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

• Acquired immunity• Antibody• Antigen • APC• B cell• CD4 • CD8• Clonal selection • Cytokines • Histamine

• Inflammatory response• Innate immunity • Interferons • Lymphocyte • MHC I• MHC II• Non specific response• Specific response• T cell

Innate vs Acquired Immunity

Nonspecific – effective at Nonspecific – effective at birth birth

Specific

Abnormal signals signals from ‘self’ cellsfrom ‘self’ cells

Defend against ‘non-self’Get rid of abnormal cellsTwo kinds of defense

Innate immunity – nonspecific Acquired immunity - specific

Nonspecific Immunity - External

• 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

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

‘Regular’

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

Infected body cells use MHC to display foreign antigens

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

Primary immune response; Plasma cells secrete antibodies (2000/sec); short-lived (4-5 days)

+ cytokines

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 – 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)