Transcript Immunity Chap 5

Immunity
Body Defenses

First line - barriers
 Skin
and mucous membranes
 Flushing action
– Antimicrobial substances
 Lysozyme, acids, salts, normal
microbes
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
“non-self” 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 (Cytotoxic cells) 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
Structure of antibody

Y arm: antigen binding site
– Fab (fragment, antigen binding)

Base of Y: receptor binding site
– Fc (fragment, crystalizable)
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





IgG - monomer (only one crosses placenta,
involve majority of immune responses)
IgA – dimer – 2 units - in secretions, found in the
mucus area like gut, respiratory and urogenital
tract, also in saliva, milk, tears
IgM – pentamer – 5 units, present early, before IgG
is abundant
IgD – monomer – on surface of B cells, activate
basophils and mast cells
IgE – monomer – involved in hypersensitivities,
trigger release of histamine
Cell-mediated immunity





Produced through T cytoxic 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 (APC,
macrophages) place antigen on their cell
surface in combination with the MHC
(Major Histocompatibility complex) 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 (stimulate the
growth of T cell) and/or IL-4 (proliferation
and differentiation, IgG & IgE synthesis)
Interleukin-2 has an autocrine function,
causes TH Cell to clone itself, and make
more IL-2 and /or IL-4
Interleukins are a group of
cytokines (cell signaling molecules) for
inter cellular communications, IL1 to IL
35
Helper T cells


TH1 cells produce IL -2 and IFN-ɣ
(interferon, cellular communication
agents), 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.
2.
3.
Allergies – Exaggerated immune
response against environmental
antigens
Autoimmunity – immune response
against host’s own cells
Alloimmunity – is a condition in
which the body gains immunity, from
another individual of the same
species, against its own cells , 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 – IgEmediated 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 (unusual)
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
Autoimmune hemolytic anemia

Immune system attacks own red blood
cells
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”)
Glomerulonephritis

Acute glomerulonephritis is an
inflammatory disease involving the
renal glomeruli of both kidneys. It is
thought to involve antigen-antibody
reaction which produces damage to
the glomerular capillaries
Glomerulonephritis

Acute glomerulonephritis usually
follows a streptococcal infection of the
respiratory tract or, less often, a skin
infection such as impetigo. However,
most often it is due to an allergic or
immune response to infections in
other parts of the body.
Type IV- Cell-mediated reactions
(delayed response)






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
Reverse Immunity


Graft vs. Host disease
host is immunocompromised
transplant has immunocompetent
cells