PowerPoint Lecture Presentations prepared by Bradley W ... · Soluble Ag-Ab complexes Relative concentrations of Ag and Ab determine fate of complex Ag and Abs in equal amounts with

PowerPoint® Lecture Presentations prepared by Bradley W. Christian, McLennan Community College

C H A P T E R

© 2016 Pearson Education, Inc.

Disorders Associated with the Immune System

19



Disorders of the Immune System



Not necessarily infectious diseases

Compromises response to infectious disease



3 major groups of disorders

1 Hypersensitivity – antigenic responses ie. Anaphylatic rxns., cytotoxic rxns. etc

2 Autoimmunity – loss of self-tolerance. Ex. Lupus, rheumatoid arthritis, transplant rejection.

3 Immune deficiency – congenital or acquired. Ex. HIV, DiGeorge syndrome


Hypersenitivity

An inappropriate or out of control immune response

Over reaction of the immune system causes tissue damage

4 types of hypersensitivity reactions

Type I Anaphylatic, Type II cytotoxic,

Type III immune complex, Type IV delayed cell mediated.


Type I Anaphylatic

Anaphylaxis –(against protection)

Mechanistically, it is an immune response

IgE mediated response to allergens


Type I Anaphylatic

IgE binds to basophils and mast cells

Ag binding stimulates degranulation

Released vasoactive amines cause anaphylaxis Histamines, leukotrines (cause contractions of smooth muscle), and prostaglandins (increase mucus secretions)




Localized Anaphylaxis

Cutaneous mast cells release histamine to local tissues

Allergic rhinitis (hayfever) or asthma-like complex

Food allergies


Systemic Anaphylaxis

Usually injected antigen/allergen

Subcutaneous mast cells release histamine directly to circulation

Anaphylactic shock


Type II Cytotoxic

Cytotoxic reactions

Abs bind to cells and activate Complement or cytotoxic cells


Type II Cytotoxic

Transfusion reactions

Hemolytic disease of the newborn


Type II (Cytotoxic) Reactions

•  Activation of complement by the combination of IgG or IgM antibodies with an antigenic cell •  Causes cell lysis or damage by macrophages

•  ABO blood group system •  Antibodies form against certain carbohydrate antigens

on RBCs •  A antigens, B antigens, or both •  Type O RBCs have no antigens


Table 19.2 The ABO Blood Group System


Type II (Cytotoxic) Reactions

•  Rh blood group system •  Rh factor antigen (Rh+) found on RBCs of 85% of the

population •  Rh+ blood given to an Rh– recipient will stimulate anti-

Rh antibodies in the recipient •  Hemolytic disease of the newborn (HDNB)

•  Rh– mother with an Rh+ fetus causes the mother to produce anti-Rh antibodies

•  Second Rh+ fetus will receive anti-Rh antibodies, damaging fetal RBCs



Type II Cytotoxic

Drug induced cytotoxic reactions

Thrombocytopenia purpura – platelets coated with quinine.

Agranulocytosis – WBCs destroyed

Hemolytic anemia – penicillin induced, binds to RBC. Antibodies begin complement.



Type III Immune Complex

Mediated by immune complexes

Soluble Ag-Ab complexes

Relative concentrations of Ag and Ab determine fate of complex

Ag and Abs in equal amounts with slight excess of Ag leads to complex becoming trapped in the basement layer beneath endothelial cells.



Type III Hypersensitivity

Ag excess

Smaller complexes stay soluble longer Filtered at kidney

Complex activates C’ at site

Glomerulonephritis –inflammatory damage to kidney glomeruli.


Type IV Delayed type hypersensitivity (DTH) Delayed type hypersensitivity (DTH)

Mediated by activated TH1 cells Released lymphokines attract and activate

macrophages which cause tissue damage

Delayed because mediated by T-helper cells which then become T-memory cells.

Ex. TB test. T-memory cells will proliferate.


Allergic contact dermatitis


Autoimmune Diseases

Self-reactivity due to a loss of immunological tolerance

Mechanisms somewhat parallel to hypersensitivity


Cytotoxic Autoimmune Reactions

Ab binds cells, but may not result in lysis

Graves disease – Ab mimics TSH. Thyroid produces excess hormones.

Myasthenia gravis – Abs coat acetylcholine receptors (where nerve impulses reach muscles).


Immune Complex Mediated Autoimmune Reactions

Soluble immune complexes mediate tissue damage

Systemic lupus erythematosus (SLE)- many unusual Abs

Rheumatoid arthritis- IgM, IgG, and complement accumulates in joints


Cell Mediated Autoimmune Reactions

Cytotoxic T cells (Tc) attack self cells

Multiple sclerosis – attack myelin sheath by Tc and macrophages.

Insulin-dependent diabetes mellitus – insulin secreting cells in the pancreas are destroyed by Tc cells


Transplantation Reactions

Major histocompatibility complex also called human leukocyte antigen (HLA)

A gene complex that codes for tissue specific antigens. There are four types.

MHC Ag’s are recognized by T cells in transplantation reactions

Probably resemble altered self – immune systems thinks foreign tissue is actually damanged tissue.


HLA Testing


Immune Deficiency

Impaired ability or inability to make immune responses

Congenital (primary)- genetic based

Acquired (secondary)- many specific and non-specific causes


Congenital Immune Deficiency

Deficiencies affecting T cells result in a marked increase in viral and parasitic infections, and cancer


T Cell Deficiencies

DiGeorge Syndrome – no thymus gland therefore no cell-mediated immunity.


Acquired Immune Deficiency

May be non-specific- Radiation or chemotherapy, nutritional, etc.

May be infectious- Epstein-Barr Virus, cytomegalovirus (CMV), HIV, and others


Acquired Immunodeficiency Syndrome (AIDS)

•  1981: in the United States, a cluster of cases of Pneumocystis pneumonia, Kaposi's sarcoma, and loss of immune function are discovered in young homosexual men

•  1983: the discovery of a virus causing the loss of immune function (HIV) •  Selectively infects T helper cells (CD4+)


The Origin of AIDS

•  SIV crossed over into the human population in west and central Africa from chimpanzees (around 1908, from bushmeat)

•  Spread throughout Africa as a result of urbanization and increased sexual promiscuity

•  Patient who died in 1959 in the Congo is the oldest known case

•  Norwegian sailor who died in 1976 is the first known case in Western world


The Structure of HIV

•  Genus Lentivirus •  Retrovirus •  Two identical strands of RNA, reverse

transcriptase enzyme, phospholipid envelope •  gp120 glycoprotein spikes •  Death of CD4 cells results in loss of regulation of

the immune system


Glycoprotein spike: gp120 gp41 transmembrane glycoprotein

Envelope

Reverse transcriptase enzyme

Envelope

RNA Capsid

Core with protein coat

Structure of HIV and infection of a CD4+ T cell. The gp120 glycoprotein spike on the membrane attaches to a receptor on the CD4+

cell. The gp41 transmembrane glycoprotein probably facilitates fusion by attaching to a fusion receptor on the CD4+ cell.

Figure 19.13 HIV structure and attachment to receptors on target T cell (2 of 3).


The Infectiveness and Pathogenicity of HIV

•  Spread by dendritic cells and carried to the lymphoid organs; contacts activated T cells

•  gp120 combines with CD4+ receptor and CCR5 or CXCR4 coreceptors •  CD4 molecules are carried on T helper cells,

macrophages, and dendritic cells •  Virus fuses and enters into the cell





AIDS

Terminal stage of HIV infection

Incubation time ~10 years


Diagnostic Methods

•  Seroconversion is the period of time between infection and the appearance of antibodies •  Takes up to 3 months

•  HIV antibodies detected by ELISA •  Viruses detected by Western blotting or APTIMA

(RNA testing) •  Plasma viral load (PVL) is determined by PCR or

nucleic acid hybridization


HIV Transmission

•  HIV survives 6 hours outside a cell •  HIV can survive more than 1.5 days inside a cell •  Routes of transmission: intimate sexual contact,

breast milk, transplacental infection, contaminated needles, organ transplants, and blood transfusion •  Anal-receptive intercourse is the most dangerous form

of sexual contact


Documents

PowerPoint Lecture Presentations prepared by Bradley W ... · Soluble Ag-Ab complexes Relative concentrations of Ag and Ab determine fate of complex Ag and Abs in equal amounts with