Immunology Quiz: Antibodies and B Cells

Objectives

• Compare and contrast natural and acquired immunity
• List main organs, cells, and proteins involved in the immune response
• Understand the structure of immunoglobulins and their reaction with antigens
• Explain the role of MHC in antigen presentation
• Describe the genetic basis of ABO and Rh blood groups
• Relate HLA alleles to autoimmune disease
• List the four mechanisms of hypersensitivity reactions
• Explain the principle of blood transfusion
• Distinguish between systemic and organ-specific autoimmune diseases
• Define and describe the pathogenesis and molecular basis of SLE and rheumatoid arthritis
• Describe the pathogenesis and complications of AIDS
• Differentiate the three forms of amyloid and relate them to clinical presentations of amyloidosis
• Debate the pathologic cause of transplant rejection

Innate vs Adaptive Immunity

• Innate immunity—fast response, nonspecific, no memory
• Adaptive immunity—slower response, specific, has memory

Innate Immune Cell Types

• Neutrophils - phagocytes with granules containing enzymes
• Macrophages - phagocytes, antigen-presenting cells (APCs)
• Dendritic Cells - phagocytes, APCs
• NK cells - phagocytes

Innate Immune Complement

• Chemotaxis - recruitment of leukocytes
• Opsonization - marking a target on a microbe
• MAC - attack complex forming a pore

Innate Immune Cytokines

• Induce inflammation
• Induce vasodilation
• Cause fever
• Damage microbes

Innate Immune PRR + PAMP Phagocytosis

• Phagocytes have pattern recognition receptors (PRRs) to recognize pathogen-associated molecular patterns (PAMPs)
• PAMPs are essential to pathogens' life cycles
• PRR + PAMP initiates phagocytosis and cytokine release

Innate Immune Antigen Presentation

• The adaptive immune system is introduced to foreign invaders
• The pathogen is digested inside the phagosome
• Bits of the pathogen are placed on the APC surface
• APC encounters B and T cells
• This starts a further phagocytic response

Phagocytosis and Adaptive Involvement

• 3 ways to grab a pathogen:
  • PRR + PAMP
  • C3b receptor + complement
  • Antibody + FC receptor

Adaptive Immune System Traits

• Generates specific chemical and cellular responses to destroy pathogens
• More effective than nonspecific defenses
• Has a memory component
• Mediated by lymphocytes

Adaptive Immune Cell Types

• B cells: mature in bone marrow, produce antibodies. Controls antibody-mediated (humoral) immunity
• T cells: mature in thymus. Develop from naive →effector cells with the help of antigen-presenting cells to develop cytotoxic T cells & cell-mediated (cellular) immunity

T Cells: MHC

• MHC I: expressed on all cells, T cells patrol for foreign antigens, destroys cells with missing or incorrect antigens
• MHC II: on antigen presenting cells, helper T cells activate B cells to proliferate (and B cells recognize the foreign antigens)

T-Cell Weapons

• Perforins - poke holes in membranes
• Fas ligand - activates apoptosis
• Cytokines activate apoptosis

T cells: MHC Type II

• This protein is on phagocytic APCs - a bit of the ingested pathogen is presented
• Helper T cells (CD4) recognize it and activate B cells to proliferate

Receptors

• Innate PAMP
• T cells: MHC I, MHC II

HLA

• Gene complex coding MHC in human cells
• Located on chromosome 6
• HLA genes are polymorphic
• Inheritance of particular HLA alleles can form harmful immune responses

Transition

• The presentation of adaptive immunity to the immune response
• How adaptive immunity evolved
• Explanation of adaptive immunity's key machinery

Immunoglobulins

• Y-shaped proteins that can be either an antibody or a receptor
• Fab portion - antigen binding tips
• Fc portion - stem
• Variable portion
• Hypervariable region

B cell Antibody Isotypes

• IgM: released as a pentamer
• IgD: cell doesn´t work
• IgG: monomer, strong
• IgA: mucosa
• IgE: mast cells

B cell Maturation & Activation

• B cells start in the bone marrow
• B cells have 10^12 number of cells making receptors for every possible antigen through somatic recombination.
• B cells are tested for self-tolerance
• B cells are activated during the second wave if the pathogen is found to be “correctly” defined

B cell Specialization

• Mature naïve B cell reacts to an antigen:
• Releases IgM pentameter into plasma
• IgM is fast and not specific
• Activated plasma cell releases IgM as a pentameter
• Memory B cells have IgG on cell surface, IgG releases as a monomer.

T and B cell recap

• Helper T cells (CD4+): stimulates proliferation of B cells and also stimulate phagocytes
• Cytotoxic T cells (CD8+): destroy infected cells, directly attack viruses, bacteria, cancer, & transplanted organs
• Memory T cells: activate immune response if same antigen is reintroduced
• B cells are genetically programmed to produce antibodies (plasma cells)
• Antibodies: proteins produced by B cells, bind and inactivate foreign molecules (antigens)

Antibodies Recap

• IgG: opsonizes microbes for phagocytosis, crosses the placenta
• IgM & IgG: first & second waves of immune response
• IgA: secretions in mucosal tissues
• IgE: asthma & allergies, coats helminthic parasites, works with mast cells & eosinophils to kill them.

Blood Typing

• Two primary blood groups - ABO and Rh
• Important to note antigens are not present, body produces antibodies
• Self-tolerance not developed so antibodies can be made

Rh Factor and Pregnancy

• Mother-fetus incompatibility in the Rh system can result in the destruction of fetal red blood cells
• Hemolytic disease of the newborn (HDN) - occurs when mothers are Rh- and fetus is Rh+, causing maternal antibodies to destroy the fetus's blood cells
• Rh antibodies attack Rh+ fetuses.

Hypersensitivity

• Type I: immediate hypersensitivity, allergies
• Type II: cytotoxic reaction, antibodies attack self cells
• Type III: immune complex deposition, small vessels
• Type IV: cell-mediated, T cells attack

Autoimmune Diseases

• The immune system attacks self-antigens & kills cells and tissues of the body
• Examples of systemic diseases: systemic lupus erythematosus, rheumatic fever, rheumatoid arthritis, & systemic sclerosis
• Examples of System/organ-Specific diseases: Multiple sclerosis, Hashimoto Thyroiditis, Autoimmune hemolytic anemia, Membranoproliferative glomerulonephritis, Primary biliary cirrhosis, Pemphigus vulgaris, & Myasthenia gravis

Rheumatoid Arthritis

• Chronic, systemic inflammatory, autoimmune disease affecting joints
• Also affects synovial membranes
• Prevalence of 1% (3-5X more common in women)
• Any age, usually in second to fourth decades
• Genetic predisposition
• Environmental trigger activates helper T cells
• Type IV hypersensitivity

Systemic Lupus Erythematosus

• Systemic autoimmune disease
• Caused by autoantibodies & the formation of immune complexes
• Fatigue, fever, malaise, nephritis, skin lesions, & arthritis
• More common in females & young adults over 30
• Inherited susceptibility in class II MHC and complement genes
• Type III hypersensitivity

AIDS (Acquired Immunodeficiency Syndrome)

• A collection of disorders due to HIV infection
• HIV targets and kills helper T cells
• Transmission through blood or body fluids
• Sexual contact, parenteral inoculation (IV drug users, blood transfusions), vertical transmission (infected mothers to newborns)

HIV Infection & Replication

• Viral RNA enters a helper T cell
• Viral RNA is transcribed (reverse transcription) into viral DNA
• Viral DNA integrates into host cell's DNA
• DNA including viral genes is transcribed
• Some transcripts form new viral RNA, others translated into proteins
• Proteins assemble as new virus particles

Progression of HIV Infection

• Acute phase: high levels of virus production, signs of systemic infection, seroconversion
• Chronic phase (clinical latency): virus continues to replicate, immune system largely intact
• Later stage: helper T cells decline, immune defenses diminish, opportunistic infections

Pathologic Findings in AIDS

• Catastrophic breakdown of immune defenses, marked increase in viremia, reduced CD4+ cell count (below 200 cells/L)
• Serious opportunistic infections, secondary neoplasms, neurological manifestations
• Symptoms: vary from CNS to skin and the rest of the body

Misc.

• Transplant rejection - initiates due to host T-cells recognizing foreign HLA antigens of a graft

• Types include: hyperacute, acute cellular, acute antibody-mediated, and chronic

• Treatment involves immunosuppressants for immune response

• Amyloidosis - a group of conditions where extracellular deposits of fibrillar proteins cause tissue damage

• Amyloid diagnosed by demonstration of amyloid in tissue requiring biopsy

• Primary amyloidosis: usually AL type, clonal proliferations of plasma cells such as multiple myeloma

• Reactive systemic amyloidosis: occurs secondary to inflammation, AA type