Chapter 43 The Immune System A macrophage engulfing bacteria

Chapter 43

The Immune System

A macrophage engulfing bacteria

Smallpox virus

The Body’s Defenses

Anthrax bacteria


Protozoan Trypanosoma

(African sleeping sickness)


Sac fungus Candida albicans

(yeast infections)


Heartworm nematodes...


How does the human body defend against invaders?

INNATE IMMUNITY Rapid responses to a

broad range of microbes

ACQUIRED IMMUNITYSlower responses to

specific microbes

External defenses Internal defenses

Skin

Mucous membranes

Secretions

Phagocytic cells

Antimicrobial proteins

Inflammatory response

Natural killer cells

Humoral response(antibodies)

Cell-mediated response(cytotoxic lymphocytes)

Invadingmicrobes

(pathogens)

Figure 43.2

Skin is an inhospitable barrier of dead, dry cells, & secretions containing oil & lactic acid

Mucous membranes in respiratory, digestive & urogenital tracts secrete mucus & antibiotic chemicals (e.g., lysozyme,

which digests bacterial cell walls)





specific microbes


Skin

Mucous membranes

Secretions

Phagocytic cells






Invadingmicrobes

(pathogens)

Figure 43.2

If external defenses are not effective – nonspecific, innate response

E.g., macrophages, dendritic cells

Four types of phagocytic leucocytes (WBCs) engulf invaders


Microbes

VacuoleLysosome

Macrophage

Figure 43.4

Natural killer cells (WBCs) – destroy infected cells & cancer cells by inducing

apoptosis (programmed cell death)


Antimicrobial proteins – (e.g., lysozyme) produced by many cells of the body, often in response to infection; actively destroy

microbes


Local inflammatory response – injury or pathogens can cause mast cells of

connective tissues to release histamine, triggering dilation and increased

permeability of capillaries


Fever – systemic (widespread) response that increases the body’s thermostat





specific microbes


Skin

Mucous membranes

Secretions

Phagocytic cells






Invadingmicrobes

(pathogens)

Figure 43.2

ImmuneImmune

SystemSystem

Circulatory

System

Lymphatic

System

Immune system – mounts attack on specific disease agents

2 main types of lymphocytes (WBCs):

B cells – produced in bone marrowdifferentiate in bone marrow

T cells – produced in bone marrowdifferentiate in thymus


Mature B and T cells are found throughout the body in lymph and blood

2 main types of lymphocytes (WBCs):


Bone marrowLymphoid

stem cell

B cell

Blood, lymph, and lymphoid tissues

T cell

Thymus

Figure 43.10

Lymphocytes recognize and respond to particular microbes and foreign molecules, i.e.,

they display specificity

A foreign molecule that induces an

immune response is known as an

antigen

RECOGNITION

RECOGNITION

Fig. 43.7

Multiple antibodies may recognize the same antigen by different epitopes (small accessible portions

of the larger molecule)

B cells produce antibodies, that are either secreted out of the cells or remain embedded in the B cell

membranes, and that bind to antigens

RECOGNITION

B cells produce antibodies, that are either secreted out of the cells or remain embedded in the B cell

membranes, and that bind to antigens

T cells have T-cell receptors, embedded in their cell membranes, that bind to antigens

RECOGNITION

RECOGNITION

Even though many receptors (antibodies or T-cell receptors) encounter a given type of antigen, only the receptors that are compatible will bind to them

Fig. 43.12

Illustrated here for B cells, but the process for T cells is similar

This process is known as clonal selection

Fig. 43.8

RECOGNITION Secreted antibodies con-stitute a group of proteins called immunoglobulins

Antibodies have 2 heavy chain and 2 light chain subunits

Each subunit has a constant region and a variable region

The variable region can bind to an antigen

Construction of antibodies(and T-cell receptors)

Millions of antigens are recognized by randomly combining the protein products of hundreds of genes

RECOGNITION of non-self molecules

Card analogy: although there are only 52 cards in the deck, random combinations can produce an

enormous number of different hands

Construction of antibodies

B


BB


B BB

In a healthy immune system, as B and T cells mature they are destroyed by apoptosis if they attack self

molecules

RECOGNITION of self molecules

Healthy, mature B and T cells then have the capacity to distinguish self from non-self molecules

Almost all cells in an individual human’s body have major histocompatibility complex (MHC)

glycoproteins embedded in their cell membranes


Class I MHC molecules are found on almost every nucleated cell

Class II MHC molecules are restricted to a few specialized cells, including macrophages,

dendritic cells, B cells, etc.

MHC glycoproteins migrate to the cellmembrane after they are produced


MHC glycoproteins pick up molecules from the cytosol that are presented at the cell’s surface

T cells bind to MHC glycoproteins and the molecules they present

An individual’s own MHC glycoproteins, and molecules of its own body that the MHC glycoproteins present, are

treated as self

However, T cells treat foreign molecules presented by MHC glycoproteins as antigens


Fig. 43.9

Cytotoxic T cells bind to cells that carry Class I MHC glycoproteins


Fig. 43.9

Helper T cells bind to cells that carry Class II MHC glycoproteins


Fig. 43.9

Fig. 43.12

ATTACK & MEMORY The B and T cells that recognize a given foreign

antigen produce two types of clones:effector cells (attackers) and memory cells


ATTACK & MEMORY The B and T cells that first recognize a given foreign

antigen are short lived, whereas immune memory cells can have long lifetimes


Fig. 43.12

Fig. 43.13

ATTACK & MEMORY Memory cells help produce a secondary immune

response that is faster, of greater magnitude, and of longer duration than the primary immune response

ATTACK & MEMORY There are two types of immune response:

Humoral responseB cells and antibodies

Attack antigens that have not yet infected cells (toxins, bacteria, and viruses in body fluids)

Deactivate, coat, and clump antigens (which are then often engulfed and destroyed by macrophages)

ATTACK & MEMORY There are two types of immune response:

Cell-mediated responseT cells

Attack antigens after they have entered cells, as well as fungi, protozoa, and parasitic worms

Activated T cells kill antigen-containing cells by creating pores in their cell membranes

RECOGNITION, ATTACK, & MEMORY

Figure 43.14

Humoral response Cell-mediated response

First exposure to antigen

Antigens Dendritic cells Infected cells

Activate Activate Activate

Gives rise to Gives rise to Gives rise to

B cell HelperT cell

CytotoxicT cell

Plasmacells

MemoryB cells

Active and memory helperT cells

Memory cytotoxic

T cells

Active cytotoxic

T cells

Secrete antibodies that defend againstpathogens and toxins in extracellular fluid

Defend against infected cells, cancer cells, and transplanted tissues

Cytokinesactivate

Involves the activation and

clonal selection of B cells

Results in the production of

antibodies that circulate in the

blood and lymph

MHC II MHC I


Figure 43.14



Antigens Dendritic cells Infected cells



B cell HelperT cell

CytotoxicT cell

Plasmacells

MemoryB cells


Memory cytotoxic

T cells

Active cytotoxic

T cells



Cytokinesactivate

Involves the activation and

clonal selection of cytotoxic T

cells

Cytotoxic T cells directly

destroy certain target cells

MHC II MHC I


Figure 43.14



Antigens



B cell HelperT cell

CytotoxicT cell

Plasmacells

MemoryB cells


Memory cytotoxic

T cells

Active cytotoxic

T cells



Cytokinesactivate

A primary immune

response begins with the

first exposure to an antigen

A secondary immune

response begins with a re-exposure to an

antigen, and stimulates

memory cells

Dendritic cells Infected cells

MHC II MHC I

Medical practices can augment our immune response by inhibiting invaders or

enhancing the immune response

Antibiotics Inhibit microbial reproduction

Potent agents of natural selection

Vaccines (weakened or dead microbes, or their toxins)

Stimulate development of memory cells = faster response to invasion

Selectively effective

The immune system and blood types

Table 43.1

antigen antigen antigens

Allergies

Exaggerated immune responses to otherwise benign substances

What happens when the immune system malfunctions?


1. Antibodies are produced

Fig. 43.20


1. Antibodies are produced 2. Stems of antibodies attach to mast cells, especially in the respiratory tract

Fig. 43.20


1. Antibodies are produced 2. Stems of antibodies attach to mast cells, especially in the respiratory tract

3. When antibodies attached to mast cells bind antigens, the mast cells release histamine, which causes inflammation

Fig. 43.20

Autoimmune diseasesThe immune system lacks or loses its ability to

distinguish self vs. non-self molecules, i.e., it loses its self-tolerance and produces anti-self antibodies


Rheumatoid arthritis (cartilage of joints)

Multiple sclerosis (mylein sheaths of neurons)

Insulin-dependent diabetes mellitus (insulin-secreting cells of the pancreas)


Severe Combined Immunodeficiency (SCID)

An inherited disorder

Acquired Immunodeficiency Syndrome (AIDS)

Caused by retroviruses (Human Immunodeficiency Viruses –

HIV) that especially infect helper T cells

Immunodeficiency diseasesInhibit effective immune response; either

inherited or acquired

Adults and children estimated to be living with HIV as of the end of 2001

Western Europe

560,000560,000North Africa & Middle East

440,000440,000Sub-Saharan

Africa

28.1 28.1 millionmillion

Eastern Europe & Central Asia

1 million1 million

South & South-East Asia

6.1 million6.1 million

Australia & New Zealand

15,00015,000

North America

940,000940,000Caribbean

420,000420,000

Latin America


Total: 40 million

East Asia & Pacific

1 million1 million


Estimated number of deaths from AIDS during 2001

Western Europe

6,8006,800North Africa & Middle East

30,00030,000Sub-Saharan

Africa


Eastern Europe &Central Asia

23,00023,000East Asia & Pacific

35,00035,000South & South-East Asia

400,000400,000

Australia & New Zealand

120120

North America

20,00020,000Caribbean

30,00030,000

Latin America

80,00080,000

Total: 3 million



HIV destroy helper T cells– Victims die from other diseases

The global AIDS epidemic

Transmission– Direct contact between broken skin, mucous membranes & body

fluids

No cure – Treatments = inhibitors of reverse-transcriptase and protease– Problem = virus evolves quickly

How to reduce your risk– Practice safe sex– Avoid used needles

Cancer

Malfunction in cell production combined with a lack of recognition by the

immune system of aberrant cells or too many of them

Uncontrolled growth = tumor


Causes

Carcinogens, viruses, inheritance

No guaranteed cure

Most treatments also destroy healthy cells

How to reduce your risk

Reduce exposure to carcinogens

Documents

Chapter 43 The Immune System A macrophage engulfing bacteria