Unit 2 - Immune system disorders

Antibody

What the immune system makes

• A Y-shaped protein made by B cells (plasma cells) in response to an antigen.

• It specifically binds to an antigen to help neutralize it or mark it for destruction.

Antibody = “body’s defense”

Antigen

what the immune system recognizes

• A foreign substance that triggers an immune response.

• The immune system recognizes it as something that doesn't belong.

• Examples: proteins on the surface of bacteria, viruses, or allergens.

Antigen = “attacker” / target

Hypersensitivity

• Altered immunologic response to an antigen, resulting in disease or damage

• First exposure: slow initial response; memory cells produced In the case of hypersensitivity, no observable response may occur with the first exposure.

• Subsequent exposures: rapid, highly increased response = observable disease symptoms and signs

Immediate hypersensitivity reaction

Type 1 hypersensitivity reactions have a very rapid onset - occur within 5 to 30 minutes of exposure to an antigen.

These reactions have a significant genetic component, in that for example a child born to two parents that display a local Type 1 hypersensitivity reaction to a given allergen will have a 50% chance of also being allergic to that allergen.

mediated by IgE antibodies being produced that sensitized mast cells to an antigen.

Type I = Immediate = IgE + Mast cells → Histamine → Allergy

Delayed hypersensitivity reaction

Type 4 hypersensitivity is an immune reaction mediated by T lymphocytes, NOT antibodies.

2 mechanisms:

1. Direct cell-mediated cytotoxicity

   • Involves CD8+ cytotoxic T cells

   • Cytotoxic T cells directly kill the target cells.

2. Delayed hypersensitivity

   • Involves CD4+ TH1 helper T cells

   • TH1 cells activate/recruit macrophages and other inflammatory cells.

   • The reaction is delayed, typically peaking 48–72 hours after exposure.

Allergy

A harmful or exaggerated immune response to an environmental antigen (allergen), usually involving IgE antibodies that sensitize mast cells/basophils. Some allergies, such as poison ivy, are Type IV and T-cell mediated.

Allergen

An environmental antigen that triggers an exaggerated or inappropriate immune response (allergy) in a sensitized individual.

Anaphylaxis

A severe, life-threatening systemic allergic reaction that causes widespread vascular changes and fluid shifts throughout the body.

Shock

A life-threatening condition in which the circulatory system fails to provide adequate blood flow and oxygen to the body’s tissues, resulting in inadequate tissue perfusion and potentially organ dysfunction or failure.

inadequate tissue perfusion → not enough oxygen/nutrients reaching cells → cellular and organ dysfunction.

Immunotolerance

Immunotolerance: The ability of the immune system to recognize and tolerate the body’s own (“self”) cells and tissues without mounting a detrimental immune response against them.

Self = tolerated → no harmful immune attack.

Autoimmune response

An inappropriate immune response in which the immune system attacks the body’s own (“self”) cells, tissues, or molecules because immunotolerance to self has been lost, causing tissue damage and potentially disease.

Loss of self-tolerance → immune system attacks self → tissue damage.

Alloimmune response

An immune response against cells, tissues, or organs from another genetically different individual of the same species, because the recipient’s immune system recognizes the donor’s cells as foreign.

Same species, genetically different → recognized as foreign → immune response.

MHC-1 protein

A protein found on the surface of almost all nucleated cells that displays peptide antigens from inside the cell to CD8⁺ cytotoxic T cells. This allows the immune system to detect cells that may be infected or abnormal.

MHC I → intracellular antigens → CD8⁺ T cells → destroys infected/abnormal cells.

Easy memory trick: MHC I = “Inside” → shows what’s happening inside the cell.

MHC-2 protein

A protein found primarily on the surface of antigen-presenting cells (APCs), such as macrophages, dendritic cells, and B cells, that displays peptide antigens from outside the cell to CD4⁺ helper T cells. This helps activate and coordinate the immune response.

MHC II → extracellular antigens → CD4⁺ T cells → activates immune response.

Easy memory trick:

• MHC I = Inside → CD8

• MHC II = Outside → CD4

HLA

Human Leukocyte Antigen: The human version of the major histocompatibility complex (MHC) proteins found on cell surfaces. HLAs help the immune system distinguish the body’s own cells (“self”) from foreign cells or substances by presenting antigen fragments to T cells.

HLA = human MHC → helps distinguish self from non-self.

For your flashcard:
HLA: Human MHC proteins that present antigen fragments to T cells and help the immune system distinguish self from foreign.

Immunodeficiency

A condition in which the immune system is weakened or impaired, resulting in an inadequate or ineffective immune response and making an individual more susceptible to infections and certain diseases.

Impaired immune system → inadequate immune response → increased susceptibility to infection.

Primary immune deficiency

An immune system deficiency caused by an inherited or genetic defect that is present from birth, resulting in an impaired or ineffective immune response and increased susceptibility to infections.

Primary = genetic/inherited → present from birth → impaired immune function.

Secondary immune deficiency

An immune system deficiency that develops after birth as a result of an external factor or another condition, rather than being caused by an inherited genetic defect. It can impair immune function and increase susceptibility to infections.

Examples: HIV infection, malnutrition, cancer, or certain medications/treatments that suppress the immune system.

Secondary = acquired after birth → caused by an external factor/condition → impaired immunity.

Urticaria

A.K.A Hives

A skin reaction characterized by raised, itchy, red or pale welts that occur when histamine and other inflammatory chemicals are released, often in response to an allergen or other trigger.

Urticaria = hives → itchy, raised welts → often caused by histamine release.

Pruritus

An unpleasant sensation of itching that creates the urge to scratch the skin, often caused by histamine release, inflammation, allergic reactions, or skin irritation.

Pruritus = itching → urge to scratch.

For Type I hypersensitivity, state its mediator

IgE antibodies and mast cells/basophils

I = IgE

For Type II hypersensitivity, state its mediator

IgG or IgM antibodies and complement

Type II = IgG or IgM

For Type III hypersensitivity, state its mediator

Antigen-antibody immune complexes and complement

III = Immune complexes

For Type IV hypersensitivity, state its mediator

T cells (especially CD4 and CD8 T cells

IV = T cells

Name 3 areas of the body where the effects of mast cell degranulation can be significant

1. Respiratory tract (airways/lungs) → bronchoconstriction, mucus production, and difficulty breathing

2. Skin → redness, swelling, itching, and urticaria (hives)

   1. Blood vessels/circulatory system → vasodilation and increased vascular permeability, causing low blood pressure and potentially shock

Lungs → Skin → Blood vessels

Name 4 possible treatments and 1 potentially curative therapy for allergic rhinitis.

Treatments:

• Antihistamines → reduce the effects of histamine and relieve allergy symptoms.

• Decongestants → reduce nasal congestion.

• Nasal corticosteroids → reduce inflammation in the nasal passages.

• Allergen avoidance → avoiding the offending allergen prevents symptoms from occurring.

1 potentially curative therapy:
5. Desensitization (allergen immunotherapy) → regular injections of the allergen stimulate IgG antibody production. The IgG antibodies can bind/capture the allergen before it combines with cell-bound IgE, helping prevent the allergic reaction.

Name 2 types of drug given for quick relief of bronchial asthma

1. Bronchodilators (β-adrenergic agonists)
2. Adrenaline (epinephrine)

Quick relief: Bronchodilators (β-adrenergic agonists) and adrenaline → relieve acute airway constriction.

Name 4 types of drug used for long-term treatment of bronchial asthma

• Corticosteroids → decrease airway hyper-responsiveness and inflammation.

• Mast cell stabilizers → prevent mast cells from degranulating and releasing inflammatory mediators.

• Smooth muscle relaxants → help prevent bronchospasm.

• Leukotriene modifiers (anti-leukotrienes) → prevent the effects/synthesis of leukotrienes and reduce late-phase responses.

List the 3 patterns of transplant rejection

Hyperacute → immediate–days → pre-existing antibodies
Acute → days–months → T cells (Type IV)
Chronic → months–years → progressive organ failure, vascular damage & fibrosis

List the 5 main types of primary immune deficiency.

1. B-lymphocyte (humoral) immunodeficiency → impaired antibody production

2. T-lymphocyte (cell-mediated) immunodeficiency → impaired T-cell function

3. Combined immunodeficiency → both B and T lymphocytes are deficient

4. Complement deficiency → defective complement system

5. Phagocyte deficiency → decreased number or impaired function of phagocytes

B → T → Combined → Complement → Phagocytes

List 4 opportunistic infections that commonly affect AIDS patients

1. Pneumocystosis (Pneumocystis pneumonia) – caused by Pneumocystis jirovecii
2. Candidiasis – especially oropharyngeal or esophageal Candida (“thrush”)
3. Mycobacterium avium complex (MAC) – bacterial/mycobacterial infection
4. Cytomegalovirus (CMV) – viral infection that can cause retinitis, encephalitis, or GI disease

P-C-M-C → Pneumocystosis, Candidiasis, MAC, CMV.

Name 2 malignancies associated with AIDS

• Kaposi sarcoma – HHV-8-induced cancer involving endothelial cells of small blood vessels.

• Non-Hodgkin lymphomas – cancers of lymphocytes involving uncontrolled growth of lymphoid tissue

Of the 4 types of hypersensitivity reactions, which ones involve antibodies

Types I, II, and III

• Type I: IgE antibodies

• Type II: IgG or IgM antibodies

• Type III: Antigen-antibody immune complexes

Of the 4 types of hypersensitivity reactions, which ones involve T cells

Type IV: T-cell mediated, involving CD4+ helper T cells and CD8+ cytotoxic T cells

Of the 4 types of hypersensitivity reactions, which ones involve B cells

Types I, II, and III indirectly

B cells produce the antibodies involved in Types I, II, and III.

Describe in detail the development of a Type I hypersensitivity reaction

Absolutely — for a detailed flashcard, I’d break it into clear steps like this:

Q: Describe in detail the development of a Type I hypersensitivity reaction.

A: Type I hypersensitivity = immediate, IgE-mediated reaction

1. First exposure to allergen (sensitization):

• An allergen enters the body.

• The allergen is presented to CD4+ helper T cells.

• Helper T cells stimulate B cells to produce IgE antibodies specific to the allergen.

• IgE antibodies attach to receptors on mast cells and basophils.

• The mast cells and basophils are now sensitized.

• Usually, there is little or no allergic reaction during the first exposure.

2. Second exposure to the same allergen:

• The allergen enters the body again.

• The allergen binds to the IgE antibodies already attached to mast cells and basophils.

• IgE antibodies are cross-linked by the allergen.

• This triggers degranulation of mast cells and basophils.

3. Release of chemical mediators:

• Mast cells and basophils release histamine and other inflammatory mediators.

• These mediators produce the symptoms of the allergic reaction.

4. Effects of the mediators:

• Vasodilation → increased blood flow → redness

• Increased vascular permeability → fluid moves into tissues → swelling/edema

• Smooth muscle contraction/bronchoconstriction → difficulty breathing

• Increased mucus secretion

• Itching (pruritus)

Allergen → CD4+ T cells → B cells → IgE → mast cell/basophil sensitization → re-exposure → IgE cross-linking → degranulation → histamine/inflammatory mediators → allergic symptoms

During a Type II hypersensitivity reaction, where are the relevant antigens located?

The relevant antigens are located on the surface of cells or within the extracellular matrix.

• Cell-surface antigens → antibodies bind to antigens on the surface of cells.

• Extracellular matrix antigens → antibodies bind to antigens within tissues.

Describe in detail each of the following mechanisms of a Type II hypersensitivity reaction: Cell destruction

• IgG or IgM antibodies bind to antigens on the surface of a cell.

• The antibodies can activate the complement system.

• Complement can form a membrane attack complex (MAC) in the cell membrane.

• This causes cell lysis and destruction.

• Antibody-coated cells can also be recognized and destroyed by phagocytes or natural killer (NK) cells.

Key idea: Antibody binds cell → complement/immune cells → cell destroyed

Cell destruction → cell is killed

Describe in detail each of the following mechanisms of a Type II hypersensitivity reaction: Inflammation

• IgG or IgM antibodies bind to antigens on the surface of cells or tissues.

• This activates the complement system.

• Complement products attract and activate neutrophils and other inflammatory cells.

• These cells release enzymes and inflammatory chemicals.

• The resulting inflammation causes tissue damage.

Key idea: Antibody binds tissue → complement → inflammatory cells → tissue damage

Inflammation → tissue is damaged

Describe in detail each of the following mechanisms of a Type II hypersensitivity reaction: Altered cell metabolism

• Antibodies bind to receptors on the surface of cells.

• Instead of destroying the cell, the antibodies interfere with the normal function of the receptor.

• The receptor may be blocked or stimulated, altering normal cell activity.

• This changes the cell's metabolism or function without necessarily causing cell destruction.

Key idea: Antibody binds receptor → receptor function altered → cell function changes

Altered metabolism → cell functions abnormally

During a Type III hypersensitivity reaction, where are the relevant antigens initially located?

The relevant antigens are initially located in the extracellular environment, such as in the bloodstream or tissues.

• They are soluble antigens, meaning they are not fixed to the surface of cells.

• The antigens combine with IgG or IgM antibodies to form antigen-antibody immune complexes.

• These immune complexes can then deposit in tissues, where they activate complement and cause inflammation.

Type III = soluble antigen → immune complexes → tissue deposition → inflammation.

Describe the development of a Type III hypersensitivity reaction.

Type III Hypersensitivity — Development

A: Type III = immune complex–mediated reaction

1. Antigen enters the body:

• A soluble antigen is present in the blood or tissues.

• The antigen is not attached to a cell surface.

2. Antibody production:

• B cells produce IgG or IgM antibodies against the antigen.

• The antibodies bind to the soluble antigens.

3. Immune complex formation:

• Antigen + antibody combine to form antigen-antibody immune complexes.

• These immune complexes circulate through the bloodstream.

4. Immune complex deposition:

• The immune complexes can become deposited in tissues, especially in areas such as blood vessel walls, joints, kidneys, and lungs.

5. Complement activation:

• The deposited immune complexes activate the complement system.

• Complement products attract and activate neutrophils and other inflammatory cells.

6. Inflammation and tissue damage:

• Inflammatory cells release enzymes and other inflammatory substances.

• This causes inflammation and tissue damage at the site where the immune complexes have deposited.

Soluble antigen → IgG/IgM → immune complexes → deposition in tissues → complement activation → inflammation → tissue damage

Describe in detail the development of each of the following types of Type IV hypersensitivity reaction: Direct cell-mediated cytotoxicity

• Type IV hypersensitivity is T-cell mediated and does not involve antibodies.

• An antigen is presented to CD8+ cytotoxic T cells (TC cells).

• The CD8+ T cells become activated and recognize cells displaying the antigen.

• The cytotoxic T cells attach to the target cells.

• They release cytotoxic substances that cause the target cell to undergo cell death.

• This results in direct destruction of the antigen-containing cells.

Key idea:
Antigen → CD8+ T cell activation → cytotoxic T cell attacks target cell → cell death

Describe in detail the development of each of the following types of Type IV hypersensitivity reaction: Delayed hypersensitivity

• An antigen is presented to CD4+ helper T cells.

• The helper T cells become sensitized/activated.

• On re-exposure to the antigen, the sensitized T cells recognize the antigen.

• The T cells release cytokines and other chemical signals.

• These signals attract and activate macrophages and other inflammatory cells.

• The activated cells release substances that cause inflammation and tissue damage.

• The reaction is called delayed because it generally develops 24–72 hours after exposure.

Key idea:
Antigen → CD4+ T cell activation → cytokines → macrophages/inflammatory cells → inflammation → tissue damage

Summarize how immunotolerance could be lost.

Immunotolerance can be lost when the immune system fails to recognize the body's own cells and tissues as “self,” causing an autoimmune response.

• Normally: Self-antigens are tolerated → no harmful immune response.

• Loss of tolerance: Self-antigens are incorrectly recognized as foreign → self-reactive immune cells become activated.

• This can result in autoimmune reactions and tissue damage.

Key idea:
Loss of self-tolerance → immune system attacks self → autoimmune response → tissue damage.

Summarize the consequences of immunotolerance being lost.

Loss of immunotolerance causes the immune system to recognize and attack the body's own (“self”) cells, tissues, or molecules, resulting in an autoimmune response.

• Self-tolerance is lost

• → Self-reactive immune cells become activated

• → Immune system attacks the body's own tissues

• → Inflammation and tissue damage

• → May result in autoimmune disease

Loss of immunotolerance → autoimmune response → tissue damage → autoimmune disease.

By which hypersensitivity reaction types are autoimmune reactions usually caused?

Autoimmune reactions are usually caused by Type II, Type III, and Type IV hypersensitivity reactions.

• Type II → antibodies (IgG/IgM) attack self-antigens on cells or tissues

• Type III → antigen-antibody immune complexes deposit in tissues and cause inflammation

• Type IV → T cells attack or cause inflammation against the body's own tissues

⭐ Key idea: Autoimmune = usually Types II, III, and IV.

Describe each of the following characteristics of systemic lupus erythematosus (SLE): The general underlying cause defining SLE.

The general underlying cause defining SLE

• SLE is an autoimmune disease caused by a loss of immunotolerance to self-antigens.

• The immune system produces antibodies against the body's own cells and tissues.

• This results in widespread inflammation and tissue damage.

Describe each of the following characteristics of systemic lupus erythematosus (SLE): Two types of molecular self-antigens that may be present in SLE. What type of hypersensitivity would this represent?

• Self-antigens can include DNA and RNA.

• Antibodies bind to these soluble self-antigens and form antigen-antibody immune complexes.

• The immune complexes can deposit in tissues and trigger inflammation.

• This represents a Type III hypersensitivity reaction.

Key: DNA/RNA → immune complexes → Type III

Describe each of the following characteristics of systemic lupus erythematosus (SLE): Three specific cellular self-antigens that may be present in SLE. What type of hypersensitivity would this represent?

• Self-antigens can be present on red blood cells (RBCs), platelets, and white blood cells (WBCs).

• IgG or IgM antibodies can bind to these cell-surface antigens.

• The antibody-coated cells may then be destroyed by the immune system.

• This represents a Type II hypersensitivity reaction.

Key: RBCs + platelets + WBCs → antibodies → Type II

Describe each of the following characteristics of systemic lupus erythematosus (SLE): Which specific type of self-antigen is particularly characteristic of SLE?

• Nuclear antigens are particularly characteristic of SLE.

• These include components such as DNA and other nuclear material.

• Antibodies against nuclear antigens are an important feature of SLE.

Key: SLE → anti-nuclear antibodies (ANA)

Describe each of the following characteristics of systemic lupus erythematosus (SLE): Refer to your answers above to explain why the symptoms of SLE involve all body systems.

• SLE can involve both Type II and Type III hypersensitivity reactions.

• Type II: antibodies can attack cells throughout the body.

• Type III: immune complexes circulate through the blood and can deposit in different tissues.

• Therefore, many different organs and body systems can be affected, producing widespread symptoms.

Key sequence: Autoantibodies → cells/immune complexes throughout body → widespread inflammation and tissue damage → multiple organ systems affected

Describe each of the following characteristics of systemic lupus erythematosus (SLE): Explain why in SLE it is important to use treatments that counteract the inflammatory response.

Why is it important to use treatments that counteract the inflammatory response?

• SLE causes widespread immune-mediated inflammation.

• Immune complexes and antibodies trigger inflammatory responses that can damage tissues.

• Therefore, reducing inflammation helps limit tissue and organ damage and reduce symptoms.

Key: Less inflammation → less tissue damage

Describe each of the following characteristics of systemic lupus erythematosus (SLE): Explain how immunosuppressant drugs would help alleviate the symptoms of SLE, and explain why this treatment is only used in severe cases.

• Immunosuppressant drugs reduce immune system activity.

• This decreases the production/activity of immune cells and antibodies involved in the autoimmune response.

• As a result, there is less inflammation and tissue damage, which helps relieve SLE symptoms.

• However, suppressing the immune system also reduces the body's ability to fight infections and other pathogens.

• Therefore, immunosuppressant drugs are generally reserved for severe cases where the benefits outweigh the risks.

Key idea: Immunosuppressants → ↓ immune response → ↓ inflammation/tissue damage, but also ↓ ability to fight infection.

Describe the characteristics of each of the following classes of primary immune deficiency (PID): B lymphocyte PID

• Deficiency of B lymphocytes → impaired antibody production.

• May involve the absence of one or more antibody classes (e.g., IgE, IgG).

• Increased susceptibility to infections, particularly encapsulated bacteria.

Key: B cells → antibodies → encapsulated bacteria

Describe the characteristics of each of the following classes of primary immune deficiency (PID): T lymphocyte PID

• Deficiency of T lymphocytes, including CD4+ helper T cells (TH) and/or CD8+ cytotoxic T cells (TC).

• Causes impaired cell-mediated immunity.

• Increased susceptibility to fungal, protozoan, viral, and intracellular bacterial infections.

• Also increases susceptibility to oncogenic viruses and tumours.

• Circulating antibody levels may be low because B-cell function depends on helper T cells.

Key: T cells → cell-mediated immunity → fungi, protozoa, viruses, intracellular bacteria

Describe the characteristics of each of the following classes of primary immune deficiency (PID): Combined PID

• Deficiency of T lymphocytes, including CD4+ helper T cells (TH) and/or CD8+ cytotoxic T cells (TC).

• Causes impaired cell-mediated immunity.

• Increased susceptibility to fungal, protozoan, viral, and intracellular bacterial infections.

• Also increases susceptibility to oncogenic viruses and tumours.

• Circulating antibody levels may be low because B-cell function depends on helper T cells.

Key: T cells → cell-mediated immunity → fungi, protozoa, viruses, intracellular bacteria

Describe the characteristics of each of the following classes of primary immune deficiency (PID): Complement PID

• Deficiency of T lymphocytes, including CD4+ helper T cells (TH) and/or CD8+ cytotoxic T cells (TC).

• Causes impaired cell-mediated immunity.

• Increased susceptibility to fungal, protozoan, viral, and intracellular bacterial infections.

• Also increases susceptibility to oncogenic viruses and tumours.

• Circulating antibody levels may be low because B-cell function depends on helper T cells.

Key: T cells → cell-mediated immunity → fungi, protozoa, viruses, intracellular bacteria

Describe the characteristics of each of the following classes of primary immune deficiency (PID): Phagocyte PID

• Defects involving phagocytes, including neutrophils and macrophages.

• The defect may involve phagocyte number, function, or both.

• Results in increased susceptibility to bacterial infections.

Key: Phagocyte defect → impaired phagocytosis → bacterial infections