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.
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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