THE IMMUNE SYSTEM!

The Cosico Twins.

The Terrible Threesome!

• The Integumentary System• Nonspecific (Innate) Immunity System• Specific Immune System

The Integumentary System1st Line of D-

• Skin-15% of an adults body weight-Oils and sweat glands-Normal Flora

Epidermis!

• Stratum Corneum• Stratum Basale• Stratum Spinosum

*Psoriasis- chronic skin disorder which replaces epidermal cells 8 x’s faster than normal

Dermis

• Structural Support for epidermis• Matrix for blood vessels, nerve endings,

muscles & etc.• Subcutaneous Tissue

- Adipose (fat) cells

Mucosal epithelial surfaces

• Digestive Tract• Respiratory Tract• Urogenital Tract

Nonspecific Immunity 2nd line of Defense

• Leukocytes- Macrophages- Neutrophils-Natural killer Cells*immune surveillance

Inflammatory Response

• Localized or systemic• Hallmark Signs!

- Dilation of local blood cells- increased blood flow = red and warm- Tissue Swelling- Pain- Loss of function

Localized Inflammation

1. Chemical Signals2. Dilation of blood vessels3. Swelling 4. Accumulation of phagocytic cells

Acute-phase Response

• Fever• Intereukin-1 (IL-1)

•39.4⁰C (103⁰F) & 40.6⁰C (105⁰F)

Complement proteins

• Complement System• Membrane Attack Complex• Interferons

Evolution of the nonspecifics?

• All vertebrates and many invertebrates posses phagocytic cells that attack invading pathogens

• Evolved from amoebas? …maybe

The Specific Immune Response: The Third Line of Defense

• Immunity-Jenner and the smallpox virus -Vaccination

• Antigens provoke specific immune responses.-the more foreign the greater the immune response.-Epitopes-different parts of an antigen which each part stimulates distinct immune responses

Lymphocytes

1. Specificity of recognition of antigen,2. The wide diversity of antigens that can be

specifically recognized,3. Memory, such that the immune system responds

more quickly to an antigen it has previously encountered than to one it is meeting for the first time, and

4. The ability to distinguish self-antigens from nonself.

Lymphocyte and their receptors

• Receptor Proteins• Naïve Lymphocyte

-clonal selection• B Lymphocytes (B Cells)• T Lymphocytes (T Cells)

Specific Immunity

• Active Immunity• Passive Immunity

Hematopoiesis

• Lymphoid Progenitor- B, T, and natural killers cells• Myeloid Progenitor- everything else• Monocytes- macrophages & neutrophils• Eosinophils- elimination of parasites• Basophils and Mast cells-secrete histamine and

prostaglandin; activated during allergic response• Dendritic Cells- activate T-Cells• Page 1047

The support of two classes

• Primary Lymphoid organs-Bone Marrow-Thymus

• Secondary Lymphoid organs-Lymph Nodes-Spleen-Mucosal-Associated Lymphoid Tissue (MALT)

T Cells: Cell-Mediated Immunity

• Cytotoxic T cells vs helper T cells • Human Leukocyte Antigens• Major Histocompatibility Complex (MHC)

- MHC class I proteins vs MHC class II proteins

Cytotoxic T cells

• Recognize “altered-self” -virally infected or tumor cells

• Destroy cells in a similar fashion to Natural killer cells

Helper T cells

• Cytokines-Determines whether immune response is humoral or cell-mediated

• Activated TH cells and TC cells produce effector and memory cells

• T- Cells are the cause of transplant rejection-ex. Kidneys

B cells

• Immunoglobulin molecules • 105 • Naïve B cells• Plasma B cell

Immunoglobulin structure

• Light chain • Heavy chain

Antibody Specifity

• Variable region• Constant region

light chain- Mammalian immunoglobulins 2 different amino acid sequences heavy chains – 5 different amino acid sequences

GOOD PICTURES ON 1053

• Antigen-binding site• Ig binds two identical epitopes– Function allows formation of antigen-antibody

complexes

Binding of antibodies

Function of antibody classes

• Function of Ig depend on class• Cells have Fc receptors that bind to Fc region

Five Classes of Ig

• Based on the sequences of constant regions of their heavy chains (mu, delta, gamma, alpha, epsilon)

• Different function in the protection of an individual

THE FIVE

IgM

• receptor on the surface of all mature naïve B cells

• 1st type of antibody to be secreted in an immune response

• Secreted as a pentamer • Large size is good yet bad

IgD

• Present on naïve b cells • Bell cell activation• Antigen receptor• monomer

IgG

• Major form – makes up 75% plasma antibody– Blood plasma– Tissues

• Macrophages + netrophils• Passive immunity to a fetus • Activate complement • monomer

IgA

• Major form in external secretion • Dimer• In Malt under mucosal surfaces • Passive immunity to nursing infants

IgE

• Present in low concentration in the plasma • Bound to mast cells and basophils • Secreted in response to helminth worms – eosinophils

Ig Diversity

• B cells create antibodies w/ 1010 different antigen-binding sites

• DNA rearrangement– Like crossing over in meiosis – Occurs as a progenitor B cell matures in the bone

marrow– RNA – Allelic exclusion

Variable region DNA rearrangement

• Sequencing of human Ig heavy chain loci – V segment – D segment– J segment

Transcription and translation

• Pre-mRNA transcripts • Start at VDJ• Alternate splicing • Translation results– Mu or delta heavy chain light chain in rough er– 1056

T-cell receptors

• TCR= fab region of Ig • Dimeric – alpha and beta • Bind to self-MHC + peptide• Also contain multiple DNA segments

2nd better than 1st

• First response– Few cells

• Second response– MEMORY CELLS

Autoimmunity and Hypersensitivity

Immune system flaws

• Inappropriate response • Immunological tolerance• Evolutionary traits– Fetus undergoes the process of tolerance to lose

the ability to self-molecules as development proceeds

• Self reactive lymphocytes

Autoimmune diseases

• Result from immune system attack on own body

• Autoreactive T cells and B cells • 40 known auto immune diseases• Resulted from different mechanisms– Self-antigens hidden

• Allergies- most common form is immediate hyper sensitivity

• Allergens – Binds to B cells to activate and secretes allergen-

specific Ig

• TH cells release cytokines such as IL-4

• Systemic anaphylaxis • Local anaphylaxis

IgE secretion

Delayed hypersensitivity

• Mediated by– TH

cells

– macrophages

Blood type

• Indicates antigen is present on an individual’s rbcs

• Blood type determined by certain antigens on rbc surfaces

• ABO groups – IA , IB , I– Protein sugar complex act as an antigen

Rh factor

• Blood borne antigen – Either present or absent on rbc surface

• Problems– Transfusion – Fetuses

Blood

• Typed by aggulation – Taking advantage of IgM antibodies ( if type A

blood mixes with serum type B or O, anti-A antibodies cause it to aggulinate)

• 20 blood groups– mismatch blood- stock pile – autologous

blood donation– Includes ABO and Rh groups

Transfusions gone wrong

• Mismatched blood transfusion- 5 to 8 hours – Hemolysis of transfused rbcs detected – IgM binding to foreign antigens activating

complement systems formation of MACs in rbc membranes + rapid osmotic lysis of the cells

• Hemoglobin changed into bilirium • Treatment is to wash from system

Monoclonal antibodies

• Tool for diagnosis and treatment• Specifity for one epitope • Preparation• Clonal hybrid or hybridoma

Acquired immune deficiency syndrome

• Abbreviated?• Characterized in part by destruction of TH cells

• Progression of this disease monitored by activity of patients leukocytes – Done with a monoclonal antibody against CD4,

tracks decrease in number of TH cells

Monoclonal cells and cancer treatment

• Immunotoxin production• Antibodies to fight against tumors best raid in

other species

Its like someone getting away from a crime

• Pathogens change structure of surface area – Immune system selects mutated pathogens

• And some pathogens evolved to just evade the immune system completely

Structure of surface changes

• Influenza virus – because they change so much yearly immunization is recommended – Antigen drift– Antigen shift- bird flu

• Malaria- plasmodium is the cause has several life cycles and can alter different proteins w/in the life cycle

Mechanisms used to evade

• Salmonella typhimurium – Alternate between 2 flagellar proteins

• Mycobacterium tuberculosis bacteria– Inhibits fusion of phagosomes with lysosomes – Multiply successfully w/in macrophages

• Neisseria meningitis or Neisseria gonorrhoeae – Secrete proteases that degrade that degrade IgA

antibodies that protect the mucosal surface

HIV

• Causes immunosuppression • CD4+ TH cells – the cytokines they secrete

directly or indirectly affects activity of all other cells in the immune system

• Progression of infection– Cytotoxin T cells take control for a bit – HIV- encoded proteins also cause a decrease of

MHC class I on the infected cells

• hiv process

• Combine effect is to wipe out the immune system

• Death by cancer seems more likely • AIDS first recognized when men died of

Pneumocytosis jiroveci • 35 to 42 million people living with the disease – Sub- Sahara 25 million, south east Asia 6.5– Fatality fate close to 100% end of 2004 514,000

died in the US