CHAPTER 21

The Immne system: innate and adaptive body defenses

OVERVIEW

1. Innate (nonspecific) defenses

1. Surface barriers: skin and mucosae

1. First line of defense
2. Unbroken skin and mucosae
3. Chemicals produced by these

1. Acid on skin-pH 3-5
2. HCL in stomach
3. Enzymes in stomach
4. Lysozyme-saliva and lacrimal fluid
5. Sticky mucous in digestive tract and respiratory trap pathogens

4. Respiratory tract modifications

a. __________ keep pathogens from entering lower respiratory tract

2. Internal defenses: cells and chemicals

1. Phagocytes

1. Introduction

1. Macrophages

1. Free macrophages—

2. Fixed macrophages—

2. Neutrophils

3. Eosinophils

4. Mast cells

2. Mechanisms of phagocytosis

1. Microbe adheres to cytoplasmic extension of phagocyte—must bind to something on microbe such as polysaccharide, antibody or complement
2. Phagocyte engulfs microbe
3. Forms__________
4. Phagosome fuses with lysosome to form__________
5. Microbe digested
6. Exocytosis

2. Natural killer cells

1. Recognize surface sugars of__________and__________
2. Nonspecific
3. Target membrane with chemical called___________

3. Inflammation: tissue response to injury

1. Introduction

1. What does it do?

a.         Prevents the spread of damaging agents

b.         Disposes of cell debris and pathogens

2. Sets up for repair

2. Five cardinal signs of inflammation

a.

b.

c.

d.

e.

3. Vasodilation and increased permeability

1. Chemicals released into extracellular fluid

1. Most important are

 __________,__________,__________,__________,_________

2. Vessels dilated
3. Hyperemia
4. Increased permeability

1. Exudate seeps out causing__________
2. Swelling, bacterial toxins, prostaglandins cause pain
3. Fluid dilutes harmful substances
4. Brings O2 and nutrients
5. Brings clotting factors that form mesh to isolate area to prevent spreading
6. Amount of defensins released increases

4. Phagocyte mobilization

1. Leukocytosis—leukocytosis inducing factors which causes increase in neutrophil production from __________
2. Margination—neutrophils bind to CAMs on wall of vessels in inflamed areas
3. Diapedesis—cells squeeze through endothelial cells
4. Chemotaxis—inflammation releases chemotaxic agents that attract neutrophils
5. Monocytes follow neutrophils and become macrophages

4. Antimicrobial proteins

1. Interferon

1. Secreted by virus infected cells to protect other cells
2. Block protein synthesis
3. Lymphocyes secrete__________
4. Other leukocytes secrete __________
5. Fibroblasts secrete_________
6. Activate macrophages and NK cells

2. Complement

1. 2 pathways, classical and alternative
2. Cascade of steps converging with C3 which cleaves into C3a and C3b
3. C3b causes cell lysis by inserting MAC, also causes __________ which signals phagocytes to ingest particle
4. C3a enhances inflammation

5. Fever

1. Caused by __________secreted by macrophages and leukocytes
2. Extremely high can degrade enzymes
3. High temp speeds rate of metabolism, causes liver and spleen to remove iron and zinc from blood necessary for bacterial growth

2. Adaptive (specific) defenses

1. Introduction

1. Three important aspects

1. It is antigen specific
2. It is systemic
3. It has memory

2. Two mechanisms

1. Humoral or __________mediated
2. Cell mediated

2. Antigens (particles that invoke an immune response)

1. Complete antigens and haptens        

1. Complete antigens

1. Immunogenicity
2. Reactivity
3. Proteins are strongest

2. Haptens

1. Small molecule
2. Only immunogenic if coupled with protein carrier

2. Antigenic determinants

1. Certain parts of an antigen that trigger an immune response
2. One antigen can mobilize several cell populations, multiple determinents

3. Self-antigens: MHC proteins

1. Cell surface protein tags cell as self
2. Antigen responsible for Transfusion rxn
3. Many combinations of genes
4. These proteins display anything inside the cell to surface

1. If foreign particle, immune cells will recognize as foreign

5. MHC I displayed on all cells
6. MHC II only by specific immune cells

3. Cells of the adaptive immune system: an overview

1. Lymphocytes

1. T cells formed in thymus—become immunocompetent

1. Early in life, strong binding cells are destroyed (negative selection)
2. Weak binding cells survive (positive selection)

2. B cells formed in marrow—become immunocompetent

1. Some inactivated
2. Some destroyed

3. Each has a unique receptor to bind one particular antigen
4. These receptors present before meeting antigens so__________determine what substances our immune system will recognize
5. These new T and B cells with go to lymph organs and wait to be exposed to their antigens
6. Maturity reached after exposure

2. Antigen presenting cells

1. Role:__________
2. Types of cells

i.

ii.

iii.

3. Remember some immune cells migrate, some remain fixed
4. DCs actively migrate to lymph organs, bring antigen to T and B cells

4. Humoral immune response (antibody production to first time antigen challenge)

1. Clonal selection and differentiation of B cells

1. Cell is activated by antigen binding and crosslinking
2. Endocytosis of antigen and receptor
3. Clonal selection begins (cell replicates itself into identical daughters)
4. Most of these clones become__________

1. Secrete large amounts of free antibody
2. These antibodies will circulate and target antigen for destruction

5. Other clones become memory cells

2. Immunological memory

1. First exposure to antigen is primary immune response

1. Slow, lower peak of antibody titer

2. Any exposure after first is secondary immune response

1. Same events as primary just faster with higher peak in antibody titer

3. Active and passive humoral immunity

1. Active immunity

1. Our body produces its own antibodies
2. Two types

a.

b.

2. Passive immunity

1. We borrow antibodies from another source
2. Two types

a.

b.

4. Antibodies

1. Basic antibody structure

1. Two heavy chains—long with a hinge
2. Two light chains—short
3. Linked by disulfide bonds
4. These together form antibody monomer
5. Y shaped
6. Variable end (binds to antigen)
7. Constant end (provides function and class specification)

2. Antibody classes

1. Five classes with different function

a.

b.

c.

d.

e.

3. Mechanisms of antibody diversity

1.       Somatic recombination inside B cell

2. Heavy and light chains produced separately and connected
3. B cells can switch antibody type

4. Antibody targets and functions

1. Formation of antigen antibody complexes, targets pathogens for destruction
2. Complement fixation and activation

1. .
2. Opsinization—targets for phagocytosis

3. Neutralization—inactivates antigen
4. Agglutination—clumping of cells
5. Precipitation—clumping of molecules or particles

5. Monoclonal antibodies

1. Production of pure antibody to use for diagnostic purposes

5. Cell-mediated immune response

1. Introduction

1. Destroys hidden pathogens
2. Display 2 different cell surface proteins in addition to antigen receptor

i.

ii.

3. CD4 are mostly__________cells
4. CD8 are mostly__________cells
5. T cells can only respond to antigen fragments displayed on surface of a cell

2. Clonal selection and differentiation of T cells

1. Antigen recognition and MHC restriction

1. T cells activated when they bind antigen plus MHC

1. Class I MHC recognized by CD8 cells

2. Class II MHC recognized by CD4 cells

2. T-cell activation

1. Step 1: antigen binding

1. TCR bind to MHC/antigen complex on surface of cell
2. MHC restriction

2. Step 2: costimulation

1. T cell must receive one other signal to launch an attack
2. This can be cytokine, interleukin, another cell surface receptor on APC
3. If no costimulation, T cell goes into anergy and will not respond to antigen—this is a safeguard against autoimmunity
4. Now T cells will proliferate and fight infection then die
5. Memory T cells will survive for next encounter

3. Cytokines

1. Chemical mediators

1. Intrerleukin 1—
2. Interleukin 2—

2. Help amplify and regulate immune and nonspecific defenses

1. Cell toxins
2. Enhance killing power of macrophages

3. Specific T cell roles

1. Helper T cells

1. Regulate immune response
2. Release chemicals
3. Involved in specific and nonspecific defense

2. Cytotoxic T cells

1. Directly attack and kill other cells

1. T cell binds tightly to cell (cancer cell, infected cell, foreign cell)
2. Perforin released
3. Granzyme released into cell
4. Pathogenic cell undergoes apoptosis

2. Lymphotoxin, gamma interfeuron, tumor necrosis factor all released by these cells and  have different functions

3. Other T cells

1. Regulatory  T cells—
2. NK cells--

4. Organ transplants and prevention of rejection

a.    Four types of grafts

1. Autografts
2. Isografts
3. Allographs
4. Xenographs

b.   What happens?

3. Homeostatic imbalances of immunity

A. Immunodeficiencies

1. Congenital conditions

a.   Severe combined immunodeficiency syndromes

                 b.  Treatment is bone marrow transplant

                        2.   Acquired immunodeficiencies

1. Hodgkin’s disease
2. AIDS

1. Characterized by weight loss, night sweats, swollen lymph nodes
2. Increasing frequency of opportunistic infections like pheumocystis

pneumonia and Karposis sarcoma

3. Pts die from infection
4. Caused by HIV through blood or body fluids—sex, IV drug use and blood transfusions are primary infection routes

1. HIV destroys helper T cells
2. Immune system slowly degenerates while virus replicates inside nodes--a symptomatic
3. Nodes eventually explode releasing virus to body—symptomatic
4. Virus targets CD4 and enters cell, using its mechanisms to replicate
5. Uses reverse transcriptase to produce DNA—has high mutation rate

B.  Autoimmune diseases

1.   Examples

                a.

                b.

                c.

                d.

                e.

                f.

                g.

2. How does it occur?

1. Lymphocyte programming is ineffective
2. New self antigens appear
3. Foreign antigens resemble self antigens

C.  Hypersensitivities

1. Immediate hypersensitivities

1. Acute (type I)

1. Primary example__________
2. Usually localized to respiratory, GI and skin
3. Anaphylactic shock if systemic

2. Atopy

2. Subacute hypersensitivities

a.   Cytotoxic (type II) reactions

                           i.            antibodies bind to cells causing lysis through complement

b.   Immune complex (type III) hypersensitivity

i.           antigen-antibody complexes can not be cleared and cells begin to destroy nearby tissue

3.   Delayed hypersensitivities (type IV)

3. Allergic contact dermatitis

1. skin contact with metals or chemicals
2. agents are haptens.
3. Poison ivy as an example