Introduction to Immunology

by

Angelica D. Francisco, MD, MSc

towards modern times

War on smallpox
1718- Lady Montague became

Lady Mary Wortley Montague (1689-1762)

aware of a practice, called variolation or inoculation, and introduced it to Britain after first having her own children treated. 1798 Edward Jenner noticed immunity bestowed to milkmaids injected fluid from cowpox blister into skin of patient (orphan or prisoner) 1989- WHO announced smallpox was eradicated from the world

www.longwood.edu/staff/buckalewdw/Immlec/

Louie Louie
Louis Pasteur
1879- discovered that old bacterial cultures of Pasteurella lost virulence. Referred to injection of weakened culture a vaccine in honor of Jenner 1881- He applied the same technique vs. anthrax .and then rabies
Pasteur inoculating sheep at Msr. Rossignols farm May, 1881

www.longwood.edu/staff/buckalewdw/Immlec/

First insights into mechanics of immunity

Emil von Behring

S. Kitasato

1880s- Metchnikoff discovered phagocytic cells that ingest microbes and particles cells conferred immunity

1890- von Behring and Kitasato discovered blood sera could transfer immunity liquid of blood conferred
immunity

www.longwood.edu/staff/buckalewdw/Immlec/

Elie Metchnikoff

THE IMMUNE SYSTEM

Cells in our bone marrow, thymus, and the lymphatic system of ducts and nodes, spleen, and blood that function to protect us.

IMMUNITY
Mechanisms used by the body as protection against agents that are foreign to the body Discrimination between self and nonself

DEFINITIONS
Antigen Any material (usually foreign) that elicits and/or is specifically bound by an antibody Pathogen Any disease causing micro-organism.

DEFINITION
Antibody A protein that interacts with a particular site (epitope) on an antigen and facilitates clearance of that antigen by various mechanisms (immunoglobulin)

DEFINITIONS
Tolerance Non-reactivity of the immune system, usually refers to "self" but may include foreign tissue in organ transplants. Autoimmunity A failure of tolerance, the immune system reacts to self.

DEFINITION
Cytokines Signaling molecules released by cells involved in innate and acquired immune response Regulate innate and acquired immune response Stimulate hematopoiesis
eg.,interferons, interleukins

TYPES OF IMMUNITY
Innate immune mechanisms Acquired immune mechanisms

INNATE IMMUNITY
Protection conferred by mechanisms that are inborn in the individual
External
Physical barriers: skin, mucus membranes Chemical barriers: pH of secretions

Internal
Phagocytes, interferon, fever

ACQUIRED IMMUNITY
Protective mechanisms that are specific against invading agents

INNATE IMMUNITY
Non-specific defense mechanisms Does not recognize every possible antigen The initial response against microbes and prevention of infection

biology.umt.edu/biol103/lecturenotes/ Driver/Driver%20spring%2005/Biol%20103%20Chap%

INNATE IMMUNITY
Anatomical barriers
Skin
Dry, acidic T<37oC Exfoliation

Mucus membrane
Mucus secretion traps microbes Lysozymes, lactoferrin & lactoperoxidase Secretory IgA

INNATE IMMUNITY
Mechanical removal
Mucus & cilia: airways Cough & sneeze Vomiting & diarrhea Flushing by body fluids (urine, tears, saliva, perspiration)

INNATE IMMUNITY
Normal bacterial flora
Metabolic products Adhering to target host cells Depleting nutrients Clinical: opportunistic infection

INNATE IMMUNITY
Phagocytosis
Monocyte-macrophage Neutrophils Chemical mediators from basophils, mast cells, eosinophils

Acute inflammatory reactions Complement proteins Fever

WHITE BLOOD CELLS

Leukocytes Protect against disease Interleukins and colony-stimulating factors stimulate development
Granulocytes neutrophils eosinophils basophils
Holes Human Anatomy and Physiology Tenth Edition Shier w Butler w Lewis

Agranulocytes lymphocytes monocytes

GRANULAR LEUKOCYTES
Eosinophil

Neutrophil Basophil

www.apsu.edu/pittsg/2020/Chapter%2017%20-%20Blood.ppt

AGRANULAR LEUKOCYTES
Lymphocyte

Monocyte

www.apsu.edu/pittsg/2020/Chapter%2017%20-%20Blood.ppt

NEUTROPHILS
Light blue granules in acid-base stain Lobed nucleus Phagocytic 54% - 62% of leukocyte Elevated in bacterial infections
Holes Human Anatomy and Physiology Tenth Edition Shier w Butler w Lewis

14-13

BASOPHILS
Deep blue granules is basic stain Release histamine Release heparin Less than 1% of leukocytes

Holes Human Anatomy and Physiology Tenth Edition Shier w Butler w Lewis

14-14

EOSINOPHILS
Deep red granules in acid stain Bilobed nucleus Moderate allergic reactions 1% - 3% of leukocytes Elevated in worm infestations and allergic reactions
Holes Human Anatomy and Physiology Tenth Edition Shier w Butler w Lewis

14-15

MONOCYTES
Largest blood cell Kidney-shaped or oval nuclei Leave bloodstream to become macrophages 3% - 9% of leukocytes Elevated in typhoid fever, malaria, tuberculosis
Holes Human Anatomy and Physiology Tenth Edition Shier w Butler w Lewis

14-16

LYMPHOCYTES
About the size of RBC Large spherical nuclei Thin rims of cytoplasm
(T cells & B cells)

Produce antibodies 25% - 33% of leukocytes Decreased T Cells in AIDS

Holes Human Anatomy and Physiology Tenth Edition Shier w Butler w Lewis

14-17

MAST CELLS
Found in almost all tissues and organs Derived from bone marrow cells Contain heparin, histamine & proteases Involved in allergy and anaphylactic reactions

IMMUNOBIOLOGY at http://www.ncbi.nlm.nih.gov/books/

WHITE BLOOD CELLS IN INFLAMMATION

Margination of blood vessel Pavementing of endothelium Diapedesis
Cells squeeze through capillary walls to enter tissue space outside the blood vessel

Chemotaxis
Purposive migration towards injury in response to chemotaxins

Phagocytosis

http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html

Margination

Pavementing

Diapedesis
http://medweb.bham.ac.uk/http/mod/3/1/a/acute.html

http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html

INFLAMMATORY REACTION
1. Vasodilation leading to excess local blood flow 2. Increased permeability of capillary 3. Clotting of extravasated fluid in the interstitium 4. Migration of neutrophils and monocytes from blood vessels into tissue 5. Swelling

Chemical signals released by macs and mast cells

Capillaries get leaky, agents move from blood to site

Chemokines released, attract more cells

Neutrophils and Macs eat em up

biology.umt.edu/biol103/lecturenotes/ Driver/Driver%20spring%2005/Biol%20103%20Chap%

DEFINITION
Chemokines Soluble proteins secreted by cells that promote inflammation by enhancing leukocyte activation
i.e., margination, diapedesis & chemotaxis

INFLAMMATION
Chemical Mediators
Lysosomal compounds (proteases) Histamine Prostaglandins
Cyclo-oxygenase pathway of arachidonic acid metabolism Anti-inflammatory drugs: aspirin & COX-2 inhibitors

Leukotrienes
Lipo-oxygenase pathway

Serotonin (5 hydroxytryptamine, 5HT)

INFLAMMATION
Redness (rubor) Heat (calor) Swelling (tumor) Pain (dolor) Loss of function

INNATE IMMUNITY
Designed to recognize a few highly conserved structures present in many different microorganisms

PATHOGEN ASSOCIATED MOLECULAR PATTERNS

Bacterial molecules
peptidoglycan, teichoic acids, lipopolysaccharide, mannans, flagellin, pilin, and bacterial DNA

Viruses
double-stranded RNA (dsRNA) and

Fungal cell wall components

lipoteichoic acids, glycolipids, mannans, and zymosan

Structure of a Gram-Negative Cell Wall

http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html

Structure of a Gram-Positive Cell Wall

http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html

http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html

http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html

http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html

LEWIS TRIPLE RESPONSE TO INJURY

White reaction Flush
A momentary white line Due to arteriolar vasoconstriction A dull red line Due to capillary dilatation. A red, irregular, surrounding zone Due to arteriolar dilatation Both nervous and chemical factors Zone of oedema Due to fluid exudation into the extravascular space

Flare

Wheal

WBC Counts
WBCs in peripheral circulation Leukocytosis
5,000 10,000 per cubic millimeter
High WBC count acute infections, vigorous exercise, dehydration Low WBC count Typhoid fever, flu, measles, mumps, chicken pox, AIDS

Leukopenia

COMPLEMENT
A group of cytotoxic serum proteins involved in the mediation of immune responses.

COMPLEMENT
Activated by Antigen-antibody complexes
classical pathway

Microbial cell walls

Alternative pathway

COMPLEMENT
Actions
Lysis of microorganisms or infected cells Opsonization
Enhance phagocytosis by attaching to antigen

Chemotaxis
Attract phagocytes to infection

COMPLEMENT ACTIVATION

www.utmem.edu/obgyn/res_pres/ faculty_pres/ImmunologyMicrobiology_Thorpe.pdf -

CLASSICAL COMPLEMENT ACTIVATION

ASSEMBLY OF C1

http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html

CLASSICAL COMPLEMENT ACTIVATION

C1 cleaves C4 to C4a & C4b

http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html

CLASSICAL COMPLEMENT ACTIVATION

Formation of C4a2b,
the C3 convertase

http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html

CLASSICAL COMPLEMENT ACTIVATION

C4a2b functions as a C3 convertase

http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html

CLASSICAL COMPLEMENT ACTIVATION

C4b2a3b C5 convertase

C5 C5a and C5b

C5b6789n Membrane Attack Complex

http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html

COMPLEMENT ACTIVATION
C3a C5a
Vascular Stimulate permeability release histamine Activation of cells from mast phagocytes (inflammation &

diapedesis) Chemoattractant C3b

OPSONIN on bacterial membrane

http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html

FEVER
Tissue Necrosis Factor-alpha, TNF- & Interleukin-1, IL-1
Produced by activated macrophage & leukocytes Act on anterior hypothalamus

FEVER
FUNCTIONS
Alters temperature vs. microbial growth Enhance secretion of inflammatory proteins in immune cells
Heat shock proteins, hsp

Enhanced metabolism, increased rate of production of cells by bone marrow

INTERFERON

Source: http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/if.html

ACQUIRED IMMUNITY
2 TYPES Cellular Immunity Humoral Immunity

ACQUIRED IMMUNITY
Cellular immunity
Cell-mediated immunity Immune response mediated T lymphocytes, including macrophages

Humoral Immunity
Antibody-mediated immunity Immune response mediated by Blymphocytes & plasma cells

ACQUIRED IMMUNITY
PLASMA CELLS
DIFFERENTIATE FROM B LYMPHOCYTES DURING IMMUNE RESPONSES SECRETE ANTIBODIES

T CELLS- CELL MEDIATED IMMUNITY

CYTOTOXIC T CELLS, CTL CELLS OR CD8 CELLS HELPER T CELLS, TH CELLS OR CD4 CELLS SUPPRESSOR T CELLS

ORIGIN OF CELLS MEDIATING IMMUNE RESPONSES

BONE MARROW
MONOCYTE/MACROPHAGE

RETICULOENDOTHELIAL SYSTEM PRIMARY LYMPHOID ORGANS SECONDARY LYMPHOID ORGANS

PRIMARY LYMPHOID ORGANS

SECONDARY LYMPHOID ORGANS

ORIGIN OF CELLS MEDIATING IMMUNE RESPONSES

PRIMARY LYMPHOID ORGANS
SITES FOR MATURATION OF T AND B CELLS INTO ANTIGEN-RECOGNIZING LYMPHOCYTES THYMUS GLAND FOR T CELLS BURSA OF FABRICIUS & BONE MARROW FOR B CELLS

ORIGIN OF CELLS MEDIATING IMMUNE RESPONSES

THYMUS GLAND FOR T CELLS
CELLS MIGRATE FROM BONE MARROW LYMPHOCYTES MATURATION OCCUR DURING FETAL LIFE CELLS EVENTUALLY POPULATE THE SECONDARY LYMPHOID ORGANS

ORIGIN OF CELLS MEDIATING IMMUNE RESPONSES

BURSA OF FABRICIUS & BONE MARROW FOR B CELLS
EMBRYONIC B CELLS ORIGINATE FROM HEMATOPOIETIC CELLS FROM FETAL LIVER FUNCTION TRANSFERRED TO BONE MARROW AT BIRTH AND FOR LIFE B CELLS EVENTUALLY TRANSPORTED TO SECONDARY LYMPHOID ORGANS

ORIGIN OF CELLS MEDIATING IMMUNE RESPONSES

SECONDARY LYMPHOID ORGANS
SITES WHERE ANTIGEN-COMMITTED B & T CELLS ARE STIMULATED BY ANTIGEN AND UNDERGO FURTHER DIVISION & DIFFERENTIATION SPLEEN MUCOSA ASSOCIATED LYMPHOID TISSUE (MALT)

CHARACTERISTICS OF ACQUIRED IMMUNE RESPONSE

1. DISCRIMINATION BETWEEN SELF AND NONSELF
ABILITY TO RECOGNIZE AND RESPOND TO MOLECULES THAT ARE FOREIGN OR NONSELF AND AVOID MAKING A RESPONSE TO THOSE MOLECULES THAT ARE SELF

CHARACTERISTICS OF ACQUIRED IMMUNE RESPONSE

2. SPECIFICITY
ABILITY TO DISCRIMINATE AMONG DIFFERENT MOLECULAR ENTITIES PRESENTED TO IT TO RESPOND ONLY TO THOSE UNIQUELY REQUIRED, RATHER THAN MAKING A RANDOM, UNDIFFERENTIATED RESPONSE

Figure 43.8 Antigen receptors on lymphocytes

Antigenbinding site

Antigenbinding site
V

Disulfide bridge

Antigenbinding site Variable regions Constant regions Transmembrane region

V

Light chain

C
C C

V V C C

Plasma chain Heavy chains membrane chain Disulfide bridge T cell B cell Cytoplasm of B cell Cytoplasm of T cell (a) A B cell receptor consists of two identical heavy (b) A T cell receptor consists of one chains and two identical light chains linked by chain and one chain linked by several disulfide bridges. a disulfide bridge.

Copyright 2005 Pearson Education, Inc. publishing as Benjamin Cummings

CHARACTERISTICS OF ACQUIRED IMMUNE RESPONSE

3. ADAPTIVENESS
THE ABILITY TO RESPOND TO PREVIOUSLY UNSEEN MOLECULES

CHARACTERISTICS OF ACQUIRED IMMUNE RESPONSE

4. MEMORY or ANAMNESIS
ABILITY TO RECALL PREVIOUS CONTACT WITH A FOREIGN MOLECULE AND RESPOND TO IT IN A LEARNED MANNER, i.e., A MORE RAPID AND LARGER RESPONSE

biology.umt.edu/biol103/lecturenotes/ Driver/Driver%20spring%2005/Biol%20103%20Chap%

TYPES OF IMMUNITY
Natural active immunity
Immunization is a natural outcome of infection

Artificial active immunity

Individual purposely exposed to an antigen to induce the formation of antibodies
vaccination immunization

TYPES OF IMMUNITY
Artificial passive immunity
Individuals receive antibodies that play no role in the antibody production process used to cure a person suffering from a disease

Natural passive immunity

Newborns receive IgG from mothers that pass through the placenta and receive IgA through colostrum

CLONAL SELECTION THEORY

EACH LYMPHOCYTE CARRIES ON ITS SURFACE RECEPTOR MOLECULES OF ONLY A SINGLE SPECIFICITY

CLONAL SELECTION THEORY

FOREIGN Ags COMBINE WITH LYMPHOCYTES, WHICH ARE STIMULATED TO DIFFERENTIATE INTO CLONES OF CELLS MAKING ANTIBODY (Igs) OF THAT PARTICULAR SPECIFICITY, AND MEMORY CELLS (B-CELLS & T-CELLS)

REQUIREMENTS FOR IMMUNOGENICITY

FOREIGNESS
COMPOUNDS THAT ARE PART OF SELF ARE NOT IMMUNOGENIC, (ABILITY TO ELICIT AN IMMUNE RESPONSE)

HIGH MOLECULAR WEIGHT, HMW

A MINIMAL MOLECULAR WEIGHT

CHEMICAL COMPLEXITY
A CERTAIN DEGREE OF PHYSICOCHEMICAL COMPLEXITY

ANTIGENICITY
ANTIGENIC DETERMINANT or EPITOPE
PORTION OF AN ANTIGEN THAT BINDS SPECIFICALLY WITH THE BINDING SITE OF AN ANTIBODY OR A RECEPTOR ON A LYMPHOCYTE

Binding of Epitopes to Corresponding Molecules of sIg on the Surface of B--Lymphocytes

http://student.ccbcmd.edu/courses/bio141/lecguide/unit2/innate/epsig.html

HUMORAL IMMUNITY
MEDIATED BY SERUM ANTIBODIES SECRETED BY B CELLS

ACTIVATION OF B CELLS

biology.umt.edu/biol103/lecturenotes/ Driver/Driver%20spring%2005/Biol%20103%20Chap%

HUMORAL IMMUNITY
Antigen presenting cells contacts and activates helper T cells Cytokines (protein signals) released B and T cells activated

Bacterium Macrophage Peptide antigen Class II MHC molecule

1

B cell
2

Clone of plasma cells

Secreted antibody molecules

TCR

CD4 Cytokines

Endoplasmic reticulum of plasma cell

Helper T cell

Activated helper T cell

Clone of memory B cells

biology.umt.edu/biol103/lecturenotes/ Driver/Driver%20spring%2005/Biol%20103%20Chap%

HUMORAL IMMUNITY
B cells divide (clones)
B-cells release antibody (Plasma cells) Memory cells formed

ANTIBODY STRUCTURE
4 CHAINS
2H, 2L CHAINS

REGIONS
VARIABLE & CONSTANT

FRAGMENTS
Fab
ANTIGEN BINDING

Fc
BIOLOGICAL FUNCTIONS

http://www.biology.eku.edu/RITCHISO/301notes4.htm

ANTIBODY STRUCTURE
HEAVY CHAINS, H CHAINS
2 H CHAINS 5 ISOTYPES
IgM IgG IgA IgD IgE

HEAVY CHAIN

ANTIBODY STRUCTURE
LIGHT CHAINS, L CHAINS
2 L CHAINS 2 MAJOR CLASSES
KAPPA, LAMBDA,

IMMUNOGLOBULINS
IgG
PREDOMINANT IMMUNOGLOBULIN STRUCTURE
2 H CHAINS 2 L CHAINS (EITHER OR )

IMMUNOGLOBULINS
IgG
REPRESENT 15% OF TOTAL PROTEIN HALF-LIFE: 23 DAYS (LONGEST OF Igs) ONLY SUBCLASS THAT CAN PASS THROUGH PLACENTA OPSONIN

Opsonization of an Encapsulated Bacterium

http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html

Ingestion of Bacteria and Phagosome Formation

http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html

IMMUNOGLOBULINS
IgG
ROLE IN ANTIBODY-DEPENDENT, CELLMEDIATED CYTOTOXICITY, ADCC ACTIVATION OF COMPLEMENT SYSTEM NEUTRALIZATION OF TOXIN IMMOBILIZATION OF BACTERIA NEUTRALIZATION OF VIRUSES

IMMUNOGLOBULINS
IgM
CONSIST OF 5 Ig UNITS, PENTAMERIC DOES NOT CROSS THE PLACENTA
SYNTHESIZED BY THE FETUS

ELEVATION INDICATES INFECTION ANTIBODIES FOR RBC ANTIGENS ACTIVATES COMPLEMENT SYSTEM

IMMUNOGLOBULINS
IgA
FOUND IN SECRETIONS, eg., SALIVA, TEARS, SWEAT, MUCUS COLOSTRUM, INITIAL MILK IN MATERNAL LACTATION DIMERIC FORM IN BODY SECRETIONS ROLE IN MUCOSAL INFECTIONS DOES NOT ACTIVATE COMPLEMENT BACTERICIDAL vs. GRAM NEGATIVE BACTERIA

IMMUNOGLOBULINS
IgE
HAS SHORTEST HALF-LIFE, 2 DAYS LOWEST SERUM LEVELS Fc PORTION BINDS TO MAST CELLS AND BASOPHILS DOES NOT ACTIVATE COMPLEMENT ELEVATED IN PARASITIC INFECTIONS MEDIATES HYPERSENSITIVITY RXNS

IMMUNOGLOBULINS
IgD
PRESENT ON SURFACE OF B LYMPHOCYTES
ROLE IN B CELL MATURATION ANTIGEN RECOGNITION BY B CELLS

DEFINITION
Class switching
Process by which a B lymphocyte producing IgM and IgD switches to production of secondary immunoglobulin class (IgE, IgA or IgG), with the same antigen binding specificity

CELLULAR IMMUNITY
ANTIGEN-SPECIFIC ARM OF CELLMEDIATED IMMUNITY CONSISTS OF THE T LYMPHOCYTES

CELLULAR IMMUNITY
T CELLS- CELL MEDIATED IMMUNITY
CYTOTOXIC T CELLS, CTL CELLS OR CD8 CELLS HELPER T CELLS, TH CELLS OR CD4 CELLS SUPPRESSOR T CELLS MEMORY T CELLS

T CELL ACTIVATION by MACROPHAGE & IL-2

Activation of T cells by the action of macrophages and interleukin-2

www.utmem.edu/obgyn/res_pres/ faculty_pres/ImmunologyMicrobiology_Thorpe.pdf -

MAJOR HISTOCOMPATIBILITY COMPLEX

CLASS I MHC
FOUND IN ALL NUCLEATED CELLS COUPLED TO PEPTIDE FRAGMENTS SYTNTHESIZED WITHIN (INTERNAL) THE CELL RECOGNIZED BY CTLs, CYTOTOXIC TCELLS

MAJOR HISTOCOMPATIBILITY COMPLEX

CLASS II MHC
PRESENT IN ANTIGEN PRESENTING CELLS, B CELLS AND ACTIVATED T CELLS PEPTIDE FRAGMENTS FROM EXTRACELLULAR ANTIGENS RECOGNIZED BY TH CELLS, HELPER TCELLS

ACTIVATION OF CTL BY MACROPHAGE, APC

CD8 molecule

http://student.ccbcmd.edu/courses/bio141/lecguide/unit2/innate/mhc1t8.html

ACTIVATION OF CTL-CELL
1 A specific cytotoxic T cell binds to a 2 class I MHCantigen complex on a target cell via its TCR with the aid of CD8. This interaction, along with cytokines from helper T cells, leads to the activation of the cytotoxic cell. Cytotoxic T cell Perforin The activated T cell releases perforin molecules, which form pores in the target cell membrane, and proteolytic enzymes (granzymes), which enter the target cell by endocytosis. 3 The granzymes initiate apoptosis within the target cells, leading to fragmentation of the nucleus, release of small apoptotic bodies, and eventual cell death. The released cytotoxic T cell can attack other target cells.

Released cytotoxic T cell Cancer cell

Granzymes 1 TCR Class I MHC molecule CD8 2 Pore 3

Apoptotic target cell

Target cell

Peptide antigen

Cytotoxic T cell

biology.umt.edu/biol103/lecturenotes/ Driver/Driver%20spring%2005/Biol%20103%20Chap%

CELLULAR IMMUNITY
Cytotoxic T cells recognize infected self cells Bind to cell and initiate apoptosis (process of cell self-destruction)

AN EFFECTOR T4-LYMPHOCYTE RECOGNIZING EPITOPE/MHC-II ON AN ACTIVATED B-LYMPHOCYTE

http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/bcell/bcellt4.html

biology.umt.edu/biol103/lecturenotes/ Driver/Driver%20spring%2005/Biol%20103%20Chap%

biology.umt.edu/biol103/lecturenotes/ Driver/Driver%20spring%2005/Biol%20103%20Chap%

biology.umt.edu/biol103/lecturenotes/ Driver/Driver%20spring%2005/Biol%20103%20Chap%

INTEGRATED IMMUNE RESPONSE

B CELLS
vs BACTERIAL INFECTIONS DEFICIENCY:
BRUTONS AGAMMAGLOBULINEMIA

T CELLS
vs. VIRAL INFECTIONS DEFICIENCY:
DIGEORGES SYNDROME

Acquired Immunodeficiency Syndrome (AIDS)

Human immunodeficiency virus (HIV) infects and kills helper T cells HIV is an RNA virus
incorporates into DNA

Autoimmune Disease
Loss of tolerance to self-antigens Mechanisms
Destruction of cell or tissue barriers
eg. sympathetic opthalmia

Binding of antigen to self-proteins

eg. interstitial nephritis

Molecular mimicry
eg. rheumatic fever, diabetes, ms

INTEGRATED IMMUNE RESPONSE

ANTIGEN ANTIGEN PROCESSING CELL (MACROPHAGE) MHC-II + Ag

IL1
TCR HELPER T CELL CD4 ACTIVATE B-CELLS Igs

IL2 ACTIVATE CYTOTOXIC T-CELLS CD8 CYTOKINES/ ILs

IMMUNOBIOLOGY at http://www.ncbi.nlm.nih.gov/books/

The nude mouse has a defect in its immune system, and can only live if protected from pathogens. The mouse has a transplant of rabbit skin, and can't reject the foreign tissue. Mice with immune deficiencies are very useful in cancer research because human cancer cells can grow into tumors allowing new ways to test cancer therapy.

http://www.biology.arizona.edu/immunology/tutorials/immunology/intro.html

References
GANONG, W: REV of MEDICAL PHYSIOLOGY, 22nd ed, Chapter 27 GUYTON & HALL. MEDICAL PHYSIOLOGY, 10th ed, Chapters 33 & 34 LODISH etal: MOLECULAR CELL BIOLOGY, 3rd ed, Chapter 27 VANDER, SHERMAN & LUCIANO. HUMAN PHYSIOLOGY, 6th ed, Chapter 20