Transcript AP.Blog Immunity

College Board 2.D.3 – Biological Systems
Are Affected By Disruptions to Their
Dynamic Homeostasis
• Disruptions at the molecular level and cellular
levels affect the health of the organism
– Dehydration
– Immunological responses to pathogens, toxins,
and allergens
2.D.4 - Plants and Animals Have a Variety
of Chemical Defenses Against Infections
That Affect Dynamic Homeostasis
• Plants, invertebrates and vertebrates have multiple,
nonspecific immune responses
– Invertebrates lack pathogen-specific defense responses
– Plant defenses include molecular recognition with systemic
responses, infection triggers chemical responses that
destroy infected and adjacent cells, localizing the effects.
• Mammals use specific immune response triggered by
natural or artificial agents
– Two types of response: humoral and cell-mediated
– Cell-mediated – cytotoxic T cells target pathogens when
antigens are displayed on the outside of cells
– Humoral – B cells produce antibodies against specific
antigens
– Antigens are recognized by antibodies
– Antibodies are proteins produced by B cells and are
specific
– A second exposure to the antigen produces a faster and
enhanced response
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Acquired immunity
Antibody
Antigen
APC
B cell
CD4
CD8
Clonal selection
Cytokines
Histamine
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Inflammatory response
Innate immunity
Interferons
Lymphocyte
MHC I
MHC II
Non specific response
Specific response
T cell
Innate vs Acquired Immunity
Defend against ‘non-self’
Get rid of abnormal cells
Two kinds of defense
Innate immunity – nonspecific
Acquired immunity - specific
Nonspecific – effective at birth
Specific
Abnormal signals
from ‘self’ cells
Nonspecific Immunity - External
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Skin – low pH, oily
Lysozyme – breaks down bacterial cell walls
Gastric juice
Symbiotic bacteria in gut and on skin
NonSpecific - Chemicals
• Interferons – secreted by virus-invaded cells to warn
other cells
• Inflammatory response
– Histamine
• Vasodilation (swelling, heat and redness)
• Attracts phagocytes
Damage
causes release
of histamine
Capillaries dilate:
clotting factors,
WBC’s arrive
Interleukins +
histamine attract
leukocytes
WBC’s eat microbes.
More histamine (+
feedback)
Specific Immunity
• Cell receptors for antigens
– Distinguish ‘Self’ from ‘nonself’
Macrophages
• Antigen-presenting cell (APC) – macrophage that
has engulfed a microbe and displays pieces on its
surface
MHC
• Major Histocompatibility Complex – molecules encoded
by a family of genes
– ‘Self’ recognition
– Prevents your body from attacking itself
– Glycoproteins
• Diversity –
– 20 different genes (polygenic)
– 50 different alleles – (multi-allelic)
– MHC is a unique ‘fingerprint’ of you
‘Regular’
A fragment of (antigen) inside
an invaded cell attaches to an
MHC molecule and is
transported to the cell surface
MHC/antigen combo is
recognized by a T cell
Infected body cells use MHC to
display foreign antigens
Antigen inside an Antigen-presenting
cell attaches to an MHC molecule and
is transported to the cell surface.
MHC – antigen combo is
recognized by a T cell
Acquired Immunity: Specificity
• Antigen – molecule that elicits an immune response
• Viruses, pollen, parasites, venom, transplants
– Unique molecular (3-d) shape
– Wide variety of lymphocyte’s in your blood in order
to recognize all the possible antigens (genetic
variation)
• Antibody – bind to antigens
– Immunoglobulin – protein (specific 3d shape for each antigen)
– Inactivate antigens by binding to the epitope
– Also bind to surface antigens of ‘non-self’ cells
Acquired Immunity
• Lymphocytes – produced in bone marrow, hang out in
lymph
• B and T cells
• Respond to specific ‘invaders’ (transplants, cancer)
• Have 100,000 antigen-specific receptors in their
membranes
• Antigen receptors (‘membrane antibodies’,
‘membrane immunoglobulins’) - bind to specific
antigens
Lymphocytes – Leukocytes
Produced in Bone Marrow
• B cells:
– Mature in bone marrow
– Respond to antigens
– Clone into Plasma cells or
Memory cells
• T Cells:
– Mature in thymus
– Respond to funky self or
non-self antigens
– Clone into cytotoxic T’s or
Helper T’s
T Cell Receptors and MHC
• T cell antigen receptors recognize specific pieces of
antigens bound to MHC molecules
• T cells detect the antigen fragment
in
two ways:
– An ‘infected’ body cell
– An APC
Humoral and Cell-mediated Immunity
• Lymphocytes only respond to specific antigens
• Clonal selection – when the lymphocyte attaches to an
antigen the lymphocyte clones itself:
– One clone - effector cells
• Short-lived cells that fight that antigen
– One clone - memory cells
• Long-lived cells with receptors for that antigen
Two Branches of Acquired Immunity
• Humoral Response:
• Activate and clone B cells
• B’s differentiate into:
– Plasma cells
– Memory cells
• Antibodies are secreted and
attack antigens in body
fluids
• Cell-mediated Response:
• Activate and clone cytotoxic T
cells
• T’s differentiate into:
– Cytotoxic T’s
– Memory T’s
• Attack targeted specific body
cells with an MHC-antigen
complex
Clonal Selection of Lymphocytes
• Primary (specific) immune response
• Clonal selection – an antigen binds to a B or T cell
receptor and activates it to clone and differentiate
• Secondary response – memory cell clones
– Faster response (2-7 days)
• Provides resistance to infection
– Vaccines
Helper T’s
• Both humoral and cell-mediated
• Helper T’s are activated by APCs, or infected cells
– MHC
Cytotoxic T Cells
• Cytotoxic T becomes a killer (effector) cell when it binds
to an infected body cell
– Secretes perforin
• Body cell releases antigens into humor and B cells
attack released antigens
• Also attack cancer – (cancer cells have ‘non-self’
molecules)
Cytotoxic T cell binds
to a class I MHC–
antigen complex on a
target cell (TCR +
CD8). TCR/MHC, +
cytokines from helper
T cells, activates
cytotoxic T’s
Activated T cell
releases perforin,
proteolytic enzymes
(granzymes); enter the
cell by endocytosis
Granzymes initiate apoptosis;
(‘cell suicide’). Cytotoxic T’s
then attack other target cells
B Cells: Humoral Response
• Helper T’s activate B cells
• B cells clone into plasma cells and memory cells
– Plasma cells (effectors) secrete antibodies into fluids
(humor)
– Memory cells enable rapid response to subsequent
infections
B cell w/same antigens
display them to helper T.
TCR + CD4 + cytokines
stimulates B to clone
+ cytokines
Primary immune response;
Plasma cells secrete antibodies
(2000/sec); short-lived (4-5 days)
Effectors
Types of Immunity
• Active:
– Immunity develops from
exposure to a pathogen
(memory)
– Naturally
– Artificially – vaccination
• Pathogens change
• Passive
– Passed via placenta or
mother’s milk
– Lasts weeks – months
– Can be via immunization
• Emergency – short term
(rabies)
Autoimmune Diseases
• Immune system loses ‘self-tolerance’
– Systemic lupus erythematosus
(lupus)
• Rash, fever, kidney problems, arthritis
– Multiple sclerosis
• T cells attack myelin sheath of CNS
• Senses weakened, muscular control, paralysis
Auto Immune Disorders
• Insulin-dependent diabetes mellitus
– T’s attack Beta cells of pancreas (insulin)
• Rheumatoid arthritis
– Damage and painful inflammation of the cartilage and
bone of joints
• Acquired immunodeficiency Syndrome (AIDS)
– Loss of Helper T’s (HIV)
– Patients die from opportunistic infections and cancers
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Kaposi’s sarcoma
Pneumonia (Pneumocystis carinii)
Non-Specific; Innate Immunity
• Response is always the same
• Physical barriers – skin, mucous, tears
• Inflammatory response
– Histamine – mast cells
– Dilation, fever activates other players
• Chemicals – interferon
• Phagocytic cells – macrophages
• NK cells – abnormal cells (cancer, transplants)