Disturbances IN Inflammatory and Immunologic FUNCTIONING

by:

Joanne T. Tolentino, RN

Overview of Immune System

Central and Peripheral Lymphoid System
Primary Secondary

Immune Function

Defenses

A. Innate Immunity
Barriers Defensive cells Chemical defenses

B. Adaptive Immunity
Cell mediated immunity Antibody mediated immunity

 Types of Immunity 1. Active immunity 2. Passive immunity

THE IMMUNE SYSTEM

We all get sick sometimes...but then we get better.
What happens when we get sick?
Why do we get better?

Immune/ Lymphatic System

A collection of cells and proteins that works together to protect the body from harmful/ infectious micro organisms

Parts of Lymphatic System

Lymphthe tissue fluid that enters lymph capillaries Lymph Vessels are found in most tissue spaces; collect tissue fluid and proteins

Lymphatic tissue consists mainly of lymphocytes

 The immune system is localized in several parts of the body immune cells develop in the primary organs - bone marrow and thymus immune responses occur in the secondary organs

Primary Lymphatic Organs

Thymus glandular organ near the heart where T cells learn their jobs

 Bone marrow bloodproducing tissue located inside certain bones

blood stem cells give rise
to all of the different types of blood cells

Secondary Lymphatic Organs

Lymph Nodesencapsulated masses of lymphatic tissue

Lymph Nodulessmall unencapsulated masses of lymphatic tissue Spleenlocated in the upper left abdominal quadrant behind the stomach

Interstitial fluid
Adenoid Tonsil

Lymph nodes Spleen Peyers patches (small intestine) Appendix Tissue cells

Blood capillary Lymphatic vessel

Lymphatic vessels

Lymph node

Masses of defensive cells

Immunity may be defined as the ability to destroy pathogens or other foreign material and to prevent further cases of certain infectious diseases.

INDUCTION OF AN IMMUNE RESPONSE

reign invaders - viruses, bacteria, allergens, toxins and rasites- constantly bombard our body.

YOUR ACTIVE IMMUNE DEFENSES

Adaptive Immunity Innate Immunity

- invariant (generalized) - early, limited specificity - the first line of defense - variable (custom) - later, highly specific - remembers infection

Pathogens (microorganisms and viruses)

INNATE IMMUNITY Recognition of traits shared by broad ranges of pathogens, using a small set of receptors Rapid response

Barrier defenses: Skin Mucous membranes Secretions Internal defenses: Phagocytic cells Antimicrobial proteins Inflammatory response Natural killer cells

ACQUIRED IMMUNITY Recognition of traits specific to particular pathogens, using a vast array of receptors Slower response

Humoral response: Antibodies defend against infection in body fluids. Cell-mediated response: Cytotoxic lymphocytes defend against infection in body cells.

INNATE IMMUNITY
When you were born, you brought with you several mechanisms to prevent illness. This type of immunity is also called nonspecific immunity. Innate immunity consists of: Barriers Defensive cells Chemical defenses

INNATE IMMUNITY Barriers

Physical
skin hair mucous

Chemical
sweat tears saliva stomach acid urine

Defensive cells Phagocytesmacrophages, neutrophils, eosinophils Langerhans cells and other dendritic cells Natural killer cells Basophils and mast cells

Phagocytic cells include:

Macrophages engulf pathogens and dead cell remains

Neutrophils release chemicals that kill nearby bacteria

pus = neutrophils, tissue cells and dead pathogens

Phagocyte migration

CELLS alive!

Neutrophils and macrophages recognize chemicals produced by bacteria in a cut or scratch and migrate "toward the smell".

Macrophages WBCs that ingest bacteria, viruses, dead cells, dust most circulate in the blood, lymph and extracellular fluid Macrophages, both fixed and wandering, have receptors for the pathogens humans are likely to encounter

Macrophage and E. coli

Macrophage ingesting yeast

This human macrophage, like the neutrophil, is a professional "phagocyte" or eating cell (phago="eating", cyte = "cell"). Here, it envelops cells of a yeast, Candida albicans. After ingestion, the white cell must kill the organisms by some means, such as the oxidative burst.

Neutrophils

WBCs are phagocytic, like macrophages neutrophils also release toxic chemicals that destroy everything in the area, including the neutrophils themselves

Neutrophil phagocytosing S. pyogenes, the cause of strep throat

Human neutrophils are WBCs that arrive quickly at the site of a bacterial infection and whose primary function is to eat and kill bacteria. This neutrophil ingesting Streptococcus pyogenes was imaged in gray scale with phase contrast optics and colorized.

Neutrophil killing yeast

NEUTROPHIL

YEAST

One way that neutrophils kill is by producing an antibacterial compound called superoxide anion, a process called oxidative burst. Here, an amoeboid human neutrophil senses, moves toward and ingests an ovoid yeast. In the next two panels, oxidation can be seen by using a dye, and is colorized here.

Langerhans cells and other dendritic cells activate lymphocytes Natural killer cellsdestroy foreign cells by rupturing their cell membranes Basophils and mast cellsproduce histamine and leukotrienes (inflammation)

Chemical defenses

Interferon blocks viral reproduction

Complement proteins lyse foreign cells, attract WBCs, & contribute to inflammation Inflammation

Types of Inflammation
Acute inflammation Chronic inflammation

Acute Inflammation
the early (almost immediate) response to injury It is nonspecific and may be evoked by any injury short of one that is immediately fatal.

The Inflammatory Response

The cardinal signs of inflammation
Heat (calor) redness (rubor) swelling (tumor) pain (dolor) loss of function (functio laesa)

The manifestation of acute inflammation can be divided into two categories:

vascular response cellular responses

Vascular Response
immediate vascular changes that occur (vasodilation and increased capillary permeability)

Three Patterns of Response

1. immediate transient response

2. immediate sustained response

3. delayed hemodynamic response

Vascular and Surrounding Tissues at Steady State

Inflammation

The Cellular Stage

marked by movement of phagocytic white blood cells (leukocytes) into the area of injury.

two types of leukocytes participate in the acute inflammatory responsethe granulocytes and monocytes.

The sequence of events in the cellular response to inflammation includes: (1) pavementing (2) emigration (3) chemotaxis (4) phagocytosis

Phagocytosis involves three distinct steps:

(1) adherence plus opsonization (2) Engulfment (3) intracellular killing

Phagocytosis

Inflammatory Mediators
Histamine Plasma Proteases Prostaglandins Leukotrienes Platelet-Activating Factor

Chronic Inflammation
is self perpetuating and may last for weeks, months, or even years it may develop during a recurrent or progressive acute inflammatory process characterized by an infiltration by mononuclear cells (macrophages) and lymphocytes

Healing of a skin wound by primary and secondary intention (A) The inflammatory phase (B) The proliferative phase (C) Remodeling stage

 Your moms antibodies were effective for just a short time at birth, but your innate immune system can be activated quickly. It is always your first line of defense during an infection, but it cant always eliminate the germ. When this happens, your body initiates a focused attack against the specific pathogen that is causing the infection. This attack may lead to long-term protection against that pathogen.

This type of immunity is called adaptive immunity, the customized second line of defense.

 Acquired immunity, or adaptive immunity, develops after exposure to agents such as microbes, toxins, or other foreign substances It involves a very specific response to pathogens

Acquired Immunity: An Overview

B cells and T cells have receptor proteins that can bind to foreign molecules Each individual lymphocyte is specialized to recognize a specific type of molecule

STARTING AN IMMUNE RESPONSE

Foreign invaders - viruses, bacteria, allergens, toxins and parasites - constantly bombard our body.

The response to this assault is a carefully orchestrated and controlled interaction between immune cells with the ultimate goal to eliminate the invader by pathogen-specific mechanisms.

Antigen Recognition by Lymphocytes

An antigen is any foreign molecule to which a lymphocyte responds A single B cell or T cell has about 100,000 identical antigen receptors

Antigenbinding site Disulfide bridge

Antigenbinding site

Antigenbinding site

Variable regions

C
Light chain

Constant regions
Transmembrane region Plasma membrane

Heavy chains B cell (a) B cell receptor Cytoplasm of B cell

chain

chain
T cell

Disulfide bridge Cytoplasm of T cell (b) T cell receptor

Antigenbinding site Disulfide bridge

Antigenbinding site

Variable regions C Light chain C Constant regions

Transmembrane region
Plasma membrane Heavy chains B cell (a) B cell receptor Cytoplasm of B cell

Antigenbinding site

Variable regions Constant regions

V C

V C

Transmembrane region Plasma membrane

chain

chain

Disulfide bridge Cytoplasm of T cell (b) T cell receptor T cell

 All antigen receptors on a single lymphocyte recognize the same epitope, or antigenic determinant, on an antigen
B cells give rise to plasma cells, which secrete proteins called antibodies or immunoglobulins

Antigenbinding sites Antigen-binding sites Antibody A Antigen Antibody C

Epitopes (antigenic determinants)

C Antibody B

The Antigen Receptors of B Cells and T Cells

B cell receptors bind to specific, intact antigens The B cell receptor consists of two identical heavy chains and two identical light chains The tips of the chains form a constant (C) region, and each chain contains a variable (V) region, so named because its amino acid sequence varies extensively from one B cell to another

 Secreted antibodies, or immunoglobulins, are structurally similar to B cell receptors but lack transmembrane regions that anchor receptors in the plasma membrane

 Each T cell receptor consists of two different polypeptide chains The tips of the chain form a variable (V) region; the rest is a constant (C) region T cells can bind to an antigen that is free or on the surface of a pathogen

 T cells bind to antigen fragments presented on a host cell These antigen fragments are bound to cell-surface proteins called MHC molecules MHC molecules are so named because they are encoded by a family of genes called the major histocompatibility complex

The Role of the MHC

In infected cells, MHC molecules bind and transport antigen fragments to the cell surface, a process called antigen presentation

A nearby T cell can then detect the antigen fragment displayed on the cells surface Depending on their source, peptide antigens are handled by different classes of MHC molecules

Fig. 43-11

Top view: binding surface exposed to antigen receptors

Antigen Class I MHC molecule

Antigen

Plasma membrane of infected cell

 Class I MHC molecules are found on almost all nucleated cells of the body They display peptide antigens to cytotoxic T cells

Fig. 43-12

Infected cell
1 Antigen associates with MHC molecule 1 Class I MHC molecule T cell receptor

Microbe

Antigenpresenting cell

Antigen fragment

Antigen fragment 1 2 2 T cell recognizes combination Class II MHC molecule T cell receptor

(a)

Cytotoxic T cell

(b)

Helper T cell

 Class II MHC molecules are located mainly on dendritic cells, macrophages, and B cells

Dendritic cells, macrophages, and B cells are antigen-presenting cells that display antigens to cytotoxic T cells and helper T cells

Lymphocyte Development
The acquired immune system has three important properties:
Receptor diversity A lack of reactivity against host cells Immunological memory

Generation of Lymphocyte Diversity by Gene Rearrangement

Differences in the variable region account for specificity of antigen receptors
The immunoglobulin (Ig) gene encodes one chain of the B cell receptor Many different chains can be produced from the same Ig chain gene by rearrangement of the DNA Rearranged DNA is transcribed and translated and the antigen receptor formed

Fig. 43-13

DNA of undifferentiated B cell V37 V38 V39 V40 J1 J2 J3 J4 J5 Intron C

1 DNA deleted between randomly selected V and J segments DNA of differentiated B cell V37 V38 V39 J5 Intron C

Functional gene 2 Transcription

pre-mRNA

V39 J5

Intron

3 RNA processing V39 J5 B cell receptor

V V V C C C C

mRNA Cap

Poly-A tail
V

4 Translation

Light-chain polypeptide

C Constant region

Variable region

B cell

Origin of Self-Tolerance
Antigen receptors are generated by random rearrangement of DNA As lymphocytes mature in bone marrow or the thymus, they are tested for self-reactivity Lymphocytes with receptors specific for the bodys own molecules are destroyed by apoptosis, or rendered nonfunctional

Amplifying Lymphocytes by Clonal Selection

In the body there are few lymphocytes with antigen receptors for any particular epitope

The binding of a mature lymphocyte to an antigen induces the lymphocyte to divide rapidly This proliferation of lymphocytes is called clonal selection Two types of clones are produced: short-lived activated effector cells and long-lived memory cells

Fig. 43-14

Antigen molecules B cells that differ in antigen specificity

Antigen receptor

Antibody molecules

Clone of memory cells

Clone of plasma cells

 The first exposure to a specific antigen represents the primary immune response
During this time, effector B cells called plasma cells are generated, and T cells are activated to their effector forms In the secondary immune response, memory cells facilitate a faster, more efficient response

Primary immune response to antigen A produces antibodies to A.

Secondary immune response to antigen A produces antibodies to A; primary immune response to antigen B produces antibodies to B.

Antibody concentration (arbitrary units)

104 103 102 101 100 Antibodies to A Antibodies to B

14

21

28

35

42

49

56

Exposure to antigen A

Exposure to antigens A and B Time (days)

Acquired immunity defends against infection of body cells and fluids

Acquired immunity has two branches: the humoral immune response and the cell-mediated immune response Humoral immune response involves activation and clonal selection of B cells, resulting in production of secreted antibodies Cell-mediated immune response involves activation and clonal selection of cytotoxic T cells Helper T cells aid both responses

Fig. 43-16
Humoral (antibody-mediated) immune response Cell-mediated immune response Key + Stimulates Gives rise to

Antigen (1st exposure) Engulfed by

Antigenpresenting cell

B cell

Helper T cell

Cytotoxic T cell

Memory Helper T cells

+ Antigen (2nd exposure)

Plasma cells

Memory B cells

Memory Cytotoxic T cells

Active Cytotoxic T cells

Secreted antibodies Defend against extra cellular pathogens by binding to antigens, thereby neutralizing pathogens or making them better targets for phagocytes and complement proteins. Defend against intracellular pathogens and cancer by binding to and lysing the infected cells or cancer cells.

Humoral (antibody-mediated) immune response Key + Antigen (1st exposure) Stimulates Gives rise to + Engulfed by Antigenpresenting cell

+ B cell + Helper T cell

Memory Helper T cells

+ Plasma cells Memory B cells

+ Antigen (2nd exposure) +

Secreted antibodies Defend against extracellular pathogens

Cell-mediated immune response Antigen (1st exposure) Engulfed by Antigenpresenting cell Key + Stimulates Gives rise to

+ Helper T cell + Cytotoxic T cell

Memory Helper T cells

+ + Antigen (2nd exposure) + Memory Cytotoxic T cells

Active Cytotoxic T cells

Defend against intracellular pathogens

Helper T Cells: A Response to Nearly All Antigens

A surface protein called CD4 binds the class II MHC molecule This binding keeps the helper T cell joined to the antigen-presenting cell while activation occurs Activated helper T cells secrete cytokines that stimulate other lymphocytes

Antigenpresenting cell Bacterium

Peptide antigen

Class II MHC molecule CD4 TCR (T cell receptor) Helper T cell Humoral immunity (secretion of antibodies by plasma cells) Cytokines + B cell + + + Cytotoxic T cell Cell-mediated immunity (attack on infected cells)

Cytotoxic T Cells: A Response to Infected Cells

Cytotoxic T cells are the effector cells in cellmediated immune response Cytotoxic T cells make CD8, a surface protein that greatly enhances interaction between a target cell and a cytotoxic T cell Binding to a class I MHC complex on an infected cell activates a cytotoxic T cell and makes it an active killer The activated cytotoxic T cell secretes proteins that destroy the infected target cell

Cytotoxic T cell Perforin Granzymes CD8 Class I MHC molecule TCR

Target cell

Peptide antigen

Cytotoxic T cell Perforin Granzymes CD8 Class I MHC molecule TCR Pore

Target cell

Peptide antigen

Released cytotoxic T cell Cytotoxic T cell Perforin Granzymes CD8 Class I MHC molecule TCR Pore Dying target cell

Target cell

Peptide antigen

B Cells: A Response to Extracellular Pathogens

The humoral response is characterized by secretion of antibodies by B cells Activation of B cells is aided by cytokines and antigen binding to helper T cells Clonal selection of B cells generates antibodysecreting plasma cells, the effector cells of humoral immunity

Antigen-presenting cell

Bacterium Peptide antigen

Class II MHC molecule TCR CD4

Helper T cell

Antigen-presenting cell

Bacterium Peptide antigen B cell

Class II MHC molecule TCR CD4

+ Cytokines

Helper T cell

Activated helper T cell

Antigen-presenting cell

Bacterium Peptide antigen B cell

Class II MHC molecule TCR CD4

+ Cytokines

Clone of plasma cells

Secreted antibody molecules

Helper T cell

Activated helper T cell

Clone of memory B cells

Antigen-presenting cell

Bacterium Peptide antigen B cell

Class II MHC molecule TCR CD4

+ Cytokines

Clone of plasma cells

Secreted antibody molecules

Endoplasmic reticulum of plasma cell Helper T cell Activated helper T cell Clone of memory B cells

2 m

Antibody Classes
The five major classes of antibodies, or immunoglobulins, differ in distribution and function Polyclonal antibodies are the products of many different clones of B cells following exposure to a microbial antigen

Monoclonal antibodies are prepared from a single clone of B cells grown in culture

Class of Immunoglobulin (Antibody) IgG (monomer)

Distribution

Function

Most abundant Ig class in blood; also present in tissue fluids

Promotes opsonization, neutralization, and cross-linking of antigens; less effective in activation of complement system than IgM Only Ig class that crosses placenta, thus conferring passive immunity on fetus

Class of Immunoglobulin (Antibody) IgA (dimer) J chain

Distribution

Function Provides localized defense of mucous membranes by cross-linking and neutralization of antigens Presence in breast milk confers passive immunity on nursing infant

Present in secretions such as tears, saliva, mucus, and breast milk

Secretory component

Class of Immunoglobulin (Antibody)

IgM (pentamer)

Distribution

Function

First Ig class produced after initial exposure to antigen; then its concentration in the blood declines

Promotes neutralization and crosslinking of antigens; very effective in complement system activation

J chain

Class of Immunoglobulin (Antibody) IgE (monomer)

Distribution

Function

Present in blood at low concentrations

Triggers release from mast cells and basophils of histamine and other chemicals that cause allergic reactions

Class of Immunoglobulin (Antibody) IgD (monomer)

Distribution

Function

Present primarily on surface of B cells that have not been exposed to antigens

Transmembrane region

Acts as antigen receptor in the antigen-stimulated proliferation and differentiation of B cells (clonal selection)

The Role of Antibodies in Immunity

Neutralization occurs when a pathogen can no longer infect a host because it is bound to an antibody
Opsonization occurs when antibodies bound to antigens increase phagocytosis Antibodies together with proteins of the complement system generate a membrane attack complex and cell lysis

Viral neutralization

Virus

Fig. 43-21b

Opsonization Bacterium

Macrophage

Activation of complement system and pore formation

Complement proteins
Formation of membrane attack complex

Flow of water and ions

Pore

Foreign cell

Viral neutralization

Opsonization Bacterium

Activation of complement system and pore formation

Complement proteins Virus

Formation of membrane attack complex

Macrophage Flow of water and ions

Pore

Foreign cell

Active and Passive Immunization

Active immunity develops naturally in response to an infection
It can also develop following immunization, also called vaccination In immunization, a nonpathogenic form of a microbe or part of a microbe elicits an immune response to an immunological memory

 Passive immunity provides immediate, short-term protection It is conferred naturally when IgG crosses the placenta from mother to fetus or when IgA passes from mother to infant in breast milk It can be conferred artificially by injecting antibodies into a nonimmune person

Fig. 43-22

How does an immune response end?

The immune response will end when the antigen that caused the response is no longer present

Induction of an immune response to infection requires several days or weeks What can you do while youre waiting???????

Temporary protection against infection can be established by giving pre-formed antibody

THE IMMUNE SYSTEM IN HEALTH AND DISEASE

How does your everyday life affect your immune system?

Exercise and stress

exercise has been shown to boost the immune response
moderate exercise increases the immune response in all age groups intensive exercise can stress the immune system

lack of sleep and exhaustion decrease immune function psychological stress has also been found to decrease immune function

Diet
a well-balanced diet is essential for good immune system health
fats are very important in the production of WBCs, cytokines and natural killer cells selenium, zinc, and copper are required in small amounts, which you get if you eat a balanced diet vitamin E has been shown to boost antibody production in the elderly vitamin B6 aids in antibody synthesis

but mega-dosing can be harmful, too!

Environment
Exposure to certain things in their environment may activate the immune systems of some people
Chemicals dioxin pesticides solvents Sunlight Viruses

Bacteria

Medication

Food

Gender and the immune system

women respond to antigens more strongly than men
estrogen may affect the development or function of immune cells may explain why more women develop autoimmune diseases