CD4 Cells

• The immune system's primary functions include recognizing and eliminating foreign antigens, forming immunologic memory, and developing tolerance to self-antigens. 
• The lymphocyte population consists mainly of thymus-derived T-lymphocytes, bone marrow-derived B-lymphocytes, and natural killer (NK) cells. T-lymphocytes are responsible for cellular immunity, while B-lymphocytes mediate humoral immunity. Together, they provide adaptive immunity, closely coordinating with the innate immune system.

1.0Introduction of CD4 cells

• It is also referred to as helper T cells (TH cells) and is characterized by the presence of the CD4 glycoprotein on their cell membrane, which is part of their T cell receptor. These cells are vital to the immune system, playing a key role in defending the body against infections. They activate other immune cells, including B lymphocytes, macrophages, and CD8 T lymphocytes, to target and destroy pathogens. CD4 T cells orchestrate the immune response by releasing various cytokines, which can either stimulate or inhibit the activity of these immune cells.
• Antigen-presenting cells (APCs) such as macrophages, neutrophils, and dendritic cells engulf and degrade extracellular pathogens like bacteria and viruses. These APCs display the processed antigens on their surface, paired with MHC class II molecules. CD4 T cells recognize these antigens through their T cell receptors and, in response, secrete cytokines, including interleukins and interferon-gamma (IFN-γ). The type of cytokines produced varies depending on the CD4 T cell subtype, which includes TH1, TH2, TH17, and TFH cells.
• The primary effects of CD4 T cells are directed towards B cells, CD8 T cells, and macrophages. The cytokines they release are essential for the maturation of B cells into plasma cells and memory B cells. Additionally, CD8 T cells perform cytotoxic functions, while macrophages remove pathogens through phagocytosis.

2.0Function of CD4 Cells

• CD4 T cells do not directly neutralize foreign substances but are crucial in orchestrating a strong immune response. 
• Although there are different subsets of CD4 T cells, their primary function is to activate other immune cells. Some CD4 T cells can also differentiate into memory T cells, essential for maintaining long-term immunity against infections. 
• Measuring the number of CD4 T cells in a person's blood is often used in diagnosing HIV, as the virus specifically targets and replicates within these cells. As the virus multiplies, it gradually depletes CD4 T cells, weakening the immune system.

3.0Types of CD4 cells

1. T Helper Cell 1 (TH1): TH1 cells coordinate immune responses against intracellular pathogens like bacteria. They produce cytokines, proteins that can influence the immune system or directly attack pathogens. Key cytokines produced by TH1 cells include:

• Interferon-gamma
• Interleukin-2
• Tumor necrosis factor-beta

2. T Helper Cell 2 (TH2):  TH2 cells manage immune responses against extracellular pathogens, such as parasitic worms (helminths). They also produce cytokines that activate other lymphocytes and regulate allergic reactions. Important cytokines produced by TH2 cells include:

• Interleukin-4 
• Interleukin-5 
• Interleukin-13

3. T Helper Cell 17 (TH17)-  TH17 cells produce interleukin-17, a signalling molecule that activates other immune cells. TH17 cells are essential for defending the body against extracellular bacteria and fungi.
4. Regulatory T Cells (Treg)-  Treg cells play a crucial role in monitoring and suppressing immune responses, helping to prevent autoimmune diseases and maintain immune system balance.

4.0Memory CD4+ T-cells

• These cells play a crucial role in sustaining a person's immunity. 
• These cells develop from naive CD4+ T cells, the precursors to memory cells. Once formed, they can recognize and respond to pathogens the body has previously encountered. 
• Memory CD4+ T cells trigger a more rapid and robust immune response when the body reencounters the same pathogen.

How does the body produce them?

• The production of memory CD4 T cells begins when an antigen or germ activates a naive CD4 T cell. This activation occurs when a naive CD4 T cell interacts with an antigen-presenting cell (APC), a specialized cell located in the lymph nodes. 
• APCs can recognize and process pathogens, presenting their antigens so CD4 T cells can identify as foreign. 
• Once activated, the naive CD4 T cells undergo division, creating multiple clones. Some of these clones differentiate into memory cells, which can produce cytokines that activate other immune cells, a function naive CD4 T cells do not have. 
• These memory CD4 T cells typically remain inactive in the body until they encounter the same germ, at which point they quickly respond.

What is a CD4 count?

• A blood test measures the number of CD4 cells in your blood. CD4 cells, also known as CD4 T lymphocytes or "helper T cells," are white blood cells that play a crucial role in your immune system. 
• They help protect your body by activating the immune response to fight off infections, including viruses, bacteria, and other harmful organisms. 
• This test is particularly important for people with HIV (human immunodeficiency virus) as it helps monitor the health of their immune system.

5.0HIV and CD4 cells

• The CD4 count test measures the number of CD4 cells in the blood, which are white blood cells known as T cells. 
• These cells play a key role in the immune system by identifying and destroying harmful bacteria, viruses, and other invaders. 
• The test results provide insight into the extent of damage to your immune system and help predict potential health outcomes if antiretroviral treatment (ART) is not started. Regardless of your CD4 count, ART is recommended for everyone with HIV. 
• Doctors monitor CD4 levels to assess the effectiveness of your treatment and make any necessary adjustments. 

What Does HIV do to CD4 Cells?

• HIV weakens your immune system by specifically attacking CD4 cells, a type of white blood cell crucial for defending your body against infections. 
• The virus attaches to the surface of a CD4 cell, enters it, and integrates itself into the cell's structure. As the infected CD4 cell dies, it releases new copies of the virus into your bloodstream, infecting more CD4 cells and perpetuating the cycle. 
• Over time, this process reduces the number of healthy CD4 cells, leaving your body vulnerable to infections. 
• HIV can destroy entire groups of CD4 cells, making it easier for harmful germs to invade your body, leading to what are known as opportunistic infections (OIs). 

How Do CD4 Levels Affect Viral Load?

• The aim of antiretroviral therapy (ART) is to reduce the amount of HIV in blood, known as  "viral load," to an undetectable level. 
• This means the virus is present at such low levels that standard tests cannot detect it, although it remains in your body. 
• If you stop treatment, HIV levels can rise again. When ART is adhered to properly, it can suppress HIV so effectively that it becomes undetectable in lab tests. This has two main effects:
• Lower Viral Load: ART reduces the viral load, which helps your immune system recover and produce more CD4 cells. These CD4 cells enhance your body's ability to fight infections and HIV-related cancers.
• Increased CD4 Levels: As the viral load decreases, your CD4 levels (also referred to as T cell levels) can rise, reflecting improved immune function.
• Secondly, maintaining an undetectable viral load with antiretroviral therapy (ART) significantly reduces the risk of transmitting HIV to sexual partners. People who achieve and sustain an undetectable viral load have an almost negligible chance of passing HIV on through sex.
• With consistent ART, many individuals can live for decades without advancing to the most severe stage of HIV, known as acquired immunodeficiency syndrome (AIDS). 
• ART is crucial because, without it, HIV levels will rise, and CD4 counts will decline, typically leading to AIDS within about ten years if left untreated. AIDS is a serious condition, and people with AIDS who do not receive treatment have a life expectancy of around three years. 
• Additionally, those with AIDS are more likely to have a higher viral load, increasing the risk of transmitting HIV to sexual partners.

What the Results Mean

• A normal CD4 count ranges from 500 to 1,400 cells per cubic millimetre of blood. Without antiretroviral therapy (ART), CD4 counts decrease over time. 
• When CD4 levels drop below 200 cells per cubic millimetre, the risk of developing various opportunistic infections (OIs), some of which can be life-threatening, increases. CD4 levels can vary based on the stage of HIV:

Stage 1: Acute HIV Infection

• During this early stage, HIV rapidly multiplies and destroys CD4 cells, causing a rapid decline in CD4 counts. As your immune system begins to respond, the viral load decreases, and CD4 levels may rise again, though they might not return to their pre-infection levels.

Stage 2: Chronic HIV Infection

• In this stage, HIV remains active but reproduces at a much slower rate. With effective antiretroviral therapy (ART), you can remain in this stage for many years, maintaining healthy CD4 levels and potentially avoiding progression to the next stage. If your condition progresses toward stage 3, you'll see an increase in viral load and a decrease in CD4 levels.

Stage 3: AIDS

• In this advanced stage, the immune system is severely compromised, making you vulnerable to opportunistic infections. AIDS may be diagnosed based on these infections or by a significant drop in CD4 levels, typically below 200. 
• It's important to note that test results sometimes align with your feelings. Some individuals may have high CD4 counts but experience other health issues, while others with low CD4 counts might feel relatively well but are at risk of serious complications if they don't start treatment. 
• Regardless of your CD4 count or symptoms, anyone with HIV should be on ART. Effective treatment should stabilize or increase your CD4 count. If your CD4 count continues to decline despite ART, your HIV may be developing resistance to the medication, which should be detected through regular viral load tests. In such cases, your doctor may adjust your ART regimen.

Other Factors Affecting CD4 Count

• Several factors aside from HIV can influence your CD4 count. Infections like the flu, pneumonia, or herpes simplex can temporarily lower your CD4 count. 
• Chemotherapy for cancer can also cause significant drops. Lifestyle factors, such as smoking, changes in sleep or exercise habits, and regular alcohol use, can also impact your CD4 levels.

When to Get a CD4 Test

• Immediately after your HIV diagnosis, you'll have a CD4 count done to establish a "baseline measurement." 
• This initial test helps your doctor track changes over time and determine if additional medications are needed to prevent specific opportunistic infections (OIs) alongside your HIV treatment.
• A viral load test, typically performed 2 to 8 weeks after starting or adjusting your antiretroviral therapy (ART), assesses the treatment's effectiveness. 
• The CD4 test at this point will indicate whether your immune system is improving in response to ART.
• After the initial tests should have a CD4 test every 3 to 6 months, or as frequently as your doctor advises, to monitor your immune system's status, if CD4 counts are low and you're on medications for OIs in addition to ART, you may be able to discontinue the OI drugs as your immune system improves with ART.
• If your CD4 counts remain above 500 and you achieve and maintain viral suppression, you might only need further CD4 testing if your health changes.

Similarities Between CD4 and CD8 T Cells

• Both types of T cells have T cell receptors, which vary and help distinguish between them.
• Both originate from a common lymphoid progenitor in the bone marrow and mature in the thymus.
• Additionally, both are crucial in initiating and regulating cell-mediated immune responses.

6.0Difference Between CD4 and CD8 T Cells