Microbiology Lecture 7 Review: Chapter 17, 27.6 (error-27.5)

Lecture Review

Chapter 17 - Immunologic Disorders

1.    [17-01] Compare allergies and autoimmune diseases. Give examples for both – Lecture 7, Slide 2 –
Allergies: Damaging immune responses to usually harmless foreign antigens.

·      Type I (IgE-mediated allergy) – Involves IgE class antibodies localized on mast cells/basophiles. Ex: Asthma, anaphylaxis

·      Type II (Antibody-dependent cytotoxic allergy) – Involves IgG, IgM antibodies, cytotoxic T cells and Natural killers. Ex: Transfusion reactions

·      Type III (Immune complex-mediated allergy – Involves IgG class antibodies that have formed immune complexes w/ soluble antigen persisting in blood stream. Ex: Glomerulonephritis, arthus reaction, serum sickness, disseminated intravascular coag

·      Type IV (Delayed cell-mediated allergy) – Involves only previously activated cytotoxic T cells or helper T cells. NO antibodies involved. Ex: Tuberculin skin test, contact dermatitis, rejection of transplants.

VS

      Autoimmune diseases: Damaging immune responses directed against self-antigen of one’s own cells and tissues. Caused when:

·      Injury – Parts not exposed to immune system are exposed. Ex: Rheumatoid arthritis.

·      Infection – Antibodies produced during infection, cross reaction with human antigens, Ex: Rheumatoid arthritis.

·      Imperfect clonal deletion of naïve B cells. Ex: Type 1 diabetes mellitus

2.    [17-02] Compare allergy and immunodeficiencies. Give examples for both – Lecture 7, Slide 2 –
Allergies = Immune response to harmless foreign antigens (overreaction).
Ex: Hives, hay fever, asthma, anaphylaxis.
VS
Immunodeficiencies =Immune insufficiency in responding to foreign antigens (weakness).

·      Primary – Gene mutation of immune system. Ex: SCID, agammaglobulinemia

·      Secondary – Individual is exposed to poor living conditions or infected with microbes. Ex: AIDS from HIV infection, malnutrition

3.    [17-03] Compare autoimmune diseases and immunodeficiencies. Give examples of both – Lecture 7, Slide 2 –
Autoimmune diseases = Immune response targeting one’s own cells and tissues. Ex: Rheumatoid arthritis, DM1
Immunodeficiencies= Immune insufficiency in responding to foreign antigens. Ex: SCID (primary – congenital), HIV (secondary).

4.    [17-04] Describe the general mechanism of type I allergy development – Lecture 7, Slide 3 –
Type 1 allergy = Immediate IgE-mediated allergy
Develops in < 1hr and involves IgE antibodies on surface of mast cells and basophils.

1)    Exposure to antigen – Leads to sensitization of individual.

·      Allergen binds to B cell receptor

·      Allergen taken into cells and its fragments exposed on MHCII receptors

·      MHCII-allergen complex recognized by T helper cell, gives Interleukin-4, activates B cell

·      Immune response class switching IgM replaced with IgE antibodies

·      IgE antibodies bind to mast cells (mucous membranes) and basophils (circulatory system)

2)    Subsequent exposure to antigen – Allergic reaction

·      Allergen binds to IgE antibody on mast cells or basophils

·      If cross-links at least 2 molecules of cell-bound IgE, triggers massive release of histamines.
Mast cells – Local allergic reaction (Ex: Hives, asthma)
Basophils – Systemic allergic reaction (Ex: Anaphylaxis)

5.    [17-05] Compare localized and systemic immediate IgE-mediated allergies. Give examples of each – Lecture 7, Slide 4 –
Localized immediate IgE-mediated allergies – mast cells = local inflammation. Ex: Hives(urticarial), asthma.
Systemic immediate IgE-mediated allergies – basophils = systemic vasodilation, BP↓. Ex: Anaphylaxis (Histamine released from basophils throughout entire body).

6.    [17-06] Describe general mechanism of type II allergy. Give examples – Lecture 7, Slides 5 –
Type 2 allergy = Antibody-dependent Cytotoxicity
Antibody (IgG/IgM) binds to the cell surface triggering compliment fixation via classical pathway forming membrane attack complex (MAC) OR antibody-dependent cellular cytotoxicity (ADCC) where Fc domain of cell-bound antibody is recognized by natural killer cells or macrophages.
Ex: Transfusion reactions:Host antibodies bind to transfer RBC and triggers compliment fixation classical pathway, membrane attack complex (MAC) and or natural killer cells. Both processes lyse transferred RBC.

7.    [17-07] Describe blood types, mechanism of transfusion reaction – Lecture 7, Slide 5 –

Four blood types: O, A, B, AB

Blood type	O (I)	A (II)	B (III)	AB (IV)
Antigens	None	A	B	A, B
Host Antibodies	A, B	B	A	None
Accepts	O	A, O	B, O	O,A,B, AB

When the wrong blood types are transfused the host’s antibodies attach to the antigens on the transfused blood lead to either complement fixation, classical pathway membrane attack complexes OR Antibody-dependent cellular cytotoxicity (ADCC), natural killer cells and macrophages attack antibody marked transfused RBCs.

8.    [17-08] Describe the mechanism of hemolytic disease of newborn. How hemolytic disease of newborn can be prevented and treated? – Lecture 7, Slide 6 –

Blood sometimes has additional antigen D (Rh factor, usually indicated as +/-). Hemolytic disease of the newborn occurs when the antibodies from an Rh– mother attack her Rh+ fetus causing lyses of the fetus’ red blood cells. Like with type 1 allergy takes a second exposure to Rh+ blood for the antibodies to attack.

·      Rh– mother carries Rh+ fetus, no development of antibodies b/c placental barrier

·      During delivery of Rh+ fetus, mother is exposed and her body creates anti-Rhesus IgG antibodies (1^st child okay).

·      During 2^nd pregnancy of Rh+ fetus, mother’s anti-Rhesus IgG are capable of crossing placenta and attacking RBCs of fetus. Leads to hemolysis of fetus RBCs.

Can be treated by only by blood transfusion in newborn to replace lysed RBCs.

More important to prevent disease: Prior blood typing of Rh factor, during pregnancy with first child mother is given Rh immune globulins (RhoGAM®) at 28^th week of pregnancy and within 72 hrs of delivery to prevent sensitization of mother to rhesus antigen.

9.    [17-09] Describe the mechanism of type III allergy. Give examples – Lecture 7, Slide 7 –
Type III allergy = Immune complex-mediated allergy
IgG-antigen complexes trigger wave of immune response that causes clotting resulting in tissue necrosis.

1)    IgG react with foreign soluble foreign antigen to form immune complex.

2)    Formed immune complex remains after NOT being cleared promptly by phagocytes. Continue to persist in blood stream and lymph for extended period.

3)    Persisting immune complexes activate compliment system, attracting basophils that release mediators causing vasodilation.

4)    Immune complexes become entrapped in walls of vasodilated vessels, and neutrophils arrive.

5)    Neutrophils release proteases that damage lining of blood vessels.

6)    Damage blood vessels start hemostasis chain causing disseminated intravascular coagulation (small vessel blood clots) leading to blockage of capillaries.

7)    With blood vessels blocked, tissue necrosis sets in with organ failure if severe.

Ex: Post-streptococcal glomerulonephritis – Untreated streptococcal infection (ex: S. pyogenes) may lead to immune complex-mediated allergy, resulting in kidney failure.

10. [17-10] Describe mechanism of autoimmune disease development – Lecture 7, Slide 10
Autoimmune disease: Immune system attacks self-antigens.
Three possible developments:

·      Imperfect clonal deletion of B cells/cytotoxic T cells

·      Tissue injury when normally hidden self-antigens exposed to immune system.

·      Infections leadings to immune response attack to similar self-antigens.

Ex: Imperfect clonal deletion (DM1), Tissue injury (Rheumatoid arthritis), Infections leading to immune system attacks on similar self-antigens (Rheumatic fever, as induced by S. pyogenes).

11. [17-11] Describe mechanism of type 1 diabetes mellitus development – Lecture 7, Slide 10 –
Type 1 Diabetes Mellitus (DM1) – Pancreas unable to secrete insulin, required for glucose absorption.

·      Imperfect clonal deletion of T cytotoxic cells = Tc cells that attack antigens on surface of insulin-producing pancreatic ß cells.

·      Killing off pancreatic ß cells → NO insulin produced.

·      Human cells starving despite glucose presence in blood.

 Signs and Symptoms: excessive urination, increase thirst, dry mouth, increase hunger, fatigue, weight loss, eventual death.
* DM1 individuals require regular insulin injections for life.

12. [17-12] Distinguish between primary and secondary immunodeficiency disorders. Give examples for both – Lecture 7, Slides 11, 2 –
Primary immunodeficiency disorders: Congenital, resulting from genetic mutations.
Ex: Selective IgA deficiency (mutations chromosome 6,14, or 18) → B cells cannot produce IgA antibodies.
Agammaglobulinemia (mutations in X chromosome) → inability of B cells to maturation.
Severe combined immunodeficiency disorder (SCID, mutation of gene on X chromosome that encodes common gamma chain shared by interleukin receptors) → B & T lymphocytes non-functional. Imagine: Bubble boy.

Secondary immunodeficiency disorders: Acquired depletions of certain immune cells.
Ex: Environmental factors, advanced age, immunosuppressive drugs, infections that weaken immune system (syphilis, malaria, leprosy, AIDS).

Chapter 27.5 - Viral STIs

1.    [27.6-01] Explain why is it impossible to get rid of the virus once person became infected with HIV? Can you think of other viral infections that cannot be eliminated from infected person? – Lecture 7, Slides 17, 18, 19 –

The HIV virus uses glycoprotein 120 (gp120) to dock onto the CD4 (receptor) and CXCR4 (coreceptor) of T helper cell → virus fuses with envelope → virus undergoes uncoats → reverse transcriptase turns viral ssRNA to dsDNA → Integrase combines viral dsDNA with host cell chromosome → Provirus (latent stage) → In host chromosome, viral genes constantly expressed in cell → production of new virons → HIV assembled at plasma membrane and released from cell via budding → Protease cleaves long polypeptide chains in the virus to make reverse transcriptase, integrase, and protease.

By integrating into host chromosome and by avoiding the infected cell’s death with budding, HIV is able to hide and grow within host T helper cells and macrophages.

Ex: Herpes Zoster – Recurrent outbreaks of Shingles b/c virus lays dormant in ganglia adjacent to spinal cord OR trigeminal ganglion as base of skull. First infection is from varicella zoster virus usually during childhood (as chickenpox). Virus reemerges when switching from lysogenic cycle to lytic cycle.

2.    [27.6-02] Why are macrophages becoming a major reservoir of HIV in an infected individual? – Lecture 7, Slides 19 –
Macrophages provide a second host cell for the virus to hide in (1^st one being the T helper cells). The body eventually catches on to the HIV infection and neutralizes HIV in the blood with antibodies and kills the infected T helper cells.

However, some HIV viruses attacked by anti-HIV antibodies are opsonized to be attacked by macrophages. Unfortunate, once inside macrophages HIV envelope prevents fusion of phagosomes with lysosomes. HIV survives inside macrophages.

HIVthen undergoes uncoating and repeats the process (ssRNA → dsDNA → integration to host DNA → provirus → Viral genes expressed making more of HIV → HIV released via budding  

3. [27.6-07] Describe statistical data for new HIV infections in the USA reported for 2011 – Lecture 7, Slide 27 –
2011 New HIV Cases = 37,417:
Acquired Through
Male-to-male sexual contact – 64.1% ≈ (2/3) of all new cases
Heterosexual contact – 28.1% ≈ (3/10)of all new cases
Injected drug use – 7.7% ≈ (1/10)of all new cases

Race of New Cases
African American – 2011:15,958; Cumulative total # of cases: 486,282
Whites – 2011:8,304; Cumulative total # of cases: 435,613
Hispanics – 2011:6,355; Cumulative total # of cases: 202,182 ≈ 200,000

Age Range of New Cases
20-24 years old –8,054
25-29 years old –7,484
30-34 years old – 6,209
*** Majority of new cases are during the sexually active periods from 20-35 years old.