Immune Deficiency Diseases and Hypersensitivity: Mechanisms, Disorders, and HIV/AIDS

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Immune Deficiency Diseases and Hypersensitivity

Introduction

This study guide covers the mechanisms and clinical implications of immune deficiency diseases and hypersensitivity reactions, including autoimmune disorders, transplantation immunology, and HIV/AIDS. These topics are central to understanding the immune system's role in health and disease, as outlined in microbiology curricula.

Hypersensitivity

Overview of Hypersensitivity

Hypersensitivity refers to an exaggerated immune response to antigens (allergens) that results in tissue damage. There are four main types, each with distinct mechanisms and clinical presentations.

Type I (Anaphylactic): Rapid onset, mediated by IgE antibodies.
Type II (Cytotoxic): Involves IgG or IgM antibodies and complement, leading to cell lysis.
Type III (Immune Complex): Immune complexes deposit in tissues, causing inflammation.
Type IV (Delayed Cell-Mediated): T cell-mediated, with delayed onset.

Hygiene Hypothesis: Suggests that reduced exposure to antigens in overly clean environments lowers immune tolerance, increasing hypersensitivity risk.

Types of Hypersensitivity Reactions

Type of Reaction	Time After Exposure
Type I (Anaphylactic)	<30 min
Type II (Cytotoxic)	5–12 hours
Type III (Immune Complex)	3–8 hours
Type IV (Delayed Cell-Mediated)	≥1 day

Type I (Anaphylactic) Reactions

Type I hypersensitivity involves IgE antibodies bound to mast cells and basophils. Upon exposure to the allergen, cross-linking of IgE triggers degranulation and release of mediators such as histamine, leukotrienes, and prostaglandins, leading to allergic symptoms.

Systemic anaphylaxis: Can cause circulatory collapse and death.
Localized anaphylaxis: Includes hives, hay fever, and asthma.

The mechanism of anaphylaxis: IgE antibodies on mast cells trigger degranulation and mediator release SEM of degranulated mast cell after antigen exposure

Diagnosis: Skin tests are used to identify specific allergens.

A skin test to identify allergens

Prevention: Desensitization injections stimulate IgG production, which blocks allergen binding to IgE.

Type II (Cytotoxic) Reactions

Type II reactions involve IgG or IgM antibodies directed against cell surface antigens, activating complement and leading to cell lysis or phagocytosis. Classic examples include transfusion reactions and hemolytic disease of the newborn.

ABO Blood Group System: Incompatibility leads to hemolysis.

Blood Group	Erythrocyte Antigens	Plasma Antibodies	Blood That Can Be Received	Frequency (%)
AB	A and B	Neither anti-A nor anti-B	AB, A, B, O	White: 4, Black: 4, Asian: 5
B	B	Anti-A	B, O	White: 11, Black: 20, Asian: 27
A	A	Anti-B	A, O	White: 41, Black: 27, Asian: 28
O	Neither A nor B	Anti-A and Anti-B	O	White: 47, Black: 49, Asian: 40

Table: The ABO Blood Group System

Hemolytic Disease of the Newborn: Occurs when an Rh– mother produces anti-Rh antibodies that attack Rh+ fetal red blood cells in subsequent pregnancies.

Hemolytic disease of the newborn: maternal anti-Rh antibodies attack fetal RBCs

Type III (Immune Complex) Reactions

Type III hypersensitivity is mediated by immune complexes (antigen-antibody aggregates) that deposit in tissues, activating complement and attracting neutrophils, which release enzymes causing tissue damage. Examples include systemic lupus erythematosus and glomerulonephritis.

Immune complexes deposited in vessel wall, attracting neutrophils and causing damage Steps in immune complex–mediated hypersensitivity

Type IV (Delayed Cell-Mediated) Reactions

Type IV hypersensitivity is mediated by T cells (especially cytotoxic T lymphocytes, CTLs). The reaction is delayed (24–48 hours) and involves cytokine-mediated recruitment of macrophages and cytotoxic cells, leading to tissue damage. Examples include allergic contact dermatitis (e.g., poison ivy) and latex allergy.

Development of allergic contact dermatitis to poison ivy Allergic contact dermatitis on the hand

Autoimmune Diseases

Mechanisms and Types

Autoimmunity is the loss of self-tolerance, leading to immune responses against the body's own tissues. Mechanisms include:

Cytotoxic: Antibodies react with cell-surface antigens (e.g., Graves’ disease).
Immune Complex: Immune complexes deposit in tissues (e.g., systemic lupus erythematosus).
Cell-Mediated: T cell-mediated tissue damage (e.g., psoriasis).

Clonal deletion during fetal development normally ensures self-tolerance.

Transplantation Immunology

HLA and Graft Types

Histocompatibility antigens (encoded by the major histocompatibility complex, MHC, or HLA in humans) are critical for tissue compatibility. Tissue typing is used to match donor and recipient HLAs to minimize rejection.

Tissue typing: anti-HLA antibodies and complement test

Autograft: Self-tissue
Isograft: Identical twin
Allograft: Another person
Xenograft: Nonhuman tissue

Immunosuppression is required to prevent rejection, using drugs such as cyclosporine, tacrolimus, and others that inhibit T cell activation.

The Immune System and Cancer

Immune Surveillance and Immunotherapy

Cancer cells express tumor-associated antigens and are targeted by cytotoxic T lymphocytes (CTLs). Immunotherapies include monoclonal antibodies, cytokines (e.g., TNF, IL-2), and vaccines targeting tumor antigens.

CTL attacking and lysing a cancer cell

Immunodeficiencies

Types and Examples

Immunodeficiencies are conditions where the immune system is impaired. They can be:

Congenital: Genetic defects (e.g., severe combined immunodeficiency, SCID).
Acquired: Result from infections (e.g., HIV), drugs, or cancers.

Disease	Cells Affected
AIDS	TH (CD4+) cells
Selective IgA immunodeficiency	B, T cells
Common variable hypogammaglobulinemia	B, T cells (decreased immunoglobulins)
Reticular dysgenesis	B, T, and stem cells
Severe combined immunodeficiency	B, T, and stem cells
Thymic aplasia (DiGeorge syndrome)	T cells (defective thymus)
Wiskott-Aldrich syndrome	B, T cells
X-linked infantile (Bruton’s) agammaglobulinemia	B cells (decreased immunoglobulins)

HIV/AIDS

HIV Structure and Infection Mechanism

HIV is a retrovirus that infects CD4+ T cells, leading to acquired immunodeficiency syndrome (AIDS). The virus attaches to CD4 and coreceptors (CCR5 or CXCR4), fuses with the cell membrane, and releases its RNA genome, which is reverse transcribed and integrated into the host genome as a provirus.

CD4+ T cell with HIV particles HIV structure and attachment to CD4+ T cell Attachment of HIV to CD4 and coreceptor Fusion of HIV with cell membrane Entry of HIV and uncoating of viral RNA

HIV Replication and Latency

After integration, HIV can remain latent or become active, producing new virions that bud from the host cell. Latency allows the virus to evade immune detection and antiretroviral drugs.

Active HIV infection in CD4+ T cells Active HIV infection in macrophages and dendritic cells Latent HIV infection in CD4+ T cells Latent HIV infection in macrophages

HIV Types and Global Distribution

HIV-1: Main type, with subtypes (clades) B, C, E, etc.
HIV-2: Less common, mainly in West Africa.

Clinical Stages of HIV Infection

Phase 1: Asymptomatic or chronic lymphadenopathy.
Phase 2: Symptomatic, early immune failure.
Phase 3: AIDS-defining conditions (e.g., opportunistic infections).

Diagnosis and Transmission

Diagnosis: ELISA for antibodies, Western blot, PCR for viral RNA.
Transmission: Sexual contact, blood, perinatal, breast milk, contaminated needles.

Prevention and Treatment

Prevention: Safe sex, sterile needles, universal precautions for healthcare workers.
Antiretroviral Therapy (ART): Includes reverse transcriptase inhibitors, protease inhibitors, entry inhibitors, and integrase inhibitors.
HAART (Highly Active Antiretroviral Therapy): Combination of drugs to suppress viral replication and delay progression to AIDS.

Acyclovir structure compared to deoxyguanosine

Vaccine development is challenging due to HIV's high mutation rate, clade diversity, and latent reservoirs.

Summary Table: Types of Hypersensitivity

Type	Immune Mechanism	Example
I (Anaphylactic)	IgE-mediated, mast cell degranulation	Allergic rhinitis, anaphylaxis
II (Cytotoxic)	IgG/IgM + complement, cell lysis	Transfusion reaction, hemolytic disease of newborn
III (Immune Complex)	Immune complex deposition, complement activation	Serum sickness, lupus
IV (Delayed Cell-Mediated)	T cell-mediated, cytokine release	Contact dermatitis, TB skin test

Additional info: This guide integrates textbook-level explanations and visual aids to reinforce key concepts in immunology, hypersensitivity, autoimmunity, transplantation, and HIV/AIDS for microbiology students.