Transcript The Immune System - Chicagoland Jewish High School

•The Immune System
• The body’s defense
• 1. Nonspecific
• 2. Specific
• Cell mediated
• Antibody mediated
• Three cooperative lines of defense have
evolved to counter these threats.
• Two of these are nonspecific - that is, they
do not distinguish one infectious agent from
another.
•Nonspecific defenses
• “Nonspecific” = don’t have to recognize
an invader to fight it
• Skin: physical barrier
• Sweat glands: chemical defense
• Mucous membranes:
• Line body openings- physical barrier
• Secretions:
• Antimicrobial proteins present in secretions
• Mucous traps particles
• Acid in stomach-destroy most except hept.A
• Besides being a physical barrier, the
skin and mucous membranes
chemically destroy pathogens.
• Secretions from oil and sweat glands give
the skin a pH ranging from 3 to 5, acidic
enough to kill most microbes.
• Growth is also inhibited by saliva, tears,
and mucous secretions that continually
bathe the exposed epithelium.
• All these secretions contain antimicrobial
proteins.
• One of these, the enzyme lysozyme, digests
the cell walls of many bacteria, destroying
them.
•2ND LINE-Internal
• Microbes that penetrate the first line of
defense face the second line of defense,
which depends mainly on phagocytosis,
the ingestion of invading organisms by
certain types of white cells.
• Phagocyte function is intimately
associated with an effective
inflammatory response and also with
certain antimicrobial proteins.
• Second line of defense cells function
like roaming patrols
• 1. Nonspecific defenses of chemicals
and cells-Stimulated by cytokinnins
• 2. Act rapidly with infection
• 3. Employ negative test that cannot
be foiled by copycat foreign cells
• 4. All cells possess major histocompatibility
complex (MHC) proteins
• 5. Different in each individual. Distinguish
self from non self. Due to MHC
proteins-before birth
• 1. MHC 1-nucleated cells-body cells
• 2. MHC II- Nucleated cells-macrophages-B cellssome t cells
• a. 50 alleles-20 genes
• b. In autoimmune diseases defensive cells attack body's
own tissues
• c.Autoimmune diseases like arthritis have inflammation
without infection
•Major Histocompatibility
Complex
• The basis of “self”
• Genes for cell surface glycoproteins
• In humans: human leukocyte antigens (HLA)
• ENORMOUS variation (polymorphic)
• 2 Types:
• Class 1: found on all nucleated cells
• Class 2 : found on macrophages, B cells, CD4 T cells
•Phagocytic and Natural
Killer Cells
• Neutrophils:
• Most abundant WBC’s
• Chemotaxic
• Engulf invaders, then self-destruct
• Monocytes:
• Less abundant, but more effective than
neutrophils
• Form macrophages
• Reach pathogen with pseudopodia
• Engulf pathogen, fuse it with a lysosome
• Kill pathogen with toxic oxygen or enzymes
•More WBC’s
• Eosinophils:
• Fight large invaders (ex: parasites)
• Natural Killer (NK) cells: destroy
“self” cells infected with viruses,
cancer cells
•The Inflammatory Response
• Histamine is released by circulating leucocytes called
basophils and by mast cells in connective tissue.
• Histamine triggers both dilation and increased
permeability of nearby capillaries.
• Also discharge prostaglandins and other substances that
promote blood flow to the site of injury.
• Greater clotting capacity, faster repair
• Initiated by chemical signals
• From microbe- Chemotactic factor
• From damaged ‘self’ cells (ex: histamine)
• Chemokines from damaged cells attract
phagocytes
• Pus = dead phagocytes + fluids
• Extreme = septic shock
•The Complement System
• Antimicrobial proteins
• ~ 20 serum proteins
• Function: microbe lysis
• Another set of proteins that provide
nonspecific defenses are the interferons,
which are secreted by virus-infected cells.
– While they do not seem to benefit the infected
cell, these proteins diffuse to neighboring cells
and induce them to produce other chemicals
that inhibit viral reproduction.
– Interferon limits cell-to-cell spread of viruses,
helping to control viral infection.
– Because they are nonspecific, interferons
produced in response to one virus may confer
short-term resistance to unrelated viruses.
– One type of interferon activates phagocytes.
•Temperature Response
• Pyrogens
• Ex: Interleukin-1
• Detected in blood by hypothalamus -raise in body temp
• How it works:
• Speeds cellular reactions
• Stimulates phagocytosis
• Stimulates liver/spleen to store Fe
• Endotherms - may regulate behaviorally
•Immunity terms
Humoral vs Cell mediated
Acquired/active vs Passive
Lymphocytes: T and B cells, specific
Antigen: Foreign molecule (from
pathogens, pollen, transplanted tissue,
etc.)
• Antibodies: made by B cells, specific
• Antigen receptors: on membranes of T
& B cells
•
•
•
•
• B cells: membrane antibodies
• T cells: similar, but never secreted
•T cells
• TI = inducer
• TC = cytotoxic
• killers
• TH = helpers
• Activate others
• TS = suppressor
• Causes B cells to ignore antigens
•Antigen presentation
• Antigen binds to MHC within cell
• MHC molecules bring proteins to
surface
•Cell mediated response
• TC cells kill cancer cells, viral infected
cells
• All cells have class 1 MHCs (all
susceptible to viral infection)
• Class 1 MHC captures viral protein
• MHC + antigen move to cell surface
• Present to T cytotoxic cell
• Enhanced by CD8
• Active killer cell
•Mechanism
• T cytotoxic cell releases perforin
• Forms pores in membrane of
target cell
• Cell lyses, pathogen inside is
exposed to circulating antibodies
• T cytotoxic cell moves on to other
cells infected w/ same pathogen
•Antibody mediated
immunity
• Aka Humoral immunity, B cells
activated, antibody production
•
•
•
•
Ex: macrophage engulfs a bacterium
Class 2 MHC picks up bacterial peptide
MHC + antigen move to cell surface
Presents to T helper cell/releases Il-1
• Enhanced by CD4 receptor on T helper cell
• T cell proliferates
• Activated T helper cells: secrete cytokines to
stimulate other lymphocytes
•Humoral response in
detail
• B cell activation by IL-2, proliferate into
plasma and memory cells
• Plasma cells: secrete antibodies
• Memory cells: long-lived
• Some antigens are T-independent
• Bind to membrane antibodies on B cells
• Plasma cells made w/ out signal from T cells
•Structure of antibodies
• Globular protein, in plasma,
• aka: immunoglobulins (Igs)
• Structure: 4 chains: 2 heavy, 2 light
• Constant region
• Variable region
• Epitope: part of the antigen where antibody
binds
• 5 classes
• Made in vitro
• Polyclonal: made from many B cell clones
• Work on different epitopes of the same antigen
• Monoclonal: made from one B cell clone
• All work at the same epitope of the same antigen
•How antibodies work
• Neutralization:
• Block antigen activity
• Opsonization:
• Enhance macrophage
attachment/phagocytosis
• Agglutination:
• Clumping
• Complement fixation:
• can be activated by antibodies or by
pathogens
• Antibodies attach to antigens
• Complement proteins activate, cause lysis
•Active vs. Passive Immunity
• Active immunity: your own response
• Natural: from infection
• Artificial: from vaccinations
• Passive: antibodies from another individual
• Ex: across placenta, through breast milk
• Ex: antivenoms,Rhogam
• Rhogam: injection given to Rh- mothers
after birth of Rh+ child.
•
Destroy fetal cells before her immune
system responds to them, develops
antibodies
• Anti Rh antibodies are class IgG - can cross
placenta
•Tissue transplantation
• Blood types: ‘A’ and ‘B’ antigens
• T-independent humoral response
• Antibodies don’t cross the placenta
• Organ transplants
• Rejection due to MHCs that are too
dissimilar
• Suppress immune system to decrease
rejection
• Bone marrow: graft rejection
•Overactive/under active
Immune Systems
• Allergies: antigen induces
inflammatory response
• Histamine released from mast cells
• Anaphylactic shock: severe allergic
reaction, may cause death (due to 
BP)
• Epinephrine may counteract
• Autoimmune diseases: immune system
attacks self tissue
• Lupus, rheumatoid arthritis, MS, type 1
diabetes
•Under active Immune
System
• Immunodeficiency diseases:
• Severe combine immunodeficiency (SCID)
• Genetic, need marrow transplant
• May treat w/ gene therapy
• Hodgkin’s: damages lymphatic system
• AIDS
• Susceptible to opportunistic infections
• Caused by HIV, 2 strains
• Infect CD4 cells: requires CD4 receptor and
co-receptor
• Implications for treatment:
• Chemokines bind to coreceptor - may block entry
•More on AIDS
• High mutation rate
• Test is actually for HIV antibodies
• T cell count indicates disease
progression
• Drugs only slow the progression,
are very expensive
• 30-40 million (?) world wide cases
• 70% in sub-saharan Africa