Immunology - Lecture 21

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Immunity

Effector Cells

Non-Specific Immune Response

Specific Immune Response

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Immunity - Body's defense against foreign matter

1700s-1800s great epidemics (small pox) killed 1000s of people- if got it once and survived - never again - Inoculation with the disease cow pox (Jenner - physician 1770) - not as severe - never get small pox -

First example of Immunization

I. Immunity - all physiological mechanisms which allow the body to recognize foreign materials and neutralize or eliminate them - now entire class in immunology

A) What foreign materials are the body concerned with?

1. microbes

- viruses - nucleic acids + protein - need other cells:

measles, small pox, flu, AIDS, colds, etc

 

- bacteria - single cell organisms:

typhoid fever, diphtheria, venereal disease, lyme, pneumonia, legionnaires, cholera, plague, ulcers

- protozoa - malaria

2. toxins - poison produced by animals or plants, tetanus, botulism

3. fungi, worms

4. worn out or old body cells i.e. rbc's

5. cancer

How do bacteria and viruses cause damage?

a. multiply rapidly - kill cells by depleting components

b. turn cells into cancer cells

c. destroy cells by releasing enzymes or give off toxins

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B) Effector Cells of Immune System

cells that respond to a stimulus -

Leukocytes - white blood cells

Neutrophils phagocytosis, inflammation 60-70%

Eosinophils Destruction of Parasitic Worms 1-4%

Basophils Releases of Histamine 0.5%

these are the granular leukocytes - Polymorphonuclear Leukocytes (PMNs)

Lymphocytes B cells - produce antibodies - 30% - T cells - help B cells (destroy cells)

Monocytes become macrophages when leave tissue - Phagocytosis 5%

these are agranular leukocytes - Mononuclear Leukocytes

1) Non-specific Immune Response (fast reaction) - no previous exposure to foreign material

Body has barriers to invasion

- skin, sweat (toxic), mucous membrane (sticky), hair (nose), lysozyme (kills bacteria)

If invader makes it in

Inflammatory Response - inflammation (or tissue damage - sprain ankle)

if step on a splinter with your foot (bacteria on splinter) - gross manifestations:

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redness, swelling, heat, pain.

A) Sequence of events

1. Initial entry of bacteria (Splinter), or tissue damage (sprain)

2.Vasodilation of vessels in microcirculation - increases blood flow (redness)

1. histamine release from mast cells, antihistamine: stops nose from running

2. chemicals released by bacteria

3. Increased vascular permeability - leakage of fluid (swelling) - histamine

increase delivery of WBCs - increase plasma proteins moving into tissue.

4. Increased delivery of WBCs

5. Exit of neutrophils and later monocytes from vessels into tissue.

 

Chemotaxis

WBCs crawl along conc. gradient

1.adhesion

2.movement through wall

6. Destruction of bacteria - phagocytosis or direct killing

A. Phagocytosis

combines with lysosomes which contains lysosomal enzymes and hydrogen peroxide - (put on cuts); breaks down bacteria).

some things can not be completely degraded i.e.lead, tattoo dyes, wood, metal

B. Direct killing - release of antimicrobial chemicals destroy bacteria, etc.

release oxygen radicals - H₂O₂, hydrogen peroxide

in lungs these radicals are induced by smoking - leads to cancer

vitamins serve as antioxidants

7. Tissue Repair

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B) Part of Non-specific Immune Response is the - Complement System

A) -involves plasma proteins A---B----C----D----E----F----etc

20 proteins - cascade mechanism - the proteins are called kinins

can be activated

intermediate proteins -

chemotaxis

increase blood flow

enhance phagocytosis

final proteins directly kill invaders

2) Specific Immune Responses - depend upon prior exposure to a foreign material - SLOW

takes 2-3 weeks for peak response if first exposure,

takes 1 week for peak response if a second exposure

2 Basic types of response-

A. Humoral or antibody mediated immunity - recognition by antibodies produced by B lymphocytes

B. Cell-mediated immunity - recognition by T lymphocytes, recognize histocompatability antigen, for viral infected cells, cancer, tissue transplants

Lymphocytes - precursor cells in bone marrow enter blood - take up residence in lymph nodes, thymus, spleen

thymus - T cell

lymph, spleen - B cell (bone marrow)

A) Humoral or Antibody - Immunity

Unlike nonspecific defense mechanisms - lymphocytes respond only to cells and foreign materials they recognize (slow reaction)

i.e. specific sites on foreign cell - antigens - bind with lymphocyte receptors

If first time only a few cells will respond

1. macrophage presents antigen to a specific B lymphocyte

2. macrophage produces interleukin I - IL- 1; B lymphocyte proliferation (clones via mitosis)

3. macrophage activates specific helper T cell by presenting antigen to helper T cells - Helper T cell produces B cell growth factor, further proliferation

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4. now a lot of B cells

antibodies - proteins - immunoglobulins

5 classes - 1000s of antibodies

IgG - gammaglobulin

IgM - plasma cell response

IgE - allergy

IgA

IgD - not known

each with specific duty

2) antibodies have several roles in immunity

1. enhanced phagocytosis - the antibody draws the attention of the phagocytic cells

2. activation of lymphocyte - K cells - Killer T Cells - lyse outer membrane

3. Activate complement system

4. Directly kills invader

Antibodies Amplify the whole system

first recognition of foreign invader requires 2-3 days to make antibodies

a second invasion - memory cells produce antibodies in hours, but still may take 1 week to reach peak

How can one speed up initial response - vaccines - inject inactivated microbial derivative recognized as foreign and produce antibodies

works for polio, influenza; unfortunately not for common cold viruses, no memory cells

B) Cell-Mediated immunity

cytotoxic T cells have specific receptors for antigen but most also have a second antigen - called self antigen (Major Histocompatibilty antigen, MHC)

the cells that will have these 2 antigens are:

1)viral - infected host cells

2) cancer cells

3) tissue transplant

therefore cytotoxic T cells are more restricted than B cells

Helper T cells - secrete interleukin 2, this causes proliferation of cytotoxic T cells

Cytotoxic T cells also produce interferon (this also comes from viral infected cells)

-enhances killing action - good in cancer

-inhibit viral replication

Drug cyclosporin blocks blocks production of interleukin 2 - therefore no proliferation of cytotoxic T cells

C) Lack of Basic resistance mechanisms - AIDS - acquired immune deficiency syndrome; cannot resist infection

major defect is lack of helper T cells caused by destruction or alteration in these cells by a virus - transmitted by blood or sexual intercourse - body fluids,

therefore no IL - 2, no proliferation of cytotoxic T cells, no B cell growth factor, and thus reduced antibody production

virus developed within past 2 decades in Central Africa - mutant virus that occurs in blood of green monkey; somehow it was transferred to humans

virus - retroviruses - (HIV) - Human immunodeficiency virus transmitted through blood or intercourse

Allergies - hair, dust, food

immunity system responds to harmless substance

produces antibodies

increase histamine - dilation - runny nose

increase prostaglandin - constriction of air passages - can't breathe

anaphylactic shock, increases permeability - loose plasma, blood pressure falls

therapy - blocking antibodies - before stimulate immunological response

REVIEW QUESTIONS

1. The physician that first use immunization was:
   1. Lister
   2. Fleming
   3. Huxley
   4. Jenner
   5. Pasteur
2. The body's immune system responds to all of the following except:
   1. viruses that produce small pox
   2. toxins such as tetanus
   3. worms
   4. bacteria that produce AIDS
   5. protozoa that produce malaria
3. White blood cells
   1. include eosinophils that produce the antibody IgE.
   2. include macrophages that are agranular leukocytes.
   3. include basophils that release histamine.
   4. include PMNs that are lymphocytes and monocytes.
   5. All of the above are correct.
4. Which of the following are true about inflammation?
   1. blood vessels constrict
   2. permeability increases so that the microbes can move through the tissue and not be so concentrated
   3. WBCs moves through the endothelium in a process called chemotaxis
   4. macrophages respond in a matter of minutes to phagocytose microbes
   5. All of the above occur during inflammation. 
5. The kinins such as C3, C5, etc that are produced during infection
   1. increase blood flow
   2. enhance phagocytosis
   3. directly kill microbes
   4. increase chemotaxis
   5. All of the above are true about kinins.
6. Which of the following is not true about the specific immune response?
   1. The specific immune response is much slower than the non-specific immune response.
   2. Helper T cells produce IL-1 to help increase the production of antibodies.
   3. Antibodies produced during a specific immune response can be measured in the blood in hours if memory cells are present.
   4. B lymphocytes produce antibodies.
   5. Macrophages present an antigen to lymphocytes.
7. Antibodies do all of the following except:
   1. increase the complement system
   2. enhance phagocytosis
   3. directly kill microbes
   4. activate killer T cells
   5. All of the above are true about antibodies.
8. Cancer cells are susceptible to the
   1. humoral immune response
   2. antibody immune response
   3. inflammatory response
   4. cell mediated immune response
   5. None of these immune responses can fight cancer cells.
9. WBCs do not produce:
   1. cyclosporin
   2. interferon
   3. interleukin-1
   4. B cell growth factor
   5. WBCs produce all of the above.

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