PowerPoint Presentation - I. Introduction to class

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INNATE IMMUNITY

 

BARRIERS CELLS: MACROPHAGES, PLASMA CELLS, NK CELLS LYMPHOCYTES,



CYTOKINES /CHEMOKINES



PLASMA PROTEINS: Coagulation Factors Complement,



Toll-Like Receptors, TLR’s

Innate immunity

 A hallmark of the innate immune system is that it has no memory of a previous encounter with a foreign organism. The system is good at dealing with extracellular bacteria, fungi and intracellular viruses .

ADAPTIVE IMMUNITY



CELLULAR,

i.e., direct cellular reactions to antigens



HUMORAL,

antibodies i.e.,

Adaptive (acquired) immunity

Refers to antigen-specific defense mechanisms that take several days to become protective and are

designed to remove a specific antigen. This is the immunity one develops throughout life. There are two major branches of the adaptive immune responses: 1. Humoral immunity : involves the production of antibody molecules in response to an antigen and is mediated by B-lymphocytes.

2. cell-mediated immunity : involves the production of cytotoxic T-lymphocytes, activated macrophages, activated NK cells, and cytokines in response to an antigen and is mediated by T-lymphocytes.

CELLS

of the IMMUNE SYSTEM

     

LYMPHOCYTES,

T

LYMPHOCYTES,

B PLASMA CELLS (MODIFIED B CELLS) MACROPHAGES

, aka “HISTIOCYTES”, (APCs, i.e., Antigen Presenting Cells) “

DENDRITIC

” CELLS (APCs, i.e., Antigen Presenting Cells)

NK

(NATURAL KILLER)

CELLS

NK CELLS

MHC M



ajor

istocompatibility

omplex

A genetic “LOCUS” on Chromosome 6, which codes for cell surface compatibility



Also called HLA (Human Leukocyte Antigens) in humans and H-2 in mice



It’s major job is to make sure all self cell antigens are recognized and “tolerated”, because the general rule of the immune system is that all UN-recognized antigens will NOT be tolerated

GENERAL SCHEME of CELLULAR EVENTS

 

APCs (Macrophages, Dendritic Cells)



T-Cells



(Control Everything)



CD4



“REGULATORS” (Helper)

  

CD8



“EFFECTORS” B-Cells



NK Cells



Plasma Cells



AB’s

    

CYTOKINES

Cytokines are produced by a broad range of cells, including immune cells like macrophages , B lymphocytes as endothelial cells , fibroblasts , and various stromal cells ; , T lymphocytes and mast cells , as well

MEDIATE INNATE (NATURAL) IMMUNITY, IL-1, TNF, INTERFERONS REGULATE ILs) LYMPHOCYTE GROWTH (many interleukins, ACTIVATE INFLAMMATORY CELLS STIMULATE HEMATOPOESIS, (CSFs, or S timulating F actors ) C olony

CYTOKINES/CHEMOKINES

  

CYTOKINES are PROTEINS produced by MANY cells, but usually LYMPHOCYTES and MACROPHAGES, numerous roles in acute and chronic inflammation, AND immunity



TNF

,

IL-1

, by macrophages

CHEMOKINES are small proteins which are attractants for PMNs

They are important in health and disease, specifically in host responses to infection, immune responses, inflammation , trauma, sepsis , cancer, and reproduction.

MHC MOLECULES



(Gene Products)

(All nucleated cells and platelets), cell surface glycoproteins, ANTIGENS 

(APC’s, i.e., macs and dendritics, lymphs), cell surface glycoproteins, ANTIGENS 

III

Complement System Proteins

IMMUNE SYSTEM DISORDERS WHAT CAN GO WRONG?

 

HYPERSENSITIVITY REACTIONS, I-IV “AUTO”-IMMUNE DISEASES, aka “COLLAGEN” DISEASES (BAD TERM) Inflammation NOT due to external pathogens, MHC failure.

 

IMMUNE DEFICIENCY SYNDROMES, IDS : PRIMARY (GENETIC)



SECONDARY ( A CQUIRED)

HYPERSENSITIVITY

When the immune systems cause harm to the body, it is referred to as a hypersensitivity

Four Types of Hypersensitivity Reactions:



Type I (Anaphylactic) Reactions



Type II (Cytotoxic) Reactions



Type III (Immune Complex) Reactions



Type IV (Cell-Mediated) Reactions

1.Anaphylactic hypersensitivity

•

systemic anaphylaxis

- the allergin is usually picked up by the blood and the reactions occur throughout the body. Examples include severe allergy to insect stings, drugs, and antisera.

•

localized anaphylaxis

- the allergin is usually found localized in the mucous membranes or the skin. Examples include allergy to hair, pollen, dust, dander, feathers, and food.

•

Disorders

- Atopy ( Atopic syndrome ) - Asthma - Anaphylaxis

 The process of anaphylaxis consists of the following sequential events: 

First exposure:

to an antigen (allergen),such as bee venom, results in production of IgE class of antibodies by plasma cells.

 The surface of mast cells contains specific receptors for IgE.

 IgE molecules are bound to their receptors on the surface of mast cells and basophils.



Second exposure:

• • • • results in binding of the antigen to IgE on the mast cells .

 This then triggers the release of mast cell granules, which are : Histamine secretion. -causes constriction of smooth muscles ( ex bronchioles ), vasodilatation, Increased capillary permeability, increase bronchial mucus Chemotactic factors for eosinophils, proteases.

Leukotrienes -causes bronchial spasms.

Prostaglandins

 

Histamine : Dilates and increases permeability of blood vessels (swelling and redness), increases mucus secretion (runny nose), smooth muscle contraction (bronchi).



Prostaglandins : Contraction of smooth muscle of respiratory system and increased mucus secretion.



Leukotrienes : Bronchial spasms.

Anaphylactic shock : Massive drop in blood pressure. Can be fatal in minutes.

Mast Cells and the Allergic Response

Antibody-dependent cytotoxicity



Mechanism:

Either

IgG or IgM

is made against normal self antigens

as a result of a failure in immune tolerance, or a foreign antigen

resembling some molecule on the

surface of host cells enters the body

and IgG or IgM made against that antigen then cross reacts with the host cell surface.

The binding of these antibodies to the surface of host cells then leads to:

 

Opsonization of the host cell. Activation of the classical complement pathway causing MAC lysis ( membrane attack complex ) of the cells.



ADCC (Antibody-Dependent Cell Mediated Cytotoxicity ) destruction of the host cells.

Complement system

    It consists of series of proteins synthesised by liver as acute phase reactants.

1. Augments host immune defenses 2.Lysis bacteria directly with MAC 3. Participates in cytotoxic immunity and immune complex hypersensitivity reactions.

     The multiple activities of the complement system: Lysis Opsonization Activation of inflammatory response Clearance of immune complexes

      C3a……….Anaphylotoxin

C3b………..opsonin

C5a………..Anaphylotoxin, Adhesion, Chemotactic C5b67…………..Chemotactic complex C5b6789…………………MAC MAC; Membrane attack complex

OPSONIZATION

MAC LYSIS

ADCC

•

Disorders: -Mismatched blood group

Autoimmune hemolytic anemia -Thrombocytopenia -Erythroblastosis fetalis -Goodpasture's syndrome -Membranous nephropathy

3. Immune complex-mediated

Mechanism:

This is caused when soluble antigen-antibody (IgG or IgM) complexes, which are normally removed by macrophages in the spleen and liver, form in large amounts and overwhelm the body . These small complexes lodge in the capillaries, pass between the endothelial cells of blood vessels - especially those in the skin, joints, and kidneys - and become trapped on the surrounding basement membrane beneath these cells.

• The antigen/antibody complexes then activate the classical complement pathway. This may cause: 

Massive inflammation

, due to complement protein C5a triggering mast cells to release inflammatory mediators;



Influx of neutrophils

, due to complement protein C5a , resulting in neutrophils discharging their lysosomes and causing tissue destruction and further inflammation



MAC lysis

of surrounding tissue cells, due to the membrane attack complex, C5b6789n; 

Aggregation of platelets

, resulting in more inflammation and the formation of microthrombi that block capillaries;



Activation of macrophages

, resulting in production of inflammatory cytokines and extracellular killing causing tissue destruction.

•

Associated disorders:



serum sickness, a combination type I and

    

type III hypersensitivity.

autoimmune acute glomerulonephritis.

 

rheumatoid arthritis.

systemic lupus erythematosus.



the skin lesions of syphilis and leprosy.

Arthus reaction.

Post streptococcal glomerulonephritis.

Lupus Nephritis.

Extrinsic allergic alveolitis (Hypersensitivity pneumonitis)



Delayed hypersensitivity

•

cell-mediated rather than antibody mediated.

•

T8-lymphocytes become sensitized to an antigen and differentiate into cytotoxic T lymphocytes while effector T4 lymphocytes become sensitized to an

antigen and produce cytokines . CTLs, cytokines, eosinophils, and/or macrophages then cause harm rather than benefit.

Summary of Hypersensitivity reactions

Production of antibodies to substances most tolerate, ie allergies.

 Type I (acute)    Most common, starts within seconds and most often ends within 30 minutes .

Anaphylaxis – causes edema, mucus, and congestion Asthma – reaction to inhaled allergen.

 Causes massive release of histamine and spasmatic contraction of the bronchioles.

Anaphylactic shock – systemic response to an injected allergen.  Can cause bronchiolar constriction, circulatory shock, and possible death.

 Type II (antibody-dependant cytotoxic) transfusion reaction.

as in  Type III (immune complex) large antibody-antigen complexes that get trapped under the tunic interna of blood vessels and cause inflammation.

 Type IV (delayed) occur 12 to 72 hours after exposure. Delay commonly associated with travel time to lymph nodes. Cosmetics and poison ivy hapten commonly do this.

Hypersensitivity