THE IMMUNE SYSTEM! The Cosico Twins.. The Terrible Threesome! The Integumentary System Nonspecific...
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Transcript of THE IMMUNE SYSTEM! The Cosico Twins.. The Terrible Threesome! The Integumentary System Nonspecific...
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
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
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)
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
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
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
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
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
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