Transcript Immunity and Hypersensitivities

Immunity
Body Defenses
• First line - barriers
• Skin and mucous membranes
• Flushing action
– Antimicrobial substances
• Lysozyme, acids, salts, normal
microbiota
Second line defenses
• Cells – neutrophils, macrophages, natural
killer cells
– Toll-like receptors on phagocytes recognize
carbohydrates on the surface of bacteria
• Inflammation
• Proteins
– Complement
– Interferon
• Fever
• All of the previous mechanisms are
NON-SPECIFIC
• Third line – immune response
1.Specific
2.Memory
3.Inducibility
•Antigens - substances recognized as “nonself” These can be:
•Infectious agents - bacteria, viruses,
fungi or parasites
•Noninfectious substances –
•Environmental - pollen, foods, bee
venoms
•Drugs, vaccines, transfusions and
transplanted tissues
Antigen
Antibody Generator
The best antigens are:
1. large
2. recognized as foreign
3. complex
proteins and complex carbohydrates –
good
nucleic acids and lipids – not good
Haptens – too small by themselves, piggyback on larger molecules, us. Proteins
Epitopes (antigenic determinants) – regions
of large molecules recognized by the
immune system
Two cell types give us the immune response;
both are lymphocytes, which are a type of
leukocyte, or white blood cell.
B lymphocytes or B cells
T lymphocytes or T cells
The cells of the immune response differ from
the cells of the inflammatory response in three
ways:
1. They are SPECIFIC and each cell
recognizes only one specific antigen.
B cells produce antibodies
Tc cells attack antigen directly
2. Both produce groups of cells called
“memory cells” that act quickly the
second time the antigen is encountered.
3. An antigen induces an immune
response. Only small amounts of
antibodies or T Cells are present before
encountering an antigen.
Long lasting protection against a specific
antigen is immunity.
Natural immunity:
Not produced by the immune response
Species specific
Acquired immunity
Active – person produces immunity (by
producing antibodies or Tc cells)
natural
artificial
Passive – temporary immunity is given
(by giving antibodies)
natural
artificial
Lymphocytes
Originate :
in liver, spleen and bone marrow of fetus
in bone marrow after birth
From stem cells – hemocytoblasts – that
produce all blood cells.
To become mature, immunocompetent cells,
they must pass through lymphoid tissues in
other parts of the body.
As they do so, they become committed to
becoming either T cells or B cells
Cells that migrate through the bone
marrow (bursal equivalent) become B cells,
and will produce antigens and
participate in humoral immunity.
Cells that migrate through the thymus
glands become T cells and participate in
Cell-mediated immunity.
Humoral Immunity
Humoral immune response : B cells that
produce antibodies that travel through the
blood.
Antibodies are proteins that match the
molecular structure of an antigen, and bind to
that antigen. This leads to the destruction of
the antigen.
Antibody
B cells mature in the human bursal equivalent –
in bone marrow – and obtain the ability to bind
antigens and produce antibodies.
Clonal selection theory:
During fetal development, B cells are produced
which can bind with any potential antigen. Each
B cell binds only one antigen.
When antigen binds to antibody receptors on
the surface of the B cell, the B cell divides
and differentiates into antibody producing
plasma cells and also memory cells.
Immunoglobulins
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IgG - monomer (crosses placenta)
IgA – dimer – 2 units - in secretions
IgM – pentamer – 5 units
IgD – monomer – on surface of B cells
IgE – monomer – involved in
hypersensitivities
Cell-mediated immunity
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Produced through Tcytoxic or Tc Cells (T8 cell)
DO NOT produce antibodies
Attack invaders directly
May produce toxic chemicals – such as
perforins, cytolytic enzymes, etc.
• May stimulate cell’s self-destruct mechanism
Primary and Secondary Immune
Responses
• Primary response
– Latent period
– IgM produced
– IgG produced later
•Secondary response
•Anamnestic response –much more rapid
due to memory cells
•Primarily IgG
Cellular Interactions in the Immune
Response
• Few antigens can activate B cells all by
themselves
• For activation of B cells and Tc Cells need
a second signal – cytokine ( “cell
mover”)
Antigen-Presenting cells (macrophages)
place antigen on their cell surface in
combination with the MHC II complex
Antigen is presented to a specific helper T
cell that has receptors that match the
antigen – MHC II complex
After binding, the APC produces Interleukin
-1 (IL-1) which stimulates the TH Cell to
produce IL-2 and/or IL-4
Interleukin-2 has an autocrine function,
causes TH Cell to clone itself, and make
more IL-2 and /or IL-4
Helper T cells
• TH1 cells produce IL -2 and IFN-ɣ and
influence cell-mediated immunity
• TH2 cells produce IL -4 (and other IL’s) and
influence antibody-mediated (humoral)
immunity
When B cell comes in contact with the
antigen and IL-4, the B cell produces plasma
cells and memory cells
Tc Cells come in contact with the antigen on
the surface of infected cells in combination
with the MHC 1 complex. When also have
binding with IL-2, cells produce activated Tc
Cells and memory cells.
http://en.wikipedia.org/wiki/B_cell
Hypersensitivities
“The Immune System Gone Bad”
Hypersensitivities
1. Allergies – Exaggerated immune
response against environmental antigens
2. Autoimmunity – immune response
against host’s own cells
3. Alloimmunity – immune response
against beneficial foreign tissues, such
as transfusions or transplants
These immune processes initiate inflammation
and destroy healthy tissue. Four types:
Type I – IgE-mediated allergic reactions
immediate type hypersensitivity
Type II – tissue-specific reactions
antibody-dependent cytotoxicity
Type III – immune-complex-mediated
reactions
Type IV - cell-mediated reactions
delayed-type hypersensitivity
Type I - IgE-mediated allergic reactions or
immediate hypersensitivity
Characterized by production of IgE
Most common allergic reactions
Most Type I reactions are against
environmental antigens - allergens
Selected B cells produce IgE
Need repeated exposure to large quantities
of allergen to become sensitized
IgE binds by Fc end to mast cells after first
exposure
Second exposure (and subsequent
exposures) – antigen binds with Fab portion of
antibody on mast cells, and cross-links
adjacent antibodies, causing mast cell to
release granules.
Response is immediate ( 5- 30 minutes)
Sometimes beneficial to host – IgE-mediated
destruction of parasites, especially parasitic
worms.
Histamine release:
• Increases vascular permeability, causing
edema
• Causes vasodilation
• Constricts bronchial smooth muscle
• Stimulates secretion from nasal, bronchial
and gastric glands
• Also hives (skin), conjunctivitis (eyes) and
rhinitis (mucous membranes of nose).
Late phase reaction
• 2 – 8 hours; lasts for 2 - 3 days
• Other mediators that take longer to be
released or act:
– Chemotactic factors for eosinophils and
neutrophils
– Leukotrienes
– Prostaglandins
– Platelet-activating factor
– Protein-digesting enzymes
Genetic predisposition
• Allergy prone or atopic
• Can be life threatening, so individuals
should be aware
• Skin tests – injection – see wheal and flare
• Lab tests for circulating IgE
Treatment
• First wave – antihistamines or epinephrine
(blocks mast cell degranulation)
• Second wave – corticosteroids and
nonsteroidal anti-inflammatory agents that
block synthesis of leukotrienes and
prostaglandins
• Desensitization by repeated injections of
allergen – formation of IgG
Anaphylaxis – Type I allergic reaction
may be localized or general
immediate – within a few minutes of
exposure
Systemic anaphylaxis:
pruritus(intense itching)
urticaria (hives)
Wheezing; dyspnea; swelling of the
larynx
Give epinephrine
Anaphylactic shock
• Hypotension, edema (esp. of larynx), rash,
tachycardia, pale cool skin, convulsions
and cyanosis
• Treatment:
– Maintain airway
– Epinephrine, antihistamines, corticosteroids
– Fluids
– Oxygen
Type II – Tissue specific reactions
(antibody-dependent cytotoxicity)
• Most tissues have specific antigens in their
membranes expressed only by that tissue
• Antibodies bind to cells or surface of a
solid tissue (glomerular basement
membrane)
Destruction of tissue occurs:
– Destruction by Tc Cells which are not
antigen specific- K cells
– Complement-mediated lysis
– Phagocytosis by macrophages
(“frustrated phagocytosis”)
– Binding of antibody causes cell to
malfunction
Type III – Immune-complexmediated reactions
• Caused by antigen-antibody complexes
formed in circulation and deposited in
vessel walls or other tissues
• Not organ specific
• Effects caused by activation of
complement – chemotaxis of neutrophils
• Neutrophils release lysosomal enzymes
into tissues (“frustrated phagocytosis”)
Type IV- Cell-mediated reactions
• Sensitized T lymphocytes – either Tc Cells
or lymphokine producing Td cells
• Takes 24 – 72 hours to develop
• Damage by Tc Cell or inflammatory
response by Td Cells (lymphokines)
• Graft rejection, tumor rejection, TB reaction,
poison ivy and metal reactions
• Immune diseases
• Tissue rejection
Systemic lupus erythematosus SLE
Autoanitbodies against nucleic acids
and other self components
Graft vs. Host disease
host is immunocompromised
transplant has immunocompetent cells