Overview on the Immune System

A M Musa

Introduction

Immune system: Why is it evolved? Immune response: Machinery? Primary;

secondary;- Definition- The outcome is determined by:

host immune status

pathogen, virulence, route

dose of the pathogen

  The main types of immunity in man

 

                                                      

  

Immune System consists of: Primary lymphoid organs----necessary for

development & maturation of lymphocytes: thymus & bone-marrow.

Secondary lymphoid organs--------- trap Ags, site where mature lymph. Can interact effectively with Ags: lymph-nodes, spleen, tonsils,peyer’s patches.

Blood vessels & LS connect the organs uniting them into a functional whole.

The immune response

Immune response: It is the response made by the host to defend itself

against a pathogen. It is described as appropriate (protective).

Manipulation of the immune response:- Induction (vaccination, immunotherapy etc)- Measurements (diagnosis, prognosis) Immunoregulation:- ?? Why do we need it?- Clinical application (specific suppression)

Migration and homing of the lymphocytes

Blood lymphocyte pool

Bone marrowthymus

MALT

Lymph node

Spleen

Peripheral tissue

Immune System Overview

There are two major functions of the immune system:

destroy pathogens detect and kill abnormal cells, such as cancerous cells

Pathogens are classified according to their size and where they are located in the body; there are 5 types of pathogens:

1. parasitic worms

2. fungi

3. protozoa

4. bacteria

5. viruses

Immune System Overview

INNATE DEFENSES (nonspecific defenses)

innate external defenses - these are surface barriers, such as the skin and mucous membranes; if the innate external defenses are penetrated then the next line of defense is the innate internal defenses

innate internal defenses - these include cells and chemicals in body fluids (e.g. phagocytes and NK cells), fever, and inflammation; internal defenses identify enemies by recognizing markers that are unique to the pathogens; when they are overwhelmed, they secrete chemical messengers to mobilize adaptive defenses

Immune System Overview ADAPTIVE DEFENSES differ from innate defenses:

specific (directed against an identifiable enemy)

B and T lymphocytes

memory; they recognize an enemy if it attacks the body in the future

systemic (can act anywhere in the body)

B and T lymphocytes recognize pathogens by binding to them; they recognize antigens of the pathogen by shape, also known as the antigenic determinant

specific B cells called plasma cells secrete antibodies, which bind to the antigens

Immune System Overview Humoral (antibody-mediated) vs. Cellular (cell-mediated)

Immunity

humoral, or antibody-mediated, immunity is directed against pathogens in extracellular fluid; this immunity involves B lymphocytes and antibodies

cellular, or cell-mediated, immunity is directed against pathogens within the cells; this immunity involves T lymphocytes; for example T cells would be activated if a cell has become cancerous or attacked by a virus, or if a cell has been transplanted from another individual

Innate defenses: External and Internal

Innate External Defense System - first line of defense

surface barriers include the skin and mucous membranes of the respiratory, digestive, urinary, and reproductive tracts

characteristics of skin that help it to resist invasion:

water-resistant and tough keratin outer layer

intercellular junctions hold skin cells tightly together

skin secrections are acidic and have chemicals that make the skin inhospitable to pathogens; e.g. lysozyme destroys cell walls of certain bacteria

mucous membranes not only provide a barrier, but also produce a variety of protective chemicals (e.g. lysozyme) and acidic secretions

the stomach secretes digestive enzymes and has a very low pH

the digestive and respiratory pathways are lined with sticky mucous that traps pathogens

Innate Host Defenses Innate Internal Defense System - second line of

defense; attempts to limit the spread of pathogens; this system is fast-acting and nonspecific

the internal defense system has 5 components: phagocytic cells (e.g. neutrophils and

monocytes/macrophages) NK cells (natural killer cells) antimicrobial proteins (complement and

interferon) inflammation fever

Innate Host Defenses Innate Internal Defense System - second line of defense; attempts to limit the spread of

pathogens; this system is fast-acting and nonspecific

phagocytes

neutrophils are the first cells to leave the blood and enter tissues at the sites of infection or trauma; these cells are short-lived

monocytes follow the influx of neutrophils into the affected tissue; once in the tissue, they transform into macrophages; they phagocytize many more pathogens than neutrophils

phagocytes use special membrane receptors to recognize and bind molecules that are found on pathogens, but not on normal body cells

when a phagocyte recognizes a pathogen it:

- ingests the pathogen

- releases chemical alarm signals that mobilize other cells of innate and adaptive immunity

OPSONIZATION - some bacteria have capsules that make it difficult for phagocytes to grab them; the immune system makes molecules that “coat” the bacteria and enhance phagocytosis; this is called opsonization; both complement and antibodies can act as opsonins

Innate Host Defenses

Innate Internal Defense System - second line of defense; attempts to limit the spread of pathogens; this system is fast-acting and nonspecific

NK cells (natural killer cells)

type of lymphocyte involved in innate immunity

attack body cells that have been invaded by pathogens (e.g. viruses) or cancer; they will also attack the cells of transplanted tissues

NK cells are larger than B and T cells, and unlike B and T cells, do not have antigen receptors

both NK cells and T cells are involved in IMMUNE SURVEILLANCE (they continually scan our cells for abnormalities)

Innate Host Defenses

Innate Internal Defense System - second line of defense; attempts to limit the spread of pathogens; this system is fast-acting and nonspecific

antimicrobial proteins

interferons- interfere with viral replication and activate immune cells; cells that have been attacked by a virus release interferon to help protect neighboring cells that have not yet been affected

complement (complement system) - it “complements” or enhances other components of both innate and adaptive defenses; it can mark cells for phagocytosis, promote inflammation, and kill some bacteria

Innate Host Defenses

Innate Internal Defense System - second line of defense; attempts to limit the spread of pathogens; this system is fast-acting and nonspecific

inflammation

when the body is injured (e.g. a cut, abrasion, or bruise) a sequence of events called inflammation is initiated

tonsillitis, tendonitis, and laryngitis are examples of short-lived, or acute, inflammation; arthritis is an example of long-term, or chronic, inflammation

there are 4 cardinal signs of inflammation: pain, swelling, redness, and heat

the purpose of inflammation is to bring white blood cells and plasma proteins into an injured area; inflammatory mediators (e.g. histamine from basophils and mast cells) cause vasodilation (increasing blood flow to the area) and an increase in vascular permeability (allowing phagocytes and plasma proteins to enter the tissue)

plasma proteins and more fluid than usual leak into the injured area causing EDEMA (increased interstitial fluid); edema causes swelling, which can contribute to the sensation of pain

Innate Host Defenses

Innate Internal Defense System - second line of defense; attempts to limit the spread of pathogens; this system is fast-acting and nonspecific

fever

generalized increase in body temperature

PYROGENS - chemicals secreted by leukocytes and macrophages that have been exposed to foreign substances in the body; they cause the body’s thermostat (located in the hypothalamus) to set its temperature higher

higher body temperatures enhance phagocytosis and cause the liver and spleen to sequester iron and zinc (making these essential elements less available to bacteria); pathogens also do not grow very well at higher temperatures

Adaptive Defenses- B and T Lymphocytes

Adaptive Defenses are Specific, Systemic, and have Memory; they include Humoral Immunity (antibody-mediated) and Cellular Immunity (cell-meditated)

B and T Lymphocytes are key players in adaptive immunity

Antigens have multiple antigenic determinants (based on shapes)

self-antigens are the shapes that lymphocytes expect to find in the body (thus lymphocytes do not normally attack them)

antigen receptors are specific and diverse

Adaptive Defenses “Education” of Lymphocytes

immunocompetence - the lymphocyte is able to recognize its one specific antigen by binding to it

self-tolerance - the lymphocyte is unresponsive to self-antigens, so that it does not attack the body’s own cells

T cells become immunocompetent and self-tolerant in the thymus, whereas for B cells this occurs in the bone marrow

Autoimmune Diseases - lymphocytes attack the body’s own cells; e.g. Type 1 Diabetes mellitus, Grave’s disease, and Multiple sclerosis

Memory Cells - are created in large numbers during a primary immune response (exposed to antigen for first time); memory cells create a larger number of effector cells during a secondary immune response (exposed to antigen again); thus, the response to the second attack will be much greater