Dr.

Vince Scialli
BSC 1086

Rev. 7-18-08

IMMUNOLOGY
NON-SPECIFIC
DEFENSES
LECTURE 4

Immune System ~ Chapter 22 ~ 1/30/2017

Dr. Vince Scialli

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IMMUNE SYSTEM

Rev. 5-15-08

Specialized body defense system

Made up of billions of cells ~ MOSTLY lymphocytes
Provides specific resistance to disease ~ IMMUNITY
1.

Microorganisms ~ pathogens & parasites

Bacteria
Viruses
Fungi
Parasites

2.

Foreign tissue cells & Foreign Proteins Allergens

Blood transfusions
Tissue transplants

3.

Cancer Cells

Types of Immune Protection

1.

Innate ~ Natural ~ Local Non-specific Body Defenses

Intact surface membranes ~ barriers to entry
Specialized cells & chemicals ~ mucous, NK
phagocytes

2.

Acquired ~ Adaptive ~ Specific Defense System

Antibodies
Immune Modulators ~ interferons & cytokines

Immune System ~ Chapter 22 ~ 1/30/2017

Dr. Vince Scialli

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NON-SPECIFIC BODY DEFENSES

Barriers to entry ~ Prevents foreign invasion & infection

Mechanisms of Protection
1.

Surface Membrane Barriers ~ first line of defense

Prevent Pathogens from entering the body
Skin ~ Hair
Dermal Secretions ~ sweat, sebum
Mucous Membranes

2.

Internal Cellular & Chemical Defenses ~ second line

Phagocytes ~ remove foreign debris
Macrophages
Monocytes

Neutrophils
Eosinophils

Natural Killer Cells ~ surveillance ~ T-cells

Interferons ~ increase resistance against virus
Complement ~ destroys invader cell walls
Attract Phagocytes
Stimulate Inflammation
Inflammatory Response ~ many effects
Fever ~ mobilizes defenses
Accelerates Repairs ~ Inhibits pathogens
Immune System ~ Chapter 22 ~ 1/30/2017

Dr. Vince Scialli

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SURFACE MEMBRANE BARRIERS

First Line of Defense - Nonspecific defenses
Provide mechanical barrier for entry of pathogens
Produce chemical substances ~ enhance defense effects

SKIN ~ microorganisms CANNOT penetrate intact skin

Keratinized Epithelial Cells

Keratin ~ resistant to toxins & enzymes produced

by bacteria

Sebum from sebaceous glands

Toxic to bacteria
pH of skin ~ 3 to 5 (acid) ~ Inhibits bacterial growth
Most bacteria need alkaline media

MUCOUS MEMBRANES ~ mucosa

Protective membranes ~ contain goblet cells
Line body passageways exposed to outside
Digestive Tract
Respiratory Tract
Immune System ~ Chapter 22 ~ 1/30/2017

Dr. Vince Scialli

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PROTECTIVE MECHANISMS
Digestive Tract
Mucous ~ produced by mucous membranes in
intestine traps bacteria

Saliva ~ from salivary glands ~ in oral cavity

Contains Lysozyme ~ destroy bacteria

Lacrimal secretion ~ tears contains Lysozyme

Other Digestive Secretions ~ kills bacteria
HCl in Stomach . . . Proteolytic Enzymes in Intestine

Respiratory Tract
Mucous ~ produced by mucous membranes in
trachea & nose traps bacteria

Cilia ~ of upper respiratory tract & trachea trap dust

& bacteria ~ cough into mouth and swallow
Fine mucous-coated hairs ~ inside nose traps
particles when inhaled ~ stimulates sneezing reflex

Urogenital System
Normal urine is slightly acid ~ pH < 7.0
Prevents bacterial growth ~ urinary acidifiers
Vaginal secretions are very acid ~ inhibits bacteria
Immune System ~ Chapter 22 ~ 1/30/2017

Dr. Vince Scialli

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CELLULAR & CHEMICAL DEFENSES

Second Line of Defense ~ Nonspecific defenses

PHAGOCYTES
Engulf & destroy pathogens & foreign debris ~ pac-man
Attack invaders that cross epithelial barriers ~ clean up
Enhanced by complement or antibodies which attach to
bacteria & provide binding surface for phagocyte

Microphage ~ small ~ usually circulate in blood

Leave blood ~ move into damaged tissue
Neutrophils ~ abundant WBC ~ become phagocytic
Attack bacteria and other foreign
Eosinophils ~ Weak phagocytes ~ attack Parasitic
Mast Cell ~ phagocytic cell ~ releases histamine

Macrophage ~ large ~ most important type of phagocyte

Derived from monocytes ~ large WBCs
Monocytes enter tissue & become enlarged
Free Macrophages ~ wander through tissue
Fixed Macrophages ~ stationary
Kupffer cells & Microglia
Immune System ~ Chapter 22 ~ 1/30/2017

Dr. Vince Scialli

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CELLULAR & CHEMICAL DEFENSES

Natural Killer Cells ~ NK Cells
Immune Surveillance Cells ~ Police ~ Army
Constant monitoring of normal tissue by NK cells
Recognize & destroy abnormal or foreign cells
Large granular lymphocytes in blood & lymph
T-lymphocytes ~ from thymus
Non-specific ~ kill viruses, bacteria & malignant cells
Help fight cancer
Early Protection ~ Act before immune system is activated
Action is NON-phagocytic

First ~ Disrupt the membranes of those cells

they attack

Second- release cytolytic chemicals ~ Perforin

Cause breakdown of cytoplasm of cell foreign
or abnormal cell being attacked ~ lysis

Antimicrobial Proteins
Enhance bodys ability to defend against invaders
Two MOST important:
Immune System ~ Chapter 22 ~ 1/30/2017

Interferon & Complement

Dr. Vince Scialli

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Interferon ~ produced by virus infected cells

Anti-viral ~ anti-microbial protein
Cytokine ~ Produced by lymphocytes, macrophages,
virus infected cells & other immune cells
Prevents viruses from multiplying in other normal
adjacent body cells
Activates macrophages . . . Stimulates natural killer cells

Complement
Anti-microbial circulating protein

Complement Activation ~ Complement Fixation

Activated after binding to antibody-covered
antigens complex
FIXES on bacteria surfaces & makes bacteria more
susceptible to body defenses

Marks bacteria for phagocytosis

Intensifies inflammatory & immune response
Enhances phagocytosis by phagocytes
Stimulates mast cells & basophils to release
histamine & heparin
Attracts neutrophils & other WBCs to area
Lyses microorganisms~ destroys microorganism
Immune System ~ Chapter 22 ~ 1/30/2017

Dr. Vince Scialli

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CELLULAR & CHEMICAL DEFENSES

Inflammation ~ Inflammatory Response
Tissue response to injury or breakdown
Response triggered in an area where injury occurs
Trauma
Heat or Burn
Irritating Chemicals
Infection ~ viral, bacteria, parasitic, fungi

Signs or symptoms of inflammation

Four Cardinal Signs
Swelling
Redness ~ hyperemia
Pain
Heat
Impairment of Function (5th sign) ~ sometimes

Functions of Inflammation
1.

Prevents spread of damaging agents

2.

Disposal of cellular debris & pathogens

3.

Helps to prepare for repair & regeneration

4.

MUST occur prior to the healing process

Immune System ~ Chapter 22 ~ 1/30/2017

Dr. Vince Scialli

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INFLAMMATORY PROCESS ~ Overview

1.

Vasodilation & Increased Vascular Permeability

Chemical Mediators ~ released from tissue
Histamine & Heparin
Kinins ~ plasma proteins
Prostaglandins ~ attract platelets & swelling
Complement ~ marks invaders
Lymphokines ~ cytokines
Exudate formation ~ Pus or Purulent Exudate
Local edema
Pus ~ Purulent Exudate
Pain

2.

Phagocyte Mobilization ~ army moves in

Leukocytosis ~ increased WBC count
Margination ~ neutrophil pavementing in vessels
Diapedesis ~ neutrophil emigration into tissue
Chemotaxis ~ macrophages remove cellular debris

Immune System ~ Chapter 22 ~ 1/30/2017

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READ ABOUT INFLAMMATION DETAIL IN NOTES . . .

NOT COVERED IN LECTURE

INTERNAL CELLULAR & CHEMICAL DEFENSES

FEVER
Increased body temperature common during pathogenic
infection > 99.2 oF

Pyrogens ~ produced by macrophages & leukocytes

following pathogenic exposure
Stimulate febrile response ~ increase temperature

Effects of Fever ~ Good & Bad

Increase metabolic rate of tissue cells
Faster immune response & tissue repair
Inhibit some viruses & bacteria
NOT very comfortable

Immune System ~ Chapter 22 ~ 1/30/2017

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Dr. Vince Scialli

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IMMUNOLOGY
SPECIFIC
DEFENSES
LECTURE 5 & 6

Immune System ~ Chapter 22 ~ 1/30/2017

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Dr. Vince Scialli

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IMMUNE SYSTEM
Specific Body Immunity ~ Adaptive Immunity ~ Acquired
Third Line of Defense . . . A Very Specific Defense
Immune system recognizes something as foreign
Body responds to immobilize, neutralize or remove
foreign substances

Properties of Acquired Immunity

1.

Specificity ~ NOT general ~ NOT local

Immunity recognizes & is directed against a
particular foreign substance

Antigen ~ foreign substance ~ NOT SELF

2.

Versitle & Systemic

Not restricted to location of infection ~ systemic
Can respond to millions of different antigens
Tolerance ~ NO normal response to self

3.

Memory
After initial exposure to an antigen . . .
Sensitization ~ it remembers

Immune system responds stronger the second time around

Immune System ~ Chapter 22 ~ 1/30/2017

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FORMS OF IMMUNITY
Innate Immunity
Genetically Determined at Birth ~ species specific
NO prior exposure to foreign substance needed

Acquired Immunity
Produced by PRIOR EXPOSURE
Develop own or receive antibodies to foreign substance

Acquired Passively ~ Passive Immunity

Produced by transfer of antibodies from another
person or another source

Induced ~ Receive antibodies directly

Tetanus anti-toxin . . . Snake anti-venom

Natural ~ Receive antibodies from mother ~ milk

Acquired Actively ~ Active Immunity
Make OWN antibodies in response to antigens

Induced ~ Develops from artificial exposure

Vaccines

Acquired ~ from exposure to environment

Natural exposure/recovery
Immune System ~ Chapter 22 ~ 1/30/2017

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MECHANISMS OF ACQUIRED IMMUNITY

Cell Mediated Immunity ~ occurs within cells
From t-cells ~ T-lymphocytes
Defends against abnormal pathogens or antigens
within cells

Humoral Immunity ~ occurs outside cells

Antibody Mediated Immunity ~ classical
Defends against abnormal pathogens or antigens in
body fluids outside cells
Antibodies produced by B-lymphocyte plasma cell
Antibodies circulate freely in blood
Circulating antibodies bind to a pathogen or toxins
produced by pathogen -----> neutralization

Neutralization ~ marks foreign substance for

destruction, removal by phagocytes, or complement

Specific Body Defense Involves the Immune Response

Cell-mediated Immunity
Antibody Mediated Immunity
Long Term Immunity ~ memory

Immune System ~ Chapter 22 ~ 1/30/2017

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Dr. Vince Scialli

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CELLS OF THE IMMUNE SYSTEM

T - LYMPHOCYTES ~ T-cells ~ Controls Immune System
From hemocytoblasts stem cells in bone marrow
Migrate to thymus & mature
Develop immunocompetence in thymus
Sub-populations: Cytotoxic T-cells ~ NK cells
T-helper cells
T-suppressor cells
Memory cells
Recognize foreign antigens & respond
Non-antibody producing ~ stimulate cell-mediated
immunity
Activated by macrophages ~ cytokines
Migrate to blood, lymph nodes, spleen & other organs of
lymphatic system in ready position ~ memory

B - LYMPHOCYTES ~ B-cells
From hemocytoblasts stem cells in bone marrow
Important in humoral immunity ~ antibody mediated
Sub-populations: Plasma Cells ~ become antibodies
Memory cells
Migrate to blood, lymph nodes, spleen & other organs of
lymphatic system in ready position ~ memory
Immune System ~ Chapter 22 ~ 1/30/2017

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ANTIGENS ~ Ag
Substances recognized as foreign by body ~ NOT SELF
Usually large complex molecules
Proteins ~ strongest & MOST COMMON antigens
SOME Lipids . . . Nucleic Acids . . . Polysaccharides
Provoke immune response specific to foreign substance

Antigenic Determinant ~ portion recognized as foreign

Complete Antigens
Immunogenic ~ Protective & Neutralizing ~ GOOD
Stimulate a proliferation of specific B-lymphocytes to
produce specific antibodies ~ lock & key fit
Reactive ~ Anaphylaxis & Hypersensitivity ~ BAD
React with specific lymphocytes & IgE antibodies

Partial Antigens ~ Haptens >>> ALLERGY

Small foreign particles NOT immunogenic by themselves
Become immunogenic antigens & reactive when linked to
other body proteins in some people
Poison ivy
Animal dander
Detergents
Penicillin
Cosmetics
Pollens
Grasses & Weeds
Household Products Foods
Thus . . . allergic in some individuals & not in others
Immune System ~ Chapter 22 ~ 1/30/2017

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MACROPHAGES ~ antigen presenting cells

Arise from Monocytes
Distributed throughout lymphoid organs
Engulf foreign particles ~ phagocytosis

Antigen Presenting Cells ~ APC

Present antigenic determinants on surfaces of
pathogen recognized as foreign
Present to T-cells
Stimulates engulfment by macrophage
Secrete Cytokines
Chemicals which mediate cellular immunity
Activate T-cells to become phagocytic
Enhance Inflammatory response
Stimulate B & T-cell proliferation
Stimulate immature helper T-cells
Secrete bactericidal chemicals ~ kill bacteria
EG:

Immune System ~ Chapter 22 ~ 1/30/2017

Interferons, interleukins, etc.

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Antigen Presentation
T-cells MUST be activated by exposure to antigen
Antigen-Presenting Cells ~ Macrophages ~ APCs
Macrophages respond to activated T-cells
Release lysosomes ~ lyse foreign invader
Presents marked antigen on surface for destruction

MHC Proteins ~ Self Antigens ~ produced by SELF

MHC = major histo-compatability complex
Proteins on our own cells ~ Mark Self as NOT foreign
Only identical twins have same MHC proteins
If cells infected by foreign invader . . .
MHC proteins sense foreign proteins ~ warning flag
MHC proteins become marked by foreign protein
Body MUST get rid of marked MHC complex
before it causes harm
Self MHC Antigens are antigenic to other persons
Blood Transfusion ~ ABO blood type
Tissue or Organ Transplants
Could be recognized as foreign in autoimmune disease
Immune System ~ Chapter 22 ~ 1/30/2017

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Dr. Vince Scialli

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CELL MEDIATED IMMUNITY

Defends against abnormal cells & pathogens inside cells
Involves T-lymphocytes ~T-cells
Needed where humoral immunity is ineffective or slow
When pathogens attack quickly & replicate
Target cells infected with viruses, bacteria, parasites &
cancerous cells ~ all have abnormal foreign protein (not self)

Types of T- lymphocytes ~ T-cells ~ many & diverse

Cytotoxic ~ Killer T-Cells ~ NK Cells
Kill invaded, damaged or cancerous cells ~ perforin

Helper T Cells ~ the master switch

Promote development of other T-cells
Also stimulate B-cells to produce antibodies

Suppressor T Cells ~ the regulator

Release chemicals which inhibit T & B-cells
End immune response ~ turn off

Memory T-Cells ~ the ready position

Trigger differentiation into cytotoxic T-cells upon
repeated exposure to same foreign antigen
Immune System ~ Chapter 22 ~ 1/30/2017

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Dr. Vince Scialli

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CELL MEDIATED IMMUNITY

Antigen engulfed by Macrophage ~ becomes APC
Activates immature Helper T-cells
Antigen displayed on surface of infected cell ~ marked MHC
Activates immature Cytotoxic T-cells

Helper T Cells ~ the master switch

Become primed & activated by APC & MHC

APC ~ antigen presenting cells ~ macrophages

MHC ~ major histocompatability complex ~ marked
Release cytokines & lymphokines that attract other
types of WBCs to infection site
Interferons & Interleukins
Stimulate proliferation of mature B & T cells ~ MAJOR

T- cells ~ cell mediated immunity

B-cells ~ humoral immunity & antibody production
Enhance nonspecific defense system & inflammation

HIV (Aids Virus) ~ inhibits Helper T-Cells

Causes massive immunodeficiency
Immune System ~ Chapter 22 ~ 1/30/2017

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Cytotoxic T-cells ~ NK cells ~ the weapon

Only T-cell that can attack & kill other cells
Attack & lyse invading foreign protein ~ MHC marked
Release PERFORIN ~ kills target cell
Roam through body via blood and lymph ~ mobile
Search for MHC cells displaying foreign antigens
Target infected cells (virus & bacteria), foreign cells, &
cancer cells

NK Cell Lethal Hit Mechanism

1.

Killer T-cell docks to target cell ~ APC ~ Macrophage

2.

PERFORIN is released from T-cell & inserted into

target cell plasma membrane

3.

Killer T- cell detaches

4.

PERFORIN molecules cause cell membrane lysis

5.

Other lethal mechanisms:

DNA fragmentation in target cells
Slow destruction of tumor cells
Stimulation of macrophages

Immune System ~ Chapter 22 ~ 1/30/2017

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Memory T-Cells
Remain in reserve to differentiate into cytotoxic T-cells
Differentiation occurs immediately after a second attack
Overwhelms attacking organism before it can become
established

Memory B-Cells
Remain in reserve to differentiate into plasma cells
Differentiation occurs immediately after a second attack
Very rapid antibody response occurs
Overwhelms attacking organism & neutralizes it before it
can become established

Suppressor T-Cells ~ the regulator

Regulatory cells which inhibit activity of B & T-cells
Stop immune response after foreign antigens have
been destroyed
Suppression occurs slowly

Immune System ~ Chapter 22 ~ 1/30/2017

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Dr. Vince Scialli

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HUMORAL IMMUNE RESPONSE ~ Antibodies

Antibody Mediated Immunity ~ Humoral Immunity
Very specific antibody response to an antigen challenge
Formation of Antigen-Antibody Complex

ANTIGEN ~ Antigenic Determinates

Portion of antigen recognized as foreign
Could be many antigenic determinates on an antigen
Determines the immunogenicity of antigens
Stimulates production of Antibodies

ANTIBODIES ~ Immunoglobulins ~ Ig
Proteins produced by B-lymphocytes & plasma cells
Attach to antigenic determinants on antigen

Antibody Structure
Four chains arranged in a Y or T shape
Two short light & two long heavy chains
Tips are Variable . . . Heavy Chains are Constant
Specialized Binding Sites ~ very specific
For Antigens . . . Complement . . . Macrophage
Immune System ~ Chapter 22 ~ 1/30/2017

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ACTIVE IMMUNITY ~ body response to antigen challenge

1.

Naturally Acquired ~ antibodies self produced

Exposure to bacteria, viruses or other pathogens

2.

Artificially Acquired ~ antibodies self produced

Induced from vaccines or vaccination

PASSIVE IMMUNITY ~ immediate but temporary ~ NO

ANTIBODIES
PRODUCED
Antibodies received directly from an external source
Antibodies in mothers milk or in serum infusion
Tetanus Anti-toxin antibodies
Snake Anti-venom antibodies

Immune System ~ Chapter 22 ~ 1/30/2017

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Antigen-Antibody Complex Formation ~ STEPS

1.

Antigen Challenge ~ Primary Challenge

First encounter between B-lymphocytes & invading
foreign substance ~ the antigen
B-cell lymphocytes ~ recognize antigen challenge
B-lymphocyte multiplies into army of sensitized B-cells

Sensitization ~ B-cell Activation

Occurs in spleen, lymph nodes or lymphoid tissue
2.

Primary Response ~ a humoral antibody response

Differentiate into a specific antibody against the antigen

B-cells become Plasma Cells ~ Takes 3 - 6 days LAG

Secrete specific antibodies ~ last for 4 - 5 days

B-cells become Memory B - cells for future attacks

READY in case of a second invasion by antigen
3.

Future Antigen Challenge ~ Secondary Challenge

The next time same antigen invades body by exposure

4.

Secondary Response ~ Anamnestic Response

Memory B - cells mount an immediate humoral response
if specific antigen is ever encountered again

Immune System ~ Chapter 22 ~ 1/30/2017

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Dr. Vince Scialli

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SECONDARY RESPONSE ~ Anamnestic Response

Results in MANY MORE antibodies produced VERY RAPIDLY
Overwhelms secondary foreign invader
Memory B-cells provide body with IMMUNE MEMORY
Memory can last a life time ~ but decreases with age
Secondary response involves an encounter of memory B-cells
with a previous recognized antigen
Anamnistic Antibody Response is . . .
1.

Faster ~ immediate
Response occurs in only 2 - 3 days ~ NOT 5 - 7 days

2.

Stronger
Plasma level antibodies rise to much HIGHER levels
than the primary response

3.

Longer
Plasma antibody levels REMAIN HIGH for weeks to
months ~ not 4 - 5 days

4.

More Effective
Antibodies bind with greater affinity to antigen as
compared to primary response
Overwhelms the invading antigen or attacker

Immune System ~ Chapter 22 ~ 1/30/2017

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Antibody Classification
Heavy chain structure determines way antibody is secreted &
how it is distributed in body

Heavy Chain = Constant Segment

Five major classes
IgM early protecting antibody ~ first antibodies
IgA local immunity antibody ~ in glandular secretions
IgG MOST common in serum ~ 80%
IgD B-cell activation
IgE antibodies of allergic reactions ~ histamine
Mechanism of Antibody Action
Antibodies function to inactivate & tag foreign invaders
1.

Neutralization
Simple mechanism
Antibody blocks binding sites on virus or bacteria or
on toxins secreted by pathogenic organisms
Prevents toxins from binding to receptor sites on
tissue cells
Antigen-antibody complex engulfed & phagocytized

Immune System ~ Chapter 22 ~ 1/30/2017

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2.

Agglutination ~ ABO Blood

Antibodies bind to more than one antigen ~
clumping
Antigen-antibody complex become cross linked
forming matrix or lattice
Matrix engulfed & phagocytized

3.

Precipitation
Antibodies cause soluble antigenic molecules to
become cross-linked with other soluble antigenic
molecules
Antigen-antibody complexes settle out of solution as
precipitates
Precipitates engulfed & phagocytized

4.

Complement Fixation and Activation

MOST COMMON of primary mechanism of antigenantibody interaction
Antibodies bind to antigenic determinant target sites
on pathogen
Results in complement fixation & activation
Chemicals released attracts macrophages &
enhances inflammatory response & lysis
Complement coated invaders attracted to Blymphocytes

Immune System ~ Chapter 22 ~ 1/30/2017

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Dr. Vince Scialli

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IMMUNE SYSTEM IMBALANCES

Hypersensitivities & Allergy ~ COMMON
Intense reaction to allergen AFTER an initial sensitivity
Initial exposure ----> release of very reactive IgE antibody
Second encounter with antigen results in antigenantibody reaction with MOSTLY IgE
Common foreign antigens:

Bee sting
Fire ants
Poison ivy
Animal dander

Symptoms caused by Histamine release from mast cells

& basophils
Vasodilation of blood vessels
Constriction of bronchioles
Immediate hypersensitivity ~ anaphylaxis
IgE induced
Anaphylactic Shock ~ serious
Sub-acute hypersensitivity ~ less severe
IgM or IgG induced
Delayed hypersensitivity ~ cell mediated response ~ slow
Skin Allergy contact dermatitis
Immune System ~ Chapter 22 ~ 1/30/2017

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Organ Transplants
Graft Rejection of foreign organ transplant is COMMON
Due to cell mediated response ~ cytotoxic T-cells attack
foreign graft
Organs from others recognized as foreign ~ NOT SELF
Must immunosuppress first ~ with cortisone
Infections are major complications

Immunodeficiencies
Involves many syndromes AIDS
Body destroys its own Helper t-cells
Body CANNOT mount humoral or cell mediated response
Overwhelming infections fatal if not treated (antibiotics)

Autoimmune Diseases
Body recognizes itself as foreign ~ NOT SELF
Mounts an immune response against self antigens ~ MHC
Auto-antibodies ~ antibodies against self
Examples:

Graves Disease ~ anti-TSH antibody

Rheumatoid arthritis
Multiple Sclerosis

Immune System ~ Chapter 22 ~ 1/30/2017

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