Immune systemBasics

Immune system

= complex set of tissues + mobile elements

self/non self discrimination

▶ the exogenous microscopic life forms▶ the defective, damaged, malignantly transformed cells

organism protection

Immune cellscirculate through the lymphatic and blood vesselsform the major immune organs

circulate

extravascularspace

Modulating leukocyte recruitment in inflammationMargaret Kelly et al.J Allergy and Cl Immunology, 2007http://www.sciencedirect.com/science/article/pii/S0091674907009864

recirculate

Immune system responses to pathogens

Innate immune system Adaptive immune system

▶ first line of defense▶ exists before exposure to microbes▶ non-specific immune system

▶ second line of defense▶ adaptive – specific response▶affords protection against re-exposure to the same pathogen

has cellular and humoral components by which they carry out their protective function

Non-specific Immunity Specific Immunity

Response is antigen-independent

There is immediate maximal response

Not antigen-specific

Exposure results in no immunologic memory

Response is antigen-dependent

There is a lag time between exposure and maximal response

Antigen-specific

Exposure results in immunologic memory

Innate Immune Systemhttp://thyroid.about.com/library/immune/blimm12.htm

Anatomical barriers Defense mechanisms

Skin (1st line of defense) sweat – desquamation – flushing – organic acids

Nasopharynx mucus – saliva – lysozyme

Eyes tears – lysozyme - phospholipase

Respiratory system mucociliary elevator – surfactant – defensins (low molecular weight proteins)

GI tract peristalsis – gastric acid – bile – digestive enzymes – gut flora

Inflammationstimulated by chemical factors released by injured cells

Macrophages and mast cells release chemical signals such as Histamine.

h"p://bio1152.nicerweb.com/Locked/media/ch43/inflamma:on.html

Local inflammatory response:Capillaries widen. Fluid containing antimicrobial proteins enter the tissue. More phagocytes invade the site.

Phagocytic cells digest pathogens, and the tissue heals.

one of the first responses

Symptoms: redness, heat, swelling, pain and possible dysfunction of the organs or tissues involved

Complement system - a biochemical cascade

Alternative pathway Lectin pathway Classical pathway

Pathogen surface creates localenvironment conducive to

complement activation

Mannose-binding lectin bindsto pathogen surface

C-reactive protein or antibodybinds to specific antigen on

pathogen surface

First to act Second to act Third to act

COMPLEMENT ACTIVATION

Cleavage of C3 to C3a and C3bC3b covalently bound to surface components of pathogen

Recruitment of inflammatory cells

Opsonization of pathogens, facilitating uptake and killing by phagocytes

Perforation of pathogen cell membranes

Death of pathogen

Cells of the innate immune response

Leukocytes:

are the products of multipotent hematopoietic stem cells from the bone marrow

are able to move freely and interact with and capture cellular debris, foreign particles, or invading microorganisms

Include: natural killer cells mast cells eosinophils basophils phagocytes: macrophages,neutrophils, dendritic cells

Hierarchies of organization in the innate immune system - sciencemag.org

Adaptive (specific) immune system

Trigger a pathogen that evades the innate immune system

       an$gen-­‐specific  defense  mechanisms

major functions ▶ recognition of specific “non-self” antigens▶ response to eliminate specific pathogens▶ development of immunological memory

Adaptive (specific) immune system

Active immunity Passive immunity

is  produced  by  the  person’s  own  immune  system  –  highly  adaptable

is  usually  permanent  (immunologicmemory)

the  transfer  of  an:body  produced  by  onehuman  or  other  animal  to  another

provides  protec:on  against  some  infec:ons–  is  temporary

Lymphocytes. A scanning electron micrograph showing lymphocytes (yellow, like cotton candy), red blood cells, and platelets.(Copyright Dennis Kunkel Microscopy, Inc.)

Foreign substance (non self)= antigenes (infectious agents X noninfectious substance: pollens, foods, transplant tissue)

Specific immune cells

Lymphocytes B and T

Lymphoid tissues - Sites of B cells and T cells differentiation

Immature lymphocytes migrate through primary lymphoid tissues:bone marrow – for B lymphocytesthymus – for T lymphocytes

Mature B and T lymphocytes rich the secondary lymphoid tissues

The peripheral lymphoid organs contain a mix of B and T cells in different stages of differentiation:

▶ naive – mature cells – they didn’t encounter the cognate antigen

▶ effector cells – they have been activated by their cognate antigen → active in pathogen elimination

▶ memory cells – long-lived survivors of past infections

1 2 3

Immunogen= a molecule or molecular fragment

CAN bind with antibodies or antigen B and T cells receptors

induce an immune response

ALL Immunogens = AntigensNOT ALL Antigens = Immunogens(ex: urushiol from the ivy poison)

Immunogenicity includes:

foreignness to the host adequate size sufficient quantity

Criteria used in developing vaccines

=> which must be highly immunogenic to produce protective immune responses against pathogenic microorganisms

Humoral and Cell-Mediated Immunity

Humoral immunity

deals with infectious agents in the blood and body tissuesmanaged by B-cells

(with help from T-cells)

Cell-Mediated immunity

deals with body cells that have been infectedmanaged by T-cells

Humoral immune system = the antibody-mediated system because of its use of specific immune-

system structures called antibodies

Humoral immune system

Activation phase

Ingestion (phagocytosis) of foreign matter by macrophages

Digest the infectious agent and then display some of its components on their surfaces

Cells called helper-T cells - recognize this presentation, activate their immune response, and multiply rapidly

Effector phaseActivated helper-T cells use chemical signals to contact B-cells

B-cell descendants become either plasma cells or B memory cells

The plasma cells manufacture huge quantities of antibodies that will bind to the antigen and prime it for destruction

The Cell-Mediated System

http://www.trinity.edu/lespey/biol1307/lectures/lect1/lect1.html

killer-T cells recognize components of the foreign matter material on the surfaces of the infected body cells

destroy the invaders (primary response)

T memory cells

secondary response

Secondary Immune Response - Memory

Immunity as an Adaptation

The Human Immune System = important evolutionary adaptation

allows humans to better cope with an often hostile environment

a highly favorable adaptation for the humanto protect the human cellular machineryfrom benefiting parasitical organisms instead of human cells

Disorders of human immunityImmunodeficiency

= one or more of the components of the immune system are inactive:

Humoral immune deficiency – hypogammaglobulinemia

T cell deficiency – acquired immune deficiency syndrome

Granulocyte deficiency – granulocytopenia/agranulocytosis

Asplenia

Complement deficiency

Disorders of human immunityAutoimmunity

= overactive immune response

the immune system fails to properly distinguish between self and non-self, and attacks part of the body

Disorders of human immunityHypersensitivity

Occasionally – inappropriate response of immune system to the presence of antigen

Four different types of hypersensitivity:

Type I: Immediate HypersensitivityEx: Allergies to penicillin, insect bites,etc

Type II: Cytotoxic Hypersensitivity Ex: Pemphigus, Autoimmune hemolytic anemia (AHA),

Goodpasture's syndrome

Type III: Immune Complex HypersensitivityEx: Serum sickness

Type IV: Delayed Hypersensitivity