-Plasma cells which manufacture and secrete antibody specific for the antigen that activated the B cell -Memory B cells that recognize and remember the antigen so the next time its encountered, response is much more rapid

Inflammation characteristics:

-Redness -Heat -Swelling -Pain

Chemical Factors

-Sebum- Subcutaneous glands contain bacteriostatic fatty acids that inhibit growth of certain bacterial and fungal pathogens -Perspiration- sweat glands flush away microorganisms -Lysozyme- found in tears, saliva, snot, sweat and breakdown cell walls of Gram (+) bacteria and lesser Gram(-) -Cerumen (ear wax)- traps microbes/debris and helps clean outer ear Gastric juices- secreted by stomach- highly acidic and enzymes, prevents and kills microbes

T Cells

-T-Cell activated when Antigen receptors on its surface come in contact with an Antigen for which they are specific -This causes T-Cell multiplication and differentiation into several different types of T-Cells (all of which are specific for the Antigen that elicited their formation)

Body elevates temperature by:

-Vasoconstriction -Increasing metabolic rate -Shivering

When the thermostat is reset to normal body temperature, the body cools by:

-Vasodilation -Sweating

Interferons

-antiviral proteins produced by certain animal cells when infected with a virus that interfere with viral reproduction in uninfected cells

Antigen binding sites

-areas on an antibody that bind to specific antigenic determinants of antigen

Antigens (Ag) or Immunogen (complete antigen)

-chemical substance, usually foreign, that stimulates the body to produce specific antibodies or sensitized T cells that react with it

Aggluntination

-clumping together of insoluble Antigens on being cross-linked by specific Antibody. these complexes (clumps) are usually phagocytized and destroyed.

Antibody Monomer

-consists of 4 polypeptide chains: 2 identical light (L) chains and 2 identical heavy (H) chains -H and L chains joined together by disulfide bonds and have variable regions at the ends of the Y shaped molecule arms, causing the specificity of the antigen binding sites

Purpose of inflammation:

-destroy injurious agent and remove it from the body -if it can't be destroyed, contain or wall off -repair or replace damaged tissue

Precipitation

-formation of precipitate when soluble Antigens are cross-linked by specific Antibody, which is usually phagocytized

Cytotoxic T-Cells (Killer T-Cells, or T8 Cells)

-have CD8 protein on their cell membrane -lyse, thus kill target cells, such as cancer cells, cells of transplanted tissue, and cells infected with viruses and intercellular bacteria -cell lysis due to perforin (protein released by Cytotoxic T-Cells that form pores in target cells cytoplasmic membrane, causing it to leak and eventually disintegrate) -Cytotoxic T-Cells also kill target cells by releasing Lymphotoxin (substance secreted by cytotoxic T-Cells that activates enzymes in target cells which fragment it DNA

IgM

-human antibody too large to cross the placenta -FIRST antibody to appear in response to initial antigen exposure and concentration declines as IgG increases

Naturally acquired active immunity

-immunity resulting from having a disease -may be life long for some diseases, like yellow fever, or only a few years for others

Naturally acquired passive immunity

-immunity resulting from the transfer of antibodies from mother to fetus in utero or from mother to infant via breast milk -only lasts a few months, it's only temporary

Suppressor T-Cells or Regulatory T-Cells

-inhibit development if plasma cells from B-Cells and suppress activity of other T-Cells -Along with Helper T-Cells, they act as regulators of the immune response

Hapten (Partial antigen)

-low molecular weight molecule that can react with a specific antibody, but can't; stimulate antibody formation unless attached to a larger, carrier molecule - this is responsible for many allergies, including food and drug allergies

Natural Killer (NK) Cells

-lymphocytes that lyse and kill tumor cells and virus infected body cells -not immunologically specific

Delayed Hypersensitivity T-Cells

-may have CD4 or CD8 proteins on cell membrane -delayed allergic reaction and rejection of transplanted tissues -also important in fighting cancer and TB

Interleukin 12

-naturally produced by dendritic cells, macrophages, neutrophils, and human B Cells -involved with T Cells

T Lymphocytes

-primarily directed against intercellular bacteria and viruses, protozoa, fungi, helminths and transplanted tissue such as organ grafts and cancer cells -Not associated with Antibodies- strictly immune cells

Valance of antibody

-refers to the number of antigen binding sites on an antibody molecule -Most human antibodies are Bivalent- having 2 antigen binding sites

Antigenic Determinate (Epitopes)

-regions on the surface that specific antibodies recognize and react to -most have many different types of determinates on their surface, so that one Antigen may stimulate production of several different antibodies

B cells in humans

-remains in Red Bone Marrow to mature (spleen and liver in the fetus) then they migrate via the blood to the lymphatic organs and other tissues where they encounter antigens -Mature B cells have thousands of antibodies on the surface that act as antigen receptors for a specific antigen

T-Dependent Antigens

-require the intervention of T helper cells to activate B cells. Ex. bacteria -they are attacked and partially digested by antigen-presenting cells that present part of antigen on the surface of their cell membrane along with Self antigens.

Artificially Acquired Active Immunity

-resulting from a vaccination -can be long lasting (sometimes requiring a booster)

Artificially Acquired Passive Immunity

-resulting from injection of antiserum ex. rabies shot -lasts only a few weeks

Memory T-Cells

-retain memory of antigens encountered for more rapid production of T-Cells to react -also remember distinction between "Self" and "Non-self" (foreign antigens)

Monomer

-single bivalent antibody unit, multivalent are those with 2 or more monomers

IFNs

-small proteins produced by virus infected cells diffused to uninfected cells in an area, causing synthesis of PKR -don't interfere with viral multiplication in cells already infected but protects adjacent cells that haven't been infected yet

IFNs Host Cell Specific

-those that are produced by human cells protects other human cells, but not those of other animals. -Human cells protect only human cells

Immunoglobin (Ig) classses

IgG IgM IgA IgD IgE

Antigen- Presenting Cells (APC's)

usually macrophages or dendritic cells

NK and other cells involved in nonspecific defense include:

Macrophages Neutrophils Eosinophils

Phagocytic Migration - accumulation (inflammation)

Phagocytes in blood attracted to area of injury by chemotaxis -> Phagocytes then involved in diapedesis->Pus

Vasodilation

when the skin warms by increasing blood flow through it (increasing in heat loss)

Non-Specific (Innate) Defenses- first line of defense

Skin and mucous membranes: Mechanical Factors Chemical Factors

Repair

Tissue repair begins during active phases of inflammation, but not completed until all harmful substances are gone or neutralized. Tissue repaired when STOMA and Parenchyma produce new cells.

Associated to inflammation:

Vasodilation and increased permeability of blood vessels -Release of histamine primarily from mast cells in CT and Basophils/Platelets in the blood

Specific (Adaptive) Defenses are:

a specific immune response that: -is specific- it recognizes and is directed against a particular pathogen and foreign substances -is systemic- body wide -has memory- it remembers pathogens and foreign substances previously encountered and responds much quicker when encountering them again

Fever

a systemic response to microbial infection while inflammation a local response, occurs when the body's thermostat in the hypothalamus reset by release of prostaglandins from the hypothalamus

Fever definition

abnormally high body temp due to bacterial or viral infection

Pus

accumulation of dead cells (host cells, phagocytes, and bacteria) and body fluids may appear in area of phagocytic activity

Interleukin 2

activates lymphocytes

Adherence

attaches to the surface of microorganism

Inflammation

bodily response to cell damage

Inflammation Enhancement

by binding to Mast Cells, Basophils, and Platelets and triggering the release of histamine, also by acting as powerful chemotactic factor attracting phagocytes

Staphylococcus species and Myobacterium Tuberculosis

can multiply inside phagocytes, eventually killing them

High fever

causes damage by inactivating or denaturing enzymes

Cytolysis (cell lysis)

cell destruction by antigen-antibody complexes activating Complement (initiating a series of reactions in Complement System that breaks down the cell membrane)

Major Histocompatibility Complex (MHC) Antigen or Human Leukocyte Antigen (HLA)

cell membrane surface glycoproteins that are unique to the cells of a person (SELF antigens of a person)

Opsonization

coating of cells with specific antibody that enhances phagocytosis of the cells

Sweating

cools by extracting heat (energy) from body tissues which is used to evaporate sweat. This is the CRISIS- phase of the fever, characterized by vasodilation and sweating (which indicates the body temperature is falling)

Vasoconstriction

cools the skin by reducing blood flow through it (thus reducing heat loss there)

Phagolysosome

digestive vacuole

Ingestion

engulf microbe enclosing it in sac with cytoplasm phagosome and after completely surrounding microbe, detach and carry the sac into cytoplasm

Opsonization (Immune Adherence)

enhancement of phagocytosis by coating cells with Opsonins Plasma Proteins (like Complement or antibodies) Coating cells results in a cell being marked for destruction by phagocytes Inherited deficiencies of Complement component can cause diseases or increase susceptibility to diseases

Type 2 Gamma Interferons

enhances cell-killing ability of phagocytes and Natural Killer Cells

Class 1 MHC Antigen

found on cell membrane surface of all body cells except RBCs

Increasing metabolic rate

generated heat

Hematopoietic Stem Cells (hemocytoblasts)

in RBM give rise to RBCs, all WBCs and platelets

Type 1 Alpha and Beta Interferons

inhibit cell growth and suppress tumor formation

Bacteriostatic

inhibit growth of bacteria

Shivering

involves skeletal muscle contraction (which generates heat by release of ATP)

Endotoxin-producing microbe

kill phagocytes

Wandering Macrophages

leave blood and migrate through the tissues to infected area

Cytolysis

lysis of cells by damaging their cytoplasmic membranes, causing cell components to leak

Digestion

membranes of phagocytes lysosomes and phagosomes fuse causing phagolysosome which discharge digestive enzymes into vacuole containing microorganisms, usually killing and digesting it

Chemotaxis

movement in response to presence of a chemical, phagocytes are attracted to microorganisms by chemotaxis

Class 2 MHC Antigen

occurs only on cell membrane surface of antigen presenting cells, B cells, and activated T cells

Constant Region

of H chains makes of the stem of the Y shaped molecule and its AA sequence has only 5 variations, causing different classes of immunoglobins

Opsonins

plasma protein such as antibodies (like gamma globulins) or complement proteins that aid in phagocytosis by coating the microbe

Vaccine

preparation of killed, inactivated, or attenuated (weakened) microorganisms or toxoids ex. Tetanus

Gamma Interferons

produced by activated lymphocytes

Beta Interferons

produced by fibroblasts

Alpha interferon

produced by leukocytes and other lymphocytes

Interleukin 1

production of inflammation, promotion of fever and sepsis

Fever remains until interleukin 1 is eliminated

prostaglandin synthesis is inhibited by the presence of drugs such as aspirin or acetaminophen

Antibody (Ab) or Immunoglobin (Ig)

protein produced in the body by the plasma cells (antibody manufacturing cells derived from B cells) in response to presence of specific antigens with which it reacts

Interleukin 1 (a pyrogen)

released by phagocytes in response to bacterial endotoxins can stimulate this release

Phagocytosis

secreted of indigestion of any particulate matter (including microorganisms) by a cell

Moderate fever is beneficial to the host since:

1. Interleukin 1 stimulates B and T lymphocyte production (specific immunity) 2. Intensifies effect of interferon (antiviral protein) 3. Inhibits growth from bacteria by sequestering (hiding away) much Fe (Iron) and Zn (zinc) in the liver and spleen (needed for bacterial multiplication) 4. Accelerates tissue repair (by increasing metabolic rate)

Antibody - Antigen Reactions

Antibodies react with antigens that stimulated their formation to form antigen-antibody complexes and protect the body by the following means: -Neutralization -Agglutination -Precipitation -Cytolysis -Opsonization

Self Antigens

surface antigens on cell that identify it to the host's body as belonging to it