Immune System

transcript

Immune System

Introduction• An animal must defend itself against

pathogens (organism or virus that causes a disease)

– Viruses

– Bacteria

– Fungi

– Parasites• Protozoa –heterotrophic protists (eukaryotes,

usually unicellular); giardia, trypanosoma, plasmodium (malaria)

• Worms (flatworms & roundworms)

– Prions

3 Types of Defense

Fig. 43.1

Nonspecific: doesn’t distinguish one pathogen from another

Specific: recognition of a pathogen by lymphocytes; development of

immunity

1st Line of Defense:

Nonspecific

Skin, Mucous Membranes, Secretions

Physical barriers: skin & mucous membranes

• Mucus: viscous fluid secreted by cells of mucous

membranes, traps microbes and other particles

• Washing: tears, saliva, sweat

Chemical barriers:

• Stomach acid: kills most pathogens, but not all (ie.

giardia, hep A)

• Skin secretions: from sebaceous and sweat glands in

– pH 3-5 to prevent colonization of microbes

– lysozymes: antimicrobial enzymes, digest cell walls of

bacteria

2nd Line of Defense:

Nonspecific

Inflammatory Response

& Phagocytosis

Tissue damage leads to:

• Inflammatory Response: enhanced blood

flow and vessel permeability

characteristic swelling, redness, and heat

of inflammation

• Phagocytosis: ingestion of pathogens by

phagocytes (leukocytes/WBCs)

Systemic Inflammatory Response

Severe tissue damage or infection

widespread response

– Rapid increase in leukocytes in the blood within a few hours after the initial events

– Fever can be triggered by toxins from pathogens or by pyrogens released by certain leukocytes

– Inhibits growth of some microbes, facilitating phagocytosis, and speeding up tissue repair

Septic shock: characterized by high fever and low blood pressure; most common cause of death in U.S. critical care units

Fig. 43.5

1. Damaged cells release chem signals (histamine, prostaglandins)

2. Nearby capillaries dilate & become more permeable; fluid and

clotting agents move from the blood to the site

3. Chemokines & other chemotactic factors attract phagocytes from

the blood

4. Phagocytes consume pathogens & cell debris, producing pus

Localized Inflammatory Response

Blood Clotting: prevention of blood loss, pathogens from entering

Fig. 42.16

Blood clotting steps1. Endothelium of blood vessel is damaged and connective

tissue is exposed to blood

2. Platelets (cell fragments) adhere to collagen fibers(glycoprotein in the extracellular matrix; nonelastic; does not tear easily) in connective tissue

3. Platelets and tissue release chemicals that makes nearby platelets sticky

4. Platelets form a ‘plug’ that provides emergency protection against blood loss

5. When vessel damage is more severe, a clot of fibrin reinforces this ‘plug’

Fibrinogen Fibrin

Fibrinogen: ‘inactive’ soluble plasma protein

Fibrin: ‘active’ insoluble plasma protein

clotting factors released from clumped platelets or

damaged cells + clotting factors in blood plasma

prothrombin thrombin

(inactive plasma protein) (an active enzyme)

thrombin catalyzes the conversion of

fibrinogen (soluble) fibrin (insoluble)

fibrin threads get woven into a ‘patch’

Red blood cells trapped in a clot of fibrin

http://media-2.web.britannica.com/eb-media/28/98328-004-5514AFAC.jpg

http://www.textbookofbacteriology.net/Phago.jpeg

Phagocytosis: ingestion of pathogens by

phagocytes (leukocytes/WBCs)

Phagocytes

1. Neutrophils

2. Monocytes

3. Eosinophils

Neutrophils

• 60%-70% of leukocytes (WBCs)

• damaged cells (by invading pathogens) release chemical

signals (cytokines) that attract neutrophils from the blood

• neutrophils enter infected tissue, engulfing and

destroying pathogens by

• self-destruct as they destroy foreign invaders

• avg life span = days

http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab6/IMAGES/Neutrophil%20Blood%20WITH%20LABEL%20copy.jpg

Monocytes

Cummings

Fig. 43.3: phagocytosis by a macrophage

• 5% of WBCs

• more effective than neutrophils

• circulate in blood a few hours

• then migrate into tissues and develop into macrophages

macrophages: large, long-lived phagocytes

• avg. life span = months

(macrophages)

Locations of macrophages:- circulate in body: blood & lymph

- tissues: lung, liver, kidney,

connective tissue, brain,

lymph nodes, spleen

Fig. 43.4a

Lymphatic system

Eosinophils

• 1.5% of WBCs

• large parasitic invaders (ie blood fluke, Schistosoma

mansoni)

• position themselves against external wall of a parasite,

discharge destructive enzymes from cytoplasmic

granules

http://www.funsci.com/fun3_en/blood/blood_09.gif

NOT Phagocytes: Natural Killer (NK) cells

(but part of the nonspecific response)

• destroy virus-infected body cells

• also attack abnormal body cells that could become

cancerous

• NOT phagocytic: mount an attack on the cell’s

membrane, causing the cell to lyse

A natural killer cell (NK cell, yellow)

of the immune cell attacking a cancer

cell (red).

http://www.bio-pro.de/imperia/md/images/artikelgebunden/stern/nk_tumor_338x319.jpg

3rd Line of Defense:

Specific Immunity

http://www.biooncology.com/bioonc/images/b-cell-lg.jpg

http://www.besthealth.com/besthealth/bodyguide/reftext/im

ages/tcell.jpg

T cell

B cell

Specific immunity: lymphocytes (leukocytes)

recognize and respond to particular foreign

bodies by generating selective immunity

responses throughout the body specificity

Antigens

Antigen: a foreign ‘invader’ (pathogens, transplanted

cells, cancer cells) that elicits a specific response by

lymphocytes (T cells & B cells)

– Each antigen has a particular molecular shape

– Stimulates B cells to secrete antibodies antibody

generator

Antigen receptors: membrane proteins on lymphocytes

responsible for recognizing antigens

B cell: immunoglobulins

T cell: T cell receptors

1. Lymphocytes

2 main types of lymphocytes:B lymphocytes (B cells)

T lymphocytes (T cells)

– both circulate throughout the blood and lymph

– concentrated in the spleen, lymph nodes, &

other lymphatic tissue

– specialize in recognizing different types of

antigens

– carry out specific defensive actions that

complement each other

All lymphocytes come from

stem cells

B cells

remain and mature in the

bone marrow

T cells

migrate from the bone marrow

& develop in the thymus

Fig. 43.8

2. Immune Responses

Immunity

Antibodies: proteins produced by B cells that function as ‘effectors’ of an immune response; produced in humoral response/clonal selection; responsible for immunity

Challenge and response: immunity to a disease is only developed if the immune system is challenged by the disease

Types of Immunity

Humoral

bacteria, toxins, viruses

blood plasma & lymph

(body fluids)

B cells

Cell-Mediated

bacteria, viruses, fungi, protozoa, parasitic

worms, cancer

T cells

http://library.thinkquest.org/03oct/01254/images/immune_map.jpg

Overview of immune response

Macrophage engulfs pathogen, presents antigen for

immune response

Cell Mediated

Cytotoxic (Killer)

T cells

• Cancer

• viruses

Helper

T cells

• produce cytokines

• phagocytosis

• inflammatory response

• B cells

• Memory T cells

http://library.thinkquest.org/03oct/00520/home.html

Humoral

B cell with antibodies

Helper T cell antigen

activated B cellproliferate

lots of activated B cells

plasma cells memory B cells

antibodies find/attach to pathogens phagocytosis

http://library.thinkquest.org/03oct/00520/home.html

Clonal Selection: antigen-driven cloning of

lymphocytes

Active vs Passive Immunity

Active immunity: immunological memory is

developed by the immune system when

exposed to an antigen

• Natural: the body actively produces antibodies

after being exposed to an infectious disease

• Artificial: vaccination (also called immunization)

= antigens transferred into an individual

Vaccination

• Vaccine: inactivated, killed, parts

(proteins), viable but weakened

(attenuated)

• No longer cause disease, but they can act

as antigens, stimulating an immune

response and immunological memory

• Examples: flu, yellow fever, hepatitis A & B

Immunological Memory in

Vaccination

Fig. 43.7

Active vs passive immunity (cont.)

Passive immunity: antibodies are transferred

from one individual to another; only temporary

b/c immune system has not developed

immunological memory

• Natural: antibodies are transferred from a

pregnant mother to her fetus (blood) and from a

nursing mother to an infant (breast milk)

• Artificial: antibodies from an animal already

immune to a disease are transferred via blood

transfusion or injection (ie snake antivenin)

Monoclonal Antibodies• antibodies specific for one antigen

• production

– Isolation & purification of an antigen

– Injection of antigen into healthy animal

– Immune system stimulated to form activated plasma cells which produce antibodies

– Plasma cells extracted and cultured with cancer cells

– Plasma/cancer cell hybridomas which survive for long periods of time and produce lots of antibodies

Monoclonal antibodies (cont.)

• diagnostic tests

– target antigen identification: antibodies detect

and mark antigens; signals are sent; Western

Blot, ELIZA

• colorimetric – enzymes

• chemiluminescent agents

• radioactive labels

• Fluorescent labels

– gonorrhea, HIV, Lyme disease

Monoclonal antibodies (cont.)

• Treatment

– cancer

• attach to cancer cell antigens, causes immune

response; Rituximab (B cell non-Hodgkin

lymphoma, CD20 antigen)

• Stops cancer cells from growing by blocking cell

surface protein activation

– autoimmune disorders (i.e. MS)

– delivery of medicine

Aquired ImmunoDeficiency Syndrome

• In U.S., late 1970s/early 1980s, increased rate

of Kaposi’s sarcoma & pneumonia in

homosexual men, hemopheliacs, blood

transfusion recipients, children of these gps

• Symptoms: opportunistic infections (pulmonary,

gastrointestinal), cancer (Kaposi’s sarcoma,

lymphoma), neurological disorders

(encephalopathy), fevers, sweats, weight loss

• Almost 100% mortality; most lethal pathogen

Karposi’s Sarcoma is a symptom of

Human ImmunoVirus

http://www.stanford.edu/group/virus/retro/2005gongishmail/hiv1.jpg

HIV (cont.)

• Retrovirus: RNA virus transcribes RNA into DNA; retro = backwards

• 2 major strains: HIV-1 & HIV-2

• Infects CD4 cell surface proteins on T helper cells, macrophages, some lymphocytes, some brain cells

• Transmission: via genital or colonic mucosa during sexual intercourse; blood to blood contact; breast milk

Did you know condoms (when used correctly) are 99% effective?!!

For HIV/AIDS,

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