ImmunityImmunity

Body DefensesBody Defenses First line - barriersFirst line - barriers

Skin and mucous membranesSkin and mucous membranesFlushing actionFlushing action

– Antimicrobial substancesAntimicrobial substancesLysozyme, acids, salts, normal Lysozyme, acids, salts, normal microbesmicrobes

Second line defensesSecond line defenses– Cells – neutrophils, macrophages, Cells – neutrophils, macrophages,

natural killer cellsnatural killer cells– Toll-like receptors on phagocytes Toll-like receptors on phagocytes

recognize carbohydrates on the surface recognize carbohydrates on the surface of bacteriaof bacteria

– InflammationInflammation– ProteinsProteins– ComplementComplement– InterferonInterferon– FeverFever

• All of the previous mechanisms are

NON-SPECIFIC

• Third line – immune response

1.Specific

2.Memory

3.Inducibility

•Antigens - substances recognized as “non-self” These can be:

•Infectious agents - bacteria, viruses, fungi or parasites

•Noninfectious substances – •Environmental - pollen, foods, bee

venoms•Drugs, vaccines, transfusions and transplanted tissues

AntigenAntigen

AntiAntibody body GenGeneratoreratorThe best antigens are:The best antigens are:

1.1. largelarge

2.2. recognized as foreignrecognized as foreign

3.3. complex complex

proteins and complex carbohydrates – good

nucleic acids and lipids – not good

Haptens – too small by themselves, piggy-back on larger molecules, us. Proteins

Epitopes (antigenic determinants) – regions of large molecules recognized by the immune system

Two cell types give us the immune response;both are lymphocytes, which are a type of leukocyte, or white blood cell.

B lymphocytes or B cellsT lymphocytes or T cells

The cells of the immune response differ from the cells of the inflammatory response in three ways:

1. They are SPECIFIC and each cell recognizes only one specific antigen.

B cells produce antibodies

Tc (Cytotoxic cells) cells attack antigen directly

2. Both produce groups of cells called “memory cells” that act quickly the second time the antigen is encountered.

3. An antigen induces an immune response. Only small amounts of antibodies or T Cells are present before encountering an antigen.

Long lasting protection against a specific antigen is immunity.

Natural immunity:

Not produced by the immune response

Species specific

Acquired immunity

Active – person produces immunity (by producing antibodies or Tc cells)

natural

artificial

Passive – temporary immunity is given(by giving antibodies)

natural

artificial

LymphocytesLymphocytesOriginate :

in liver, spleen and bone marrow of fetus

in bone marrow after birth

From stem cells – hemocytoblasts – that produce all blood cells.

To become mature, immunocompetent cells, they must pass through lymphoid tissues in other parts of the body.

As they do so, they become committed to becoming either T cells or B cells

Cells that migrate through the bone marrow (bursal equivalent) become B cells, and will produce antigens andparticipate in humoral immunity.

Cells that migrate through the thymus glands become T cells and participate in Cell-mediated immunity.

Humoral ImmunityHumoral Immunity

Humoral immune response : B cells that produce antibodies that travel through the blood.

Antibodies are proteins that match the molecular structure of an antigen, and bind to that antigen. This leads to the destruction of the antigen.

AntibodyAntibody

Structure of antibodyStructure of antibody

Y arm: antigen binding siteY arm: antigen binding site– Fab (fragment, antigen binding)Fab (fragment, antigen binding)

Base of Y: receptor binding siteBase of Y: receptor binding site– Fc (fragment, crystalizable)Fc (fragment, crystalizable)

B cells mature in the human bursal equivalent – in bone marrow – and obtain the ability to bind antigens and produce antibodies.

Clonal selection theory:

During fetal development, B cells are produced which can bind with any potential antigen. Each B cell binds only one antigen.

When antigen binds to antibody receptors on the surface of the B cell, the B cell divides and differentiates into antibody producing plasma cells and also memory cells.

ImmunoglobulinsImmunoglobulins

IgG - monomer (only one crosses placenta, IgG - monomer (only one crosses placenta, involve majority of immune responses)involve majority of immune responses)

IgA – dimer – 2 units - in secretions, found in IgA – dimer – 2 units - in secretions, found in the mucus area like gut, respiratory and the mucus area like gut, respiratory and urogenital tract, also in saliva, milk, tears urogenital tract, also in saliva, milk, tears

IgM – pentamer – 5 units, present early, before IgM – pentamer – 5 units, present early, before IgG is abundant IgG is abundant

IgD – monomer – on surface of B cells, activate IgD – monomer – on surface of B cells, activate basophils and mast cells basophils and mast cells

IgE – monomer – involved in hypersensitivities, IgE – monomer – involved in hypersensitivities, trigger release of histaminetrigger release of histamine

Cell-mediated Cell-mediated immunityimmunity

Produced through T cytoxic or Tc Cells Produced through T cytoxic or Tc Cells (T(T88 cell) cell)

DO NOTDO NOT produce antibodies produce antibodies Attack invaders directlyAttack invaders directly May produce toxic chemicals – such as May produce toxic chemicals – such as

perforins, cytolytic enzymes, etc.perforins, cytolytic enzymes, etc. May stimulate cell’s self-destruct May stimulate cell’s self-destruct

mechanismmechanism

Primary and Secondary Primary and Secondary Immune ResponsesImmune Responses

Primary response Primary response – Latent periodLatent period– IgM producedIgM produced– IgG produced laterIgG produced later

•Secondary response

•Anamnestic response –much more rapid due to memory cells

•Primarily IgG

Cellular Interactions in Cellular Interactions in the Immune Responsethe Immune Response

Few antigens can activate B cells Few antigens can activate B cells all by themselvesall by themselves

For activation of B cells and Tc For activation of B cells and Tc Cells need a Cells need a second signal – second signal – cytokine ( “cell mover”)cytokine ( “cell mover”)

Antigen-Presenting cells (APC, macrophages) place antigen on their cell surface in combination with the MHC (Major Histocompatibility complex) II complex

Antigen is presented to a specific helper T cell that has receptors that match the antigen – MHC II complex

After binding, the APC produces Interleukin -1 (IL-1) which stimulates the TH Cell to produce IL-2 (stimulate the growth of T cell) and/or IL-4 (proliferation and differentiation, IgG & IgE synthesis)

Interleukin-2 has an autocrine function, causes TH Cell to clone itself, and make more IL-2 and /or IL-4

Interleukins are a group of cytokines (cell signaling molecules) for inter cellular communications, IL1 to IL 35

Helper T cellsHelper T cells

TTH1H1 cells produce IL -2 and IFN-ɣ cells produce IL -2 and IFN-ɣ (interferon, cellular (interferon, cellular communication agents), and communication agents), and influence cell-mediated immunityinfluence cell-mediated immunity

TTH2H2 cells produce IL -4 (and other cells produce IL -4 (and other IL’s) and influence antibody-IL’s) and influence antibody-mediated (humoral) immunitymediated (humoral) immunity

When B cell comes in contact with the antigen and IL-4, the B cell produces plasma cells and memory cells

Tc Cells come in contact with the antigen on the surface of infected cells in combination with the MHC 1 complex. When also have binding with IL-2, cells produce activated Tc Cells and memory cells.

http://en.wikipedia.org/wiki/B_cell

HypersensitivitiesHypersensitivities

““The Immune System Gone The Immune System Gone Bad”Bad”

HypersensitivitiesHypersensitivities

1.1. AllergiesAllergies – Exaggerated immune – Exaggerated immune response against environmental response against environmental antigensantigens

2.2. AutoimmunityAutoimmunity – immune response – immune response against host’s own cellsagainst host’s own cells

3.3. AlloimmunityAlloimmunity – is a condition in – is a condition in which the body gains immunity, which the body gains immunity, from another individual of the same from another individual of the same species, against its own cells , such species, against its own cells , such as transfusions or transplantsas transfusions or transplants

These immune processes initiate inflammation and destroy healthy tissue. Four types:

Type I – IgE-mediated allergic reactions immediate type hypersensitivity

Type II – tissue-specific reactions antibody-dependent cytotoxicity

Type III – immune-complex-mediated reactions

Type IV - cell-mediated reactionsdelayed-type hypersensitivity

Type I - IgE-mediated allergic reactions or immediate hypersensitivity

Characterized by production of IgE

Most common allergic reactions

Most Type I reactions are against environmental antigens - allergens

Selected B cells produce IgE

Need repeated exposure to large quantities of allergen to become sensitized

IgE binds by Fc end to mast cells after first exposure

Second exposure (and subsequent exposures) – antigen binds with Fab portion of antibody on mast cells, and cross-links adjacent antibodies, causing mast cell to release granules.

Response is immediate ( 5- 30 minutes)

Sometimes beneficial to host – IgE-mediated destruction of parasites, especially parasitic worms.

Histamine release:Histamine release: Increases vascular permeability, Increases vascular permeability,

causing edemacausing edema Causes vasodilationCauses vasodilation Constricts bronchial smooth muscleConstricts bronchial smooth muscle Stimulates secretion from nasal, Stimulates secretion from nasal,

bronchial and gastric glandsbronchial and gastric glands Also hives (skin), conjunctivitis (eyes) Also hives (skin), conjunctivitis (eyes)

and rhinitis (mucous membranes of and rhinitis (mucous membranes of nose).nose).

Late phase reactionLate phase reaction 2 – 8 hours; lasts for 2 - 3 days2 – 8 hours; lasts for 2 - 3 days Other mediators that take longer to Other mediators that take longer to

be released or act:be released or act:– Chemotactic factors for eosinophils and Chemotactic factors for eosinophils and

neutrophilsneutrophils– LeukotrienesLeukotrienes– ProstaglandinsProstaglandins– Platelet-activating factor Platelet-activating factor – Protein-digesting enzymesProtein-digesting enzymes

Genetic predispositionGenetic predisposition

Allergy prone or atopic (unusual)Allergy prone or atopic (unusual) Can be life threatening, so Can be life threatening, so

individuals should be awareindividuals should be aware Skin tests – injection – see wheal Skin tests – injection – see wheal

and flareand flare Lab tests for circulating IgELab tests for circulating IgE

TreatmentTreatment First wave – antihistamines or First wave – antihistamines or

epinephrine (blocks mast cell epinephrine (blocks mast cell degranulation)degranulation)

Second wave – corticosteroids and Second wave – corticosteroids and nonsteroidal anti-inflammatory agents nonsteroidal anti-inflammatory agents that block synthesis of leukotrienes that block synthesis of leukotrienes and prostaglandinsand prostaglandins

Desensitization by repeated injections Desensitization by repeated injections of allergen – formation of IgGof allergen – formation of IgG

Anaphylaxis – Type I allergic reaction

may be localized or general

immediate – within a few minutes of exposure

Systemic anaphylaxis:pruritus(intense itching)urticaria (hives)Wheezing; dyspnea; swelling of the larynx

Give epinephrine

Anaphylactic shockAnaphylactic shock

Hypotension, edema (esp. of larynx), Hypotension, edema (esp. of larynx), rash, tachycardia, pale cool skin, rash, tachycardia, pale cool skin, convulsions and cyanosisconvulsions and cyanosis

Treatment:Treatment:– Maintain airwayMaintain airway– Epinephrine, antihistamines, Epinephrine, antihistamines,

corticosteroidscorticosteroids– FluidsFluids– OxygenOxygen

Type II – Tissue specific reactionsType II – Tissue specific reactions(antibody-dependent cytotoxicity)(antibody-dependent cytotoxicity)

Most tissues have specific antigens in Most tissues have specific antigens in their membranes expressed only by their membranes expressed only by that tissuethat tissue

Antibodies bind to cells or surface of Antibodies bind to cells or surface of a solid tissue (glomerular basement a solid tissue (glomerular basement membrane)membrane)

Destruction of tissue Destruction of tissue occurs:occurs:

– Destruction by Tc Cells which are Destruction by Tc Cells which are not antigen specific- K cellsnot antigen specific- K cells

– Complement-mediated lysisComplement-mediated lysis– Phagocytosis by macrophagesPhagocytosis by macrophages

(“frustrated phagocytosis”)(“frustrated phagocytosis”)– Binding of antibody causes cell to Binding of antibody causes cell to

malfunctionmalfunction

Autoimmune hemolytic anemiaAutoimmune hemolytic anemia

Immune system attacks own red Immune system attacks own red blood cellsblood cells

Type III – Immune-complex-Type III – Immune-complex-mediated reactionsmediated reactions

Caused by antigen-antibody complexes Caused by antigen-antibody complexes formed in circulation and deposited in formed in circulation and deposited in vessel walls or other tissuesvessel walls or other tissues

Not organ specificNot organ specific Effects caused by Effects caused by activation of activation of

complementcomplement – chemotaxis of – chemotaxis of neutrophilsneutrophils

Neutrophils release lysosomal enzymes Neutrophils release lysosomal enzymes into tissues (“frustrated phagocytosis”)into tissues (“frustrated phagocytosis”)

Glomerulonephritis Glomerulonephritis

Acute glomerulonephritis is an Acute glomerulonephritis is an inflammatory disease involving inflammatory disease involving the renal glomeruli of both the renal glomeruli of both kidneys. It is thought to involve kidneys. It is thought to involve antigen-antibody reaction which antigen-antibody reaction which produces damage to the produces damage to the glomerular capillaries glomerular capillaries

GlomerulonephritisGlomerulonephritis

Acute glomerulonephritis usually Acute glomerulonephritis usually follows a streptococcal infection follows a streptococcal infection of the respiratory tract or, less of the respiratory tract or, less often, a skin infection such as often, a skin infection such as impetigo. However, most often it . However, most often it is due to an allergic or immune is due to an allergic or immune response to infections in other response to infections in other parts of the body. parts of the body.

Type IV- Cell-mediated Type IV- Cell-mediated reactions (delayed response)reactions (delayed response)

Sensitized T lymphocytes – either Tc Cells Sensitized T lymphocytes – either Tc Cells or lymphokine producing Td cellsor lymphokine producing Td cells

Takes 24 – 72 hours to developTakes 24 – 72 hours to develop Damage by Tc Cell or inflammatory Damage by Tc Cell or inflammatory

response by Td Cells (lymphokines)response by Td Cells (lymphokines) Graft rejection, tumor rejection, TB reaction, Graft rejection, tumor rejection, TB reaction,

poison ivy and metal reactionspoison ivy and metal reactions Immune diseasesImmune diseases Tissue rejectionTissue rejection

Systemic lupus erythematosus SLE

Autoanitbodies against nucleic acids and other self components

Reverse ImmunityReverse Immunity

Graft vs. Host disease host is immunocompromised

transplant has immunocompetent cells