Chapter 20: Immune System

nonspecific defense system—innate defenses

1. surface barriers

2. internal defenses

surface barriers

1. 1st line of defense

2. skin

3. mucous membranes

internal defenses

1. 2nd line of defense

2. phagocytes

3. natural killer cells

4. inflammation

5. antimicrobial proteins

6. fever

specific defense system—adaptive defenses

1. humoral immunity

2. cellular immunity

humoral immunity

1. 3rd line of defense

2. B cells

cellular immunity

1. 3rd line of defense

2. T cells

first line of defense—surface barrier

physical barrier to most microorganisms

skin structure and features

1. stratified epithelium

2. sheets of tightly packed cells

3. keratin outer layer

4. cells slough off

5. perspiration

6. normal flora (microbiome)

7. turf war

chemical barriers (1st line)

1. inhibits microorganisms

2. salty

3. acidity—skin and mucous secretions called acid mantle that destroys microorganisms

4. lysozyme from salvia, respiratory mucus, and lacrimal fluid

mucus

traps microorganisms in respiratory and digestive tracts

if invasion occurs (2nd line of defense)

1. phagocytes

2. natural killer (NK) cells

3. inflammatory response (macrophages, mast cells, WBCs)

4. antimicrobial proteins (interferons and complement proteins)

5. fever

phagocytes

WBCs that ingest and digest foreign invaders

neutrophils

1. most abundant phagocytes

2. die fighting

3. defensins help by piercing membrane of pathogen

macrophages

1. develop from monocytes

2. robust

3. waiting in tissues (skin, digestive tract) to ingest invaders

steps of phagocytosis

1. phagocyte adheres to pathogens or debris (using receptors)

2. phagocyte forms pseudopods that engulf the particles, forming a phagosome

3. lysosome fuses with the vesicle, forming a phagolysosome

4. toxic compounds and lysosomal enzymes destroy pathogens

5. sometimes exocytosis of the vesicle removes indigestible and residual material

mycobacterium tuberculosis

1. dangerous

2. blocks the merging of lysosomes with phagosome

3. macrophage eats so many that it ruptures

NK cells

1. nonphagocytic lymphocytes that police blood and lymph

2. kill cancer and virus-infected cells before adaptive immune system is activated

3. induce apoptosis

lymphoblast

progenitor cell to B, T, and NK cells

inflammation

1. triggered when tissues are damaged

2. trauma, heat, chemicals, or infections

benefits of inflammation

1. prevents spread of infection

2. disposes cell debris

3. pathogens alerts immune system

4. sets the stage for repair

4 cardinal signs of acute inflammation

1. redness

2. heat

3. swelling

4. pain

stages of inflammation

1. inflammatory chemical release

2. vasodilation

3. increased vascular permeability

4. phagocyte mobilization

phagocyte mobilization

1. leukocytosis: neutrophils enter blood from bone marrow

2. margination: neutrophils cling to capillary wall

3. diapedesis: neutrophils flatten and squeeze out of capillaries

4. chemotaxis: neutrophils follow chemical trail

steps of acute inflammation

1. physical wound or pathogen damages an area

2. injured cels release pro-inflammatory cytokines altering nearby cells

3. mast cells release histamine

4. macrophages eat pathogens and release cytokines calling for assistance

5. neutrophils show up to fight

histamine effects

1. vasodilation (more blood flow)

2. increases vascular permeability

3. recruitment of more leukocytes

pus is made out of

1. cell debris

2. dead pathogens

3. neutrophils that have eaten themselves to death

interferons

cells infected with virus can secrete IFNs that “warn” healthy neighboring cells

interferon mechanism against viruses

1. virus enters cell and replicates

2. interferon genes switch on

3. cell produces interferon molecules

4. interferon binding stimulates cell to turn on genes for antiviral proteins

5. antiviral proteins block viral reproduction

host cell 1

1. infected by virus

2. makes interferon

3. killed by virus

host cell 2

1. binds interferon from cell 1

2. interferon induces synthesis of protective proteins

complement activation pathways

1. classical pathways

2. lectin pathway

3. alternative pathway

classical pathway

activated by antibodies coating target cell

lectin pathway

activated by lectins binding to specific sugars on microorganism’s surface

alternative pathway

1. activated spontaneously

2. lack of inhibitors on microorganism’s surface allows process to proceed

all 3 activation pathways…

1. converge to initiate final activation of complement (C3)

2. C3 is split into C3a and C3b

opsonization (C3b)

coats pathogen surfaces, enhancing phagocytosis

enhances inflammation (C3a)

1. stimulates histamine release

2. increases blood vessel permeability

3. attracts phagocytes by chemotaxis

membrane attack complexes (MACs)

1. form when C3b activates other complement components (C5b and C6-C9)

2. occurs on target cell surfaces (bac)

3. insert into target cell mem

4. lyse cell

fever

1. abnormally high BT

2. leukocytes/macrophages secrete pyrogens

3. inhibits pathogen growth

pyrogen

1. acts on body’s thermostat in hypothalamus

2. raises BT

adaptive immune characterisitics

1. specific: recognizes and binds to specific antigens

2. systemic: not restricted to initial site

3. memory: stronger attack to “known” antigens

branches of adaptive immunity

1. humoral (antibody-mediated) immunity B cells

2. cellular (cell-mediated) T cells

antigens

1. provoke an immune response

2. immunogenicity: ability to stimulate production of T or B cells

3. most are not found in body

4. antigenic determinants

antigenic determinants

the parts that antibodies or lymphocyte receptors bind to

examples of antigens

foreign proteins, polysaccharides, lipids, and nucleic acids seen on foreign invaders

self-antigens (our own self)

our own cells are covered with proteins that are not antigenic to us but may be to others

MHC proteins (self-antigens)

coded by genes by major histocompatibility complex (MHC) and unique to each individual

two types of lymphocytes

1. B cells

2. T cells

antigen-presenting cells (APCs)

1. do not respond to specific antigens

2. engulf antigens

3. present fragments of antigens to T cells for recognition

origin site for B and T lymphocytes

red bone marrow

maturation of T cells

lymphocyte precursors destined to become T cells migrate (in blood) to the thymus and mature there

bone marrow

where B cells mature

during maturation lymphocytes…

develop immunocompetence and self-tolerance

seeding secondary lymphoid organs and circulation

1. immunocompetent but still naive lymphocytes leave thymus and bone marrow

2. colonize secondary lymphoid organs and circulate through blood and lymph

antigen encounter and activation of lymphocytes

when a lymphocyte’s antigen receptors bind to its antigen, that lymphocyte can be activated

proliferation and differentiation of lymphocytes

1. activated lymphocytes proliferate and differentiate into effector cells and memory cells

2. memory and effector T cells circulate in blood, lymph, secondary lymphoid organs

lymphocytes lifecycle

1. origin

2. maturation

3. seeding secondary lymphoid organs and circulation

4. antigen encounter and activation

5. proliferation and differentiation

major types of APCs

1. dendritic cells

2. macrophages

3. B cells

dendritic cells

1. found in CT and epidermis

2. mobile sentinels of boundary tissues

3. phagocytize pathogens then enter lymphatics to present antigens to T cells in lymph node

4. most effective antigen presenter

5. key link between innate and adaptive immunity

macrophages

1. phagocytosis to fight invaders

2. present antigens and macrophages

3. activates T cell and macrophages

activated macrophages

1. voracious phagocytic killer

2. recruit additional defenses

antibodies

1. circulate freely in body fluids

2. bind to target to mark for destruction by phagocytes or complement

   1. innate or other adaptive mechanisms

humoral immunity targets…

extracellular targets

clonal selection of a B cell

1. primary response: initial encounter with antigen

   1. antigen binds to a receptor on a specific B lymphocyte (clonal selection)

2. proliferation to form a clone—activated B cells

3. either plasma cells (effector B) or memory B cells (primed to respond to same antigen) are produced

4. both cells secrete antibodies

plasma cells

1. antibody-secreting effector cells

2. secrete at rate of 2000 molecules per second for 4 to 5 days then die

primary immune response

1. first exposure

2. lag period: 3 to 6 days

3. peak levels in 10 days

4. antibody levels decline

secondary immune response

1. re-exposure

2. respond within hours, not days

3. antibody peaks in 2 to 3 days

4. remain high for weeks to months

active humoral immunity

B cells encounter antigens and produce antibodies
1. Naturally acquired
2. Artificially acquired

naturally acquired (active)

exposure to actual bacterial or viral infection

artificially acquired (active)

vaccine of dead or attenuated pathogens

passive humoral immunity

1. occurs when ready-made antibodies are administered into body

2. protection ends when antibodies degrade

naturally acquired (passive)

antibodies delivered to fetus—placenta to infant through milk

artificially acquired (passive)

injection of serum

antibodies composition

1. also called immunoglobulins (Igs)

2. proteins secreted by plasma cells

3. make up gamma globulin portion of blood

4. capable of binding specifically with antigen

antibody targets and functions

1. do not destroy antigens

2. inactivate and tag them

3. form antigen-antibody (immune) complexes

defensive mechanisms used by antibodies

1. neutralization

2. agglutination

   1. precipitation

   2. complement fixation

antibody classes

1. IgM

2. IgA

3. IgD

4. IgG

5. IgE

IgM

1. the first antibody secreted by the primary response

2. readily activates complement

3. monomer or pentamer

4. numerous antigen-binding sites make it a potent agglutinating agent

IgM monomer

antigen receptor on B cell surface

IgM pentamer

circulates in blood plasma

IgA

1. dimer

2. found in body secretions

3. stops pathogens from attaching to epithelial cell surfaces

4. monomer exists in limited amounts in plasma

IgD

1. found on B cell surface

2. functions as a B cell antigen receptor

3. monomer

IgG

1. monomer

2. most abundant antibody

3. main antibody of both secondary and late primary responses

4. activates complement

5. protects against bacteria, viruses, and toxins circulating in blood and lymph

6. crosses the placenta and confers passive immunity from the mother to the fetus

IgE

1. monomer

2. stem end binds to mast cells or basophils—histamine release

3. secreted by plasma cells in skin, mucosae of the gastrointestinal and respiratory tracts, and tonsils

4. traces found in plasma

5. levels rise during severe allergic attacks or chronic parasitic infections of the gastrointestinal tract

Cellular immune response

1. T cells provide defense against intracellular antigens

   1. viruses

   2. cancer cells

   3. foreign cells

T cell functions

directly kill cells or release chemicals that regulate immune response

T cell classification is based on…

glycoprotein receptors

CD4 cells

1. become helper T cells

2. activate B cells, other T cells, and macrophages

   1. become regulatory T cells

   2. moderate immune response

   3. become memory T cells

CD8 cells

1. become cytotoxic T cells

   1. destroy cells

2. become memory T cells

activated T cells

1. helper

2. cytotoxic

3. regulatory

naive T cells

1. CD4

2. CD8

T cells respond only to…

1. processed fragments of antigens displayed on surfaces of cells

2. antigen presentation is vital for activation of T cells

Class I MHC proteins

displayed by all cells

Class II MHC proteins

1. displayed by APCs

2. Dendritic cells

3. macrophages

Class I MHC proteins

1. present endogenous antigen

2. protein synthesized inside cell

self-antigen

normal proteins of cell

nonself antigen

abnormal proteins found in infected or abnormal cell

Class I MHC and CD8

Class I MHC crucial for CD8 cell activation

Class II MHC

present exogenous (extracellular) antigens that have been engulfed by an APC

Class II MHC and CD4

Class II MHC crucial for CD4 cell activation